Volume I ABCD — Delta-9-tetrahydrocannabinol
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultan...
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Volume I ABCD — Delta-9-tetrahydrocannabinol
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
Production Editor: Joyce I. Buchea Acquisitions Editor: Mark Rehn Photo Editor: Cynthia Breslin Beres Design and Graphics: James Hutson Layout: William Zimmerman
Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
First Printing
printed in the united states of america
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Contents Alopecia . . . . . . . . . . . . . . . . . . . . . . . . 47 ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . . . . 48 Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . . . . 49 Amenorrhea . . . . . . . . . . . . . . . . . . . . . . 50 American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . . . . 52 American Cancer Society (ACS) . . . . . . . . . . . 53 American Institute for Cancer Research (AICR) . . . 54 4-Aminobiphenyl . . . . . . . . . . . . . . . . . . . 56 AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . . . . 56 Amyloidosis . . . . . . . . . . . . . . . . . . . . . . 58 Anal cancer . . . . . . . . . . . . . . . . . . . . . . 59 Androgen drugs . . . . . . . . . . . . . . . . . . . . 61 Anemia . . . . . . . . . . . . . . . . . . . . . . . . 62 Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . . . . 64 Angiogenesis inhibitors . . . . . . . . . . . . . . . . 66 Angiography. . . . . . . . . . . . . . . . . . . . . . 68 Angiosarcomas . . . . . . . . . . . . . . . . . . . . 69 Anoscopy . . . . . . . . . . . . . . . . . . . . . . . 70 Anthraquinones . . . . . . . . . . . . . . . . . . . . 71 Anthrax . . . . . . . . . . . . . . . . . . . . . . . . 71 Antiandrogens . . . . . . . . . . . . . . . . . . . . . 72 Antidiarrheal agents . . . . . . . . . . . . . . . . . . 73 Antiestrogens . . . . . . . . . . . . . . . . . . . . . 75 Antifungal therapies . . . . . . . . . . . . . . . . . . 76 Antimetabolites in chemotherapy . . . . . . . . . . . 78 Antinausea medications . . . . . . . . . . . . . . . . 81 Antineoplastics in chemotherapy . . . . . . . . . . . 83 Antioxidants . . . . . . . . . . . . . . . . . . . . . . 86 Antiperspirants and breast cancer . . . . . . . . . . . 88 Antiviral therapies. . . . . . . . . . . . . . . . . . . 90 Anxiety . . . . . . . . . . . . . . . . . . . . . . . . 93 APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . . . . 94 Aplastic anemia . . . . . . . . . . . . . . . . . . . . 95 Appendix cancer . . . . . . . . . . . . . . . . . . . 97 Appetite loss. . . . . . . . . . . . . . . . . . . . . . 98 APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . . . . . . . . 100 Arterial embolization . . . . . . . . . . . . . . . . 101 Artificial sweeteners . . . . . . . . . . . . . . . . . 102 Asbestos . . . . . . . . . . . . . . . . . . . . . . . 103
Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 Alkylating agents in chemotherapy . . . . . . . . . . 45 ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin v
Salem Health: Cancer Ascites . . . . . . . . . . . . Ashkenazi Jews and cancer . Asian Americans and cancer. Astrocytomas. . . . . . . . . Ataxia telangiectasia (AT) . . Autologous blood transfusion Axillary dissection . . . . . . Azathioprine . . . . . . . . .
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105 107 109 112 114 115 116 117
Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . .
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118 118 120 121 123 124
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126 128 128 130 131 132
Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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CA 15-3 test . . . . . . . . . . . . . CA 19-9 test . . . . . . . . . . . . . CA 27-29 test . . . . . . . . . . . . CA 125 test. . . . . . . . . . . . . . Cachexia . . . . . . . . . . . . . . . Cadmium and cadmium compounds. Caffeine . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . Calcium . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . vi
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205 205 206 206 207 208 209 211 212 212
Contents Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . . . . . . . . . . . . . . . . . . . . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . . Childhood cancers . . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . .
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213 216 218 220 221
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223 224 227 230
Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . . . .
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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Salem Health: Cancer Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . . Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . .
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332 335 336 338
Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
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339 340 341 342
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344 345 346 347 347 348 350 350
D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
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Publisher’s Note not only the names of the specializations but also related subspecialists, the cancers they treat, how they are trained and certified, and the range of services and procedures they perform. Finally, a group of topics addressing social and personal issues, lifestyle choices, nutritional supplements, and complementary or alternative therapies are similarly formatted into subsections that call out key areas of interest for readers. Special features of the set include tables throughout identifying the most important chemotherapeutic and other drugs and the symptoms and conditions they address, population statistics, survival rates, and other core information. Every essay includes a section of “See also” cross-references to other essays in the set that will be of interest to those consulting the topic at hand. A fully crossreferenced “Complete List of Contents” at the beginning of every volume also assists readers in locating related topics of interest. Photographs display for readers typical instances of lesions, tumors, procedures, and anatomical cross-sections to locate areas of the body affected. In addition, 8 appendixes at the end of volume 4 provide information on the following:
Salem Health: Cancer alphabetically arranges 835 essays on all aspects of cancer for all nonspecialist interest groups—from those who have been diagnosed to caregivers, family members, students, and readers with a general interest in health. The essays in this 4-volume set address diseases, conditions, symptoms, cancer-related syndromes, chemotherapy and other drugs, cancer centers, genetics, the biology of cancer, medical specialties, tests, procedures, complementary and alternative therapies, lifestyles, healthy and preventive strategies, and the many social and personal issues surrounding cancer, from cancer’s impact on minority populations to finances, insurance, relationships, and emotional coping. Written by physicians, nurses, and professional medical writers whose credentials and degrees are clearly listed in the byline to every essay, this comprehensive reference publication will be of interest not only to public library patrons but also to premedical students and those building collections for the patient population. Essays vary in length from 400 to 2,000 words, ranging from one to five pages. The information is presented in one of six standard essay formats by type of topic covered: carcinogen, disease or condition, drug or drug class, medical specialty, procedure, or “overview” (of an aspect of cancer biology, a personal or lifestyle issue, or an area of social concern). All essays present a capsule definition of the topic, and all but the briefest essays list sources of further information from both print and online resources. The essay formats are designed for the reader for whom the information is compelling or urgent, fostering quick identification and retrieval of essential facts: Essays on diseases and conditions, for example, list “also known as” names and describe related conditions, risk factors, the disease process, incidence, symptoms, screening and diagnosis, treatment, and prognosis. Essays on carcinogens list “also known as” names for the chemical or substance, cancers related to the carcinogen, exposure routes, principal places where the substance is found, populations at risk, symptoms to watch for, and a brief history of how we came to identify the substance as a carcinogen. Essays on drugs list the Anatomical Therapeutic Chemical (ATC) classification system code if one exists; the types of cancer, side effect, or other condition for which the drug is indicated; the delivery routes (such as pill form or injection); the way the drug works; and side effects. Essays on procedures apprise patients and their caregivers of why the procedure is performed, how to prepare, aftercare, risks, and the range of results. Essays on medical specialties identify
• • • • • • • •
Drugs by Generic Name Drugs by Trade Name Associations and Agencies Cancer Centers and Hospitals Cancer Support Groups Carcinogens Glossary Bibliography
A Category List and a complete subject index round out the set. Salem Health: Cancer has been the beneficiary of many expert contributors—physicians, nurses, pharmacists, and professional medical writers—whose names and academic or professional affiliations appear in the list of contributors that follows. Finally, this publication was made possible above all by our three consulting editors: Jeffrey A. Knight, Chair of the Department of Biological Sciences at Mount Holyoke College; Laurie JacksonGrusby, Ph.D., Assistant Professor in Pathology at Harvard Medical School, Children’s Hospital Boston; and Wendy White-Ryan, M.D., FAAP, is a board-certified pediatrician and member of the American Academy of Pediatrics. ix
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About the Editors from the Sontag Foundation for her work on pediatric brain tumors.
Jeffrey A. Knight, Ph.D., is Chair of the Department of Biological Sciences at Mount Holyoke College, where he teaches courses in genetics, molecular biology, and microbiology. He has held Visiting Professor appointments at the medical schools of the Universities of Massachusetts, Florida, and Vermont. Author of several research papers on the mitochondrial genetics of baker’s yeast, he has also been a frequent contributor to Salem Press publications. He edited the first edition of the Encyclopedia of Genetics (Salem Press, 1999), winner of the American Library Association, Reference and User Services Association’s “Outstanding Reference Source,” 2000.
Wendy White-Ryan, M.D., FAAP, is a board-certified pediatrician and member of the American Academy of Pediatrics as well as Alpha Omega Alpha. She completed her B.A. at Mount Holyoke College, her M.D. at New York Medical College, and her residency training in pediatrics at Strong Memorial Hospital in Rochester, New York. She worked in toxicology research at the University of Rochester for two years between earning her bachelor’s degree and entering medical school. She practiced pediatrics full-time for nine years in the inner city of Rochester until being diagnosed with Stage IV breast cancer in 2005. She became medically stable after undergoing both conventional and integrative treatments, including changes in diet and exercise, while remaining affiliated with Golisano Children’s Hospital at Strong Memorial Hospital in Rochester. She supports mind-body work, nutritional support through nutriceuticals, and other health-promoting lifestyle changes in the prevention or treatment of cancer.
Laurie Jackson-Grusby, Ph.D., is an Assistant Professor in Pathology at Harvard Medical School, Children’s Hospital Boston, and a faculty member of the Harvard Stem Cell Institute and Kirby Center for Neuroscience. She is a visiting instructor at the Harvard Extension school, where she teaches genetics. Her laboratory investigates the role of epigenetics in development of disease. She was awarded the Distinguished Scientist Award
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Contributors
Abbie L. Abboud, M.S., C.G.C.
Kerry L. Cheesman, Ph.D.
H. Bradford Hawley, M.D.
Richard Adler, Ph.D.
Wanda E. Clark, M.T. (ASCP)
Peter B. Heller, Ph.D.
Jane Adrian, M.P.H., Ed.M., M.T. (ASCP)
Lisa M. Cockrell, B.S.
Collette Bishop Hendler, R.N., M.S.
Pam Conboy, B.S.
Michelle L. Herdman, Ph.D.
Pamela S. Cooper, Ph.D.
Jennifer M. Hickin, B.S.
Angela M. Costello, B.S.
Carl W. Hoagstrom, Ph.D.
Charlotte Crowder, M.P.H., ELS
Christine G. Holzmueller, B.L.A.
Reyniel Cruz-Aguado, Ph.D.
Mary Hurd, M.A.
D. Scott Cunningham, M.D., Ph.D.
Bernard Jacobson, Ph.D.
Arun S. Dabholkar, Ph.D.
Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP)
Robert J. Amato, D.O. Cathy Anderson, R.N., B.A. Terry A. Anderson, B.S. Wendell Anderson, B.A. Michele Arduengo, Ph.D., ELS Bryan C. Auday, Ph.D. Tanja Bekhuis, Ph.D. Paul F. Bell, Ph.D. Alvin K. Benson, Ph.D. Anna Binda, Ph.D. Robert Bockstiegel, B.S. Scott A. Boerner, M.S. Patricia Boone, Ph.D. Andrea Bradford, M.A. Wanda Todd Bradshaw, R.N.C., M.S.N. Thomas L. Brown, Ph.D. Suzette Buhr, R.T.R., C.D.A. Amy Bull, D.S.N., A.P.N. Michael A. Buratovich, Ph.D. Bharat Burman, B.A. Jaime Stockslager Buss, M.S.P.H., ELS Alex B. Cantrell, B.A. Richard P. Capriccioso, M.D. Mary Car-Blanchard, O.T.D., B.S.O.T. Christine M. Carroll, R.N., B.S.N., M.B.A.
Helen Davidson, B.A. Martiscia Davidson, A.M. Cynthia L. De Vine, B.A. Jackie Dial, Ph.D. Jeremy W. Dugosh, Ph.D. Aldo C. Dumlao, M.D Patricia Stanfill Edens, R.N., Ph.D., FACHE Renée Euchner, R.N. Jill Ferguson, Ph.D.
Susan J. Karcher, Ph.D. Sarah Kasprowicz, M.D. Michelle Kasprzak, R.N., B.S.N., O.C.N. Keller Kaufman-Fox, B.A. Debra B. Kessler, M.D., Ph.D. A. K. Khan, M.D., M.R.C.P. M. A. Q. Khan, M.D., Ph.D. Samreen F. Khan, M.A. Ing-Wei Khor, Ph.D.
Adi Ferrara, B.S. Amber L. Fields, M.S. K. Thomas Finley, Ph.D. MaryAnn Foote, M.S., Ph.D. Jo Gambosi, M.A., B.S.N. James S. Godde, Ph.D. Janet R. Green, M.S.P.H. Katrina Green, R.N., B.S.N., O.C.N. Silke Haidekker, Ph.D. Linda Hart, M.S., M.A. Melanie Hawkins, B.S.N., R.N., O.C.N. xiii
Michael R. King, Ph.D. Samuel V. A. Kisseadoo, Ph.D. Jeffrey A. Knight, Ph.D. Marylane Wade Koch, M.S.N., R.N. Robert W. Koch, D.N.S., R.N. Lalitha Krishnan, Ph.D. Anita P. Kuan, Ph.D. Steven A. Kuhl, Ph.D. Jeffrey P. Larson, P.T., B.S., A.T.C. Lindsay Lewellyn, B.S. Lisa M. Lines, M.P.H.
Salem Health: Cancer Martha O. Loustaunau, Ph.D.
Marcia Pinneau, R.N.
Amanda McQuade, Ph.D.
Nancy A. Piotrowski, Ph.D.
Kyle J. McQuade, Ph.D.
Victoria Price, Ph.D.
Marianne M. Madsen, M.S.
Christopher Pung, B.S., C.L.Sp. (CG)
Judy Majewski, M.S.
Cynthia Racer, M.A., M.P.H.
Elizabeth A. Manning, Ph.D.
Bagirathy Ravishankar, Ph.D.
Vicki Miskovsky, B.S., R.D.
Pamela Richardson, M.S.
Paul Moglia, Ph.D.
Alice C. Richer, R.D., M.B.A., L.D.
Christina J. Moose, M.A.
Elizabeth D. Schafer, Ph.D.
Linda August Vrooman, R.N., B.S.N., O.C.N.
Karen M. Nagel, Ph.D.
Jason J. Schwartz, Ph.D., J.D.
C. J. Walsh, Ph.D.
Anita Nagypál, Ph.D.
Miriam E. Schwartz, M.D., M.A., Ph.D.
Stephanie Watson, B.S.
Amy J. Neil, M.S., M.A.P. David A. Olle, M.S. Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc.
Banalata Sen, Ph.D. Terry J. Shackleford, Ph.D. Lisa J. Shientag, V.M.D.
Carol Ann Suda, B.S., M.T. (ASCP), S.M. Rena C. Tabata, M.Sc. Dorothy P. Terry, R.N. Susan E. Ullmann, M.T. (ASCP), M.A. Nicole M. Van Hoey, Pharm.D. Charles L. Vigue, Ph.D.
Marcia J. Weiss, J.D. John B. Welsh, M.D., Ph.D. Bradley R. A. Wilson, Ph.D.
Ophelia Panganiban, B.S.
R. Baird Shuman, Ph.D.
Nicola E. Wittekindt, Dr.Sc. (ETH Zürich)
Jeannie V. Pasacreta, Ph.D., A.P.R.N.
Vonne Sieve, M.A.
Geetha Yadav, Ph.D.
Anna Perez, M.Sc.
Dwight G. Smith, Ph.D.
John L. Zeller, M.D., Ph.D.
Susan H. Peterman, M.P.H.
Richard S. Spira, D.V.M.
Diego Pineda, M.S.
Kelli Miller Stacy, ELS
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Complete List of Contents Volume 1 Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 xv
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . . xvi
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Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
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269 269 271 272
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274 274 276 279 281 283 285
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
. . 313 . . 315 . . 317 . . . . . . . .
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
327 329 331 332 335 336 338
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
339 340 341 342
Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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357 357 360 362
. . . 365 . . . 365 . . . 366 . . . 368 . . . 369
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370 373 373 374 375 376
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. . . 380 xviii
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
. . . 378 . . . 378
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
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Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
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460 461 464 466 467 469 471 472 474 xix
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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475 476 478 481
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . .
. 550 . 550 . 552
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590 xx
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593 597 599 601 603 605 606 608
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
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Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
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. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 xxi
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802 xxii
. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
. . . 858
. . . 859
Complete List of Contents Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937 xxiii
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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. . . . 1021 . . . . 1023
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
. . . . . . . . . . . .
Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
. . . 1067 . . . 1070 . . . 1071
Volume 4 Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
. . . . . . 1073 . . . . . . 1073 . . . . . . 1074 . . . . . . 1076
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1078 1082 1083 1084 1084 xxiv
. . 1086 . . 1088
. . 1091 . . 1093 . . 1096
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
. . 1106
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
. . 1147 . . 1149 . . . . . . . . . . . . . . . .
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
. . . . . 1173 . . . . .
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1174 1175 1177 1179 1180 xxv
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
xxvi
Volume II Denys-Drash syndrome and cancer — Liver cancers
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
Production Editor: Joyce I. Buchea Acquisitions Editor: Mark Rehn Photo Editor: Cynthia Breslin Beres Design and Graphics: James Hutson Layout: William Zimmerman
Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
First Printing
printed in the united states of america
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Contents
Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . . Down syndrome and leukemia. . . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . . Dukes’ classification . . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . . .
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Edema . . . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . . . . Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
357 357 360 362
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370 373 373 374 375 376
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy xxxiii
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396 399 399 400 401 402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
Salem Health: Cancer Fallopian tube cancer . . . . . . . . . . . . Family history and risk assessment . . . . . Fanconi anemia . . . . . . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . . . . . . Fertility drugs and cancer . . . . . . . . . . Fertility issues . . . . . . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . . . . . . . Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . . GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . Gynecologic oncology . . . . . . . . . . . .
460 461 464 466 467 469 471 472 474 475 476 478 481
H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . Health maintenance organizations (HMOs) Helicobacter pylori. . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . Hereditary diffuse gastric cancer . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . Hereditary papillary renal cell carcinomas Hereditary polyposis syndromes . . . . . .
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512 515 517 519 522 525 527 527 530 531
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534 535 536 536 537 538 540 540 541
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
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580 580 581 582
Contents Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . . HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . . Human growth factors and tumor growth . . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . . . IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . .
Immunoelectrophoresis (IEP) . . . . . . Immunotherapy . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . Inflammatory bowel disease . . . . . . . Informed consent. . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) . . . . . . . . . . . . . . . . Interferon. . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . Invasive lobular carcinomas . . . . . . . Ionizing radiation . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . .
. 584 . 586
. 587 . 588 . 590
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593 597 599 601 603 605 606 608
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. 609 . 610
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638 638 641 643 645 646 647 648 651
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652 653 654 655 656 657 657 658 659 661 661
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665
611 612 612 613 614 615 617 618 619 620 621 622 623
Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . . Lacrimal gland tumors . . . . . . . . . Lactate dehydrogenase (LDH) test . . Laetrile . . . . . . . . . . . . . . . . . Lambert-Eaton myasthenic syndrome (LEMS) . . . . . . . . . . . . . . . Laparoscopy and laparoscopic surgery Laryngeal cancer . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . Laryngectomy . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . .
. . 625 . . 626 . . 629 . . 632 . . 633 xxxv
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667 669 670 670 671 674
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679 681 682 685 686 687 688
Salem Health: Cancer Latinos/Hispanics and cancer . . . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia
. 690 . 692
Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
. 693 . 694 . 696 . 698
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698 702 704 704 706 706 708 709 710 712 714 715
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Complete List of Contents Volume 1
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44
Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
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64 66 68 69 70 71 71 72 73 75 76 78 81 83 86 88 90 93
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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148 149 151 151 154
Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . .
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158 161 163 165 166 167 168
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180 182 184 185 188 190 193 194 195 196 196 197 197 199 199
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205 205 206 206 207
Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
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Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
. . . . . . . .
Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
. . . . . . . . .
460 461 464 466 467 469 471 472 474 xli
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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475 476 478 481
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
. . . . 484 . . . . 484
. . . . 506 . . . . 508 . . . . 511 . . . . . . . . . .
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . .
. 550 . 550 . 552
. . . . . . . . . . . . . . . . . . . . .
554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590 xlii
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593 597 599 601 603 605 606 608
. . 609
. . 609 . . 610
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
. . . . . . 675
Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
. . . 693 . . . 694
. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 xliii
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802 xliv
. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
. . . 858
. . . 859
Complete List of Contents Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937 xlv
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
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Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
. . . 1067 . . . 1070 . . . 1071
Volume 4 Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
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1078 1082 1083 1084 1084 xlvi
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
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1174 1175 1177 1179 1180 xlvii
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
xlviii
Volume III Living will — Self-image and body image
Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College
Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
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Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
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printed in the united states of america
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Contents Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . . MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . .
Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . . Lumps . . . . . . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . . . . . . Lutein . . . . . . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . . . . . . Lymphangiography . . . . . . . . . . . . Lymphangiosarcomas . . . . . . . . . . . Lymphedema. . . . . . . . . . . . . . . . Lymphocytosis . . . . . . . . . . . . . . . Lymphomas . . . . . . . . . . . . . . . .
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719 720 723 725 726
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733 737 737 738 740 741 742 743 744
M. D. Anderson Cancer Center . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . Malignant fibrous histiocytoma (MFH) . . . Malignant rhabdoid tumor of the kidney . . Malignant tumors . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . Mayo Clinic Cancer Center . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . .
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766 768 768 770 772 lv
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774 775 776 779 780
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781 782 783 785 786 788
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790 791 792 793 794 795 796 796 798 800 802
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807 808 809 812 813 815 817 817 819 820 822 823 825
Salem Health: Cancer 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . . Nutrition and cancer prevention . . . . . . . . Nutrition and cancer treatment. . . . . . . . . Obesity-associated cancers . . . . Occupational exposures and cancer Occupational therapy . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . Omega-3 fatty acids . . . . . . . . Ommaya reservoir . . . . . . . . . Oncogenes . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . Oncology . . . . . . . . . . . . . . Oncology clinical nurse specialist . Oncology social worker . . . . . . Oophorectomy . . . . . . . . . . . Ophthalmic oncology . . . . . . . Opioids . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . Oral and oropharyngeal cancers . . Orbit tumors . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . .
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
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Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy Pediatric oncology and hematology . . . . . . Pelvic examination . . . . . . . . . . . . . . . Penile cancer . . . . . . . . . . . . . . . . . . Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . Pericardial effusion . . . . . . . . . . . . . . Pericardiocentesis . . . . . . . . . . . . . . . Peritoneovenous shunts . . . . . . . . . . . . Personality and cancer . . . . . . . . . . . . . Pesticides and the food chain . . . . . . . . . PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . Pharmacy oncology . . . . . . . . . . . . . . Phenacetin . . . . . . . . . . . . . . . . . . . Phenolics . . . . . . . . . . . . . . . . . . . . Pheochromocytomas . . . . . . . . . . . . . . Pheresis . . . . . . . . . . . . . . . . . . . . Photodynamic therapy (PDT) . . . . . . . . . Phyllodes tumors. . . . . . . . . . . . . . . . Phytoestrogens . . . . . . . . . . . . . . . . . Pineoblastomas. . . . . . . . . . . . . . . . . Pituitary tumors . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 lvi
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902 903 905 908 909 911
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951 952 955 955 956 958 959 960 962 963 965
Contents PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001 Primary central nervous system lymphomas . . . . 1003 Progesterone receptor assay . . . . . . . . . . . . 1003 Prostate cancer . . . . . . . . . . . . . . . . . . . 1004 Prostate-specific antigen (PSA) test . . . . . . . . 1006 Prostatectomy. . . . . . . . . . . . . . . . . . . . 1008 Prostatitis . . . . . . . . . . . . . . . . . . . . . . 1009 Proteasome inhibitors. . . . . . . . . . . . . . . . 1010 Protein electrophoresis . . . . . . . . . . . . . . . 1010 Proteomics and cancer research . . . . . . . . . . 1012 Proton beam therapy . . . . . . . . . . . . . . . . 1014 Proto-oncogenes and carcinogenesis . . . . . . . . 1015 PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . . . . . 1016 Psychosocial aspects of cancer . . . . . . . . . . . 1018 PTHC. See Percutaneous transhepatic cholangiography
Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . . . . . Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . . Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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Complete List of Contents Volume 1 Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 lix
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64 66 68 69 70 71 71 72 73 75 76 78 81 83 86 88 90 93
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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100 101 102 103 105 107 109 112 114 115 116 117
Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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118 118 120 121 123 124
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126 128 128 130 131 132
Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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136 138 138 139
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148 149 151 151 154
CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . . lx
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158 161 163 165 166 167 168
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180 182 184 185 188 190 193 194 195 196 196 197 197 199 199
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205 205 206 206 207
Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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208 209 211 212 212 213 216 218 220 221
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223 224 227 230 232 233
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235 237 238 239 240 242
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245 245 246 247 248
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
249 251 253 254 257
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274 274 276 279 281 283 285
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
327 329 331 332 335 336 338
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
339 340 341 342
Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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357 357 360 362
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370 373 373 374 375 376
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
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Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
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460 461 464 466 467 469 471 472 474 lxiii
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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475 476 478 481
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . .
. 550 . 550 . 552
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590 lxiv
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593 597 599 601 603 605 606 608
. . 609
. . 609 . . 610
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
. . . . . . 675
Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
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. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 lxv
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802 lxvi
. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
. . . 858
. . . 859
Complete List of Contents Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937 lxvii
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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. . . . 1021 . . . . 1023
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
. . . . . . . . . . . .
Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
. . . 1067 . . . 1070 . . . 1071
Volume 4 Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
. . . . . . 1073 . . . . . . 1073 . . . . . . 1074 . . . . . . 1076
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1078 1082 1083 1084 1084 lxviii
. . 1086 . . 1088
. . 1091 . . 1093 . . 1096
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
. . 1106
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
. . 1147 . . 1149 . . . . . . . . . . . . . . . .
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
. . . . . 1173 . . . . .
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1174 1175 1177 1179 1180 lxix
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
lxx
Volume IV Sentinel lymph node (SLN) biopsy and mapping — Zollinger-Ellison syndrome Appendixes Indexes Editor
Jeffrey A. Knight, Ph.D. Mount Holyoke College Medical Consultants
Laurie Jackson-Grusby, Ph.D. Children’s Hospital Boston, Harvard Medical School
Wendy White-Ryan, M.D., FAAP Golisano Children’s Hospital at Strong Memorial Hospital
SALEM PRESS, INC. Pasadena, California Hackensack, New Jersey
Editor in Chief: Dawn P. Dawson Editorial Director: Christina J. Moose Project Editors: Tracy Irons-Georges, Rowena Wildin Dehanke Editorial Assistant: Dana Garey
Production Editor: Joyce I. Buchea Acquisitions Editor: Mark Rehn Photo Editor: Cynthia Breslin Beres Design and Graphics: James Hutson Layout: William Zimmerman
Copyright © 2009, by Salem Press, Inc. All rights in this book are reserved. No part of this work may be used or reproduced in any manner whatsoever or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the copyright owner except in the case of brief quotations embodied in critical articles and reviews or in the copying of images deemed to be freely licensed or in the public domain. For information address the publisher, Salem Press, Inc., P.O. Box 50062, Pasadena, California 91115. ∞ The paper used in these volumes conforms to the American National Standard for Permanence of Paper for Printed Library Materials, Z39.48-1992 (R1997). Note to Readers The material presented in Salem Health: Cancer is intended for broad informational and educational purposes. Readers who suspect that they or someone whom they know or provide caregiving for suffers from cancer or any other physical or psychological disorder, disease, or condition described in this set should contact a physician without delay; this work should not be used as a substitute for professional medical diagnosis or staging. Readers who are undergoing or about to undergo any treatment or procedure described in this set should refer to their physicians and other health care team members for guidance concerning preparation and possible effects. This set is not to be considered definitive on the covered topics, and readers should remember that the field of health care is characterized by a diversity of medical opinions and constant expansion in knowledge and understanding. Library of Congress Cataloging-in-Publication Data Salem health : cancer / Jeffrey A. Knight, Laurie Jackson-Grusby, Wendy White-Ryan. p. cm. Includes bibliographical references and index. ISBN 978-1-58765-505-0 (set : alk. paper) — ISBN 978-1-58765-506-7 (vol. 1 : alk. paper) — ISBN 978-1-58765-507-4 (vol. 2 : alk. paper) — ISBN 978-1-58765-508-1 (vol. 3 : alk. paper) — ISBN 978-1-58765-509-8 (vol. 4 : alk. paper) 1. Cancer. I. Knight, Jeffrey A., 1948- II. Jackson-Grusby, Laurie. III. White-Ryan, Wendy. RC265.S32 2008 616.99′4—dc22 2008030861
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Contents Superior vena cava syndrome . . . . . Support groups . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . Synovial sarcomas . . . . . . . . . . .
Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . . . . . . Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . . Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . .
. . 1073 . . 1073 . . 1074 . . 1076
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1078 1082 1083 1084 1084 1086 1088
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1097 1098 1099 1100 1102 1103 1105 1106
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 lxxvii
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1130 1132 1135 1138 1140 1143 1144
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Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . . Transitional care . . . . . . . . . . . . . Transitional cell carcinomas . . . . . . . Transrectal ultrasound . . . . . . . . . . Transvaginal ultrasound . . . . . . . . . Trichilemmal carcinomas. . . . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . . . Tubular carcinomas . . . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . . . Tumor markers . . . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . . .
. . 1091 . . 1093 . . 1096
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1174 1175 1177 1179 1180 1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193
Salem Health: Cancer Tumor-suppressor genes . . . . . . . . . . . . . . 1194 Turcot syndrome . . . . . . . . . . . . . . . . . . 1195 Tyrosine kinase inhibitors . . . . . . . . . . . . . 1196 Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . . Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
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Von Hippel-Lindau (VHL) disease. . . . . . . . . 1235 Vulvar cancer . . . . . . . . . . . . . . . . . . . . 1237 WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251 X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254 Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
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Complete List of Contents Volume 1 Alkylating agents in chemotherapy . . . . . . . ALL. See Acute lymphocytic leukemia Allicin, garlic and. See Garlic and allicin Alopecia . . . . . . . . . . . . . . . . . . . . . ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels . . . . . . . . . Alternative therapies. See Complementary and alternative therapies Alveolar soft-part sarcomas . . . . . . . . . . . Amenorrhea . . . . . . . . . . . . . . . . . . . American Association for Cancer Research (AACR) . . . . . . . . . . . . . . . . . . . . American Cancer Society (ACS) . . . . . . . . American Institute for Cancer Research (AICR) 4-Aminobiphenyl . . . . . . . . . . . . . . . . AML. See Acute myelocytic leukemia Amputation . . . . . . . . . . . . . . . . . . . Amyloidosis . . . . . . . . . . . . . . . . . . . Anal cancer . . . . . . . . . . . . . . . . . . . Androgen drugs . . . . . . . . . . . . . . . . . Anemia . . . . . . . . . . . . . . . . . . . . . Anemia, aplastic. See Aplastic anemia Anemia, hemolytic. See Hemolytic anemia Angiogenesis . . . . . . . . . . . . . . . . . . Angiogenesis inhibitors . . . . . . . . . . . . . Angiography. . . . . . . . . . . . . . . . . . . Angiosarcomas . . . . . . . . . . . . . . . . . Anoscopy . . . . . . . . . . . . . . . . . . . . Anthraquinones . . . . . . . . . . . . . . . . . Anthrax . . . . . . . . . . . . . . . . . . . . . Antiandrogens . . . . . . . . . . . . . . . . . . Antidiarrheal agents . . . . . . . . . . . . . . . Antiestrogens . . . . . . . . . . . . . . . . . . Antifungal therapies . . . . . . . . . . . . . . . Antimetabolites in chemotherapy . . . . . . . . Antinausea medications . . . . . . . . . . . . . Antineoplastics in chemotherapy . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . Antiperspirants and breast cancer . . . . . . . . Antiviral therapies. . . . . . . . . . . . . . . . Anxiety . . . . . . . . . . . . . . . . . . . . . APBI. See Accelerated partial breast irradiation APC gene testing . . . . . . . . . . . . . . . . Aplastic anemia . . . . . . . . . . . . . . . . . Appendix cancer . . . . . . . . . . . . . . . . Appetite loss. . . . . . . . . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . v Publisher’s Note . . . . . . . . . . . . . . . . . . . . ix About the Editors . . . . . . . . . . . . . . . . . . . xi Contributors . . . . . . . . . . . . . . . . . . . . . xiii Complete List of Contents . . . . . . . . . . . . . . xv AACR. See American Association for Cancer Research ABCD. . . . . . . . . . . . . . . . . . . . . . . . . . 1 ACC. See Adenoid cystic carcinoma Abdominoperineal resection (APR) . . . . . . . . . . 1 Accelerated partial breast irradiation (APBI). . . . . . 3 Achlorhydria . . . . . . . . . . . . . . . . . . . . . . 4 Acoustic neuromas . . . . . . . . . . . . . . . . . . . 4 Acquired immunodeficiency disease-related cancers. See HIV/AIDS-related cancers Acrylamides . . . . . . . . . . . . . . . . . . . . . . 6 ACS. See American Cancer Society Acupuncture and acupressure for cancer patients . . . 8 Acute lymphocytic leukemia (ALL) . . . . . . . . . 11 Acute myelocytic leukemia (AML) . . . . . . . . . . 13 Adenocarcinomas . . . . . . . . . . . . . . . . . . . 16 Adenoid cystic carcinoma (ACC) . . . . . . . . . . . 17 Adenomatoid tumors . . . . . . . . . . . . . . . . . 18 Adenomatous polyps . . . . . . . . . . . . . . . . . 18 Adenoviruses . . . . . . . . . . . . . . . . . . . . . 19 Adjuvant therapy . . . . . . . . . . . . . . . . . . . 20 Adrenal gland cancers . . . . . . . . . . . . . . . . . 21 Adrenocortical cancer . . . . . . . . . . . . . . . . . 23 Advance directives . . . . . . . . . . . . . . . . . . 24 Aflatoxins . . . . . . . . . . . . . . . . . . . . . . . 26 AFP levels. See Alpha-fetoprotein levels African Americans and cancer . . . . . . . . . . . . 28 Africans and cancer . . . . . . . . . . . . . . . . . . 31 Afterloading radiation therapy . . . . . . . . . . . . 32 Agent Orange . . . . . . . . . . . . . . . . . . . . . 34 Aging and cancer . . . . . . . . . . . . . . . . . . . 34 AICR. See American Institute for Cancer Research Aids and devices for cancer patients . . . . . . . . . 38 AIDS-related cancers. See HIV/AIDS-related cancers Air pollution . . . . . . . . . . . . . . . . . . . . . . 39 Alcohol, alcoholism, and cancer . . . . . . . . . . . 42 Aleukemia . . . . . . . . . . . . . . . . . . . . . . . 43 Alkaline phosphatase test (ALP) . . . . . . . . . . . 44 lxxix
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64 66 68 69 70 71 71 72 73 75 76 78 81 83 86 88 90 93
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Salem Health: Cancer APR. See Abdominoperineal resection Arsenic compounds . . . . . . . . . . Arterial embolization . . . . . . . . . Artificial sweeteners . . . . . . . . . . Asbestos . . . . . . . . . . . . . . . . Ascites . . . . . . . . . . . . . . . . . Ashkenazi Jews and cancer . . . . . . Asian Americans and cancer. . . . . . Astrocytomas. . . . . . . . . . . . . . Ataxia telangiectasia (AT) . . . . . . . Autologous blood transfusion . . . . . Axillary dissection . . . . . . . . . . . Azathioprine . . . . . . . . . . . . . .
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Bacillus Calmette Guérin (BCG) . . . . . . . . Bacteria as causes of cancer . . . . . . . . . . . Barium enema . . . . . . . . . . . . . . . . . . Barium swallow . . . . . . . . . . . . . . . . . Barrett esophagus . . . . . . . . . . . . . . . . Basal cell carcinomas . . . . . . . . . . . . . . BCG. See Bacillus Calmette Guérin Beckwith-Wiedemann syndrome (BWS) . . . . Benign prostatic hyperplasia (BPH) . . . . . . . Benign tumors . . . . . . . . . . . . . . . . . . Benzene . . . . . . . . . . . . . . . . . . . . . Benzidine and dyes metabolized to benzidine . . Benzodiazepines . . . . . . . . . . . . . . . . . Bereavement, grief and. See Grief and bereavement Beryllium and beryllium compounds . . . . . . Beta-carotene . . . . . . . . . . . . . . . . . . Bethesda criteria . . . . . . . . . . . . . . . . . BHDS. See Birt-Hogg-Dubé syndrome Bile duct cancer . . . . . . . . . . . . . . . . . Bilobectomy . . . . . . . . . . . . . . . . . . . Bioflavonoids . . . . . . . . . . . . . . . . . . Biological therapy . . . . . . . . . . . . . . . . Biopsy. See also Computed tomography-guided biopsy; Core needle biopsy; Liver biopsy; Needle biopsies; Pleural biopsy; Stereotactic needle biopsy; Surgical biopsies . . . . . . . Birt-Hogg-Dubé syndrome (BHDS) . . . . . . . Birth control pills and cancer . . . . . . . . . . Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether . . . . . . . . . . Bisphenol A (BPA) . . . . . . . . . . . . . . . Bisphosphonates . . . . . . . . . . . . . . . . . Bladder cancer . . . . . . . . . . . . . . . . . . Blood cancers . . . . . . . . . . . . . . . . . . BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy
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Body image. See Self-image and body image Bone cancers . . . . . . . . . . . . . . . . . . . Bone marrow aspiration and biopsy . . . . . . . Bone marrow transplantation (BMT) . . . . . . Bone pain . . . . . . . . . . . . . . . . . . . . Bone scan . . . . . . . . . . . . . . . . . . . . Boron neutron capture therapy (BNCT) . . . . . Bowen disease . . . . . . . . . . . . . . . . . . BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Brachytherapy . . . . . . . . . . . . . . . . . . BRAF gene . . . . . . . . . . . . . . . . . . . . Brain and central nervous system cancers . . . . Brain scan . . . . . . . . . . . . . . . . . . . . BRCA1 and BRCA2 genes . . . . . . . . . . . . Breakthrough pain . . . . . . . . . . . . . . . . Breast, calcifications of. See Calcifications of the breast Breast, medullary carcinoma of. See Medullary carcinoma of the breast Breast cancer, cutaneous. See Cutaneous breast cancer Breast cancer, estrogen-receptor-sensitive. See Estrogen-receptor-sensitive breast cancer Breast cancer in children and adolescents . . . . Breast cancer in men . . . . . . . . . . . . . . . Breast cancer in pregnant women . . . . . . . . Breast cancers . . . . . . . . . . . . . . . . . . Breast implants. . . . . . . . . . . . . . . . . . Breast reconstruction. . . . . . . . . . . . . . . Breast self-examination (BSE). . . . . . . . . . Breast ultrasound. . . . . . . . . . . . . . . . . Breslow’s staging . . . . . . . . . . . . . . . . Brief Pain Inventory (BPI) . . . . . . . . . . . . Brompton cocktail . . . . . . . . . . . . . . . . Bronchial adenomas . . . . . . . . . . . . . . . Bronchoalveolar lung cancer . . . . . . . . . . Bronchography. . . . . . . . . . . . . . . . . . Bronchoscopy . . . . . . . . . . . . . . . . . . BSE. See Breast self-examination Burkitt lymphoma . . . . . . . . . . . . . . . . 1,3-Butadiene . . . . . . . . . . . . . . . . . . 1,4-Butanediol dimethanesulfonate . . . . . . . BWS. See Beckwith-Wiedemann syndrome
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CA 15-3 test . CA 19-9 test . CA 27-29 test CA 125 test. . Cachexia . . . lxxx
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Complete List of Contents Cadmium and cadmium compounds. . . . . . . . Caffeine . . . . . . . . . . . . . . . . . . . . . . Calcifications of the breast. . . . . . . . . . . . . Calcium . . . . . . . . . . . . . . . . . . . . . . Cancell . . . . . . . . . . . . . . . . . . . . . . . Cancer biology . . . . . . . . . . . . . . . . . . . Cancer care team . . . . . . . . . . . . . . . . . . Cancer clusters . . . . . . . . . . . . . . . . . . . Cancer education. . . . . . . . . . . . . . . . . . Candidiasis . . . . . . . . . . . . . . . . . . . . . Carcinoembryonic antigen antibody (CEA) test . . . . . . . . . . . . . . . . . . . . . . . . Carcinogens, known . . . . . . . . . . . . . . . . Carcinogens, reasonably anticipated. . . . . . . . Carcinoid tumors and carcinoid syndrome . . . . Carcinoma of unknown primary origin (CUP) . . Carcinomas. . . . . . . . . . . . . . . . . . . . . Carcinomas, invasive ductal. See Invasive ductal carcinomas Carcinomas, invasive lobular. See Invasive lobular carcinomas Carcinomas, leptomeningeal. See Leptomeningeal carcinomas Carcinomatosis. . . . . . . . . . . . . . . . . . . Carcinomatous meningitis . . . . . . . . . . . . . Carcinosarcomas . . . . . . . . . . . . . . . . . . Cardiomyopathy in cancer patients . . . . . . . . Cardiopulmonary resuscitation (CPR) . . . . . . . Caregivers and caregiving . . . . . . . . . . . . . Caregiving, long-distance. See Long-distance caregiving Carney complex . . . . . . . . . . . . . . . . . . Carotenoids . . . . . . . . . . . . . . . . . . . . Cartilage supplements . . . . . . . . . . . . . . . Case management . . . . . . . . . . . . . . . . . Castleman disease . . . . . . . . . . . . . . . . . CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones. . . . . . . . . . . . . . . . . . . . . Cervical cancer. . . . . . . . . . . . . . . . . . . Chemoembolization . . . . . . . . . . . . . . . . Chemoprevention . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . Chemotherapy, cognitive effects of. See Cognitive effects of cancer and chemotherapy Chewing tobacco. . . . . . . . . . . . . . . . . . Childbirth and cancer . . . . . . . . . . . . . . .
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208 209 211 212 212 213 216 218 220 221
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Childhood cancers . . . . . . . . . . . . . . . . Chlorambucil. . . . . . . . . . . . . . . . . . . 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) . . . . . . . . . . . Cholecystectomy . . . . . . . . . . . . . . . . . Chordomas . . . . . . . . . . . . . . . . . . . . Choriocarcinomas . . . . . . . . . . . . . . . . CHPP. See Continuous hyperthermic peritoneal perfusion Chromium hexavalent compounds. . . . . . . . Chromosomes and cancer . . . . . . . . . . . . Chronic lymphocytic leukemia (CLL) . . . . . . Chronic myeloid leukemia (CML). . . . . . . . Cigarettes and cigars . . . . . . . . . . . . . . . Clinical breast exam (CBE) . . . . . . . . . . . Clinical trials . . . . . . . . . . . . . . . . . . . CLL. See Chronic lymphocytic leukemia CML. See Chronic myeloid leukemia Coal tars and coal tar pitches . . . . . . . . . . Cobalt 60 radiation. . . . . . . . . . . . . . . . Coenzyme Q10. . . . . . . . . . . . . . . . . . Cognitive effects of cancer and chemotherapy . Coke oven emissions. . . . . . . . . . . . . . . Cold nodule . . . . . . . . . . . . . . . . . . . Colectomy . . . . . . . . . . . . . . . . . . . . Coloanal anastomosis . . . . . . . . . . . . . . Colon polyps . . . . . . . . . . . . . . . . . . . Colonoscopy and virtual colonoscopy . . . . . . Colony-stimulating factors (CSFs) . . . . . . . Colorectal cancer. . . . . . . . . . . . . . . . . Colorectal cancer screening . . . . . . . . . . . Colostomy . . . . . . . . . . . . . . . . . . . . Colposcopy. . . . . . . . . . . . . . . . . . . . Comedo carcinomas . . . . . . . . . . . . . . . Complementary and alternative therapies . . . . Complete blood count (CBC) . . . . . . . . . . Computed tomography (CT)-guided biopsy . . . . . . . . . . . . . . . . . . . . . Computed tomography (CT) scan . . . . . . . . Conization . . . . . . . . . . . . . . . . . . . . Continuous hyperthermic peritoneal perfusion (CHPP) . . . . . . . . . . . . . . . . . . . . Cordectomy . . . . . . . . . . . . . . . . . . . Cordotomy . . . . . . . . . . . . . . . . . . . . Core needle biopsy. . . . . . . . . . . . . . . . Corticosteroids . . . . . . . . . . . . . . . . . . Coughing . . . . . . . . . . . . . . . . . . . . . Counseling for cancer patients and survivors . . Cowden syndrome . . . . . . . . . . . . . . . . COX-2 inhibitors. See Cyclooxygenase 2 inhibitors
249 251 253 254 257
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288 289 289 290 292 292 293 294 296 297 299 300 304 306 308 309 309 312
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318 318 319 321 321 322 324 326
Salem Health: Cancer CPR. See Cardiopulmonary resuscitation Craniopharyngiomas . . . . . . . . . . . . Craniosynostosis . . . . . . . . . . . . . . Craniotomy. . . . . . . . . . . . . . . . . Crohn disease . . . . . . . . . . . . . . . Cruciferous vegetables . . . . . . . . . . . Cryoablation . . . . . . . . . . . . . . . . Cryptorchidism. . . . . . . . . . . . . . . CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy. . . . . . . . . . . . . . . . . CUP. See Carcinoma of unknown primary origin Curcumin. . . . . . . . . . . . . . . . . . Cushing syndrome and cancer . . . . . . . Cutaneous breast cancer . . . . . . . . . . Cutaneous T-cell lymphoma (CTCL) . . .
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Cyclin-dependent kinase inhibitor-2A (CDKN2A). . . . . . . . . . . . . . . Cyclooxygenase 2 (COX-2) inhibitors . Cyclophosphamide. . . . . . . . . . . . Cyclosporin A . . . . . . . . . . . . . . Cystography . . . . . . . . . . . . . . . Cystoscopy . . . . . . . . . . . . . . . . Cytogenetics . . . . . . . . . . . . . . . Cytokines . . . . . . . . . . . . . . . . Cytology . . . . . . . . . . . . . . . . . Cytology, sputum. See Sputum cytology
327 329 331 332 335 336 338
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344 344 345 346 347 347 348 350 350
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D&C. See Dilation and curettage Dana-Farber Cancer Institute . . . . . . . . . . . . 354 DCIS. See Ductal carcinoma in situ DEA. See Diethanolamine DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol . . . . . . . . . . . . 355
339 340 341 342
Volume 2 Down syndrome and leukemia. . . . . . . . DPC4 gene testing . . . . . . . . . . . . . . DRE. See Digital rectal exam Drug resistance and multidrug resistance (MDR) . . . . . . . . . . . . . . . . . . . Dry mouth . . . . . . . . . . . . . . . . . . DSRCT. See Desmoplastic small round cell tumor Duct ectasia . . . . . . . . . . . . . . . . . Ductal carcinoma in situ (DCIS). . . . . . . Ductal lavage. . . . . . . . . . . . . . . . . Ductogram . . . . . . . . . . . . . . . . . . Duke Comprehensive Cancer Center . . . . Dukes’ classification . . . . . . . . . . . . . Duodenal carcinomas . . . . . . . . . . . . Dye, hair. See Hair dye Dysplastic nevus syndrome . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . xxxiii Complete List of Contents . . . . . . . . . . . . xxxvii Denys-Drash syndrome and cancer . . . . . . Depression . . . . . . . . . . . . . . . . . . . Dermatofibrosarcoma protuberans (DFSP) . . Dermatology oncology. . . . . . . . . . . . . DES. See Diethylstilbestrol Desmoid tumors . . . . . . . . . . . . . . . . Desmoplastic small round cell tumor (DSRCT) . . . . . . . . . . . . . . . . . . Developing nations and cancer . . . . . . . . DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP) . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . DIC. See Disseminated intravascular coagulation Dietary supplements . . . . . . . . . . . . . . Diethanolamine (DEA) . . . . . . . . . . . . Diethylstilbestrol (DES) . . . . . . . . . . . . Digital rectal exam (DRE) . . . . . . . . . . . Dilation and curettage (D&C) . . . . . . . . . Dioxins . . . . . . . . . . . . . . . . . . . . . Disseminated intravascular coagulation (DIC) . . . . . . . . . . . . . . . . . . . . Diverticulosis and diverticulitis . . . . . . . . DNR. See Do-not-resuscitate order Do-not-resuscitate (DNR) order . . . . . . . .
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386 387 389 389 390 392 393
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Eaton-Lambert syndrome. See Lambert-Eaton myasthenic syndrome EBRT. See External beam radiation therapy Edema . . . . . . . . . . . . . . . . . . . . . Education, cancer. See Cancer education Elderly and cancer . . . . . . . . . . . . . . . Electrolarynx . . . . . . . . . . . . . . . . . . Electromagnetic radiation . . . . . . . . . . . Electroporation therapy . . . . . . . . . . . . Electrosurgery . . . . . . . . . . . . . . . . .
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396 399 399 400 401
Complete List of Contents Embolization . . . . . . . . . . . . . . . . . . . . Embryonal cell cancer . . . . . . . . . . . . . . . End-of-life care . . . . . . . . . . . . . . . . . . Endocrine cancers . . . . . . . . . . . . . . . . . Endocrinology oncology . . . . . . . . . . . . . . Endometrial cancer . . . . . . . . . . . . . . . . Endometrial hyperplasia . . . . . . . . . . . . . . Endorectal ultrasound . . . . . . . . . . . . . . . Endoscopic retrograde cholangiopancreatography (ERCP) . . . . . . . . . . . . . . . . . . . . . Endoscopy . . . . . . . . . . . . . . . . . . . . . Endoscopy, upper gastrointestinal. See Upper gastrointestinal endoscopy Endotheliomas . . . . . . . . . . . . . . . . . . . Enteritis . . . . . . . . . . . . . . . . . . . . . . Enterostomal therapy . . . . . . . . . . . . . . . Eosinophilic leukemia . . . . . . . . . . . . . . . Ependymomas . . . . . . . . . . . . . . . . . . . Epidemiology of cancer . . . . . . . . . . . . . . Epidermoid cancers of mucous membranes . . . . Epstein-Barr virus . . . . . . . . . . . . . . . . . ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite. . . . . . . . . . . . . . . . . . . . . . . Erythroplakia. . . . . . . . . . . . . . . . . . . . Esophageal cancer . . . . . . . . . . . . . . . . . Esophageal speech . . . . . . . . . . . . . . . . . Esophagectomy . . . . . . . . . . . . . . . . . . Esophagitis . . . . . . . . . . . . . . . . . . . . . Essiac . . . . . . . . . . . . . . . . . . . . . . . Estrogen receptor downregulator (ERD) . . . . . Estrogen-receptor-sensitive breast cancer . . . . . Ethnicity and cancer . . . . . . . . . . . . . . . . Ethylene oxide . . . . . . . . . . . . . . . . . . . Ewing sarcoma . . . . . . . . . . . . . . . . . . . Exenteration . . . . . . . . . . . . . . . . . . . . Exercise and cancer . . . . . . . . . . . . . . . . External beam radiation therapy (EBRT) . . . . . Eye cancers . . . . . . . . . . . . . . . . . . . . Eyelid cancer. . . . . . . . . . . . . . . . . . . .
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Fallopian tube cancer . . . . . . . Family history and risk assessment Fanconi anemia . . . . . . . . . . Fatigue . . . . . . . . . . . . . . . Fecal occult blood test (FOBT) . . Fertility drugs and cancer . . . . . Fertility issues . . . . . . . . . . . Fever . . . . . . . . . . . . . . . . Fiber . . . . . . . . . . . . . . . .
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402 403 404 406 409 412 414 416
. 417 . 417
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420 421 422 424 425 426 429 431
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433 433 434 436 438 439 441 441 442 444 447 447 450 451 454 455 458
. . . . . . . . .
460 461 464 466 467 469 471 472 474
Fibroadenomas . . . . . . . . . . . . . . . . Fibrocystic breast changes . . . . . . . . . . Fibrosarcomas, soft-tissue . . . . . . . . . . Financial issues . . . . . . . . . . . . . . . 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome . . . . . . . . . . . . . Flow cytometry . . . . . . . . . . . . . . . FOBT. See Fecal occult blood test Folic acid. . . . . . . . . . . . . . . . . . . Formaldehyde . . . . . . . . . . . . . . . . Fox Chase Cancer Center . . . . . . . . . . Fred Hutchinson Cancer Research Center . . Free radicals . . . . . . . . . . . . . . . . . Fruits . . . . . . . . . . . . . . . . . . . . .
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486 486 487 488 490 491
Gallbladder cancer . . . . . . . . . . . . . . Gallium scan . . . . . . . . . . . . . . . . . Gamma Knife . . . . . . . . . . . . . . . . Gardner syndrome . . . . . . . . . . . . . . Garlic and allicin . . . . . . . . . . . . . . . Gastric polyps . . . . . . . . . . . . . . . . Gastrinomas . . . . . . . . . . . . . . . . . Gastrointestinal cancers . . . . . . . . . . . Gastrointestinal complications of cancer treatment. . . . . . . . . . . . . . . . . . Gastrointestinal oncology . . . . . . . . . . Gastrointestinal stromal tumors (GISTs) . . GCTs. See Giant cell tumors Gene therapy . . . . . . . . . . . . . . . . . Genetic counseling . . . . . . . . . . . . . . Genetic testing . . . . . . . . . . . . . . . . Genetics of cancer . . . . . . . . . . . . . . Geography and cancer . . . . . . . . . . . . Germ-cell tumors . . . . . . . . . . . . . . Gerson therapy . . . . . . . . . . . . . . . . Gestational trophoblastic tumors (GTTs) . . Giant cell tumors (GCTs) . . . . . . . . . . Ginseng, panax. . . . . . . . . . . . . . . . GISTs. See Gastrointestinal stromal tumors Gleason grading system . . . . . . . . . . . Gliomas . . . . . . . . . . . . . . . . . . . Glomus tumors . . . . . . . . . . . . . . . . Glossectomy . . . . . . . . . . . . . . . . . Glutamine . . . . . . . . . . . . . . . . . . Gonioscopy . . . . . . . . . . . . . . . . . Grading of tumors . . . . . . . . . . . . . . Graft-versus-host disease (GVHD) . . . . . Granulosa cell tumors . . . . . . . . . . . . Green tea . . . . . . . . . . . . . . . . . . . Grief and bereavement . . . . . . . . . . . .
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493 495 497 498 499 500 501 502
lxxxiii
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475 476 478 481
. . . . 484 . . . . 484
. . . . 506 . . . . 508 . . . . 511 . . . . . . . . . .
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512 515 517 519 522 525 527 527 530 531
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532 533 534 535 536 536 537 538 540 540 541
Salem Health: Cancer GTTs. See Gestational trophoblastic tumors GVHD. See Graft-versus-host disease Gynecologic cancers . . . . . . . . . . . . . . . . . 543 Gynecologic oncology . . . . . . . . . . . . . . . . 547 H. pylori. See Helicobacter pylori HAI. See Hepatic arterial infusion Hair dye . . . . . . . . . . . . . . . . . . . . . . Hairy cell leukemia . . . . . . . . . . . . . . . . Hand-foot syndrome (HFS) . . . . . . . . . . . . HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus Head and neck cancers . . . . . . . . . . . . . . . Health maintenance organizations (HMOs) . . . . Helicobacter pylori. . . . . . . . . . . . . . . . . Hemangioblastomas . . . . . . . . . . . . . . . . Hemangiopericytomas . . . . . . . . . . . . . . . Hemangiosarcomas . . . . . . . . . . . . . . . . Hematemesis . . . . . . . . . . . . . . . . . . . . Hematologic oncology . . . . . . . . . . . . . . . Hematuria . . . . . . . . . . . . . . . . . . . . . Hemochromatosis . . . . . . . . . . . . . . . . . Hemolytic anemia . . . . . . . . . . . . . . . . . Hemoptysis. . . . . . . . . . . . . . . . . . . . . Hemorrhoids . . . . . . . . . . . . . . . . . . . . Hepatic arterial infusion (HAI) . . . . . . . . . . Hepatitis B virus (HBV) . . . . . . . . . . . . . . Hepatitis C virus (HCV) . . . . . . . . . . . . . . Hepatomegaly . . . . . . . . . . . . . . . . . . . HER2/neu protein . . . . . . . . . . . . . . . . . Herbs as antioxidants . . . . . . . . . . . . . . . Hereditary cancer syndromes . . . . . . . . . . . Hereditary diffuse gastric cancer . . . . . . . . . Hereditary leiomyomatosis and renal cell cancer (HLRCC) . . . . . . . . . . . . . . . . Hereditary mixed polyposis syndrome . . . . . . Hereditary non-VHL clear cell renal cell carcinomas . . . . . . . . . . . . . . . . . . . Hereditary pancreatitis . . . . . . . . . . . . . . . Hereditary papillary renal cell carcinomas . . . . Hereditary polyposis syndromes . . . . . . . . . . Herpes simplex virus. . . . . . . . . . . . . . . . Herpes zoster virus. . . . . . . . . . . . . . . . . HFS. See Hand-foot syndrome Hispanics and cancer. See Latinos/Hispanics and cancer Histamine 2 antagonists . . . . . . . . . . . . . . Histiocytosis X . . . . . . . . . . . . . . . . . . . HIV/AIDS-related cancers . . . . . . . . . . . . .
. 550 . 550 . 552
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554 557 558 559 559 560 561 562 564 565 566 566 567 568 569 570 571 573 573 574 576
. 577 . 579 . . . . . .
580 580 581 582 584 586
. 587 . 588 . 590
HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations Hodgkin disease . . . . . . . . . . . . . . . . . Home health services . . . . . . . . . . . . . . Hormonal therapies . . . . . . . . . . . . . . . Hormone receptor tests . . . . . . . . . . . . . Hormone replacement therapy (HRT) . . . . . . Horner syndrome. . . . . . . . . . . . . . . . . Hospice care . . . . . . . . . . . . . . . . . . . Hot flashes . . . . . . . . . . . . . . . . . . . . HPV. See Human papillomavirus HRAS gene testing . . . . . . . . . . . . . . . . HRT. See Hormone replacement therapy HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG) . . . . . Human growth factors and tumor growth . . . . Human immunodeficiency virus-related cancers. See HIV/AIDS-related cancers Human papillomavirus (HPV) . . . . . . . . . . Human T-cell leukemia virus (HTLV) . . . . . Hydatidiform mole . . . . . . . . . . . . . . . . 5-Hydroxyindoleacetic acid (5HIAA) test . . . . Hypercalcemia . . . . . . . . . . . . . . . . . . Hypercoagulation disorders . . . . . . . . . . . Hyperthermia therapy . . . . . . . . . . . . . . Hyperthermic perfusion . . . . . . . . . . . . . Hypopharyngeal cancer . . . . . . . . . . . . . Hysterectomy . . . . . . . . . . . . . . . . . . Hysterography . . . . . . . . . . . . . . . . . . Hystero-oophorectomy. . . . . . . . . . . . . . Hysteroscopy. . . . . . . . . . . . . . . . . . . IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test Ileostomy. . . . . . . . . . . . . . . . . . . . . Imaging tests . . . . . . . . . . . . . . . . . . . Immune response to cancer . . . . . . . . . . . Immunochemical fecal occult blood test (iFOBT) . . . . . . . . . . . . . . . . . . . . Immunocytochemistry and immunohistochemistry . . . . . . . . . . . . Immunoelectrophoresis (IEP) . . . . . . . . . . Immunotherapy . . . . . . . . . . . . . . . . . IMRT. See Intensity-modulated radiation therapy Indoles . . . . . . . . . . . . . . . . . . . . . . Infection and sepsis . . . . . . . . . . . . . . . Infectious cancers . . . . . . . . . . . . . . . . Infertility and cancer . . . . . . . . . . . . . . .
lxxxiv
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593 597 599 601 603 605 606 608
. . 609
. . 609 . . 610
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611 612 612 613 614 615 617 618 619 620 621 622 623
. . 625 . . 626 . . 629 . . 632 . . 633 . . 634 . . 635
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638 638 641 643
Complete List of Contents Inflammatory bowel disease . . . . . . . . . . Informed consent. . . . . . . . . . . . . . . . Infusion therapies . . . . . . . . . . . . . . . Insurance . . . . . . . . . . . . . . . . . . . . Integrative oncology . . . . . . . . . . . . . . Intensity-modulated radiation therapy (IMRT) Interferon. . . . . . . . . . . . . . . . . . . . Interleukins. . . . . . . . . . . . . . . . . . . Invasive cancer. . . . . . . . . . . . . . . . . Invasive ductal carcinomas . . . . . . . . . . Invasive lobular carcinomas . . . . . . . . . . Ionizing radiation . . . . . . . . . . . . . . . Iridium seeds . . . . . . . . . . . . . . . . . . Islet cell tumors . . . . . . . . . . . . . . . . Isoflavones . . . . . . . . . . . . . . . . . . . Itching . . . . . . . . . . . . . . . . . . . . .
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645 646 647 648 651 652 653 654 655 656 657 657 658 659 661 661
Lambert-Eaton myasthenic syndrome (LEMS) Laparoscopy and laparoscopic surgery . . . . Laryngeal cancer . . . . . . . . . . . . . . . . Laryngeal nerve palsy . . . . . . . . . . . . . Laryngectomy . . . . . . . . . . . . . . . . . Laryngoscopy . . . . . . . . . . . . . . . . . Laser therapies . . . . . . . . . . . . . . . . . Latinos/Hispanics and cancer . . . . . . . . . Laxatives . . . . . . . . . . . . . . . . . . . . LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test Leiomyomas . . . . . . . . . . . . . . . . . . Leiomyosarcomas . . . . . . . . . . . . . . . LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas . . . . . . . . . . Leukapharesis . . . . . . . . . . . . . . . . . Leukemia, Down syndrome and. See Down syndrome and leukemia Leukemia, eosinophilic. See Eosinophilic leukemia Leukemia, hairy cell. See Hairy cell leukemia Leukemias . . . . . . . . . . . . . . . . . . . Leukoencephalopathy . . . . . . . . . . . . . Leukopenia. . . . . . . . . . . . . . . . . . . Leukoplakia . . . . . . . . . . . . . . . . . . Leydig cell tumors . . . . . . . . . . . . . . . Li-Fraumeni syndrome (LFS) . . . . . . . . . Limb salvage . . . . . . . . . . . . . . . . . . Linear accelerator . . . . . . . . . . . . . . . Lip cancers . . . . . . . . . . . . . . . . . . . Liposarcomas . . . . . . . . . . . . . . . . . Liver biopsy . . . . . . . . . . . . . . . . . . Liver cancers . . . . . . . . . . . . . . . . . .
Jonsson Comprehensive Cancer Center (JCCC) . . . . . . . . . . . . . . . . . . . . . . 664 Journaling . . . . . . . . . . . . . . . . . . . . . . 665 Juvenile polyposis syndrome . . . . . . . . . . . . 665 Kaposi sarcoma . . . . . . . . . . . . . Karnofsky performance status (KPS) . . Keratosis . . . . . . . . . . . . . . . . . Ki67 test . . . . . . . . . . . . . . . . . Kidney cancer . . . . . . . . . . . . . . Klinefelter syndrome and cancer . . . . KPS. See Karnofsky performance status Krukenberg tumors . . . . . . . . . . .
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667 669 670 670 671 674
. . . . . . 675
Lacrimal gland tumors . . . . . . . . . . . . . . . . 677 Lactate dehydrogenase (LDH) test . . . . . . . . . 678 Laetrile . . . . . . . . . . . . . . . . . . . . . . . . 679
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679 681 682 685 686 687 688 690 692
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. . . 696 . . . 698
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698 702 704 704 706 706 708 709 710 712 714 715
Volume 3 Lumps . . . . . . . . . . . . . . Lung cancer, brochoalveolar. See Bronchoalveolar lung cancer Lung cancers . . . . . . . . . . . Lutein . . . . . . . . . . . . . . Lycopene . . . . . . . . . . . . . Lymphadenectomy. . . . . . . . Lymphangiography . . . . . . . Lymphangiosarcomas . . . . . . Lymphedema. . . . . . . . . . . Lymphocytosis . . . . . . . . . . Lymphomas . . . . . . . . . . .
Contents . . . . . . . . . . . . . . . . . . . . . . . . lv Complete List of Contents . . . . . . . . . . . . . . lix Living will . . . . . . . . . . . . . . . . . Living with cancer . . . . . . . . . . . . . Lobectomy . . . . . . . . . . . . . . . . . Lobular carcinoma in situ (LCIS) . . . . . Long-distance caregiving . . . . . . . . . Loop electrosurgical excisional procedure (LEEP) . . . . . . . . . . . . . . . . . Lumbar puncture . . . . . . . . . . . . . . Lumpectomy . . . . . . . . . . . . . . . .
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719 720 723 725 726
. . . . . 727 . . . . . 728 . . . . . 730 lxxxv
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733 737 737 738 740 741 742 743 744
Salem Health: Cancer M. D. Anderson Cancer Center . . . . . . . . . Macrobiotic diet . . . . . . . . . . . . . . . . . Magnetic resonance imaging (MRI) . . . . . . . Malignant fibrous histiocytoma (MFH) . . . . . Malignant rhabdoid tumor of the kidney . . . . Malignant tumors . . . . . . . . . . . . . . . . MALT lymphomas. See Mucosa-associated lymphoid tissue lymphomas Mammography . . . . . . . . . . . . . . . . . . Managed care . . . . . . . . . . . . . . . . . . Mantle cell lymphoma (MCL) . . . . . . . . . . Mastectomy . . . . . . . . . . . . . . . . . . . Mastocytomas . . . . . . . . . . . . . . . . . . Matrix metalloproteinase inhibitors . . . . . . . Mayo Clinic Cancer Center . . . . . . . . . . . MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mediastinal tumors. . . . . . . . . . . . . . . . Mediastinoscopy . . . . . . . . . . . . . . . . . Medical marijuana . . . . . . . . . . . . . . . . Medical oncology . . . . . . . . . . . . . . . . Medicare and cancer . . . . . . . . . . . . . . . Medullary carcinoma of the breast. . . . . . . . Medulloblastomas . . . . . . . . . . . . . . . . Melanomas . . . . . . . . . . . . . . . . . . . . Melphalan . . . . . . . . . . . . . . . . . . . . Memorial Sloan-Kettering Cancer Center . . . . MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis . . . . . . . . . . . . Meningiomas. . . . . . . . . . . . . . . . . . . Merkel cell carcinomas (MCC) . . . . . . . . . Mesenchymomas, malignant. . . . . . . . . . . Mesothelioma . . . . . . . . . . . . . . . . . . Metastasis . . . . . . . . . . . . . . . . . . . . Metastatic squamous neck cancer with occult primary . . . . . . . . . . . . . . . . . . . . MFH. See Malignant fibrous histiocytoma Microcalcifications. . . . . . . . . . . . . . . . Microwave hyperthermia therapy . . . . . . . . Mineral oils . . . . . . . . . . . . . . . . . . . Mistletoe . . . . . . . . . . . . . . . . . . . . . Mitochondrial DNA mutations. . . . . . . . . . MLH1 gene. . . . . . . . . . . . . . . . . . . . Mohs surgery. . . . . . . . . . . . . . . . . . . Molecular oncology . . . . . . . . . . . . . . . Moles. . . . . . . . . . . . . . . . . . . . . . . Monoclonal antibodies . . . . . . . . . . . . . . Motion sickness devices . . . . . . . . . . . . .
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748 750 750 752 753 754
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754 757 759 761 763 764 765
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766 768 768 770 772 774 775 776 779 780
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781 782 783 785 786 788
. . 790 . . . . . . . . . . .
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790 791 792 793 794 795 796 796 798 800 802
MRI. See Magnetic resonance imaging MSH genes . . . . . . . . . . . . . . . . . . . . Mucinous carcinomas . . . . . . . . . . . . . . Mucosa-associated lymphoid tissue (MALT) lymphomas . . . . . . . . . . . . . . . . . . Mucositis . . . . . . . . . . . . . . . . . . . . . Mucous membranes, epidermoid cancers of. See Epidermoid cancers of mucous membranes Multiple endocrine neoplasia type 1 (MEN 1). . Multiple endocrine neoplasia type 2 (MEN 2). . Multiple myeloma . . . . . . . . . . . . . . . . Mustard gas . . . . . . . . . . . . . . . . . . . Mutagenesis and cancer . . . . . . . . . . . . . Myasthenia gravis . . . . . . . . . . . . . . . . MYC oncogene . . . . . . . . . . . . . . . . . . Mycosis fungoides . . . . . . . . . . . . . . . . Myelodysplastic syndromes . . . . . . . . . . . Myelofibrosis . . . . . . . . . . . . . . . . . . Myeloma . . . . . . . . . . . . . . . . . . . . . Myeloproliferative disorders. . . . . . . . . . . Myelosuppression . . . . . . . . . . . . . . . . 2-Naphthylamine. . . . . . . . . . . . . . . . Nasal cavity and paranasal sinus cancers . . . National Cancer Institute (NCI) . . . . . . . . National Science Foundation (NSF) . . . . . . Native North Americans and cancer . . . . . . Nausea and vomiting. . . . . . . . . . . . . . NCI. See National Cancer Institute Needle biopsies . . . . . . . . . . . . . . . . Needle localization. . . . . . . . . . . . . . . Nephroblastomas. . . . . . . . . . . . . . . . Nephrostomy . . . . . . . . . . . . . . . . . . Neuroblastomas . . . . . . . . . . . . . . . . Neuroectodermal tumors. . . . . . . . . . . . Neuroendocrine tumors . . . . . . . . . . . . Neurofibromatosis type 1 (NF1) . . . . . . . . Neurologic oncology. . . . . . . . . . . . . . Neutropenia . . . . . . . . . . . . . . . . . . NF1. See Neurofibromatosis type 1 Nickel compounds and metallic nickel . . . . Night sweats . . . . . . . . . . . . . . . . . . Nijmegen breakage syndrome . . . . . . . . . Nipple discharge . . . . . . . . . . . . . . . . Non-Hodgkin lymphoma . . . . . . . . . . . Nonsteroidal anti-inflammatory drugs (NSAIDs) . . . . . . . . . . . . . . . . . . NSAIDs. See Nonsteroidal anti-inflammatory drugs NSF. See National Science Foundation Nuclear medicine scan . . . . . . . . . . . . .
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. . 803 . . 803 . . 804 . . 806
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807 808 809 812 813 815 817 817 819 820 822 823 825
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826 826 829 830 832 834
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836 838 839 839 841 842 844 845 847 849
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851 852 853 854 855
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Complete List of Contents Nutrition and cancer prevention . . . . . . . . . . . 861 Nutrition and cancer treatment. . . . . . . . . . . . 864 Obesity-associated cancers . . . . . Occupational exposures and cancer . Occupational therapy . . . . . . . . OCs. See Organochlorines Oligodendrogliomas . . . . . . . . . Omega-3 fatty acids . . . . . . . . . Ommaya reservoir . . . . . . . . . . Oncogenes . . . . . . . . . . . . . . Oncogenic viruses . . . . . . . . . . Oncology . . . . . . . . . . . . . . . Oncology clinical nurse specialist . . Oncology social worker . . . . . . . Oophorectomy . . . . . . . . . . . . Ophthalmic oncology . . . . . . . . Opioids . . . . . . . . . . . . . . . . Oral and maxillofacial surgery. . . . Oral and oropharyngeal cancers . . . Orbit tumors . . . . . . . . . . . . . Orchiectomy . . . . . . . . . . . . . Organ transplantation and cancer . . Organochlorines (OCs) . . . . . . . Oropharyngeal cancers. See Oral and oropharyngeal cancers Orthopedic surgery. . . . . . . . . . Otolaryngology . . . . . . . . . . . Ovarian cancers . . . . . . . . . . . Ovarian cysts. . . . . . . . . . . . . Ovarian epithelial cancer . . . . . . Overtreatment . . . . . . . . . . . .
. . . . . . . . 868 . . . . . . . . 871 . . . . . . . . 873 . . . . . . . . . . . . . . . . .
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875 877 878 878 881 882 885 887 888 889 892 893 894 897 898 899 901
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902 903 905 908 909 911
Paget disease of bone . . . . . . . . . . . . . Pain management medications. . . . . . . . . Palliative treatment . . . . . . . . . . . . . . PALP. See Placental alkaline phosphatase Palpation . . . . . . . . . . . . . . . . . . . . Pancolitis . . . . . . . . . . . . . . . . . . . . Pancreatectomy . . . . . . . . . . . . . . . . Pancreatic cancers . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . Pap test . . . . . . . . . . . . . . . . . . . . . Paracentesis . . . . . . . . . . . . . . . . . . Paranasal sinus cancers. See Nasal cavity and paranasal sinus cancers Paraneoplastic syndromes . . . . . . . . . . . Parathyroid cancer . . . . . . . . . . . . . . . Pathology . . . . . . . . . . . . . . . . . . . PC-SPES . . . . . . . . . . . . . . . . . . . . PDT. See Photodynamic therapy
. . . 912 . . . 914 . . . 917 . . . . . . .
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920 920 921 923 927 928 929
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931 932 934 937
Pediatric oncology and hematology . . . . . . . . . 938 Pelvic examination . . . . . . . . . . . . . . . . . . 940 Penile cancer . . . . . . . . . . . . . . . . . . . . . 941 Percutaneous transhepatic cholangiography (PTHC) . . . . . . . . . . . . . . . . . . . . . . 943 Pericardial effusion . . . . . . . . . . . . . . . . . 944 Pericardiocentesis . . . . . . . . . . . . . . . . . . 946 Peritoneovenous shunts . . . . . . . . . . . . . . . 946 Personality and cancer . . . . . . . . . . . . . . . . 947 Pesticides and the food chain . . . . . . . . . . . . 948 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS) . . . . . . . . . . . . 951 Pharmacy oncology . . . . . . . . . . . . . . . . . 952 Phenacetin . . . . . . . . . . . . . . . . . . . . . . 955 Phenolics . . . . . . . . . . . . . . . . . . . . . . . 955 Pheochromocytomas . . . . . . . . . . . . . . . . . 956 Pheresis . . . . . . . . . . . . . . . . . . . . . . . 958 Photodynamic therapy (PDT) . . . . . . . . . . . . 959 Phyllodes tumors. . . . . . . . . . . . . . . . . . . 960 Phytoestrogens . . . . . . . . . . . . . . . . . . . . 962 Pineoblastomas. . . . . . . . . . . . . . . . . . . . 963 Pituitary tumors . . . . . . . . . . . . . . . . . . . 965 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP) . . . . . . . 968 Plant alkaloids and terpenoids in chemotherapy . . . . . . . . . . . . . . . . . . . 968 Plasticizers . . . . . . . . . . . . . . . . . . . . . . 971 Pleural biopsy . . . . . . . . . . . . . . . . . . . . 972 Pleural effusion . . . . . . . . . . . . . . . . . . . 973 Pleurodesis . . . . . . . . . . . . . . . . . . . . . . 975 Pleuropulmonary blastomas . . . . . . . . . . . . . 975 PMS genes . . . . . . . . . . . . . . . . . . . . . . 976 Pneumonectomy . . . . . . . . . . . . . . . . . . . 977 Pneumonia . . . . . . . . . . . . . . . . . . . . . . 979 Polycyclic aromatic hydrocarbons . . . . . . . . . . 981 Polycythemia vera . . . . . . . . . . . . . . . . . . 981 Polypectomy . . . . . . . . . . . . . . . . . . . . . 982 Polyps . . . . . . . . . . . . . . . . . . . . . . . . 983 Polyps, colon. See Colon polyps Polyps, gastric. See Gastric polyps Positron emission tomography (PET) . . . . . . . . 984 Poverty and cancer . . . . . . . . . . . . . . . . . . 987 PPOs. See Preferred provider organizations Prayer and cancer support . . . . . . . . . . . . . . 989 Preferred provider organizations (PPOs) . . . . . . 990 Pregnancy and cancer . . . . . . . . . . . . . . . . 992 Premalignancies . . . . . . . . . . . . . . . . . . . 994 Prevent Cancer Foundation . . . . . . . . . . . . . 997 Prevention . . . . . . . . . . . . . . . . . . . . . . 999 Primary care physician . . . . . . . . . . . . . . . 1001
lxxxvii
Salem Health: Cancer Primary central nervous system lymphomas . . . . . . . . . . . . . . . . Progesterone receptor assay . . . . . . . . Prostate cancer . . . . . . . . . . . . . . . Prostate-specific antigen (PSA) test . . . . Prostatectomy. . . . . . . . . . . . . . . . Prostatitis . . . . . . . . . . . . . . . . . . Proteasome inhibitors. . . . . . . . . . . . Protein electrophoresis . . . . . . . . . . . Proteomics and cancer research . . . . . . Proton beam therapy . . . . . . . . . . . . Proto-oncogenes and carcinogenesis . . . . PSA test. See Prostate-specific antigen test Psycho-oncology . . . . . . . . . . . . . . Psychosocial aspects of cancer . . . . . . . PTHC. See Percutaneous transhepatic cholangiography Radiation, ionizing. See Ionizing radiation Radiation oncology . . . . . . . . . . . . . Radiation therapies . . . . . . . . . . . . . Radiation therapy, afterloading. See Afterloading radiation therapy Radical neck dissection . . . . . . . . . . . Radiofrequency ablation . . . . . . . . . . Radionuclide scan . . . . . . . . . . . . . Radiopharmaceuticals . . . . . . . . . . . Radon . . . . . . . . . . . . . . . . . . . . RB1 gene . . . . . . . . . . . . . . . . . . Receptor analysis . . . . . . . . . . . . . .
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1003 1003 1004 1006 1008 1009 1010 1010 1012 1014 1015
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1027 1027 1030 1030 1032 1032 1033
Reconstructive surgery . . . . . . . . . . . . . . Rectal cancer . . . . . . . . . . . . . . . . . . . Recurrence . . . . . . . . . . . . . . . . . . . . Rehabilitation . . . . . . . . . . . . . . . . . . . Relationships . . . . . . . . . . . . . . . . . . . Renal pelvis tumors. . . . . . . . . . . . . . . . Report on Carcinogens (RoC) . . . . . . . . . . Resveratrol . . . . . . . . . . . . . . . . . . . . Retinoblastomas . . . . . . . . . . . . . . . . . Rhabdomyosarcomas . . . . . . . . . . . . . . . RhoGD12 gene . . . . . . . . . . . . . . . . . . Richter syndrome . . . . . . . . . . . . . . . . . Risk assessment, family history and. See Family history and risk assessment Risks for cancer. . . . . . . . . . . . . . . . . . Robert H. Lurie Cancer Center . . . . . . . . . . RoC. See Report on Carcinogens Rothmund-Thomson syndrome . . . . . . . . . .
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Salivary gland cancer . . . . . . . . . . . . . Salpingectomy and salpingo-oophorectomy . Sarcomas, soft-tissue . . . . . . . . . . . . . Saw palmetto . . . . . . . . . . . . . . . . . Schwannoma tumors . . . . . . . . . . . . . SCLC1 gene. . . . . . . . . . . . . . . . . . Screening, colorectal cancer. See Colorectal cancer screening Screening for cancer . . . . . . . . . . . . . Second opinions . . . . . . . . . . . . . . . Self-image and body image. . . . . . . . . .
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1034 1036 1038 1038 1041 1043 1044 1045 1046 1048 1050 1050
. 1052 . 1054 . 1056 1058 1060 1062 1065 1066 1067
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Volume 4 Contents . . . . . . . . . . . . . . . . . . . . . . lxxvii Complete List of Contents . . . . . . . . . . . . . lxxix Sentinel lymph node (SLN) biopsy and mapping . . . . . . . . . . . . . . . Sepsis. See Infection and sepsis Sertoli cell tumors . . . . . . . . . . . Sexuality and cancer . . . . . . . . . . Sézary syndrome . . . . . . . . . . . . SIADH. See Syndrome of inappropriate antidiuretic hormone production Side effects . . . . . . . . . . . . . . . Sigmoidoscopy . . . . . . . . . . . . . Silica, crystalline . . . . . . . . . . . . Simian virus 40 . . . . . . . . . . . . . Singlehood and cancer . . . . . . . . .
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1078 1082 1083 1084 1084
Sjögren syndrome. . . . . . . . . . . . . . . . Skin cancers . . . . . . . . . . . . . . . . . . SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small intestine cancer . . . . . . . . . . . . . Smoking cessation . . . . . . . . . . . . . . . Social Security Disability Insurance (SSDI) . . Soft-tissue fibrosarcomas. See Fibrosarcomas, soft-tissue Soots . . . . . . . . . . . . . . . . . . . . . . Soy foods . . . . . . . . . . . . . . . . . . . . Spermatocytomas . . . . . . . . . . . . . . . . Spinal axis tumors . . . . . . . . . . . . . . . Spinal cord compression . . . . . . . . . . . . Splenectomy . . . . . . . . . . . . . . . . . . Sputum cytology . . . . . . . . . . . . . . . .
lxxxviii
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1097 1098 1099 1100 1102 1103 1105
Complete List of Contents Squamous cell carcinomas . . . . . . . . . . . SRS. See Stereotactic radiosurgery SSDI. See Social Security Disability Insurance Staging of cancer . . . . . . . . . . . . . . . . Statistics of cancer . . . . . . . . . . . . . . . Stem cell transplantation . . . . . . . . . . . . Stent therapy . . . . . . . . . . . . . . . . . . Stereotactic needle biopsy . . . . . . . . . . . Stereotactic radiosurgery (SRS) . . . . . . . . Sterility . . . . . . . . . . . . . . . . . . . . . Stomach cancers . . . . . . . . . . . . . . . . Stomatitis . . . . . . . . . . . . . . . . . . . . Stress management . . . . . . . . . . . . . . . Sunlamps . . . . . . . . . . . . . . . . . . . . Sun’s soup . . . . . . . . . . . . . . . . . . . Sunscreens . . . . . . . . . . . . . . . . . . . Superior vena cava syndrome . . . . . . . . . Support groups . . . . . . . . . . . . . . . . . Surgical biopsies . . . . . . . . . . . . . . . . Surgical oncology. . . . . . . . . . . . . . . . Survival rates . . . . . . . . . . . . . . . . . . Survivorship issues . . . . . . . . . . . . . . . Symptoms and cancer. . . . . . . . . . . . . . Syndrome of inappropriate antidiuretic hormone production (SIADH) . . . . . . . . Synovial sarcomas . . . . . . . . . . . . . . . Taste alteration . . . . . . . . . . . . . . Teratocarcinomas . . . . . . . . . . . . . Teratomas . . . . . . . . . . . . . . . . . Testicular cancer . . . . . . . . . . . . . Testicular self-examination (TSE) . . . . Thermal imaging . . . . . . . . . . . . . Thiotepa. . . . . . . . . . . . . . . . . . Thoracentesis . . . . . . . . . . . . . . . Thoracoscopy . . . . . . . . . . . . . . . Thoracotomy . . . . . . . . . . . . . . . Throat cancer . . . . . . . . . . . . . . . Thrombocytopenia . . . . . . . . . . . . Thymomas . . . . . . . . . . . . . . . . Thymus cancer . . . . . . . . . . . . . . Thyroid cancer . . . . . . . . . . . . . . Thyroid nuclear medicine scan . . . . . . TNF. See Tumor necrosis factor TNM staging . . . . . . . . . . . . . . . Tobacco, chewing. See Chewing tobacco Tobacco-related cancers . . . . . . . . . Topoisomerase inhibitors . . . . . . . . . TP53 protein . . . . . . . . . . . . . . . Tracheostomy . . . . . . . . . . . . . . . Transfusion therapy. . . . . . . . . . . .
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1108 1111 1114 1116 1118 1119 1120 1121 1124 1125 1127 1128 1129 1130 1132 1135 1138 1140 1143 1144
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1151 1152 1153 1154 1156 1157 1158 1158 1160 1161 1162 1164 1166 1167 1169 1172
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1174 1175 1177 1179 1180
Transitional care . . . . . . . . . . . Transitional cell carcinomas . . . . . Transrectal ultrasound . . . . . . . . Transvaginal ultrasound . . . . . . . Trichilemmal carcinomas. . . . . . . TSE. See Testicular self-examination Tuberous sclerosis . . . . . . . . . . Tubular carcinomas . . . . . . . . . . Tumor flare . . . . . . . . . . . . . . Tumor lysis syndrome . . . . . . . . Tumor markers . . . . . . . . . . . . Tumor necrosis factor (TNF) . . . . . Tumor-suppressor genes . . . . . . . Turcot syndrome . . . . . . . . . . . Tyrosine kinase inhibitors . . . . . .
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1182 1183 1185 1186 1187
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1187 1188 1189 1189 1191 1193 1194 1195 1196
Ultrasound, breast. See Breast ultrasound Ultrasound, endorectal. See Endorectal ultrasound Ultrasound, transrectal. See Transrectal ultrasound Ultrasound, transvaginal. See Transvaginal ultrasound Ultrasound tests . . . . . . . . . . . . . . . Ultraviolet radiation and related exposures Umbilical cord blood transplantation. . . . Upper gastrointestinal (GI) endoscopy . . . Upper gastrointestinal (GI) series . . . . . Urethral cancer . . . . . . . . . . . . . . . Urinalysis . . . . . . . . . . . . . . . . . . Urinary system cancers . . . . . . . . . . . Urography . . . . . . . . . . . . . . . . . Urologic oncology . . . . . . . . . . . . . Urostomy . . . . . . . . . . . . . . . . . . Uterine cancer . . . . . . . . . . . . . . .
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1199 1200 1201 1202 1203 1205 1207 1209 1213 1214 1216 1217
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1220 1221 1223 1225 1226
Vaccines, preventive . . . . . . . . . . . Vaccines, therapeutic . . . . . . . . . . . Vaginal cancer . . . . . . . . . . . . . . Vascular access tubes. . . . . . . . . . . Vasectomy and cancer . . . . . . . . . . Vegetables, cruciferous. See Cruciferous vegetables Veterinary oncology . . . . . . . . . . . VHL disease. See Von Hippel-Lindau disease Vinyl chloride . . . . . . . . . . . . . . Viral oncology . . . . . . . . . . . . . . Virus-related cancers . . . . . . . . . . . Von Hippel-Lindau (VHL) disease. . . . Vulvar cancer . . . . . . . . . . . . . . .
lxxxix
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1230 1230 1232 1235 1237
Salem Health: Cancer WAGR syndrome. See Wilms’ tumor aniridiagenitourinary anomalies-mental retardation syndrome and cancer Waldenström macroglobulinemia (WM) . . . . . . 1240 Watchful waiting . . . . . . . . . . . . . . . . . . 1242 Weight loss . . . . . . . . . . . . . . . . . . . . . 1243 Wilms’ tumor . . . . . . . . . . . . . . . . . . . . 1245 Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome and cancer . . . . . . . . . . . . . . . . . . . . . . 1248 Wine and cancer . . . . . . . . . . . . . . . . . . 1250 Wire localization . . . . . . . . . . . . . . . . . . 1250 WM. See Waldenström macroglobulinemia Wood dust . . . . . . . . . . . . . . . . . . . . . 1251
Yolk sac carcinomas . . . . . . . . . . . . . . . . 1256 Young adult cancers . . . . . . . . . . . . . . . . 1256 Zollinger-Ellison syndrome . . . . . . . . . . . . 1260 Drugs by Generic Name . . . Drugs by Trade Name . . . . Associations and Agencies . . Cancer Centers and Hospitals Cancer Support Groups . . . . Carcinogens. . . . . . . . . . Glossary . . . . . . . . . . . Bibliography . . . . . . . . .
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1265 1309 1348 1352 1357 1362 1383 1400
Category List . . . . . . . . . . . . . . . . . . . . 1409 Index . . . . . . . . . . . . . . . . . . . . . . . . 1419
X-ray tests . . . . . . . . . . . . . . . . . . . . . 1252 Xeroderma pigmentosa . . . . . . . . . . . . . . . 1254
xc
Salem Health: Cancer
u ABCD Category: Procedures Also known as: Jewett staging system or the WhitmoreJewett staging system (for prostate cancer) Definition: There are two distinct ABCD rating systems for cancer. The first uses the symbols A, B, C, and D to define the stages of prostate cancer. The second uses these designations to describe the early warning signs of melanoma, the most serious type of skin cancer.
Abdominoperineal resection (APR)
•
A (asymmetry): The two halves of the skin lesion are dissimilar. • B (border irregularity): The lesion has ragged or poorly defined edges. • C (color): The color of the lesion is uneven with different shades of brown or black. • D (diameter): The lesion is usually greater than 6 millimeters or 0.25 inch. Anna Binda, Ph.D. See also Melanomas; Moles; Premalignancies; Prostate cancer.
Cancers monitored: Prostate cancer and melanoma (each with its own distinct ABCD rating) Why performed: After detecting prostate cancer, the physician will evaluate the stage of the tumor according to its size, its location, and the extent to which it may have spread to other parts of the body. This information is important for choosing the best treatment plan. Staging of prostate cancer is based on the findings of clinical tests, mainly a digital rectal examination, a test to measure the level of prostate-specific antigen (PSA) in the blood, and transrectal ultrasonography. For melanoma prevention, the American Cancer Society recommends monthly skin self-examinations. The ABCD guideline serves as a reference when looking for any suspicious changes in the appearance of spots or sores that do not heal. Usually, this means monitoring any variation in the size, shape, or color of a mole. Any suspicious mole should be checked by a physician, who may decide to resect an abnormal-looking lesion and send the tissue for pathological review. Results: The ABCD rating for prostate cancer is used to classify the disease into four basic stages. • Stage A: Localized disease in which the cancer is very small, confined to the prostate gland, not palpable during a rectal examination, and identified by high PSA levels and biopsy. • Stage B: Localized disease in which the cancer is larger and confined to the prostate gland, but a lump is palpable during a rectal examination. • Stage C: Regional disease in which the cancer has grown through the prostate capsule and into surrounding tissues, perhaps into the seminal vesicles. • Stage D: Metastatic disease in which the cancer has grown into the pelvic area or has spread to the lymph nodes, bones, or other parts of the body. The ABCD rule for melanoma detection lists the four usual warning signs of the disease for most types of melanoma.
u Abdominoperineal resection
(APR) Category: Procedures Also known as: Abdominoperineal excision, anorectal excision, anoproctectomy Definition: Abdominoperineal resection (APR) is the surgical removal of the anus, rectum, and surrounding membrane called the mesentery, as well as the lower part of the colon supported by that mesentery. The upper part of the colon is rerouted through a new opening (ostomy) in the lower abdomen, forming an opening called a stoma. Cancers treated: Low rectal cancer, advanced anal cancer, metastatic pelvic disease Why performed: APR is performed to remove cancerous tissue, thereby curing or controlling the cancer or relieving symptoms of advanced disease. APR is the preferred procedure for large rectal tumors and tumors near the anal sphincter, but other tumor characteristics and patientspecific factors are also considered. Patient preparation: A series of medical tests are completed to plan effective treatment and to evaluate the patient’s fitness for major surgery. A specialist counsels the patient and helps choose the location for the stoma required by an APR. Radiation therapy, chemotherapy, or both may be recommended before the procedure. Certain patient medications may need to be stopped, the patient’s bowel must be cleaned, and the patient’s stomach must be empty. Steps of the procedure: APR is scheduled in a hospital. Sensors are placed to monitor the patient’s condition. An intravenous line is started, and an antibiotic is infused. General anesthetic is administered, and a breathing tube is 1
Abdominoperineal resection (APR) placed. The patient is positioned, a urinary catheter is inserted, and the incision sites are prepared. APR is a complex operation requiring incisions first on the abdomen (abdominal resection) and then on the perineum (perineal resection), which may be performed by one or two surgeons. Abdominal resection prepares the lower colon and rectum for removal during the perineal resection and forms the stoma. Perineal resection frees the anus and removes all the diseased tissue. In some instances, the abdominal resection may be performed laparoscopically; however, this approach will remain controversial until long-term studies prove its safety and efficacy for APR. To begin, the surgeon makes an midline incision in the abdomen large enough to see the tumor and to examine lymph nodes and other organs for metastases. If the tumor is removable, then the procedure continues. Within the abdomen, rectal blood vessels are tied, and the mesentery is clamped. The lower colon is freed from attachments. The peritoneum is divided, enabling the surgeon to free the rectum. The tied blood vessels and clamped mesentery are divided and sealed. Then, the ostomy opening is made in the abdomen. The colon is divided. The lower end of the colon is covered and tucked below the peritoneum for removal during the perineal resection, and the peritoneum is closed. The upper end of the colon is passed through the ostomy opening, the colon segment is sized to an appropriate length, and the edge of the cut end is folded back and stitched to the abdomen, forming a stoma. Next, other organs are examined for cancer; if other lesions or metastases are found, then they may also be removed. Finally, the abdominal cavity is inspected and cleaned, and the abdominal incision is closed. On the perineum, the surgeon makes an elliptical incision around the anus. Blood vessels are clamped, then tied as needed. The anus is freed from attachments, including as much surrounding tissue as possible without disturbing major blood vessels, nerves, and healthy organs; however, if the cancer has spread into these structures, then part or all of these structures may be included. The anus is pulled out, as well as the rectum and lower colon freed during the abdominal resection. All tissues are taken to the laboratory for histopathologic evaluation. Finally, the pelvic cavity is inspected and cleaned, and the perineal incision is closed, with a small tube inserted to drain excess fluid. After the procedure: Anesthetic is stopped, and the breathing tube is removed. The urinary catheter and the intravenous line are kept. A clear collection pouch (ostomy appliance) is fitted over the stoma. The patient is trans2
Salem Health: Cancer ferred to the recovery room, then to a hospital room. Medications are given to control pain and infection. The patient slowly progresses to a normal diet. The ostomy is monitored; once it starts functioning, the patient learns how to care for the stoma, empty and change pouches, and manage bowel function. At home, the patient follows the physician’s instructions about medications, activities, and diet. Further treatment with radiation therapy, chemotherapy, or both may be recommended. Risks: APR is moderately safe, with low mortality. Risks relate to anesthesia, infection, and inadvertent damage to other structures. Side effects are common because of the complex anatomy and the difficulty of operating within the bony pelvis. The most frequent side effects are urinary dysfunction and infection, perineal infections or bleeding, and ostomy-related problems. Less frequent side effects are male impotence and infertility, abdominal wound infection, and intestinal obstruction. Results: The long-term outcome varies considerably with patient-specific factors (such as disease stage, overall health, and body characteristics), among medical institutions (as a result of surgical protocol and specialized experience), and with therapeutic combinations. The five-year survival rate has increased as the recurrence rate has decreased because of more complete removal of diseased tissue and more effective therapeutic combinations. Survival is improved significantly by the removal of metastases. Patricia Boone, Ph.D. u
For Further Information American Cancer Society. Detailed Guide: Colon and Rectum Cancer Surgery. Available online at http:// www.cancer.org. American Cancer Society and National Comprehensive Cancer Network. Colon and Rectal Cancer: Treatment Guidelines for Patients. Version IV. Atlanta: American Cancer Society, 2005. Available online at http://www .nccn.org. Levin, Bernard, et al., eds. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006. See also Anal cancer; Anoscopy; Appendix cancer; Colectomy; Coloanal anastomosis; Colorectal cancer; Colostomy; Crohn disease; Enterostomal therapy; Ileostomy; Laparoscopy and laparoscopic surgery; Rectal cancer; Sexuality and cancer.
Salem Health: Cancer
u Accelerated partial breast
irradiation (APBI) Category: Procedures Definition: Accelerated partial breast irradiation (APBI) is an alternative to traditional radiation therapy after lumpectomy that can reduce the time of treatment from weeks to days. It is considered an experimental procedure by many doctors. Cancers treated: Breast cancer Why performed: Radiation therapy is given after a lumpectomy to kill any cancer cells that remain in the breast. Accelerated partial breast irradiation is an alternative therapy that delivers radiation in a way that reduces the time and number of treatments required. Radiation therapy usually requires visits to the outpatient center or clinic five days a week for six or seven weeks. APBI reduces the amount of time required for treatment to about five days in total. Patient preparation: Patients who are undergoing accelerated partial breast irradiation treatment are generally enrolled in a clinical trial, because the procedure is still considered experimental. A clinical trial is a carefully controlled study, supervised by doctors who are also researchers, that is designed to investigate the risks or benefits of a new or experimental procedure. Different types of APBIs are being investigated in clinical trials, using different methods and techniques. As a result, the patient preparation for APBI will differ depending on the specifics of the therapy. In general, the preparation for APBI is the same as for any other radiation therapy treatment. Steps of the procedure: Just as with traditional radiation therapy, the actual time elapsed during a treatment of accelerated partial breast irradiation is usually very short. The time that it takes to get the equipment and patient set up, however, may be significant. First, the patient and the patient’s breast are positioned appropriately for the machine. During traditional radiation therapy, the entire breast receives radiation. During APBI, however, the only part of the breast that receives radiation is the area around the lumpectomy site. Therefore, the breast must be positioned very exactly so that the right area receives the radiation. To place the breast in the correct position, the cancer care team may label the breast with marker or tattooing. The patient should check with her cancer care team to see if these marks are temporary. Once the breast and equipment are correctly positioned, a dose of radiation is given to the breast. Radiation machines deliver beams of high-energy particles to the tis-
Accelerated partial breast irradiation (APBI) sue that destroy cancer cells. Accelerated partial breast irradiation uses amounts of radiation during treatment that are higher than those used by traditional radiation therapy. This is part of the reason that the treatment time of APBI is so short. After the procedure: After the procedure, the patient may experience fatigue, as well as pain or swelling in the breast. Aftercare depends on the procedure that is used. Patients should discuss aftercare with their cancer care team before the day of the first procedure so that anything needed, such as transportation home after the procedure, can be arranged in advance. Risks: Some risks are associated with any procedure involving radiation. With an experimental therapy such as APBI, ongoing clinical trials are trying to determine any long-term side effects that may result from the procedure. Most studies, however, have found the risks associated with APBI to be relatively mild, not greater than risks associated with traditional radiation therapy, and decreasing over time. The most common side effects of APBI are believed to be fatigue, skin changes similar to sunburn in the treated area, swelling in the breast, breast heaviness, and breast discoloration. The creation of small, hard nodes in the breast is also possible. These nodes are not dangerous, but they can occasionally be mistaken for a return of the breast cancer when felt or seen on a mammogram. A very rare but extremely serious possible complication of any radiation to the breast is the development of angiosarcoma, an aggressive form of cancer. Results: Studies done comparing women who received APBI and those who received traditional radiation therapy after lumpectomy have generally found comparable rates of recurrence, even after many years. Researchers, however, are still conducting more studies and clinical trials. Most studies have been conducted only on very specific groups of women, and more research is being done to study the larger population of women with breast cancer to help determine whether APBI is a technique that could be beneficial to all women, and should be integrated into standard breast cancer treatment practices. The results that any individual woman experiences after APBI will depend on many different factors, including genetics, the type of original cancer, and the size of the original cancer. Helen Davidson, B.A. u
For Further Information Pasqualini, Jorge R., ed. Breast Cancer: Prognosis, Treatment, and Prevention. 2d ed. New York: Informa Healthcare, 2008. 3
Achlorhydria Smith, Terry L. Breast Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Torosian, Michael H., ed. Breast Cancer: A Guide to Detection and Multidisciplinary Therapy. Totowa, N.J.: Humana Press, 2002. Winchester, David J., et al. Breast Cancer. 2d ed. Hamilton, Ont.: BC Decker, 2006. See also Afterloading radiation therapy; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Cutaneous breast cancer; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Lumpectomy; Lumps; Mastectomy; Medullary carcinoma of the breast; Radiation therapies; Radiofrequency ablation.
u Achlorhydria Category: Diseases, symptoms, and conditions Also known as: Profound hypochlorhydria Related conditions: Helicobacter pylori infection, chronic atrophic gastritis, gastric adenocarcinoma, gastric carcinoid Definition: Achlorhydria is the absence of acid secretion by the stomach caused by either atrophy of the acid-producing parietal cells or direct inactivation of the protonpumping enzyme in parietal cells responsible for acid secretion. Risk factors: The risk of achlorhydria increases with age and with long-term, untreated infection with the bacteria Helicobacter pylori. Patients with autoimmune conditions are also at increased risk. The condition has no predilection for sex or race. Etiology and the disease process: Chronic inflammation of the stomach in response to untreated H. pylori infection lasting many years leads to the atrophy of stomach cells and a corresponding loss of acid-secreting capacity. Some patients may be more predisposed to achlorhydria in the presence of H. pylori because they respond to the infection by producing a specific inflammatory agent that is also a potent proton pump inhibitor. Autoimmune disease can also produce achlorhydria if the body makes antibodies that inactivate parietal cell proteins. Achlorhydria is associated with the development of malignant cancer of the stomach. Over 60 percent of patients with gastric cancer have achlorhydria compared with 20 percent of healthy individuals. Acid normally acts 4
Salem Health: Cancer as a disinfectant to prevent overgrowth of harmful bacteria; achlorhydria contributes to cancer development because the bacteria synthesize carcinogenic chemicals from nitrates present in food. Achlorhydria is also associated with the formation of gastric carcinoid tumors. If acid output by the stomach is disrupted, the body overproduces the hormone gastrin, which stimulates overgrowth of enterochromaffinlike (ECL) cells in the stomach. This overgrowth may progress to carcinoid formation. Incidence: Gastric carcinoids constitute 0.5 percent of gastric cancers. They are typically associated with autoimmune conditions and have a low risk of malignancy. Symptoms: Achlorhydria itself causes no symptoms; rather, symptoms are secondary to the absence of acid. Lack of acid can cause vitamin B12 or calcium deficiency. Diarrhea may occur because of the overgrowth of bacteria. Screening and diagnosis: Diagnosis is made by measuring the acidity of a stomach fluid sample after an intravenous injection of pentagastrin, which stimulates acid secretion in normal patients. Acidity will not increase in the stomach fluid of achlorhydric patients. Treatment and therapy: Treatment focuses on addressing the underlying condition causing achlorhydria. Because vitamin B12 and calcium absorption are decreased, supplementation or injections of B12 may be necessary. Prognosis, prevention, and outcomes: Restoration of normal acid production depends on prognosis and treatment for the underlying condition responsible for achlorhydria. Pamela S. Cooper, Ph.D. See also Adenocarcinomas; Bacteria as causes of cancer; Gastric polyps; Gastrointestinal cancers; Helicobacter pylori; Hereditary diffuse gastric cancer; Premalignancies; Stomach cancers.
u Acoustic neuromas Category: Diseases, symptoms, and conditions Also known as: Vestibular schwannomas Related conditions: Neurofibromatosis type 2 Definition: Acoustic neuromas are benign (or nonmalignant) tumors that originate from Schwann cells surrounding the vestibular nerve (eighth cranial nerve) in the internal auditory canal. The term “neuroma” is somewhat misleading, as the tumors are not neuromas, nor do they
Salem Health: Cancer arise from the acoustic or cochlear nerve. Acoustic neuroma typically occurs as unilateral (one-sided) sporadic tumors in 95 percent of all cases, but in rare cases tumors can be bilateral (two-sided) and are associated with an inherited syndrome called neurofibromatosis type 2 (NF2). Approximately 2 to 4 percent of patients diagnosed with acoustic neuromas have NF2 type, a prevalence of 1 in 50,000 in the general population. Risk factors: Although high-dose ionizing radiation is a known risk factor of acoustic neuroma, environmental factors including noise exposure, radio frequency electromagnetic fields, and allergens have been reported as potential sources that may contribute to the formation of acoustic neuroma. One publication has reported the findings from an international multicenter case-control study that investigated the effects of these environmental factors in ninety-seven patients with acoustic neuroma and in agematched control subjects. The study reported that increased risks were found for exposure to persistent noise and hay fever, but not for ionizing radiation or for regular mobile phone use. Etiology and the disease process: Currently, the etiology of acoustic neuroma is not known. However, as an anomaly, it is rarely inherited. Nonetheless, neurofibromatosis type 2 should be suspected in young patients and those with family history. Neurofibromatosis is an autosomal dominant disease; thus patients who inherit a defective copy of the NF2 tumor-suppressor gene have a 95 percent chance of developing bilateral tumors; however, half of the cases have no family history of NF2, which could indicate mutations in the germline that were not inherited. Incidence: Sporadic acoustic tumors, the most common form of manifestation, occur in approximately 10 per 1 million persons per year—in other words the chance of an average person developing an acoustic neuroma in his or her lifetime is about 1 in 100,000. Neurofibromatosis is rarer, with only several thousand affected persons in the entire United States, corresponding to 1 in 40,000 individuals. However, a study has highlighted that the true incidence of acoustic neuroma may be higher than what has been envisaged, as 7 unsuspected schwannomas per 10,000 brain magnetic resonance imaging studies were identified, an equivalent of 0.07 percent. Acoustic neuromas, or schwannomas, occur largely in adults, typically in the fourth and fifth decades, with a mean presentation age of fifty years. They are uncommon in children; only thirty-nine cases had been reported as of 2007. Symptoms: Acoustic neuromas are histologically benign; however, if large, they can cause hydrocephalus, brain-
Acoustic neuromas stem compression, herniation, and eventually death. Hearing loss is the most prevalent symptom, occurring in more than 95 percent of patients, and the duration of hearing loss may extend to three or four years before clinical diagnosis is made—a majority of the patients experience one-sided, slowly progressing hearing impairment associated with high-frequency sounds. Alternative complaints or accompanying symptoms include tinnitus, dizziness, vertigo, and a sensation of fullness in the ear. With the progression of the tumor, patients may experience facial numbness, headaches, loss of coordination, and difficulty in swallowing. Vertigo is prevalent with smaller tumors, while unsteadiness, headache, and facial sensory disturbance are associated with large tumors. Screening and diagnosis: Acoustic neuroma can be diagnosed by a number of screening methods. These include conventional audiometry, auditory brainstem response (ABR), and gadolinium-enhanced magnetic resonance imaging (MRI). Among these, gadolinium-enhanced MRI is the optimal diagnostic test. Typically, on MRI scans acoustic neuromas appear as dense and uniformly enhanced. Acoustic neuromas are staged according to their location and size. Small tumors are less than 1.5 centimeters (cm), moderate tumors between 1.5 and 3 cm, and large tumors greater than 3 cm in size. Based on the location, they are staged as intracanalicular (located in the internal auditory canal), cisternal (extending outside the internal auditory canal), compressive (having progressed to touch the cerebellum or brainstem), and hydrocephalus (having progressed to obstruct the drainage of cerebrospinal fluid in the fourth ventricle). Treatment and therapy: The treatment options for acoustic neuroma include observation, microsurgery, stereotactic radiosurgery, and radiotherapy. Patients with advanced age or those deemed unfit for surgical intervention with small tumors at diagnosis are observed; treatment is withheld while tumor progression is monitored in serial imaging studies. However, treatment by observation has its own risks, as there is a greater risk of losing useful hearing. If microsurgery is the choice for treatment, many factors need to be assessed when evaluating its primary and secondary outcomes. First, there are three standard surgical approaches, each with its own advantages and disadvantages: suboccipital, middle fossa, and translabyrinthine. In the suboccipital approach, the tumor is reached through the skull behind the ear. As the procedure involves the retraction of the cerebellum, the approach is intrinsically dangerous and prone to complications. Although the middle fossa method can preserve hearing in theory, this 5
Acrylamides approach is also dangerous as it too requires the retraction of part of the brain. In the translabyrinthine approach, the tumor is accessed through the inner ear, and thus hearing loss is expected and inevitable. However, this method is unsuitable for large tumors. Second, microsurgery is technically challenging; therefore the rate of success is lower with a less experienced surgeon. Third, large tumors (greater than 3 cm) are difficult to resect without concomitant morbidity, such as facial palsy. Some of the complications that may arise from microsurgery are cerebrospinal fluid leak (12 percent of all cases), meningitis (5 percent), intracranial hemorrhage (2 percent), facial weakness with complete paralysis (31 percent), and delayed or partial paresis (50 percent). Radiosurgery refers to the administration of a single fraction of radiotherapy using stereotactic techniques to localize the tumor and align the fields. Radiosurgery may be performed either with a Gamma Knife or a linear accelerator (linac) based system. Gamma Knife is an emerging treatment option for those who are at high risk during microsurgery. High-dose Gamma Knife procedures are less favored due to the possibility of radiation complications; thus low-dose radiation (for example, 13 gray, or Gy) therapies are advised because of safety and lower risk of facial weakness. Radiotherapy refers to the administration of fractionated radiotherapy and includes stereotactic radiotherapy (radiation with other than gamma rays) and conventional radiotherapy techniques. Complications of Gamma Knife radiosurgery include injury to facial and trigeminal nerves. However, with the current dosing regimen of 12.5 Gy, the risk of trigeminal or facial nerve injury has decreased significantly. Although the potential for complications is higher with microsurgical procedures than with radiotherapy or radiosurgery, an important issue that should be considered with irradiation therapies is the low risk of inducing malignancies within the radiation area. Current recommendations are to offer microsurgery and radiosurgery options for patients with definite treatment indications. While microsurgery is the treatment of choice for large tumors because of the low risk of radiation-induced malignancies, microsurgery is also considered for younger patients. Prognosis, prevention, and outcomes: The microsurgical techniques for acoustic neuroma have improved the anatomical and functional preservation of the facial and cochlear nerves. These techniques, accompanied by continuous electrophysiological monitoring, have resulted in marked changes in the primary goals of management. In the past, the primary goal of acoustic neuroma manage6
Salem Health: Cancer ment was to preserve the patient’s life, whereas the objective today is to preserve the neurological function. Long-term follow-ups show negligible recurrence rates, suggesting that the preservation of neurological function does not restrict the tumor removal. Despite these advances, loss of nerve function and even deafness may occur postoperatively in some cases. Bagirathy Ravishankar, Ph.D. u
For Further Information Battaglia, A., et al. “Comparisons of Growth Patterns of Acoustic Neuromas with and Without Radiosurgery.” Otology and Neurotology 27 (2006): 705-712. Mendenhall, W., et al. “Management of Acoustic Schwannoma.” American Journal of Otolaryngology 25 (2004): 38-47. Neff, B., et al. “The Molecular Biology of Vestibular Schwannomas: Dissecting the Pathogenic Process at the Molecular Level.” Otology and Neurotology 27 (2006): 197-208. Schlehofer, B., et al. “Environmental Risk Factors for Sporadic Acoustic Neuroma.” European Journal of Cancer 43 (2007): 1741-1747. Yohay, K. “Neurofibromatosis Types 1 and 2.” The Neurologist 12 (2006): 86-93.
u
Other Resources
Acoustic Neuroma Association http://anausa.org American Cancer Society http://www.cancer.org See also Ependymomas; Neurofibromatosis type 1 (NF1); Schwannoma tumors; Stereotactic radiosurgery (SRS).
u Acrylamides Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1991 Also known as: 2-propenamide, propenamide, acrylic amide, vinyl amide, ethylene carboxamide Related cancers: Although an acrylamide-cancer connection in humans has not been established with certainty, the level of suspicion is high because under laboratory conditions in rats and mice, the following cancers have been associated with acrylamide: adrenal pheochromocytomas and mesotheliomas in the testes; adenomas in the
Salem Health: Cancer
Acrylamides
pituitary and mammary glands; adenocarcinomas of the clitoris, uterus, and thyroid gland; squamous cell carcinoma of the skin; and adenomas of the lung. Definition: Acrylamide is a compound of carbon, hydrogen, nitrogen, and oxygen resulting in the chemical formula, C3H5NO. This white, odorless, and crystalline compound is soluble in water, ethanol, ether, and chloroform, accounting for not only its many industrial uses but also its potential for uncomplicated entry into the human body. Many of its industrial and agricultural uses require the conversion of acrylamide to the polymer polyacrylamide. Exposure routes: Experimentally in rats and mice, cancer-inducing exposure routes include administration in the drinking water, intraFrench fries contain high levels of acrylamide. (©Birgit Reitz-hofmann/ Dreamstime.com) peritoneal injection, and topical application. In humans, during everyday activity and work, acrylamide gains entrance through unbroken At risk: Because of its almost ubiquitous presence at skin, mucous membranes, lungs, and the gastrointestinal the dinner table and its known neurotoxic and carcinotract. The primary occupational exposure routes are skin genic potential, acrylamide poses a health risk to humans. contact and through the inhalation of dust and vapor. Microwaving, baking, and frying will produce acrylamide, and as the food continues to cook, ever larger amounts Where found: Acrylamides are used in the treatment of of acrylamide are produced. As the risk potential for wastewater, drinking water, and sewage; in the production acrylamides in foods becomes more publicized, some of paper, plastics, and dyes; and in the manufacture of persteps are under way to modify food production methods, manent press fabrics, adhesives, and food packaging. It is such as using vacuum frying at lower temperatures. Raw also fundamental to ore processing. Acrylamide finds its or boiled foods pose little risk for acrylamides. way into a number of everyday products such as building Workers engaged in oil drilling, paper and pulp manumaterials, contact lenses, textiles, soap, food, and gelatin facture, general construction, plastics manufacture, mincapsules. Acrylamides have also established a place on ing, food processing, textile and cosmetics processing, and people’s dining tables: It is found in fried and baked agricultural industries are at increased risk of acrylamide goods, coffee, olives, and prune juice. Smoking is also a exposure. major acrylamide producer. Some acrylamide contaminates drinking water because Etiology and symptoms of associated cancers: Although of its use in water treatment facilities, but curiously, the research has not firmly established the acrylamide-cancer amount of acrylamide in a large order of fast-food french connection in humans, there is no question that acrylamide fries is more than three hundred times what the U.S. Enviis a serious neurotoxin. Depending on dosage levels, exporonmental Protection Agency allows in a single glass of sure can cause damage to the male reproductive glands, water. This pervasiveness of acrylamide prompted Dale skin, and eyes. Additionally, it may result in urinary inconHattis, a risk analysis expert at Clark University, to specutinence, numbness, weakening in the legs and hands, and late that “acrylamide causes several thousand cancers per irritation of the mucous membranes. year in Americans.” The National Institute for Occupational Health and Additionally, polyacrylamide, the polymer of acrylamSafety (NIOSH) lists the common acrylamide exposure ide, finds widespread global use in pesticides and in soil symptoms in an industrial setting: irritation of the eyes and treatment formulations. This has resulted in notable resiskin, ataxia, numbness of the limbs, paresthesia, muscle dues of polyacrylamide in the most widely consumed vegeweakness, absent deep tendon reflex, hand sweating, lassitables such as potatoes and grains. There is little governtude (weakness, exhaustion), drowsiness, and reproducment oversight or measurement of polyacrylamide in foods. 7
Acupuncture and acupressure for cancer patients tive effects. The institute further cautions that acrylamide is a potential occupational carcinogen. History: Production of acrylamide in the United States exceeds one million pounds per year. It was not until 2002 that Swedish scientists found high levels of acrylamide in certain fried and baked starchy foods. In the same year, the Center for Science in the Public Interest in the United States reported finding high levels of acrylamide in popular brands of snack chips, french fries, taco shells, and breakfast cereals. Government action concerning these findings has been very slow, but in 2005 the California attorney general filed a lawsuit requiring a warning label for french fries and potato chips. Although NIOSH considers the compound dangerous to life and health, the Food and Drug Administration allows acrylamide to be used for packaging, in plastics that are in contact with food, and in treating food to maximum levels ranging up to 0.20 percent. Although research has firmly established the canceracrylamide connection in rats and mice, the findings are still mixed in human studies. Some experts claim the very pervasiveness of acrylamide in the Western diet confuses the results. Richard S. Spira, D.V.M. u For Further Information Brown, L., M. M. Rhead, K. C. C. Bancroft, and N. Allen. “Model Studies of the Degradation of Acrylamide Monomer.” Water Research 14, no. 7 (1980): 775-778. Rice, Jerry M. “The Carcinogenicity of Acrylamide.” Mutation Research/Genetic Toxicology and Environmental Mutagenesis 580, nos. 1/2 (2005): 3-20. Smith, E., S. Prues, and F. Ochme. “Environmental Degradation of Polyacrylamides: Effect of Artificial Environmental Conditions.” Ecotoxicology and Environmental Safety 35 (1996): 121-135. Tareke, E., et al. “Analysis of Acrylamide, a Carcinogen Formed in Heated Foodstuffs.” Journal of Agriculture and Food Chemistry 50, no. 17 (2002): 4998-5006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Weiss, G. “Acrylamide in Food: Uncharted Territory.” Science 27 (2002): 297. u
Other Resources
National Institute for Occupational Safety and Health http://www.cdc.gov/niosh 8
Salem Health: Cancer National Library of Medicine Toxicology Data Network http://toxnet.nlm.nih.gov U.S. Food and Drug Administration Draft Action Plan for Acrylamide in Food http://www.cfsan.fda.gov/~dms/acrypla3.html See also Adenocarcinomas; Endocrine cancers; Testicular cancer; Vulvar cancer.
u Acupuncture and acupressure
for cancer patients Category: Procedures Also known as: Traditional Chinese medicine (TCM), complementary and alternative medicine (CAM), Oriental medicine (OM) Definition: Acupuncture is a technique in which hair-thin, sterile, disposable needles of varying lengths are inserted into the skin and muscles at specific anatomical points (called acupoints) in order to treat ailments, including pain and certain diseases. It is one branch of traditional Chinese medicine (TCM) that originated in China around four thousand years ago to prevent, diagnose, and treat diseases in both humans and animals. Acupressure is a variation of acupuncture, in which therapists or patients press on acupoints with their fingers instead of inserting needles. Only specifically trained, licensed professionals can treat patients using acupuncture needles, but patients can be taught (preferably by a licensed professional) to perform acupressure on themselves. In 1996, the Food and Drug Administration (FDA) approved the acupuncture needle as a medical device. In 1997, the National Institutes of Health (NIH) began evaluating the safety and effectiveness of acupuncture as a complementary and alternative treatment. According to TCM principles, fourteen meridians are theorized to course invisibly along the body surface, including six paired and two unpaired channels. These meridians correspond to and connect with certain internal organs and physiological systems as understood in both traditional Chinese and Western medicine. Every acupoint is named and numbered according to its location on a specific meridian (for example, P6, or pericardium 6). Upon needling, the acupuncturist attempts to unblock, move, or alter what TCM refers to as the qi or chi (pronounced “chee”) of the body. This qi is a vital force that is thought to flow along the meridians and throughout the
Salem Health: Cancer body and organ systems. TCM posits that qi is formed from a merging of yin and yang, which are opposite energy states that permeate the universe. An imbalance of yin and yang in the body is thought to lead to a disruption of qi, leading to disharmony in physical and psychic well-being and thus to certain ailments or diseases. The acupuncturist (or acupressure practitioner) tries to restore a healthier balance of yin and yang in the patient. Many Western and Eastern acupuncturists currently blend TCM theory with modern understanding of neuroanatomy and the immune and other physiological systems. Cancers diagnosed or treated: In Western cancer management, acupuncture and acupressure are primarily used to mitigate the side effects related to conventional cancer treatments such as chemotherapy, radiation treatment, and surgery, or side effects of the disease itself. These side effects include chemotherapy-related nausea and vomiting, dyspnea (shortness of breath in advanced cancer cases), pain (either from a conventional treatment or the cancer itself), fatigue, depression, vasomotor symptoms (hot flashes), and treatment- or cancerrelated immunosuppression. In most instances, the acupuncture or acupressure interventions are used in addition to state-of-the-art pharmaceutical treatments, such as antiemetic therapy (such as Odansetron) for nausea and vomiting. Why performed: Cancer patients and their clinicians often resort to acupuncture and acupressure (and other alternative medical treatment modalities) for symptoms that are not amenable or are unresponsive to traditional therapies. Sometimes they are used to augment the effectiveness of conventional medicines, as in the case of antiemetic therapies for nausea and vomiting, which can lead to weight loss and depression. Some patients (and their clinicians) are seeking a more holistic approach to healing, viewing acupuncture and acupressure as methods that restore harmony to the body, treating the whole person instead of just the disease. Often patients take solace in the “mysterious” mechanisms underlying alternative treatments. Many acupuncturists are intrigued by the TCM philosophies and theories, at the same time applying current Western knowledge of anatomy and neurophysiology to their techniques. Most acupoints correspond to specific nerve pathways or receptors and/or highly vascular areas. There is strong evidence that acupuncture modulates neurotransmitters, leading to the release of endogenous opioids (endorphins and
Acupuncture and acupressure for cancer patients enkephalins) for analgesia (pain relief). Manipulation of certain acupoints stimulates the autonomic nervous system, leading to changes in blood circulation and engaging components of the immune and endocrine systems (proteins called cytokines or the release of endogenous corticosteroids and other hormones). These procedures can also alter blood pressure, heart rhythms, and body temperature. Not all the mechanisms involved in successful acupuncture and acupressure treatment are understood, and they remain a subject of scientific investigation. Some skeptics still believe that they work primarily via the placebo effect. Patient preparation: Very little patient preparation is required for these procedures. The patient disrobes to the extent required for examination and the placement of acupuncture needles or accessibility to acupressure points. Some acupuncturists will take a patient’s medical history
A patient receives an acupuncture treatment. (PhotoDisc)
9
Acupuncture and acupressure for cancer patients and ask questions about diet and exercise. Some will also look at the patient’s tongue and feel his or her pulse in order to make a TCM diagnosis and appropriate acupoint prescription tailored to the patient’s needs. A more Westernized approach would be to apply a standard point prescription for a particular malady, omitting such TCM elements as tongue and pulse exams. Steps of the procedure: The acupuncturist will feel for the appropriate acupoints, often massaging the area prior to needle insertion. The skin is then cleaned with an alcohol wipe and the needle is inserted until the practitioner feels some resistance and/or the patient feels a tingling or cramping sensation. This is referred to as “obtaining the qi,” or De Qi. Many practitioners then manipulate the needle, using hand technique (shou fa) to move, supplement or drain the qi and/or yin and yang. The needles are then usually left in place for ten to twenty minutes. In acupressure, the patient or practitioner applies pressure to the acupoints for a few minutes, repeating this action at intermittent intervals over a specified period of time. Sometimes a band with an attached stud is applied over an acupoint and the patient is instructed to press the stud into the point at prescribed intervals in an effort to obtain a De Qi response during point stimulation. Sometimes an acupuncturist will apply a small electric current to the needles in a technique called electroacupuncture. This is another method of stimulating the acupoints. Various other methods of stimulation are employed as well. Moxibustion applies heat to the acupoints using burning mugwort herb (Artemisia vulgaris). Aquapuncture is a technique in which acupoints are injected with drugs, vitamins, flower essences, herbal extracts, or other fluids for longer-term stimulation of acupoints. After the procedure: A properly treated patient should experience relaxation, deeper respiration, and increased vitality following acupuncture, since energetic balance has supposedly been restored. For treatment of specific cancer-related symptoms, some immediate relief is expected, followed by delayed improvement, especially after multiple acupuncture or acupressure sessions. Risks: Acupuncture should be avoided in patients with thromobocytopenia or aplasia or in those treated with anticoagulants. Some common side effects are bruising, local bleeding, and mild pain in the treated areas. The risk of infection is small if sterile, disposable needles are used. There is a very small risk that the lungs or other internal organs can be punctured if a needle is placed too deep. 10
Salem Health: Cancer Results: The results of many random, controlled clinical trials have demonstrated that acupuncture is effective for reducing episodes of acute vomiting following chemotherapy for breast and other cancers. The same and other studies have shown that acupressure at certain acupoints is effective for reducing episodes of acute nausea following chemotherapy. Both acupuncture and acupressure have been more effective for prophylactic treatment of vomiting and nausea following conventional cancer treatment rather than stopping these symptoms once they have started. One study indicated that the effectiveness of acupuncture for reducing vomiting episodes following chemotherapy was increased for up to twenty-four hours when acupressure followed needling therapy. One review of acupuncture for the relief of cancerrelated pain found that ear acupuncture (stimulation of acupoints corresponding to different body areas on the ear) was effective for reducing cancer-related pain. Other clinical trials have shown that acupuncture helps reduce the number of hot flashes in men being treated with hormones or surgery for prostate cancer and women being treated with tamoxifen or related hormone therapies for breast cancer. Investigators, however, have noted a dearth of random, double-blind, controlled clinical trials for proving the effectiveness of these alternative therapies. The development of a sham acupuncture needle (the needle withdraws into the shaft upon “insertion” at true acupoints) is expected to improve the rigorousness of these trials and to provide substantive evidence for or against acupuncturerelated therapies. Lisa J. Shientag, V.M.D. u
For Further Information Ezzo, J. M., M. A. Richardson, and A. Vickers. “Acupuncture Point Stimulation for Chemotherapy-Induced Nausea or Vomiting.” The Cochrane Database of Systematic Reviews 2 (2007). Hyangsook, L., K. Schmidt, and E. Ernst. “Acupuncture for the Relief of Cancer-Related Pain: A Systematic Review.” European Journal of Pain 9, no. 4 (August, 2005): 437-444. Sagar, Stephen M. Restored Harmony: An Evidence Based Approach for Integrating Traditional Chinese Medicine into Complementary Cancer Care. Hamilton, Ont.: Dreaming DragonFly Communications, 2001. See also Bone cancers; Bone pain; Complementary and alternative therapies; Home health services; Integrative oncology; Living with cancer; Pneumonia; Side effects; Smoking cessation.
Salem Health: Cancer
Acute lymphocytic leukemia (ALL)
u Acute lymphocytic leukemia
(ALL) Category: Diseases, symptoms, and conditions Also known as: Acute childhood leukemia, acute lymphoblastic leukemia, acute lymphoid leukemia Related conditions: Acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia Definition: Acute lymphocytic leukemia (ALL) is a cancer of the white blood cells. A lymphocyte is a type of white blood cell made in the bone marrow that helps fight infection. In this fast-growing type of cancer, for unknown reasons, the bone marrow begins to make lymphocytes that develop abnormally. “Acute” means that the disease affects lymphocytes before they are fully formed and that it progresses rapidly if not treated. Risk factors: Few risk factors exist for ALL. Receiving high doses of radiation, usually as treatment for another type of cancer, is one risk factor. Exposure to benzene may also be a factor. Risk increases in people with certain other diseases, such as Down syndrome, Fanconi anemia, Bloom syndrome, and some other genetic diseases. In about 25 percent of ALL cases, the patient has a chromosome mutation in which parts of chromosome 9 and chromosome 22 have changed places. Having a sibling, especially a twin, with ALL also increases the risk for this disease. Researchers are exploring lifestyle or environmental relationships, but it appears that many factors, including a combination of genetic and environmental factors, may be involved in developing ALL.
and slightly more common in white children than in children of other races. ALL occurs in people of all ages but has a peak incidence in children between the ages of two and five. After age five, risk decreases, then increases again in people over age fifty. It is the most common type of leukemia in children under the age of fifteen, accounting for about 80 percent of childhood leukemias. It occurs more often in developed countries and in people with higher socioeconomic status. Symptoms: Symptoms of ALL include anemia, body aches, bone pain, bruises without any injury, enlarged lymph nodes, an enlarged spleen, excessive bleeding from minor injuries, fever with no illness or lasting low-grade fever, frequent infections, headaches, joint pain, nosebleeds, paleness, shortness of breath during activity, tiredness, vomiting, and unexplained weight loss. Screening and diagnosis: There is no screening test for ALL. Blood and bone marrow tests are necessary to diagnose ALL. These tests look for abnormal lymphocyte cells. A bone marrow aspirate test (using a long needle to take marrow out of the bone) and a bone marrow biopsy (surgical removal of some bone marrow) are two possible tests. The bone marrow aspirate test looks for abnormal
Etiology and the disease process: Through a genetic process that is not completely understood, cells in bone marrow begin to form abnormally. ALL can begin in two different types of lymphocytes, either B cells or T cells. As the abnormal lymphocytes quickly grow, they crowd out the red and white blood cells and platelets that the body needs and that are also created in the bone marrow. The symptoms of ALL come from the crowding out of these normal, healthy cells. These cells may then spread into the lining of the spine and brain. Incidence: About 5,200 people in the United States were diagnosed with ALL in 2007. It is slightly more common in men than in women
A nine-year-old girl with acute lymphocytic leukemia describes her condition to a health care worker. (Simon Fraser/Photo Researchers, Inc.)
11
Acute lymphocytic leukemia (ALL)
Age at Death for Acute Lymphocytic Leukemia, 2001-2005 Age Group
Deaths (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
21.4 15.9 9.7 11.2 11.7 12.7 11.5 5.8
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of death from 2001 to 2005 was fortyseven, with an age-adjusted death rate of 0.5 per 100,000 men and women.
cells in the bone marrow and can also be used for other types of analysis. A bone marrow biopsy can show how much disease is already in the bone marrow. The results of these tests help determine which type of drug therapy to use and how long treatment should last. If a patient has been diagnosed with ALL, a lumbar puncture may be performed to see if the abnormal cells have moved into the fluid surrounding the spine and brain. Chest X rays, ultrasounds, or additional blood tests may also be used to determine the spread of the disease. Depending on where the cancer started and the results of testing, ALL may be categorized into early pre-B-cell ALL, common ALL, pre-B-cell ALL, mature B-cell ALL, pre-T-cell ALL, or mature T-cell ALL. The type of ALL helps determine which therapy to use and how long treatment should last. About 85 percent of ALL cases begin in B cells, and these cases are generally classified as lower risk. ALL may also be classified or staged using the FrenchAmerican-British (FAB) classification system. In this older system, ALL is classified according to the type of abnormal cells as follows: • ALL-11: small, uniform abnormal cells • ALL-12: large, varied abnormal cells • ALL-13: large, varied, bubble-like cells Treatment and therapy: Patients diagnosed with ALL should start treatment immediately. The course and length of treatment chosen depend on the results of the patient’s bone marrow tests, the patient’s age, the number of ALL cells in the blood, whether certain chromosomal changes 12
Salem Health: Cancer have already happened, whether ALL cells began in the B cells or the T cells, and whether ALL has spread to the brain covering or spinal cord. During therapy, bone marrow tests may be done again to make sure the treatment is destroying the cancer cells. The first part of treatment for ALL is called induction therapy. This therapy helps kill ALL cells and get a patient’s blood counts back to normal (remission). Some of the drugs used in induction therapy are given by mouth. Others are given in a vein, usually through the patient’s chest. Most often, this chemotherapy for ALL involves combining drugs to improve the effects of the drugs. Often, ALL spreads into the lining of the spinal cord and the brain. To kill these ALL cells, drugs are injected directly into the spinal fluid. Radiation therapy may be used on the spine and brain either with or without the injected drugs. Post-induction therapy, the second part of treatment for ALL, begins when a patient has reached remission. This type of therapy is needed because usually some ALL cells that cannot be detected by tests remain in the body. Postinduction therapy usually happens in two- or three-year cycles. The drugs used in post-induction therapy are usually different from those used in induction therapy, and the type of drugs used depends on how the patient responded to induction therapy and whether the patient has certain chromosome abnormalities. A patient may also need maintenance therapy after post-induction therapy to prevent the cells from regrowing. T-cell ALL, infant ALL, and adult ALL are all forms of high-risk ALL. These types of ALL are usually treated with higher doses of drugs during both induction and postinduction therapy. Some patients with high-risk types of ALL may respond well to bone marrow or cord blood transplant therapy. A bone marrow or cord blood transplant may be used when high doses of drugs are given to kill the ALL cells. These high doses of drugs may also kill healthy cells in the bone marrow. This transplant gives a patient healthy cells to replace the killed bone marrow cells. A transplant is a high-risk procedure and will probably not be used unless a patient does not have a good possibility of long-term remission with chemotherapy. High-risk ALL patients are more likely to have a transplant. The timing of a transplant is important; a patient has a better chance of a successful transplant when he or she is in remission at the time of transplant. Prognosis, prevention, and outcomes: There is no known way to prevent ALL. Most children with ALL can be cured of this disease with proper treatment. The overall survival rate for children after chemotherapy is nearly 80 percent.
Salem Health: Cancer Children with low-risk ALL have even higher survival rates. Most adults also improve with treatment; the number of adults who have remissions has increased, and the length of adult remissions has improved. The overall survival rate for adults after chemotherapy is about 40 percent, and adults with low-risk ALL have even higher survival rates. Marianne M. Madsen, M.S. u For Further Information Abeloff, M. D., et al. Clinical Oncology. 3d ed. Orlando, Fla.: Churchill Livingstone, 2004. Hoffman, R., et al. Hematology: Basic Principles and Practice. 4th ed. Orlando, Fla.: Churchill Livingstone, 2005. Lichtman, M. A., et al., eds. William’s Hematology. 7th ed. New York: McGraw-Hill, 2006. Pui, C-H, ed. Childhood Leukemias. 2d ed. New York: Cambridge University Press, 2006. u
Other Resources
Association of Cancer Online Resources http://www.acor.org CureSearch: National Childhood Cancer Foundation, Children’s Oncology Group http://www.curesearch.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute http://www.cancer.gov/cancertopics/treatment/ See also Acute myelocytic leukemia (AML); Aleukemia; Blood cancers; Childhood cancers; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Hemolytic anemia; Leukemias; Myelodysplastic syndromes; Myelofibrosis; Myeloproliferative disorders; Topoisomerase inhibitors.
u Acute myelocytic leukemia
(AML) Category: Diseases, symptoms, and conditions Also known as: Acute myeloid leukemia, acute myelogenous leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, granulocytic leukemia, acute nonlymphocytic leukemia, acute promyelocytic leukemia
Acute myelocytic leukemia (AML) Related conditions: Acute lymphoblastic leukemia, myelodysplastic syndrome Definition: Acute myelocytic leukemia (AML) describes a malignant proliferation in the bone marrow of an undifferentiated blood-forming cell of the myeloid line. AML begins with the genetic alteration of a single cell. That cell, called a blast cell, is the foundation from which the leukemia follows. The process of normal blood cell formation, or hematopoiesis, begins with undifferentiated cells, known as stem cells, inside the bone marrow. Stem cells differentiate into blasts, and these primitive blast cells give rise to red blood cells, platelets, and white blood cells. It is the accumulation of blast cells in the bone marrow and their failure to differentiate that has lethal consequences within just a few weeks or months if unchecked. Although the rate of cure has improved, treatment is still associated with high morbidity and mortality. Risk factors: Certain genetic disorders have an associated AML risk, including Down syndrome, Fanconi anemia, and Shwachman-Diamond syndrome. Other risk factors include some forms of chemotherapy, radiation therapy, and exposure to tobacco smoke and benzene. Etiology and the disease process: The process leading to acute myelocytic leukemia involves the interruption in the progression of an undifferentiated progenitor cell in the bone marrow that normally matures into red blood cells, white blood cells (neutrophils, eosinophils, basophils, and monocytes), and megakaryocytes. Megakaryocytes are bone marrow cells responsible for the production of the blood platelets necessary for blood clotting. Bone marrow is the soft interior of some bones, such as the skull, shoulder blades, ribs, pelvis, and backbones. It comes in two varieties: red marrow and yellow marrow. The red marrow, also called myeloid tissue, is the source of AML activity. Red blood cells, platelets, and most white blood cells arise from a parent cell in the red marrow. Many references limit discussion of AML to only the direct descendants of the myeloid line; these are the neutrophils, eosinophils, and basophils. When blast cells do not mature properly, they accumulate in the bone marrow. It is the proliferation and the accumulation of this hemopoietic cell in the bone marrow that defines AML. Although research has not completely unraveled the process of this leukemic transformation, there is strong evidence of underlying chromosomal damage. For example, a variety of mutations are associated with AML, with damage to the gene for FMS-related tyrosine kinase (FLT3) being the most prominent. Normally, the receptor encoded by FLT3 signals undifferentiated blast 13
Acute myelocytic leukemia (AML) cells in the bone marrow to proliferate when there is a need for additional circulating blood cells. The signal stops when the supply is sufficient, but in AML, the switch stays on, and unconstrained blast cell proliferation follows. Although AML begins with defective bone marrow cells, it generally moves quickly into the peripheral blood and may spread to other parts of the body, such as the liver, spleen, testes, brain, spinal cord, and lymph nodes. Incidence: Because AML is associated with accumulating genetic defects, the incidence increases with age. AML ranges from 0.7 to 3.9 cases per 100,000 in people up through the age of sixty and increases to 6.7 to 19.2 cases per 100,000 in people who are over sixty. The median age of onset is more than sixty-seven years. Each year AML will strike about 13,400 adults and 650 children in the United States. Symptoms: Clinical findings reflect the replacement of normal bone marrow elements with malignant blast cells. Probably the most consistent early complaints in AML are a history of increasing lethargy later followed by skin, soft-tissue, or respiratory infection. Some patients will have small red or purple spots on the body, called petichia, resulting from broken blood vessels. Liver, spleen, and lymph node enlargement is common, as is weight loss. Some symptoms are nonspecific but quite common in AML patients. These include swollen gums; pale skin; black-and-blue marks; achiness in the knees, hips, or shoulder; mild fever; shortness of breath during even light exertion; and the slow healing of cuts. Screening and diagnosis: The diagnostician must distinguish AML from other myeloproliferative disorders,
Age at Diagnosis for Acute Myelocytic Leukemia, 2001-2005 Age Group
Diagnosed (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
6.3 6.3 6.8 10.9 14.8 21.1 24.6 9.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008
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Salem Health: Cancer chronic myelogenous leukemia, and myelodysplastic syndrome. Although many supporting tests and symptoms point toward a diagnosis, the definitive finding of AML will require bone marrow aspirate and biopsy. Short of biopsy examination, other indicators will raise suspicion. About one-third of AML patients will have an enlarged spleen and high levels of uric acid in the blood. The peripheral white blood cell count is not a good indicator, as it may be increased, decreased, or normal. However, there usually will be reduced numbers of granulocytes (neutrophils, basophils, and eosinophils) and platelets in the blood. Blast cells in the peripheral blood appear in only 15 percent of AML patients initially, but this number rises to half of those patients with decreased number of circulating white blood cells (leukopenia). There is no standard staging system for AML. Generally, doctors describe the status of the condition as untreated, in remission, or recurrent. However, bone marrow examination more closely defines AML as belonging to one of eight cell subtypes. Doctors tailor the treatment to the subtype. The subtypes are as follows:
• • • • • • • •
M0: Myeloblastic, on special analysis M1: Myeloblastic, without maturation M2: Myeloblastic, with maturation M3: Promyeloctic M4: Myelomonocytic M5: Monocytic M6: Erythroleukemic M7: Megakaryocytic
Treatment and therapy: The goal of AML treatment is the destruction of the leukemic cells. However, this requires the suppression of bone marrow activity, which brings unfortunate side effects. With the bone marrow suppressed, fewer white cell are available to fight infection and fewer red cells and platelets are present to maintain a healthy oxygen exchange and clot formation. This almost always requires treatment with antibiotics and blood transfusions. Initial treatment or induction therapy begins with a hospital stay of about a week using chemotherapy in a combination of drug types. Generally induction therapy requires more than one round of treatment, as it is likely that some AML cells will survive. Even if the induction therapy seems successful, the doctors assume that leukemic cells still exist though unrevealed on biopsy examination. In the unusual event that leukemia has spread to the brain or spinal cord, chemotherapy is also introduced into the cerebrospinal fluid. At a later date, a follow-up round of less intensive treat-
Salem Health: Cancer
Acute myelocytic leukemia (AML)
ments called consolidation therapy brings the patient back to the hospital to maintain remission status. Remission describes a normal peripheral blood profile, a normal bone marrow free of excess blasts, and a normal clinical status. Doctors generally reserve stem cell transplantation with more vigorous chemotherapy for those patients susceptible to relapse, although it is sometimes part of the consolidation regimen. However, there is some debate among doctors as to the risks and benefits of this treatment. For relapsed patients who are unable to undergo the rigors of stem cell transplantation, additional chemotherapy is generally not well tolerated or effective. Doctors adapt specific chemotherapies Human cells with acute myelocytic leukemia in the pericardial fluid. (National Cancer Institute) to the subtype of the leukemia. Usually this will be some combination of an anthracycline class agent with cytabrine. In u For Further Information some cases a third drug, 6-thioguanine, is added. Also facEzzone, Susan, and Kim Schmit-Pokorny, eds. Blood and tored into the treatment strategy are the patient’s age, cliniMarrow Stem Cell Transplantation: Principles, Praccal status, and leukemia profile. Although quite variable, tices, and Nursing Insights. Sudbury, Mass.: Jones and hospital stays for induction and consolidation therapies Bartlett, 2007. may require weeks or even months. Typically, chemotherHoffman, Ronald, et al. Hematology: Basic Principles and apy will drive the patient’s blood cell counts down to danPractice. 4th ed. St. Louis: Elsevier Churchill Livinggerously low levels. This will require drugs to elevate stone, 2005. white blood cell counts as well as antibiotics and blood Hutton, John J. “The Leukemias and Polcythemia Vera.” transfusions to protect against complications. In Internal Medicine, edited by Jay H. Stein. 5th ed. St. Louis: Mosby, 1998. Prognosis, prevention, and outcomes: The prognosis of Lichtman, Marshall A., and Jane A. Liesvelt. “Acute patients with AML largely depends on the patient’s age. In Myelogenous Leukemia.” In Williams Hematology, part this is due to chemoresistance or the biological reedited by Marshall A. Lichtman, et al. 7th ed. New sponse of cells to survive the toxic stress of chemotherapy. York: McGraw-Hill, 2006. Because chemoresistance tends to increase with age, important therapies are less effective in older patients. Also, the difference in the mechanisms of chromosome translou Other Resources cations in the young and older patients allows for a more The Leukemia and Lymphoma Society favorable outcome in the younger patient. Acute Lyelogenous Leukemia In the absence of treatment, most people stricken with http://www.leukemia-lymphoma.org/all_mat_toc AML will die less than two months after the diagnosis. .adp?item_id=3113 With therapy, between 20 and 40 percent of people survive for at least five years. The poorest prognoses are reserved National Marrow Donor Program for those patients older than sixty and for those developing Acute Myelogenous Leukemia AML following chemotherapy and radiation therapy for http://www.marrow.org/PATIENT/Undrstnd_ other cancers. In general, four years following consolidaDisease_Treat/Lrn_about_Disease/AML/index.html tion therapy, approximately 40 percent of patients under sixty years of age will be free of any signs of leukemia, See also Acute lymphocytic leukemia (ALL); Blood cancers; Childhood cancers; Chronic lymphocytic leukemia with that number dropping to 15 percent in older patients. (CLL); Chronic myeloid leukemia (CML); Fanconi aneRichard S. Spira, D.V.M. 15
Adenocarcinomas mia; Genetics of cancer; Leukemias; Leukopenia; Myelodysplastic syndromes; Myeloproliferative disorders; Myelosuppression.
u Adenocarcinomas Category: Diseases, symptoms, and conditions Also known as: Malignant adenomas, other names vary by type Related conditions: Lung cancer, breast cancer, colon cancer, renal cell carcinomas Definition: Adenocarcinoma is a type of cancer that develops in the epithelial tissue of glandular (secretory) organs. Although it is commonly associated with lung cancer (and is the most common form of lung cancer), adenocarcinoma can also develop in such organs as the breast, colon, kidney, liver, pancreas, prostate, and stomach. It is classified according to the kind of tissue from which it
Salem Health: Cancer arose (such as lung or breast) or according to a particular product of the cells (such as mucinous adenocarcinoma). Adenocarcinoma can spread (metastasize) to other parts of the body and also destroy surrounding tissues. Risk factors: Smoking increases the risk of almost every type of cancer. Other risk factors for adenocarcinoma vary by organ site. Age, race, family history, medication use, and lifestyle factors such as diet have been implicated in certain forms of adenocarcinoma. Etiology and the disease process: Etiology of and the disease process for adenocarcinoma vary with the involved organ. Incidence: Incidence of adenocarcinoma varies by type. Adenocarcinoma is the most common form of lung, pancreatic, prostate, and stomach cancer. Symptoms: Symptoms of adenocarcinoma vary by type. Small adenocarcinomas may produce only mild symptoms that go undetected. Large adenocarcinomas produce more noticeable symptoms that vary with the site of in-
A surgical specimen showing colonic adenocarcinoma. (Centers for Disease Control and Prevention)
16
Salem Health: Cancer volvement. The first signs of adenocarcinoma may be a noticeable lump and pain or discomfort. Screening and diagnosis: Diagnosis of adenocarcinoma begins with a medical history and physical examination. Lumps are commonly biopsied, and specialized imaging techniques, such as X rays and computed tomography (CT) scans, are used to determine the extent of the disease (staging). Staging of adenocarcinoma varies by type. Treatment and therapy: Specific treatment protocols vary by adenocarcinoma type and other factors, such as overall patient health and extent of the disease. Conventional treatment options include surgery, chemotherapy, and radiation therapy. Early-stage, localized disease may be treated by surgery alone (surgical removal of the tumor and surrounding tissue) or surgery with adjuvant chemotherapy or radiation therapy. Advanced adenocarcinoma has no cure. Newly emerging treatments for adenocarcinoma include hormone therapy and stem cell transplantation. Prognosis, prevention, and outcomes: Without treatment, adenocarcinoma is fatal. Routine physical examinations and avoidance of risk factors, such as smoking, are keys to early detection and prevention. Jaime Stockslager Buss, M.S.P.H., ELS See also Adenoid cystic carcinoma (ACC); Appendix cancer; Bile duct cancer; Breast cancer in children and adolescents; Bronchoalveolar lung cancer; Carcinomas; Duodenal carcinomas; Esophageal cancer; Fallopian tube cancer; Gallbladder cancer; Gastrointestinal cancers; Granulosa cell tumors; Head and neck cancers; Helicobacter pylori; Lung cancers; Mesothelioma; Mucinous carcinomas; Nasal cavity and paranasal sinus cancers; Oncogenic viruses; Pancreatic cancers; Prostate cancer; Rectal cancer; Salivary gland cancer; Small intestine cancer; Stomach cancers; Throat cancer; Urethral cancer; Urinary system cancers; Uterine cancer; Vaginal cancer; Vulvar cancer.
u Adenoid cystic carcinoma
(ACC) Category: Diseases, symptoms, and conditions Also known as: Adenocystic carcinoma, cribriform carcinoma, cylindroma, malignant cylindroma, AdCC Related conditions: Adenoma, adenocarcinoma Definition: Adenoid cystic carcinoma (ACC) is a rare malignant cancer of the secretory glands. Neoplasms usually
Adenoid cystic carcinoma (ACC) originate in the major and minor salivary glands of the head and neck region but can also occur in places such as in the trachea, lacrimal glands, breast, skin, and vulva. Risk factors: Environmental and genetic risk factors have not been identified. Etiology and the disease process: There is little information available regarding pathogenesis except for some evidence suggesting that the TP53 tumor-suppressor gene is inactivated in the most aggressive forms or stages of ACC. Incidence: Both children and adults may develop ACC; however, most patients are diagnosed between the fourth and sixth decades of life. ACC affects more women than men at a ratio of approximately 3:2. Symptoms: Signs and symptoms depend on the origin of the neoplasm. Screening and diagnosis: Unfortunately, no screening tests exist because of a lack of serum markers. Diagnosis is made after histologic analysis obtained through biopsy or resection of a tumor. ACC is classified into three major groups according to distinctive histologic growth pattern: cribriform, tubular, and solid. Treatment and therapy: The primary treatment option for adenoid cystic carcinoma is surgery. Postoperative radiotherapy or neutron beam therapy is sometimes recommended to help limit local failure. There is no effective chemotherapy for metastatic or unresectable ACC; however, several clinical trials are testing the effectiveness of new chemotherapeutic drugs (for example, paclitaxel and gemcitabine) when used alone or in combination with other drugs. Radiofrequency ablation and cryoablation are also being explored as treatment options. Prognosis, prevention, and outcomes: ACC growth and disease progression tend to be slow but relentless. ACC is atypical of carcinomas and seldom metastasizes to regional lymph nodes. Distant metastasis is the predominant reason for treatment failure and occurs most frequently in the lung, followed by the liver. Tumors with solid growth patterns and perineural invasion of major nerves or positive margins tend to have poor prognosis. In one study that followed 160 ACC patients, disease-specific survival was 89 percent at five years and 40 percent at fifteen years. Rena C. Tabata, M.Sc. See also Bronchial adenomas; Lacrimal gland tumors; Lung cancers; Nasal cavity and paranasal sinus cancers; Salivary gland cancer; Throat cancer. 17
Adenomatoid tumors
u Adenomatoid tumors Category: Diseases, symptoms, and conditions Also known as: Adenofibromyomas, Recklinghausen’s tumors Related conditions: None Definition: An adenomatoid tumor is a small benign tumor of mesothelial origin usually occurring in the male epididymis or female Fallopian tube, ovary, or uterus. Rarely, these tumors can be seen within the testes and prostate. Extragenital adenomatoid tumors have also been identified in the heart, mesentery, pleura, lymph nodes, omentum, and adrenal glands. Because of its glandular appearance, it may be confused with an adenocarcinoma or metastatic carcinoma, especially signet ring cell carcinoma. Risk factors: There are no known risk factors for adenomatoid tumors. Etiology and the disease process: An adenomatoid tumor is a benign hamartoma that is a malformation resulting from faulty development in an organ and is made up of an abnormal mixture of tissue elements normally present at that site. Most adenomatoid tumors are composed of fibrous tissue separated by numerous slitlike pseudotubular spaces crossed by peculiar threadlike bridging strands, which are their typical morphologic feature. The most common benign tumor of the epididymis, adenomatoid tumors usually arise in the tail of the epididymis and may rarely invade adjacent testicular parenchyma. Although they may occur at any age, they are most commonly seen in patients between twenty and fifty years of age and are usually asymptomatic. Although usually under 5 centimeters (cm) in size, they can grow quite large under hormonal influence. Incidence: In one study, the reported incidence of adenomatoid tumors is 1.2 percent, although the true incidence is probably greater, as most tumors are never biopsied because of their small size and similarity to leiomyomas of the uterus. When found in the male genital tract, these tumors are usually seen in an extratesticular location, usually involving the epididymis, representing approximately 30 percent of tumors arising in the paratesticular area. Symptoms: Adenomatoid tumors usually are asymptomatic. However, when adenomatoid tumors occur in the genital tract, they can grow quite large and can be painful. Screening and diagnosis: Often mistaken for uterine fibroids on magnetic resonance imaging, the radiologic appearance can vary from solid to cystic depending on the 18
Salem Health: Cancer relative amounts of cystic spaces, smooth muscle, and fibrous tissue contained within the tumor. Ultrasound is useful in diagnosing adenomatoid tumors of epididymal origin. They usually appear as a round or oval, solitary, solid, well-circumscribed mass of variable echogenicity measuring between 5 millimeters (mm) and 5 cm. Occasionally they may appear cystic sonographically and rarely appear plaquelike and ill-defined. Treatment and therapy: Surgical removal. Prognosis, prevention, and outcomes: Excellent. Debra B. Kessler, M.D., Ph.D. See also Endometrial cancer; Fallopian tube cancer; Fibrosarcomas, soft-tissue; Gynecologic cancers; Oophorectomy; Ovarian cancers; Ovarian cysts; Testicular cancer.
u Adenomatous polyps Category: Diseases, symptoms, and conditions Also known as: Colorectal adenomas Related conditions: Colon cancer, benign polyps, familial adenomatous polyposis (FAP) Definition: Polyps are abnormal tissue growths stemming from the lining of mucous membranes. Colorectal adenomatous polyps are benign (noncancerous) polyps that project from the inner lining of the colon or rectum and protrude into the lumen of the intestines. Despite their benign characteristics, adenomatous polyps can become cancerous if not removed. Risk factors: Adenomatous polyps are one of the most common types of colon polyp. Individuals over the age of fifty years are much more likely to develop these growths, as are those people with a family history of colon polyps. Additionally, having a mutation in the APC gene can cause a condition named familial adenomatous polyposis (FAP), a disorder that causes numerous polyps to grow in the intestines and almost always develop into tumors. Etiology and the disease process: Adenomatous polyps are a collection of cells that display uncontrolled proliferation, forming a growth that stems from the inner lining of the colon. Incidence: The prevalence of adenomatous polyps ranges from 10 to 25 percent of the population, depending on the type of screening procedure used. Symptoms: Most adenomatous polyps are asymptomatic, and patients are unaware of their presence until they are
Salem Health: Cancer identified through screening. When adenomatous polyps are not removed and continue to grow larger, they can eventually induce rectal bleeding, diarrhea, or constipation. Screening and diagnosis: The most common screening method to detect adenomatous polyps is colonoscopy, a procedure by which a doctor inserts a viewing tube into the colon and removes any visually identified polyps. Other screening methods that may be used are flexible sigmoidoscopy and barium enema. Removed polyps are then biopsied to determine if they are benign or have developed into precancerous or cancerous lesions. Treatment and therapy: When identified through screening, the general treatment is immediate removal of adenomatous polyps to prevent their possible development into cancer. Most doctors recommend that patients undergo subsequent colorectal screening on a regular basis for several years following the removal of adenomatous polyps. Prognosis, prevention, and outcomes: When discovered and removed, adenomatous polyps do not significantly change a patient’s quality of life. However, if left undetected, some of these polyps can develop into colon cancer, which has a higher mortality rate than any other cancer type in the United States. Some possible ways to prevent the development of adenomatous polyps is to maintain a diet that is high in fiber and low in fat, as well as refraining from smoking and excessive drinking. Lisa M. Cockrell, B.S.
Adenoviruses human viruses in the family Adenoviridae. Adenoviruses can be genetically engineered to serve as vectors that deliver targeted gene therapy to human cells. Cancers treated: Breast, colorectal, head and neck, liver, and prostate cancers Delivery routes: Injection How these agents work: Adenoviruses are nonenveloped, or naked, viruses, meaning that they lack a lipid and protein outer covering. Counterintuitively, viruses without this outer covering are better able to withstand environmental stressors such as an acidic environment, drying, and heat—and therefore may live longer outside a host cell. Most adenoviruses cause respiratory illnesses, conjunctivitis (pinkeye), or gastroenteritis and are transmitted via respiratory droplets or through fecal-oral transmission. Adenoviruses are well suited to gene therapy because of their environmental robustness, the ease of manipulating the adenovirus genome, and their ability to infect a number of different kinds of tissue. The DNA inside the adenovirus may one day be altered to encode up to forty genes.
See also Colon polyps; Colorectal cancer; Desmoid tumors; Duodenal carcinomas; Enterostomal therapy; Gardner syndrome; Gastric polyps; Genetics of cancer; Hereditary cancer syndromes; Hereditary polyposis syndromes; Polyps; Small intestine cancer; Stomach cancers; Turcot syndrome.
u Adenoviruses Category: Chemotherapy and other drugs Also known as: Adenoviridae viruses Definition: An adenovirus is a twenty-sided symmetrical icosahedron measuring between 80 and 100 nanometers in diameter with 252 capsomers forming its outside “capsid,” or protein shell. Adenoviruses contain double-stranded, linear deoxyribonucleic acid (DNA), sometimes referred to as dsDNA. These viruses are named for the the adenoids, as they were first isolated from human tonsils in the 1950’s. There are now more than forty identified types of
An electron micrograph of an adenovirus. (Centers for Disease Control and Prevention)
19
Adjuvant therapy In cancer therapy, adenoviruses are first inactivated to make them incapable of causing infection once inside the body. When injected into cancer cells, the virus can cause cell death or tumor suppression by producing toxic proteins, flagging cells for destruction by the immune system, breaking the cell apart (cell lysis), or activating genes that will cause the cell to die (apoptosis) or stop replicating. To gain access to host cells, adenoviruses attach to a receptor on the host cell, which triggers the host cell to surround, engulf, and coat the virus with chemicals. Once the virus is inside the host, the coating dissolves and the virus releases into the host cell cytoplasm. The virus makes its way to the host cell nucleus, where it disassembles itself and releases viral DNA into the host’s nuclear pores. Soon the host cell nucleus stops replicating its DNA and instead begins replicating the DNA of the adenovirus. Eventually the host cell breaks apart (lyses) and releases the newly created adenoviruses. Since most people have been exposed to adenoviruses, the immune system can mount an immune response to the adenoviruses before they have a chance to target the cancer cells. With more research into the specific targeting of cancer cells, however, a vigorous immune response may serve as a beneficial side effect of treatment. Side effects: The side effects of adenovirus use in cancer therapy include inflammation at site of injection, inappropriate immune response, fever, and coldlike symptoms. Pamela Richardson, M.S. See also Gene therapy; Oncogenes; Oncogenic viruses; Simian virus 40.
u Adjuvant therapy Category: Procedures Definition: An adjuvant therapy is any treatment given after the primary treatment to increase the likelihood of killing all cancer cells. Cancers treated: Many types, including cancers of the breast, colon, kidney, ovary, and testicle Why performed: After the primary treatment removes or kills a detected primary tumor, additional cancerous cells or microtumors may still be present in the body. Adjuvant therapy may be administered to help prevent the recurrence of cancer after the primary tumor is removed. Generally, the larger the primary tumor size at detection, the larger is the probability that residual cancer cells may be left behind following surgery. Cancer cells can break away 20
Salem Health: Cancer from the primary tumor and metastasize even when the disease is in an early stage, and they exist in a form too small to detect by radiological or laboratory testing. Patient preparation: In the decision regarding whether to undergo adjuvant therapy, a number of prognostic factors enter into the determination, such as patient age, size of primary tumor, spread to lymph nodes, and microscopic appearance of the cancer cells. Doctors consider these factors and others in order to estimate the likelihood of recurrence. The higher the risk for recurrence, the greater is the motivation to pursue adjuvant therapy options. Local adjuvant radiation treatment typically commences about three to six weeks following the primary treatment. If a combination of chemotherapy and radiotherapy as adjuvant therapy is chosen, then usually chemotherapy is received first followed by radiation, although they may be administered simultaneously in some cases. It is not known how effective adjuvant therapy may be if started later than six weeks following primary therapy. Steps of the procedure: The term “adjuvant therapy” actually encompasses many different treatment forms, including chemotherapy, radiation, hormonal therapy, targeted therapy, or some combination thereof. Adjuvant therapy can be either systemic or local. Chemotherapy, for instance, is given by mouth or injected into the bloodstream. Adjuvant chemotherapy is administered in cycles of treatment followed by recovery and typically lasts for three to six months. Side effects from adjuvant therapy such as chemotherapy or radiation may be experienced. For example, the effects of adjuvant chemotherapy may include loss of hair, loss of appetite, vomiting, diarrhea, mouth sores, psychological distress, and some loss of cognitive brain function. Medications are available to help control vomiting and nausea induced by chemotherapy. Researchers at the University of Rochester have reported that treatment with modafinil (Provigil) can alleviate the cognitive symptoms of so-called chemo brain experienced in certain cancer treatment regimens. Longer-term side effects may include infertility. Another example of adjuvant therapy is hormone adjuvant therapy to treat breast cancer. Hormone adjuvant therapy is used on breast cancer cells that have been found to be estrogen or progesterone receptor positive. Some standard hormone therapies include the synthetic hormone tamoxifen and aromatase inhibitors. Tamoxifen as an adjuvant therapy has been found to decrease the chance of recurrence in women with early-stage hormone receptor positive breast cancer. It is also used to treat women who are at risk of one day developing breast cancer. Aromatase inhibitors are used as adjuvants to reduce the levels of es-
Salem Health: Cancer trogen in postmenopausal women; they include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). These drugs are not to be used by premenopausal women. Combination adjuvant therapies comprising hormone treatment together with chemotherapy are also available for some patients. After the procedure: It is advised that patients undergo regular checkups following adjuvant therapy in order to monitor any cancer recurrence. Hormone adjuvant therapy, such as used to treat some forms of breast cancer, involves longer-term procedures, with five-year regimens recommended. Risks: The risks associated with different forms of adjuvant therapy are similar to the risks of corresponding primary treatments with chemotherapy, radiotherapy, or hormone therapy. The main risk of declining to participate in adjuvant therapy is the possibility of cancer cells spreading undetected to other parts of the body. While patients with invasive cancers are often urged to consider undergoing adjuvant therapy, other options are available. Patients who turn down the option of adjuvant therapy are advised to participate in regular follow-up clinical examinations to facilitate the detection of new tumors. This alternative is often referred to as “watchful waiting.” Some of the side effects of hormone adjuvant therapy mimick the symptoms of menopause, such as hot flashes and an increased risk for the development of osteoporosis. Results: The goal of adjuvant therapy is to make primary treatment more effective and result in years of disease-free survival. Successful adjuvant therapy is marked by a lack of detectable tumor recurrence or metastasis formation in the months and years following primary therapy. Michael R. King, Ph.D. u For Further Information Henderson, I. Craig, ed. Adjuvant Therapy of Breast Cancer. Boston: Kluwer Academic, 1992. Kirkwood, John M., ed. Strategies in Adjuvant Therapy. Malden, Mass.: Blackwell, 2000. Murphy, Kevin. Adjuvant Chemotherapy Guide. Available online at http://www.cancerguide.org. Salmon, Charles G. Adjuvant Therapy of Cancer. Philadelphia: Lippincott Williams & Wilkins, 1993. u
Other Resources
Mayo Clinic Adjuvant Therapy for Breast Cancer Guide http://www.MayoClinic.com
Adrenal gland cancers National Cancer Institute http://www.cancer.gov See also Biological therapy; Chemotherapy; Hormonal therapies; Pain management medications; Radiation therapies; Watchful waiting.
u Adrenal gland cancers Category: Diseases, symptoms, and conditions Also known as: Pheochromocytoma, adrenal cortical cancer, adrenocortical cancer, neuroblastoma Related conditions: Cushing syndrome, Conn syndrome, adrenogenital syndrome Definition: The adrenal glands are hormone-producing endocrine glands located directly above the kidneys. The outer layer of each gland is called the adrenal cortex. Hormones produced in the adrenal cortex include cortisol (aids in regulating blood sugar level), aldosterone (aids in regulating fluid and electrolyte balance and blood pressure), and testosterone and estrogen (male and female sex hormones). A primary malignant tumor in the adrenal cortex—one that originates in that location—is called adrenocortical cancer. The inner area of each gland is called the adrenal medulla. Hormones produced in the medulla include epinephrine and norepinephrine, which help regulate the body’s response to physical and emotional stress. A primary malignant tumor that originates in the medulla is called a pheochromocytoma. Another form of cancer that originates in the medulla is neuroblastoma, typically found in infants and children younger than age ten. Adrenal tumors are commonly classified by their effect on hormone production in the affected area. Adrenal tumors that increase hormone production are called functioning tumors; those that do not produce hormones are called nonfunctioning tumors. Risk factors: Although specific risk factors for adrenal cancers have not been identified, they have been associated with genetically linked familial syndromes, such as Li-Fraumeni syndrome, Beckwith-Wiedemann syndrome, and Carney complex. Etiology and the disease process: The cause of adrenal cancer is unknown. Functioning tumors that secrete hormones produce changes in the body systems affected by those hormones. Nonfunctioning tumors typically grow large enough to produce pressure on other organs, causing discomfort or pain in the abdomen or flank. 21
Adrenal gland cancers
Salem Health: Cancer
Incidence: Primary adrenal gland cancers are rare, affecting only 1 or 2 persons per 1 million people. Approximately 60 to 80 percent of adrenal cancers are functional, secreting large amounts of adrenal hormones. Adrenocortical cancer is most common in men between the ages of forty and fifty; neuroblastoma most commonly affects children younger than age five; and pheochromocytoma is most common between ages thirty and forty. Symptoms: A functioning adrenocortical cancer tumor typically produces excess amounts of cortisol and aldosterone, which can cause elevated blood pressure, weight gain, thirst, urinary frequency, facial swelling (moon face), cramping of the muscles in the arms and legs, and increased hair growth on the face, arms, and back. If the tu-
mor produces sex hormones, men may develop a loss of sex drive, impotence, and enlarged breasts; women may develop a deeper voice, menstrual irregularities, and increased facial hair; and children may experience early puberty. A neuroblastoma can cause an unusual abdominal lump or fullness, weight loss, extreme tiredness, persistent diarrhea, flushing, sweating, elevated blood pressure, and behavior indicating the presence of abdominal pain. A pheochromocytoma can cause elevated blood pressure that is resistant to treatment, excessive sweating, severe headaches, tremors, rapid pulse, palpitations, and extreme anxiety. A nonfunctioning adrenal cancer may not produce symptoms until the cancer is advanced or has metastasized. Typical symptoms are caused by the tumor pressing on
Adrenal Glands
Kidney
Kidney
The adrenal glands are located on top of the kidneys. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Salem Health: Cancer
Adrenocortical cancer therapy may be used after surgery or to treat metastatic pheochromocytoma.
Relative Survival Rates for Adrenal Gland Cancers, 1988-2001
Prognosis, prevention, and outcomes: There is no known prevention for adrenal cancer. The prognosis for adrenal cancer depends on the type of tumor and the stage of the disease. The five-year survival rate after surgery for adrenocortical cancer is approximately 10 to 35 percent; for localized pheochromocytomas it is about 95 percent. The prognosis for neuroblastoma varies widely depending on the child’s risk grouping. The five-year survival rate ranges from about 95 percent for a low-risk child to about 30 percent for a high-risk child. Metastatic tumors of all types have a poor prognosis. Dorothy P. Terry, R.N.
Survival Rates (%) Cancer Type Adrenal gland (all) Adrenocorticol Pheochromocytoma
1-Year
3-Year
5-Year
10-Year
59.4 66.0 84.5
45.5 48.5 73.0
38.7 41.2 64.8
29.6 31.3 44.0
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
other abdominal organs, causing pain or an abnormal feeling of fullness. Tiredness, fever, and weight loss may also be present. Screening and diagnosis: There are no screening tests for adrenal cancer. Diagnosis begins with a thorough patient and family medical history and physical examination. If adrenal cancer is suspected, the patient’s blood and urine are tested for elevated levels of adrenal hormones, and computed tomography scanning and magnetic resonance imaging are performed to identify tumors. The metaiodobenzylguanidine (MIBG) scan, during which images are taken after the injection of small amounts of radioactive materials, is used to detect the presence and location of a pheochromocytoma. Staging of adrenal cancer depends on the specific type of tumor. Treatment and therapy: Treatment for adrenal cancer usually includes surgery to remove the affected gland, followed by chemotherapy to destroy any remaining cancer cells. The type and combination of chemotherapeutic drugs used varies with the type of tumor. Mitotane, most commonly used after surgery for adrenocortical cancer, blocks hormone production and destroys adrenal cancer cells. It is also used to treat inoperable, recurrent, and metastatic adrenocortical cancer. If the patient cannot tolerate mitotane therapy or it is ineffective, cisplatin is typically used, either alone or combined with cyclophosphamide and doxorubicin, fluorouracil and doxorubicin, or VP-16. Following surgery, neuroblastoma may be treated with chemotherapy using carboplatin, doxorubicin, cyclophosphamide, and etoposide. Surgery to remove a pheochromocytoma is typically preceded by the administration of medication to block the secretion of adrenalin, which can cause very high blood pressure and serious surgical complications. MIBG radio-
u
For Further Information Bertagna, Xavier, ed. Adrenal Cancer. Montrouge, France: John Libbey Eurotext, 2006. Souhami, Robert, and Jeffrey Tobias. Cancer and Its Management. Malden, Mass.: Blackwell, 2005. Stern, Theodore A., and Mikkael A. Sekeres. Facing Cancer: A Complete Guide for People with Cancer, Their Families, and Caregivers. New York: McGraw-Hill, 2004.
u
Other Resources
American Cancer Society http://www.cancer.org Endocrine Web http://www.endocrineweb.com National Cancer Institute http://www.nci.nih.gov/cancertopics See also Adrenocortical cancer; Computed tomography (CT) scan; Cushing syndrome and cancer; Endocrine cancers; Endocrinology oncology; Hepatomegaly; Radiofrequency ablation.
u Adrenocortical cancer Category: Diseases, symptoms, and conditions Also known as: Adrenal cortex carcinoma Related conditions: Cushing syndrome, Conn syndrome, virilization Definition: Adrenocortical cancer is an aggressive malignancy that occurs when a tumor develops in the tissue of 23
Advance directives the adrenal cortex, the outer layer of tissues that surround the adrenal gland and produce steroid hormones. Risk factors: Certain hereditary diseases, including LiFraumeni syndrome, Beckwith-Wiedemann syndrome, and Carney complex, are the main known risk factors. Etiology and the disease process: The cause of these tumors is unknown. An adrenocortical cancer tumor is either nonfunctioning or functioning, meaning that it overproduces certain hormones that the adrenal cortex normally produces. These hormones include cortisol, aldosterone, testosterone, and estrogen. Adrenocortical cancer commonly becomes malignant, spreading to the lung, liver, bone, and peritoneum (lining of the abdominal cavity). Incidence: Adrenocortical cancer is relatively rare, affecting only 1 to 2 people out of 1 million every year. Although it generally occurs in adults between the ages of thirty and forty years, children can develop this cancer, usually under the age of six.
Salem Health: Cancer of the cancer at diagnosis, the general health of the patient, and whether the tumor is recurrent. Lisa M. Cockrell, B.S. See also Adrenal gland cancers.
u Advance directives Category: Social and personal issues Also known as: Living wills, durable powers of attorney for health care (DPOA), do-not-resuscitate (DNR) orders Definition: Advance directives are written instructions in the form of legal documents that allow people to communicate their desires about medical care and treatment if they cannot speak for themselves due to a terminal condition. Patients with advanced cancer may use them to allow their wishes to be known and followed.
Treatment and therapy: When discovered early, adrenocortical cancer can be cured through surgical removal of the tumor. However, because most tumors are not diagnosed until they are advanced, other treatment strategies such as radiation therapy and chemotherapy must be used. Most chemotherapy regimens to treat adrenocortical cancer include the drug mitotane, which is toxic to adrenal cortex cells, in addition to other chemotherapeutic agents such as cisplatin, doxorubicin, and etoposide.
Purposes: Advance directives are designed to allow competent patients an opportunity to express their wishes for future health decisions in the event that they are unable to participate in medical decision making because of their poor state of health. Advance directives take the pressure off family and friends by letting them know what care and services the cancer patient prefers and what treatment the patient would refuse in the event that communication is not possible. The patient can also designate a person or persons to make decisions. In families in which there is disagreement about what an ill relative would prefer, the advance directive provides clarification. If there is no advance directive and the patient becomes incapacitated with no surrogate designated, state law will dictate the order of surrogate decision makers, usually other family members. By designating a surrogate decision maker, the patient’s choice supersedes that of the state. This is particularly valuable for people without close family or in nontraditional relationships. Advance directives are important because complex choices about end-of-life care are difficult and can seem overwhelming if a someone close to the decision maker is involved. Avoiding these decisions during healthy times will place a heavy burden on family and friends later. Communicating wishes about end-of-life care will ensure that the cancer patient’s wishes are respected.
Prognosis, prevention, and outcomes: The prognosis for patients diagnosed with adrenocortical cancer is generally very poor, and dependent on several factors. These include the ability of the tumor to be surgically removed, the stage
Types: Advance directives emerged in the late 1960’s and early 1970’s as a major social and medical phenomenon resulting from the conflict between professional ethics based on the Hippocratic oath and the physician’s duty to
Symptoms: Nonfunctioning adrenocortical cancer tumors usually do not have symptoms. Functioning adrenocortical cancer tumors can generate many symptoms, owing to their overproduction of steroid hormones. Depending on the hormone, symptoms can include weight gain, high blood pressure, muscle weakness, acne, and changes in menstrual cycles. Screening and diagnosis: Laboratory testing can be used to confirm changes in steroid hormone production. Abdominal radiological examination, such as computed tomography scanning and magnetic resonance imaging, can be used to determine the exact location and extent of the tumor. Adrenocortical cancer tumors are staged on a scale of I to IV, according to the size of the tumor and the degree of invasion, both locally and to distant sites.
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Advance directives
dated, witnessed, notarized, copied, and incorporated into benefit the patient according to the physician’s own ability the patient’s medical record. A copy should be placed in and judgment and the patient’s autonomy. In Schloendorff the chart and given to the patient’s physician and attorney. v. Society of New York Hospital (1914), the Supreme Court Advance directives should be reviewed periodically and ruled that patients were entitled to complete information kept current. Some people even take their directives with about their illness and shared decision making. The Patient them when they travel. Advance directives remain in efSelf-Determination Act of 1991 mandated that all patients fect until they are revoked. admitted to acute care hospitals, long-term care facilities, health maintenance organizations, and home care proConditions: Advance directives are recognized in all fifty grams are to be informed about their rights under state law states and can be considered legally binding, provided to participate in health care decision making, including they are executed in accordance with state guidelines. their right to have written directives. Some directives are written only to apply in particular clinDespite widespread media attention, the majority of seical situations, such as when the patient has a terminal type riously ill patients do not have a written advance directive. of cancer or an incurable illness (advanced or aggressive For those without directives, family members collaborate cancers would fit these categories). Ambiguous terms with a health care provider to make decisions generally resuch as “extraordinary means” and “unnaturally prolongflective of substituted judgment or best-interest principles ing my life,” should be placed within the context of the pa(that is, what the patient would have wanted based on pretient’s values to be understood. Because these ambiguous vious statements and values). This approach, of course, is terms necessitate interpretation by caregivers, revised state problematic because often there is little evidence about the forms have attempted to overcome this problem by adpreferences of any particular patient. dressing specific interventions that are to be withheld in all Advance directives include living wills, durable powers circumstances (for example, blood transfusions, dialysis, of attorney for health care (DPOA), and do-not-resuscitate ventilators and respirators, CPR, artificial nutrition and (DNR) orders. There are two broad categories of advance hydration, withholding of food and fluids, and organ and directives: instructive and proxy. Instructive directives altissue donation). low an opportunity to express preferences regarding the It is important to understand that a decision not to reprovision of particular treatment options. Living wills ceive “aggressive medical care” is not the same as withare the most common examples of instructional directives holding all medical care. A cancer patient can still receive in which the patient’s preferences are specified, but there antibiotics, nutrition and hydration, medication, radiation are also other types such as no transfusion or no cardiopultherapy, and pain management (palliative or comfort care). monary resuscitation (CPR) directives. The proxy direcAnother approach can provide instructions in the event of tive, generally a durable power of attorney for health a specific circumstance or diagnosis (such as a prolonged care, allows the patient to designate a surrogate decision maker of the patient’s choosing. This surrogate makes health care decisions for the patient in the case of incapacity. Choosing a Surrogate Decision Maker It should be noted that advance directives Picking a proxy decision maker can be a difficult task. Generally, experts are applicable only in situations in which parecommend that the proxy has the following qualities: tients are unable to participate in their health care decision making. The assessment of ca• shares the patient’s values and beliefs about end-of-life care and death pacity for decision making is sometimes dif• is a person with whom the patient can comfortably talk about difficult ficult and may involve a psychiatric evaluaissues tion and even a legal determination. If a • is a responsible, calm, mature person patient is competent and communicative, • is willing to assume this responsibility however, the advance directive will not • ideally is a person who lives close or is able to travel to the patient’s apply. location A health care proxy or surrogate is a per• is not the patient’s health care provider (for legal reasons) son appointed to make a patient’s medical • is chosen separate from considerations of who will handle the patient’s financial issues decisions if and when the patient is unable to do so. The durable power of attorney for • is the person, whether relative or friend, that the patient trusts the most to make medical decisions health care is the legal document that names the health care proxy. It should be signed, 25
Aflatoxins state of unconsciousness, trauma, or a diagnosis of dementia). Some living wills state that patients do not want lifeprolonging treatments if their condition necessitates constant care and supervision. Alternatively, others can state that patients wish their lives to be prolonged as long as possible. Advance directives can be revised or revoked as long as the patient remains competent to participate in medical decisions. Decisions by competent patients always supersede written directives. If there is disagreement among family members about the interpretation or authority of a patient’s advance directive, the medical team or a medical ethicist should meet with the family, clarify, and attempt to resolve the issue. Limitations: Living wills cannot possibly be made allencompassing because of the great variability in end-oflife care. Pain alleviation or management is among the most controversial end-of-life issues. Laws regulating drug addiction are inconsistent among the states, and the role of lethal drugs in the management of end-of-life pain and discomfort is being debated in Congress. Cancer patients making or considering writing advance directives are encouraged to communicate their preferences with their medical providers and surrogate decision makers. Most states ensure that patients remain in charge of their medical care until at least two physicians declare them to be incapacitated. Health care providers may refuse to honor the patient’s stated wishes or decisions because of personal standards or institutional policies. If either is the case, it is up to the individual health care provider to inform the surrogate immediately and transfer the patient to another provider. Marcia J. Weiss, J.D. u
For Further Information King, Nancy. Making Sense of Advance Directives. Dordrecht, Netherlands: Kluwer, 1991. Mappes, Thomas A., and David De Grazia. Biomedical Ethics. 6th ed. New York: McGraw-Hill, 2006. Sass, Hans-Martin, Robert M. Veatch, and Ribito Kimura, eds. Advance Directives and Surrogate Decision Making in Health Care: United States, Germany, and Japan. Baltimore: Johns Hopkins University Press, 1998. Ulrich, Lawrence P. The Patient Self-Determination Act: Meeting the Challenges in Patient Care. Washington, D.C.: Georgetown University Press, 1999. Weir, Robert F. Abating Treatment with Critically Ill Patients: Ethical and Legal Limits to the Medical Prolongation of Life. New York: Oxford University Press, 1989. 26
Salem Health: Cancer u
Other Resources
American Cancer Society Advance Directives http://www.cancer.org/docroot/MIT/mit_3_1_1.asp National Cancer Institute End-of-Life Decisions http://www.cancer.gov/cancertopics/pdq/ supportivecare/transitionalcare/HealthProfessional/ page9 See also Cardiopulmonary resuscitation (CPR); Do-notresuscitate (DNR) order; End-of-life care; Living will; Long-distance caregiving; Transitional care.
u Aflatoxins Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1 Related cancers: Liver cancer, primary liver cell cancer, hepatocellular carcinoma, lung cancer Definition: Aflatoxins are naturally occurring toxic metabolites produced by certain fungi that grow on some agricultural products. At least thirteen different aflatoxins are produced in nature, with the four major aflatoxins called aflatoxin B1, B2, G1, and G2. Aflatoxin B1 is typically the most predominant as well as the most toxic. Aflatoxin M1 is found primarily in milk. Exposure routes: Ingestion and inhalation Where found: Numerous agricultural commodities, including corn and other grains, peanuts, tree nuts, and cottonseed meal. Milk, eggs, and meat products can be contaminated if animals consume aflatoxin-contaminated feed. At risk: Those living in countries where agricultural products that readily support the growth of aflatoxin-producing fungi are a dietary staple. Farmers and other agricultural workers are at risk for occupational exposure through inhalation of dust generated during handling of contaminated crops and feeds. Etiology and symptoms of associated cancers: Aflatoxin-producing fungi can grow on a wide range of agricultural products. Corn and groundnuts are major sources of human exposure because of greater susceptibility to contamination and widespread consumption. Worldwide,
Salem Health: Cancer
Aflatoxins
These peanuts are contaminated with aflatoxins. (AP/Wide World Photos)
corn is probably of greatest concern because it is grown in climates that readily support the growth of fungi and is a dietary staple in many countries. Aflatoxin-producing fungi often grow on crops in the field before harvest, particularly if the crops have experienced drought stress. After harvest, contamination can occur during storage. The growth of aflatoxin-producing fungi and subsequent production of aflatoxins are influenced by weather conditions such as temperature and humidity. As a result, aflatoxin contamination varies with geographic location, agricultural and agronomic practices, and the susceptibility of crops to fungal growth. Exposure to aflatoxins occurs primarily by consuming contaminated food. Aflatoxin consumption is commonplace in developing countries where food supplies are limited and regulations of aflatoxin levels are not enforced or nonexistent. In developed countries, food supplies are generally more abundant and diverse, and aflatoxin levels are monitored to limit toxin ingestion. Although the sale of heavily contaminated food supplies is not permitted in
developed countries, chronic exposure to low levels of aflatoxins may still be a concern. The most common aflatoxin-producing fungi are Aspergillus flavus and Aspergillus parasiticus. Although many aflatoxins are produced by these fungi, aflatoxin B1 is the most prevalent and the most toxic. Aflatoxin B1 is also the most potent naturally occurring carcinogen. Aflatoxins are both toxic and carcinogenic, with exposure to high levels resulting in toxic effects referred to as aflatoxicosis and chronic exposure to low levels potentially resulting in cancer. Susceptibility to aflatoxin-related diseases is influenced by many factors, including age, exposure level, duration of exposure, health, nutritional status, and exposure to other agents, such as the hepatitis B virus (HBV). The liver is the primary target organ of aflatoxin exposure, although other organs can also be affected. Metabolic activation by liver enzymes is required for the carcinogenic effects of aflatoxin B1. In the liver, aflatoxin B1 is metabolized to a highly reactive form that readily binds deoxyribonucleic acid (DNA) and proteins and can lead to 27
African Americans and cancer liver damage and subsequent formation of tumors in the liver. Exposure to aflatoxins in the diet has been shown to be one of the major etiological factors in the development of primary hepatocellular carcinoma in some countries, such as China and many African countries. Concurrent infection with HBV and exposure to aflatoxins results in significantly greater liver damage than either infection or exposure alone, a synergy that is likely produced because HBV interferes with the liver’s ability to detoxify aflatoxins. Although aflatoxin is most well known as an agent that promotes liver cancer, inhalation of contaminated grain dust has been associated with an increased incidence of lung cancer. Liver cancer is not associated with any symptoms in the early stages. As the cancer progresses, symptoms may include pain in the upper abdomen on the right side, which may also extend to the back and shoulder. Other symptoms include a swollen or bloated abdomen, weight loss, loss of appetite, feeling of fullness, weakness, fatigue, nausea and vomiting, yellowish skin and eyes, dark urine, and fever. History: Aflatoxins have been recognized as a significant contaminant since the 1960’s, when more than 100,000 young turkeys on poultry farms in England died from what was termed turkey X disease. The mortalities were traced to consumption of mold-contaminated peanut meal. In 1961 the toxin-producing fungus, A. flavus, was identified and the toxin given the name aflatoxin. The International Agency for Research on Cancer (IARC) first recognized aflatoxins as carcinogenic in 1976. In 1987 naturally occurring mixtures of aflatoxins and AFB1 were classified as Group I carcinogens. Aflatoxins are considered unavoidable contaminants of food and feed, even when good manufacturing practices have been followed. Although absolute safety can never be achieved, many countries have attempted to limit exposure to aflatoxins by imposing regulatory limits on commodities intended for consumption. The Food and Drug Administration has established specific guidelines that regulate this toxin to very low concentrations in human food and animal feed. Catherine J. Walsh, Ph.D. u
For Further Information Bennet, J. W., and M. Klich. “Mycotoxins.” Clinical Microbiology Reviews 16, no. 3 (2003): 497-516. Eaton, D. L., and J. D. Groopman. The Toxicology of Aflatoxins. New York: Academic Press, 1994. Goldblatt, L., ed. Aflatoxin: Scientific Background, Control, and Implications. New York: Academic Press, 1969. 28
Salem Health: Cancer U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
Centers for Disease Control and Prevention http://www.cdc.gov National Cancer Institute http://www.cancer.gov National Toxicology Program http://ntp.niehs.nih.gov U.S. Food and Drug Administration Center for Food Safety and Nutrition http://www.cfsan.fda.gov See also Free radicals; Hepatomegaly; Infectious cancers; Liver cancers; Risks for cancer.
u African Americans and cancer Category: Social and personal issues Definition: Cancer is the second leading cause of death among African Americans. African Americans experience higher cancer rates than any other racial or ethnic group in the United States, as well as higher mortality rates from those cancers. Description of the population: The U.S. government identifies as African Americans “individuals whose origins are from any of the black racial groups of Africa,” including people who self-report their ethnicity as “Black, African American, or Negro” or who describe themselves as African American, Afro-American, Angolan, Negro, West Indian, Afro-Caribbean, Nigerian, Haitian, Gullah, Creole, West African, Afro-Latin, Afro-Brazilian, Congolese, Americo-Liberian, Bantu, Guinean, Moor, Pygmy, or Liberian. According to the Census Bureau, African Americans represented more than 13 percent of the U.S. population as of 2006. Incidence, death, and survival statistics: The average U.S. life expectancy was 49.2 years in the nineteenth century. The National Vital Statistics Reports (vol. 47, no. 28) note that African American life expectancy is 70.2 years, as opposed to 76.5 years for the U.S. population overall. African American men have a life expectancy of only 66.1 years; for all U.S. men it is 73.6 years. These statistics are
Salem Health: Cancer reflected in the cancer morbidity rates for African Americans: In 2003, for example, cancer was the second leading cause of death of African Americans (topped only by heart disease). The death rate outstripped that of whites, with 234.5 African Americans (versus 188.3 whites) dying of cancer per every 100,000 in the U.S. population. Overall, African Americans have higher cancer rates than any other racial or ethnic group in the United States, and their death rates from those cancers are also higher. The five-year survival rate among African Americans for all cancers improved from 27 percent in 1960-1963 to 57 percent in 1996-2002. Nevertheless, at more than 63 percent, whites were still more likely to survive five years after diagnosis. African American men are more likely to succumb to cancer than are white men, although this disparity, after peaking in the early 1990’s, has begun to decline. Death rates for African American women are closer to those for white women—although still higher. The fact that African Americans are more likely to be diagnosed with cancer later in the disease process and have less access to high-quality care in part explains their increased likelihood of death. The American Cancer Society reported that between 2000 and 2003, the cancers afflicting African American men most often were, from highest to lowest incidence, prostate cancer, lung and bronchial cancers, colorectal cancer, kidney and renal pelvic cancers, urinary bladder cancer, oral cavity and pharyngeal cancers, stomach cancer, non-Hodgkin lymphoma, pancreatic cancer, myeloma, leukemia, liver and intrahepatic bile duct cancers, laryngeal cancer, esophageal cancer, brain and other nervous system cancers, small intestinal cancer, soft-tissue (including heart) cancers, Hodgkin disease, Kaposi sarcoma, thyroid cancer, testicular cancer, melanoma of the skin, and mesothelioma. For all these cancers combined, African American men were afflicted, on average, 1.2 times more often than white men, with particularly noticeable disparities in Kaposi sarcoma, myeloma, and small intestinal cancers. For the same period, cancers afflicting African American women were, from highest to lowest incidence, breast cancer, colorectal cancer, lung and bronchial cancers, uterine corpus cancer, pancreatic cancer, non-Hodgkin lymphoma, uterine-cervical cancer, ovary, kidney and renal pelvic cancers, stomach cancer, myeloma, leukemia, urinary bladder cancer, thyroid cancer, oral cavity and pharyngeal cancers, brain and other nervous system cancers, liver and intrahepatic bile duct cancers, esophageal cancer, soft-tissue (including heart) cancers, small intestinal cancer, Hodgkin disease, laryngeal cancer, and melanoma of the skin. The overall incidence for African Amer-
African Americans and cancer
Five-Year Relative Survival Rates for Selected Cancers for African Americans and Whites in the United States, 1996-2002 Survival Rates (%) Cancer Type Prostate Female breast Bladder Uterus Cervix Colon and rectum Non-Hodgkin lymphoma Leukemia Mouth Lungs and bronchi Esophagus
African American
White
98 77 64 60 63 55 54 40 40 12 11
100 90 82 85 73 65 64 49 61 15 16
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cancer patients diagnosed between 1996 and 2002 and followed through 2003
ican women was, on average, slightly less than for white women, although the incidence of myeloma, stomach cancer, and small intestinal cancer among African American women was more than twice that among white women— balanced by lower incidence rates for other cancers, including breast and uterine corpus. For 1996-2002 (in descending order), survival rates among African Americans as a whole were best for prostate, female breast, urinary bladder, uterine corpus, uterine cervical, colorectal, non-Hodgkin lymphoma, leukemia, oral cavity, lung and bronchial, and esophageal cancers. For these same cancers combined, white survival rates exceeded those of African Americans by an average of 11.45 percent (ranging from 2 to 25 percent). The greatest disparities in survival rates could be seen in uterine corpus and oral cavity cancers: Whites outlived blacks by 25 percent and 21 percent, respectively. For 2007, the cancers projected to be diagnosed most often in African American men were prostate (37 percent), lung (15 percent), and colorectal (12 percent) cancers. African American women were expected to be diagnosed most often with breast (27 percent), lung (13 percent), and colorectal (12 percent) cancers. Risk statistics: The major risk factors for cancer in all populations are socioeconomic status, tobacco use, and 29
African Americans and cancer being overweight or obese. African Americans are disproportionately poor: In 2004, more than 29 percent of African Americans fell below the poverty line, as opposed to 13 percent of whites. Because one-fifth of African Americans are uninsured, access to care, particularly preventive and screening care, is limited relative to the rest of the population. Limited detection, in turn, leads to later diagnoses and thus cancers that are more difficult to treat and to survive. Tobacco use—the biggest risk factor for the deadliest cancer, lung cancer—accounts for about 30 percent of cancer deaths overall. Among African Americans, lung cancer death rates are higher than those of whites, even though most African Americans begin smoking at a later age and smoke fewer cigarettes per day. The amount of each cigarette smoked, the type of cigarettes commonly smoked (mentholated, with higher concentrations of carbon monoxide), and the condition of the individuals who smoke (nutritional status and genetic differences) are predicted to account for the higher death rates. Overweight and obesity, which constitute a growing pandemic in American society generally, are defined as a body mass index (BMI) greater than 25 (overweight) or greater than 30 (obese). After tobacco use, obesity is the second leading cause of preventable deaths in the United States. According to the 2003 National Health and Nutrition Examination Survey, nearly 33 percent of U.S. adults were obese, and as early as 2002, overweight individuals formed 65 percent of the U.S. population. Among African Americans, 76 percent were either overweight or obese as of the year 2004. Obesity is positively correlated with certain cancers, particularly breast, endometrial, and colon cancers. Perspective and prospects: From the early 1970’s to 1992, rates of both incidence of and deaths from cancer increased among African Americans. After 1992, both death and incidence rates for all cancers among both sexes of African Americans, fortunately, declined. Five-year survival rates also improved, from only 27 percent in the early 1960’s to 57 percent by 2002. Nevertheless, to bring about parity with the rest of the population, some key factors must be addressed: The current health care system must educate, train, and prepare a health care workforce that is intimately aware of African American health issues and must be sensitive to perceptions, concerns, and fears that may exist in the African American population. A concerted effort must also be made to educate African Americans regarding the role they play in improving their own health. They must understand the importance of health care screenings, weight re30
Salem Health: Cancer duction and management, exercise, and regular physical examinations. Beyond prevention, however, African Americans continue to need better access to the health care system, improved medical insurance, more routine screenings, earlier detection, and better treatments upon diagnosis. With better access, informed African Americans can become empowered to take control of their health by seizing every opportunity to improve it. Christina J. Moose, M.A. u
For Further Information American Cancer Society. Cancer Facts and Figures for African Americans. Atlanta: Author, 2007. Bailey, Eric J. Medical Anthropology and African American Health. Westport, Conn.: Bergin & Garvey, 2000. Byrd, W. Michael, and Linda A. Clayton. A Medical History of African Americans and the Problem of Race, Beginnings to 1900. Foreword by Robert J. Blendon. New York: Routledge, 2000-2002. Collins, Catherine Fisher. African American Women’s Health and Social Issues. Foreword by Vivian W. Pinn. Westport, Conn.: Praeger, 2006. Rawls, George, Frank P. Lloyd, Jr., and Herbert Stern. Managing Cancer: The African American’s Guide to Prevention, Diagnosis, and Treatment. Roscoe, Ill.: Hilton, 2001. Reed, James, Neil Shulman, and Charlene Shucker. The Black Man’s Guide to Good Health: Essential Advice for the Special Concerns of African-American Men. New York: Berkley, 1994. Williams, Christopher Kwesi O., Olufunmilayo I. Olopade, and Carla I. Falkson, eds. Breast Cancer in Women of African Descent. London: Springer, 2006. u
Other Resources
African American Health Network http://www.aahn.com MedlinePlus African-American Health http://www.nlm.nih.gov/medlineplus/ africanamericanhealth.html National Cancer Institute Center to Reduce Cancer Health Disparities http://crchd.cancer.gov/index.html NetWellness African American Health Center http://www.netwellness.org/healthtopics/aahealth
Salem Health: Cancer
Africans and cancer
See also Africans and cancer; Asian Americans and cancer; Epidemiology of cancer; Ethnicity and cancer; Geography and cancer; Latinos/Hispanics and cancer; Polyps; Sézary syndrome; Smoking cessation; Statistics of cancer; Stomach cancers; Survival rates; Testicular cancer.
million people. In contrast, the average radiation machine in Europe serves a population of only about 250,000 people. Additionally, only fifteen countries in Africa have any radiation machines at all. The United Nations estimates that only about 20 percent of Africa’s population has any kind of radiation therapy available to them, and in many cases, available can mean hundreds of miles away.
u Africans and cancer
Problems of prevention and treatment: Africa faces many significant challenges to the successful prevention, early diagnosis, and treatment of cancer. Prevention of cancer requires education of the population about what types of things may increase the risks of developing cancer, and what things and lifestyle choices are believed to reduce the risk of cancer. Smoking and use of tobacco products in any form have been linked to cancer for many years. However, public education about the perils of smoking can be difficult, time-consuming, and expensive. Most African governments are already highly burdened, and there are rarely any budget dollars left to go to public education about something as intangible as smoking or tobacco use and its correlation with an increased risk for cancer. Another barrier to prevention in Africa is that what is considered a healthy lifestyle for cancer prevention is not accessible to many Africans. Most African countries have a per capita national income that labels them as low- or very low-income countries. Fresh, clean water and many different fruits, vegetables, whole grains, and lean proteins, all considered part of a healthy lifestyle in the United States and other developed countries, are not reasonably accessible to many people living in Africa. The opportunity for early diagnosis is severely lacking in most areas of Africa. Diagnosing cancer when it is in its earliest stages leads to the most positive prognosis. Many cancers that are treatable if found early are almost never treatable when diagnosed in a very late stage. Preventive health care is not readily accessible in most parts of Africa, and many people seek medical attention only when there is an obvious problem. Unfortunately, because many cancers produce severe symptoms only when in the later stages, this means that most cancers diagnosed in Africa are diagnosed at a stage too late to be treated successfully. This problem is caused by many interacting factors, including many people living too far from health care to reasonably get preventive screenings, lack of education about the benefits of early detection, and lack of medical professionals and facilities to do the screenings. The cost of preventive medicine and screenings is also often a barrier to early diagnosis. Even when an early diagnosis is made, there are many
Category: Social and personal issues Definition: According to the World Health Organization, cancer is the leading cause of death worldwide, and more than 70 percent of those deaths occur in countries that are considered low or middle income. Cancer is one of the top health problems in Africa, where access to quality health care is often barred by distance, availability, and income. Statistics: There are many barriers to good statistical analysis of cancer trends in Africa. There are no governmental agencies charged with the collection and monitoring of cancer statistics and trends as there are in the United States. In addition, many Africans live in remote areas and do not necessarily seek treatment in hospitals or clinics, so data about cancer incidence and mortality are difficult to collect and assess accurately. However, the World Health Organization (WHO) did compile statistics about cancer incidence and mortality in Africa as a whole in 2002. In that year, about 582,000 people (283,000 men and 299,000 women) living in sub-Saharan Africa developed cancer. Also in 2002, 412,100 in the same area died due to cancer. The most common forms of cancer in Africa among women were breast cancer, cervical cancer, and Kaposi sarcoma (a form of cancer common in individuals with acquired immunodeficiency syndrome, or AIDS). In men the most common cancers were Kaposi sarcoma, prostate cancer, and liver cancer. Lung cancer and stomach cancer were also very common and were especially likely to result in death. It is estimated that in 2020 804,000 people living in sub-Saharan Africa will develop cancer, and that 624,000 will die of it that year. There are many barriers to the successful treatment of cancer in Africa. In August, 2007, the World Health Organization estimated that 80 to 90 percent of the cancer cases that are encountered by doctors and hospital personnel in Africa are diagnosed when the cancer has developed and spread too far to be successfully treated. Additional difficulties occur because of significant lack of resources. According to the United Nations, Ethiopia did not receive a radiation therapy machine until 1997, and many years later it still had only one machine to serve a population of 65
31
Afterloading radiation therapy barriers to effective cancer care in Africa. There is a significant lack of the resources and equipment necessary for the treatment of cancer. Treating cancer is a process that requires many experts and technologically advanced equipment and drugs. Unfortunately, much of the necessary equipment is prohibitively expensive for most hospitals and clinics in Africa. Additionally, there is a lack of training programs and trained health professionals to run the equipment, administer medication, and oversee treatment. The dispersed nature of the population over most of Africa is also a barrier to effective care. Even if a country does have a few hospitals or centers with the staff and equipment necessary for cancer treatment, many millions of individuals may live too far from the center to be able to make effective use of what it offers. Another problem facing the African health care community in its attempts to successfully treat cancer is the AIDS epidemic. Millions of Africans are infected with the human immunodeficiency virus (HIV) or have AIDS, and it contributes to problems for cancer treatment in a number of ways. The AIDS epidemic is stretching the resources of the health care systems in most African countries very thin. Because AIDS impairs the immune system’s ability to function properly and ward off disease, individuals with AIDS need significant medical treatment for the many complications that occur. Individuals with AIDS are also more likely to develop cancer, especially Kaposi sarcoma, one of the most common cancers in Africa. This stretches the cancer resources that do exist even more thinly.
Salem Health: Cancer too bright, even small improvements in resources and education can make a huge difference in the number of Africans affected by cancer. Cancers that are usually detected early and cured in the United States and Europe could also be cured in Africa if they were detected early enough and the right treatment options were available. Progress made in improving the AIDS epidemic may also have beneficial effects on the rates of cancer incidence and mortality in Africa. As Kaposi sarcoma, a cancer common among those with AIDS, is one of the leading cancers in Africa, reducing the number of individuals infected with HIV should cause a reduction in the number of individuals with AIDS-related cancers. Helen Davidson, B.A. u
For Further Information O’Keefe, Stephen J. D., et al. “Why Do African Americans Get More Colon Cancer than Native Africans?” Journal of Nutrition 137, no. 1 (January, 2003): 175183. Sloan, Frank A., and Hellen Gelband, eds. Cancer Control Opportunities in Low- and Middle-Income Countries. Washington, D.C.: National Academies Press, 2007. U.S. Department of Health and Human Services, National Institutes of Health, and the National Cancer Institute. NCI International Portfolio: Addressing the Global Challenge of Cancer. Bethesda, Md.: National Cancer Institute, 2006.
u
Outlook for the future: The outlook for the future of cancer in Africa is not excellent, but it is improving. Although estimates suggest that there will be increasing numbers of cancer cases in Africa over the next decades, some organizations and groups are making strong efforts to stop the problem. Many of these efforts focus on increased access to prevention, early diagnosis, and access to treatment. In May, 2005, the World Health Organization adopted a resolution on cancer prevention and control. The resolution called on member states of the organization to take steps to reduce cancer incidence and mortality by creating and putting into action programs of cancer control. The WHO breaks down the areas of concern for countries that are working to stop cancer into four broad categories: prevention, early detection, diagnosis and treatment, and palliative care. Some private and corporate organizations are also working to help prevent and treat cancer in Africa. Various programs work to raise awareness of the problem of cancer in Africa and to raise money for desperately needed equipment, training, and education. Although the outlook is not 32
Other Resources
Cancer-Africa http://www.ialphan.com/cancerafrica/ World Health Organization http://www.who.int See also African Americans and cancer; HIV/AIDS-related cancers; Kaposi sarcoma; Rectal cancer.
u Afterloading radiation
therapy Category: Procedures Also known as: High dose rate remote afterloading (HDR) Definition: Afterloading radiation therapy is a form of high dose rate brachytherapy that uses a computer-controlled machine called an afterloader to deliver radiation from iridium 192 directly to a tumor. Iridium 192 is a radioac-
Salem Health: Cancer tive source that emits high-energy gamma rays, a type of radiation that is used to kill cancer cells. The radioactive source is contained in the lead-shielded machine and welded to a stainless steel cable that is inserted into the tumor through catheters, needles, or balloons placed in the tumor or tumor bed. Afterloading radiation therapy is considered a temporary implant because the radioactive source does not remain in the patient, and the patient is not radioactive. Cancers treated: Lung cancer, breast cancer, prostate cancer, head and neck cancers, uterine cancer, cervical cancer, esophageal and bile duct cancers, soft-tissue sarcoma, rectal cancer, others under study Why performed: The use of a high-dose remote afterloader provides more targeted therapy to the tumor, or to the tumor bed after the bulk of the tumor is removed in surgery. The afterloader provides more accurate dose delivery to the target site while better protecting normal tissue. Its use also provides a shorter course of therapy of approximately one week, as compared to external beam radiation therapy, which takes place over four to six weeks. The dose distribution is more even, and there are fewer hot (overdose) spots or cold (underdose) spots. Side effects occur less often with HDR therapy. Patient preparation: Planning for the use of afterloading radiation therapy often begins before an initial surgery, depending on the type of cancer and its site. The surgeon and the radiation oncologist will confer, as the catheters used in administering the radiation may be placed at the time of the initial surgery for the cancer. Catheters or needles may also be placed in an outpatient setting under local anesthesia or other sedation. Imaging or radiology studies may be used to assist in treatment planning for the optimal radiation dose delivery to the tumor site and to verify the location of the catheters, especially if it has been a few weeks since their placement. A simulation is done to visualize the tumor or tumor site in comparison to adjacent organs and tissues using a computed tomography (CT) scan or X ray. This procedure assists the radiation oncologist in planning the amount of dose that the afterloader will deliver. The simulation data are then loaded into a treatment-planning computer, which calculates the dose needed. Steps of the procedure: The patient arrives in the radiation oncology center and may change into a gown prior to receiving treatment. For some prostate treatments, needles may be placed prior to the treatment under local anesthesia. Upon entering the treatment room, the patient is assisted to a comfortable position that also allows access to
Afterloading radiation therapy the ends of the catheters or needles. The treatment catheters or needles from the patient are attached to the transfer tubes from the afterloader. The treatment personnel leave the room but can observe the patient using closed-circuit television and an intercom for communication. The treatment data loaded into the HDR unit control the movement of the source into the patient and the time that the source remains at various stops along the catheters or needles in order to achieve the distribution of dose planned. The source is placed in the patient for approximately ten to fifteen minutes, but a single treatment may take up to one hour or more. The complexity of the treatment, the site being treated, and the strength of the radioactive source will dictate the time involved. The radiation oncologist will discuss the number of treatments needed based on the disease, but treatment times vary from a few days to slightly more than a week. After the procedure: Depending on the site being treated, the patient may need to stay in the hospital or may be allowed to go home between treatments. A bandage may be placed over the catheters. After all treatments are complete, the catheters are removed by clipping the sutures holding the catheters, and they are withdrawn. A small amount of bleeding may occur, but it is quickly controlled with direct pressure, and a bandage is applied over the site. Risks: Risks are related to catheter movement out of the site being treated. It is important for patients to tell the radiation staff if a catheter seems to have moved, or if it gets snagged on clothing or the bandage at any time. A misplaced catheter or needle may deliver radiation to normal tissues or organs, causing radiation burns. There is a risk that cancer cells may be missed by the radiation. Results: Outcomes vary by the disease being treated, but success rates for HDR treatments are comparable to other forms of treatment in most instances. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Hoskin, P. J., and P. Bownes. “Innovative Technologies in Radiation Therapy: Brachytherapy.” Seminars in Radiation Oncology 16, no. 4 (October, 2006): 209-217. Hoskin, P. J., K. Motohashi, P. Bownes, L. Bryant, and P. Ostler. “High Dose Rate Brachytherapy in Combination with External Beam Radiotherapy in the Radical Treatment of Prostate Cancer: Initial Results of a Randomized Phase Three Trial.” Radiotherapy & Oncology 84, no. 2 (August, 2007): 114-120. 33
Agent Orange National Cancer Institute. Radiotherapy and You: Support for People with Cancer. Available online at http://www .cancer.gov/cancertopics/radiation-therapy-and-you. u
Other Resources
American Cancer Society http://www.cancer.org American Society for Therapeutic Radiology and Oncology Patient Web Site http://www.rtanswers.org See also Brachytherapy; Cobalt 60 radiation; External beam radiation therapy (EBRT); Intensity-modulated radiation therapy (IMRT); Iridium seeds; Proton beam therapy; Radiation therapies; Radiofrequency ablation; Stereotactic radiosurgery (SRS).
u Agent Orange Category: Carcinogens and suspected carcinogens Also known as: Super Orange Related cancers: Soft-tissue sarcoma, non-Hodgkin lymphoma, Hodgkin disease, chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML) Definition: Agent Orange was a chemical mixture used in the United States to control weeds and in Vietnam during the Vietnam War to remove forest cover. So named because of the orange stripes painted on its storage drums, Agent Orange is a blend of two herbicides: 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Although 2,4,5-T is not highly poisonous, the manufacturing process generates a toxic by-product called TCDD, or 2,3,7,8-tetrachlorodibenzop-dioxin. This dioxin, classified as a human carcinogen, tainted Agent Orange formulations. Exposure routes: Inhalation, ingestion, skin contact, ocular absorption Where found: Herbicide mixtures formerly used for agricultural, forestry, and military purposes At risk: Combatants and civilians exposed to Agent Orange during the Vietnam War and their children, workers occupationally exposed to the chemical, and populations exposed through domestic herbicide spraying Etiology and symptoms of associated cancers: Because epidemiologic data on Vietnam veterans is limited, the 34
Salem Health: Cancer health effects of Agent Orange have been studied indirectly in certain populations highly exposed to dioxin or dioxin-tainted herbicides. These studies provide sufficient evidence linking Agent Orange to chloracne, an acnelike skin disorder, and to certain cancers, induced when TCDD activates a protein receptor in target cells. The soft-tissue sarcomas develop from fat, muscle, or deep body tissues and usually appear as a lump. Hodgkin disease (highly curable) and non-Hodgkin lymphoma originate in lymphatic tissue and result in painless swelling of lymph nodes under the skin. Chronic lymphocytic leukemia, which develops from white blood cells, is often asymptomatic, but later is marked by enlarged lymph nodes. Paternal exposure to Agent Orange has been associated with acute myelogenous leukemia in children. This fastgrowing cancer of the bone marrow produces abnormal white blood cells and results in fatigue, shortness of breath, and increased susceptibility to infection. Only limited evidence links Agent Orange to respiratory cancer, prostate cancer, and multiple myeloma. History: Phenoxy herbicides, including the 2,4,5-T component of Agent Orange, were developed in the 1940’s and widely used in agriculture and forestry. Starting in 1960 during the Vietnam War, the United States military sprayed Agent Orange onto lands in Vietnam and Laos. It suspended this activity in 1970, after a study in laboratory animals linked 2,4,5-T to birth defects. Since the 1980’s, various groups of Vietnam veterans have filed lawsuits against the makers of Agent Orange. The United States has permanently banned all uses of 2,4,5-T and, consequently, Agent Orange. Anna Binda, Ph.D. See also Dioxins; Multiple myeloma; Mycosis fungoides; Organochlorines (OCs); Pesticides and the food chain.
u Aging and cancer Category: Social and personal issues Definition: The most significant risk factor associated with developing cancer is age, with 60 percent of all cancers occurring in people who are sixty-five and over. Mortality rates are also highest in this age group; older individuals typically have additional chronic medical conditions that enhance the risk for simultaneously occurring psychiatric morbidity. These complex and potentiating trends are creating new clinical challenges that threaten to overwhelm the current health care system. Based on projections that 1 in 5 Americans will be over the age of
Salem Health: Cancer
Aging and cancer
Cancer is more common and deadlier in the elderly. (Digital Stock)
sixty-five by 2030, there is an immediate need to better understand the influence of age on cancer detection, diagnosis, and treatment, with the goal of modifying infrastructure, practices, and the educational preparation of future health care providers. Biology of aging and cancer: Based on the population trends, research aimed at illuminating the biology of aging and mechanisms that enhance cancer susceptibility are increasing. A clearer understanding of the well-documented age-related increase in cancer incidence is needed to develop well-conceived primary cancer prevention strategies. This line of research has been designated as a priority by the National Cancer Institute. At present, there are three major hypotheses that explain the association between cancer and age: Hypothesis 1 holds that the link between aging and cancer is simply related to duration of carcinogenesis. In other words, the high prevalence of cancer in older individuals simply reflects more prolonged exposure to carcinogens. Hypothesis 2 proposes that age-related, progressive changes within the human organism may provide an in-
creasingly favorable environment for the induction of new cancers and the growth of preexisting but latent malignant cells. These mechanisms may be related to proliferative senescence, whereby aging cells lose their ability to undergo apoptosis (a form of cell death that leads to the sequential elimination of cells without releasing harmful substances into the body). When apoptosis does not work right, cells that should be eliminated become immortal, stimulating cancer-related mutations at the cellular level. Hypothesis 3 combines aspects of the first two hypotheses and proposes that the aging, cancer-prone human phenotype is characterized by an accumulation of dysfunctional senescent cells. These cells proliferate via synergistic, simultaneous physiologic processes that foster progressive accumulation of cancer-prone mutations; silencing of genes that previously functioned to prevent cancerpredisposing mutations from developing in response to carcinogens (failure of epigenetic gene silencing); and telomere dysfunction (telomeres are specialized structures at chromosome ends that regulate their replication and stability). These changes are particularly relevant to the production of malignancies because they occur within the 35
Aging and cancer context of an aging microenvironment of surrounding tissues. Cancer, aging, and psychiatric comorbidity: As increased longevity contributes to rising cancer incidence, those diagnosed often have one or more additional chronic medical conditions. Paradoxically, new treatment discoveries have extended survival for multiple medical illnesses but often within the context of troubling side effects and consequences that in turn have led to documented increases in the incidence of psychiatric morbidity. The incidence of psychiatric morbidity is further enhanced as the burden of cancer care progressively shifts from the health care system to family caregivers. Family caregivers are usually aging spouses with medical problems of their own or adult children, with their own families, jobs, responsibilities, and problems. When the role of providing complex cancer care for a loved one is added to their already stressful lives, risk for psychiatric morbidity is significantly enhanced. Although the preceding issues have been largely ignored, they continue to strain the U.S. health care system to its limit. The preceding trends are occurring within a system in which mental health services are a low priority. Stigma, limited knowledge regarding the nature and intensity of psychiatric symptoms associated with clinical need, and inconsistent, generally inadequate reimbursement mechanisms are a sampling of the multiple issues contributing to
Problems to Consider in Treating Pain in Older Cancer Patients Other chronic illnesses: Patients taking multiple medications may be at risk for drug interactions. Impairments in hearing, vision, and mental function: Patients may need to be monitored more frequently and tests may need to be simplified. Patient-controlled analgesia: Patients are more sensitive to the side effects of these drugs, which remain in their bodies longer. Opioids: Patients may be more sensitive to the effects of these drugs and experience longer periods of pain relief. Side effects from nonsteroidal anti-inflammatory drugs (NSAIDs): Stomach and kidney toxicity, constipation, headaches, and difficulties with the ability to think may arise. Administration of medicine: Some older patients may not be able to administer some drugs as directed (for example, inserting a drug into the rectum). Source: National Cancer Institute
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Salem Health: Cancer our dismal state of mental health services. Research, professional education, and clinical services are most deficient with regard to the psychiatric morbidity that occurs within the context of a chronic medical illness. Psychiatric symptoms are typically treated only when they emerge as disease states within an expensive, fragmented, specialtyoriented system. Reimbursement for psychiatric treatment is difficult to obtain, yet paying out of pocket is prohibitive and biases care toward the affluent. Limited solutions to these consequential problems potentiate untold human suffering, negative clinical outcomes, and high resource utilization that could be avoided if problems were dealt with before they got out of hand. Cancer screening in the elderly: Considerable uncertainty regarding the use of cancer screening procedures in the elderly is illustrated by the range of age cutoffs recommended by various guideline panels. To address inconsistencies, it has been suggested that a comprehensive framework rather than specific age parameters should inform individual screening decisions in older cancer patients. Screening decisions should encompass estimates of life expectancy, risk of cancer death, documented screening outcomes, and a risk-benefit screening ratio. For example, harm may result from screening practices that detect and treat cancers that never would have become clinically significant. Because many cancer screening decisions in older adults cannot be answered solely by quantitative estimates of benefits and harms, consideration of predicted outcomes within the context of an individual’s values and preferences is an important aspect of informed screening decisions. Statistics reveal considerable underutilization of cancer screening practices in the United States. Having health insurance, a regular doctor, and a point of usual care all are associated with higher cancer screening rates and better preventive health care overall. When these supports are absent, cancer screening rates drop considerably. The lack of preventive services reimbursed by Medicare, the limited number of elders with comprehensive, employerprovided health coverage, and growing numbers of elders who are homebound or lack a regular physician and point of care make elderly Americans especially prone to lacking supports that facilitate cancer screening practices. Age-related differences in cancer treatment: Cancer treatments may produce different therapeutic and adverse responses based on patient age. For example, chemotherapy resistance and toxicity have been shown to vary by age, being more common and severe in the elderly. Treatment toxicities may develop in old versus young recipients because of increased vulnerability of target organs and de-
Salem Health: Cancer layed renal excretion of treatment agents and metabolites. These problems should be managed with treatment modifications determined by kidney function and other relevant parameters of individual health status and treatment response. Aging cancer patients often do not receive adequate information to assist with or inform a definitive treatment plan. Understanding why these deficiencies exist is vital to reducing disparities in cancer mortality between young and old. Studies suggest that treatment uncertainty could be better addressed if elderly cancer patients were offered a choice from a group of definitive therapies. Treatment discussions should also address common concerns related to the costs and functional consequences of each treatment in relation to expected benefits. Current understanding of age-related differences in pharmacokinetics, drug interactions, adverse events, and treatment adherence is extremely limited. Palliative cancer care of the elderly: Despite ambitious research, treatment, and educational initiatives, the quality of palliative care provided to the elderly has historically been and remains poor. Research consistently demonstrates unnecessary suffering among elderly patients with advanced cancer. Their suffering is related to myriad issues, including uncontrolled physical symptoms, depression, and unaddressed existential concerns. Wide gaps in palliative care services targeted to elderly patients with cancer occur across a range of settings, including hospice, where the approach to palliative care has been largely insufficient. Some studies report lower levels of psychological distress in elderly versus young cancer patients, which has been erroneously interpreted to mean that elders are better equipped to manage existential concerns because they are at a stage in life when death is expected. However, data may more accurately reflect age-related differences in exposure to prevention, screening, and treatment practices; the resultant cancer course; and symptom profiles. Results therefore indicate the need for ongoing research and education targeted to unraveling complex relationships between aging and cancer. Knowledge development and dissemination must be met aggressively with clinical initiatives throughout the twenty-first century and beyond as population, demographic, and clinical trends continue to outpace the availability of resources for elderly individuals with cancer. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u For Further Information Hassett, M. J., et al. “Frequency and Cost of Chemotherapy-Related Serious Adverse Effects in a Population
Aging and cancer Sample of Women with Breast Cancer.” Journal of the National Cancer Institute 98, no. 16 (2006): 11081117. Kumar, H., P. Soares, L. Balducci, and B. Djulbegovic. “Treatment Tolerance and Efficacy in Geriatric Oncology: A Systematic Review of Phase III Randomized Trials Conducted by Five National Cancer InstituteSponsored Cooperative Groups.” Journal of Clinical Oncology 25, no. 10 (2007): 1272-1276. Lichtman, S. M., et al. “International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients—An Analysis of the Medical Literature.” Journal of Clinical Oncology 25, no. 14 (2007): 1832-1843. Muss, H. B. “Older Age: Not a Barrier to Cancer Treatment.” New England Journal of Medicine 345 (2001): 28-29. Talarico, Lilia, Gang Chen, and Richard Pazdur. “Enrollment of Elderly Patients in Clinical Trials for Cancer Drug Registration: A Seven-Year Experience by the U.S. Food and Drug Administration.” Journal of Clinical Oncology 22, no. 22 (2004): 4626-4631. Trimble, E. L., and M. C. Christian. “Cancer Treatment and the Older Patient.” Clinical Cancer Research 12, no. 7 (2006): 1956-1957. Yancik, R., et al. “Perspectives on Comorbidity and Cancer in Older Patients: Approaches to Expand the Knowledge Base.” Journal of Clinical Oncology 19 (2006): 1147-1151. u
Other Resources
AARP Foundation http://www.aarp.org/foundation American Cancer Society http://www.cancer.org American Geriatrics Society/Foundation http://www.americangeriatrics.org Family Caregiver Alliance http://www.caregiver.org Geriatric Mental Health Foundation http://www.gmhfonline.org/gmhf Medicare.gov http://www.medicare.gov National Institute on Aging http://www.nih.gov/nia See also Advance directives; Aids and devices for cancer patients; Caregivers and caregiving; Childbirth and can37
Aids and devices for cancer patients cer; Counseling for cancer patients and survivors; Do-notresuscitate (DNR) order; Elderly and cancer; End-of-life care; Living will; Medicare and cancer; Nutrition and cancer prevention; Occupational therapy; Overtreatment; Palliative treatment; Self-image and body image; Singlehood and cancer; Support groups; Survivorship issues; Young adult cancers.
u Aids and devices for cancer
patients Category: Social and personal issues Also known as: Prostheses, breast forms, positioning aids, nutritional aids, braces, canes, walkers, wheelchairs, aromatherapy products, music therapy products Definition: Aids and devices for cancer patients are designed to help a person live a more comfortable and enjoyable life in spite of the side effects of cancer treatment. Some aids and devices help temporarily hide the effects of a cancer treatment while others can improve mobility or provide comfort permanently.
Salem Health: Cancer Another side effect of cancer treatment can be difficulty swallowing and keeping food down. To help people facing this situation get proper nutrition, there are thickening products available to add substance to liquefied foods. These products include gelatin, tapioca flour, cornstarch, commercial thickeners, pureed vegetables, instant potatoes, and baby cereal. There are also a number of liquid nutritional supplement drinks, many available at local grocery stores, that can provide needed nutrition when other types of food cannot be eaten. Some cancer patients experience sun sensitivity. Sunscreen or protective clothing can help protect sensitive skin from the sun. Sunscreens can be found at drug and grocery stores, and a number of companies create clothing—pants, shirts, hats, and gloves—that has built-in sun protection. For both men and women, making an extra effort to maintain personal grooming routines can be a way to maintain a positive attitude. Organizations such as the American Cancer Society provide classes that address special concerns cancer patients may have about their grooming and beauty routines (for example, how to deal with thinning hair). Music can be a wonderful aid in lowering stress levels and helping cancer patients sleep better. It is also shown to reduce pain by increasing endorphins and boosting immunity. It is recommended that the music be sixty beats or less per minute to provide relaxation. Much classical music falls into this category. Many hospitals offer group music therapy sessions.
Comfort aids and devices: A number of products can help cancer patients with some of the physical and emotional discomfort they may experience because of their cancer treatment. Specialty positioning pillows and foam wedges can help patients on bed rest prevent bedsores. In addition, special seat cushions for wheelchair users can help distribute their weight evenly over a large area, preventing sores and easing discomfort. These cushions tend to be filled with either water or gel. Water-filled products help decrease body temperature and gel-filled help maintain body temperature. A simple straw can make drinking beverages easier for cancer patients with sores in the mouth. If dry mouth is a problem after the salivary glands have been removed or damaged by radiation, saliva substitute products can add moisture to a cancer patient’s mouth. A cool-mist humidifier can also help prevent dry mouth by moistening the air within a room. Note that it is important to keep the humidifier clean so that germs are not spread. A wheelchair can provide mobility for a cancer patient. (PhotoDisc) 38
Salem Health: Cancer Aromatherapy may also help ease discomfort. Scents are available to help with all kinds of ailments, from pain and discomfort to lethargy. For example, lavender is a calming scent and can help ease anxiety or sleeplessness. Aromatherapy products and books explaining how to use scents can be found at many health food stores and online. Patients should check for any side effects or interactions with medical conditions before using a particular scent. An inexpensive way that many cancer patients deal with their emotions is to keep a journal. Writing down their thoughts about their situation can be very therapeutic and make it easier to keep a positive outlook. Prosthetic devices: A second category of aids and devices includes prosthetic body parts. Prostheses are available for a large number of body parts, and cancer patients should discuss with their doctors the options available to them for replacing amputated extremities. These products can help individuals regain mobility or provide cosmetic benefits. Braces, canes, walkers, and wheelchairs can improve mobility, whether used on their own or in combination with prosthetic limbs. For breast cancer patients who have undergone mastectomies, prostheses provide more than cosmetic benefits. They can provide protection and pain relief during healing, help maintain proper posture, and help prevent back and shoulder pain. Breast forms made of silicone or fiber can be inserted into a specially made mastectomy bra or worn next to the skin with a special adhesive. Cooling pads can also be inserted into bras to help relieve pain while the area heals. Specialty vests with flat panels can provide post-radiation treatment comfort. In addition, special arm sleeves can be worn to help reduce swelling by providing graduated compression. Cancer patients experiencing hair loss may want to try using a satin pillowcase to help minimize loss and to provide comfort to their sensitive scalps. Head scarves and wigs can be worn to hide hair loss. Sleep and swim caps are also available to protect remaining hair and minimize additional hair loss. Cost and insurance coverage: Some comfort and prosthetic devices are covered by public and private insurance providers. Patients should contact the insurance company before purchasing an item to find out whether the device in question is covered and if any paperwork or special authorization is needed. Some companies may require a prescription from a physician and preauthorization before they will pay for a device. Other insurance companies ask patients to pay up front for an item and then be reimbursed. If an insurance company will not cover a product and the patient cannot afford it, sometimes local cancer sup-
Air pollution port agencies such as the American Cancer Society or CancerCare can help obtain the needed item or suggest other ways to get the necessary money to pay for the item. Jennifer M. Hickin, B.S. u
For Further Information Garrison, Kevin S. It’s Just a Matter of Balance. Baltimore: Gateway Press, 2005. Gaynor, Mitchell L. The Healing Power of Sound: Recovery from Illness by Using Sound, Voice, and Music. Boulder, Colo.: Shambhala, 2002. Kelly, Mary Olson. Number One Best Tools and Tips from the Trenches of Breast Cancer. Austin, Tex.: Books Beyond Borders, 2006. Klein, Karen. Mama Said There’d Be Days like This: A Twelve-Step Guide to Surviving a Mastectomy. Farmington, Conn.: Variegate Press, 2001. Oritz, Lori M. Facing the Mirror with Cancer: A Guide to Using Makeup to Make a Difference. Chicago: Belle Press, 2004. Shurr, Donald G., and John W. Michael. Prosthetics and Orthotics. Upper Saddle River, N.J.: Prentice Hall, 2001. Wilson, A. Bennett, Jr. A Primer on Limb Prosthetics. Springfield, Ill.: Charles C Thomas, 1998. u
Other Resources
American Cancer Society http://www.cancer.org CancerCare http://cancercare.org TLC http://www.tlcdirect.org See also Breast implants; Breast reconstruction; Caregivers and caregiving; Electrolarynx; Esophageal speech; Home health services; Hospice care; Integrative oncology; Living with cancer; Reconstructive surgery; Self-image and body image; Side effects.
u Air pollution Category: Carcinogens and suspected carcinogens RoC status: Asbestos, known human carcinogen since 1980; diesel exhaust particulate, reasonably anticipated human carcinogen since 2000. Other air pollutants that are known human carcinogens include benzene, 1,3-butadiene, radon, and tobacco smoke; 39
Air pollution
Salem Health: Cancer
those that are reasonably anticipated human carcinogens include formaldehyde and polycyclic aromatic hydrocarbons. Air pollutants such as ozone, oxides of nitrogen, and sulfur oxides are not listed in the Report on Carcinogens (RoC); however, epidemiologic studies (studies on populations) provide some evidence of their association with lung cancer. Of the many components of particulate matter (PM), only diesel exhaust particulate has been the subject of studies that led to its current classification. Also known as: Criteria air pollutants, toxic air pollutants Related cancers: Lung cancer, pleural and peritoneal mesotheliomas, gastrointestinal cancers, laryngeal cancer, cancers of the lymphatic and blood-forming systems (1,3butadiene) Definition: Air pollution is the presence of contaminants, many of which are carcinogens, in the air. Outdoors, pollution is largely a consequence of the combustion of fossil fuels for transport, power generation, and other human activities. Indoors, pollution is generated by burning solid
fuels, and the air may also contain asbestos, radon gas, environmental tobacco smoke, formaldehyde, and volatile organic compounds. Exposure routes: Inhalation Where found: Indoor and outdoor air. Outdoor pollutants can be carried far from their original source by air currents. At risk: Populations exposed to smog and particulate matter in air pollution, including inner-city residents; people living near electric-power-generating plants, factories, and refining plants; occupationally exposed railroad workers and synthetic rubber industry workers; people cooking indoors with solid fuels Etiology and symptoms of associated cancers: According to the World Health Organization, the air contains a complex mixture of pollutants, including primary emissions such as diesel soot particles and oxides of nitrogen produced during combustion processes, the products of atmospheric transformation such as ozone, and the sulfate particles formed by burning sulfur-containing fuels. Although air pollution is a minor contributor to lung
Exhaust from cars on congested freeways contains carcinogens. (©iStockphoto.com/Dan Eckert)
40
Salem Health: Cancer cancer compared with tobacco smoke, it can affect entire populations, and components of the pollutant mix might interact with other carcinogens, possibly increasing their effects. In 1995 researchers Aaron Cohen and C. Arden Pope III analyzed epidemiological studies and found that they consistently suggested that ambient air pollution, chiefly as a result of the incomplete combustion of fossil fuels, is responsible for increased rates of lung cancer. A study published in 1998 of nonsmoking adults over a fifteen-year period by David Abbey and his coworkers showed a strong association between ozone levels and lung cancer. The ozone at ground level (which people inhale) is not emitted directly into the air. It is created by chemical reactions between oxides of nitrogen, emitted in motor vehicle exhaust and by industrial facilities, and volatile organic compounds from many sources, including gasoline vapors and chemical solvents. The relation between ozone levels and lung cancer has been reported in many additional scientific studies. The major outdoor air pollutants linked to lung cancer are particulate matter, sulfur oxides, ozone, oxides of nitrogen, and volatile organic compounds. Particulate matter is the term for a mixture of solid particles and liquid droplets found in the air that come from soot, smoke, and diesel exhaust. The particles of most concern are those smaller than 10 micrometers in diameter. Once inhaled, the smaller particles can travel to the deepest regions of the lungs, where chemicals (such as those adsorbed to diesel exhaust particulate) can be released. Some of these chemicals cause deoxyribonucleic acid (DNA) mutations, which can lead to cancer. Many studies have demonstrated that exposure to indoor air pollutants has adverse effects on health. More than three billion people worldwide depend on solid fuels, including biomass fuels and coal, for their cooking and energy needs. Combustion of these materials indoors produces high levels of smoke that contains many pollutants, and there is consistent evidence of lung cancer in adults exposed to coal-generated pollutants, according to the World Health Organization. Inhaling asbestos fibers released from damaged or crumbled insulating materials or other products containing this material can lead to mesothelioma and several other cancers. Other common indoor air pollutants include formaldehyde, environmental tobacco smoke, radon gas, and polycyclic aromatic hydrocarbons (a class of volatile organic compounds). History: Many of the components of air pollution are recognized as known or reasonably anticipated carginogens, such as asbestos, benzene, 1,3-butadiene, radon, tobacco
Air pollution smoke, diesel exhaust particulate, formaldehyde, and polycyclic aromatic hydrocarbons. Other components have scientific research supporting their link to human cancer. The Clean Air Act as amended in 1990 requires the U.S. Environmental Protection Agency to set national ambient air quality standards for ozone, oxides of nitrogen, particulate matter, and sulfur oxides. The agency is mandated to work with state and local governments to reduce the release of other air pollutants classified as toxic air pollutants. Bernard Jacobson, Ph.D. u
For Further Information Beeson, W. L., D. E. Abbey, and S. F. Knutsen. “LongTerm Concentrations of Ambient Air Pollutants and Incident Lung Cancer in California Adults.” Environmental Health Perspectives 106 (1998): 813-822. Cohen, A. J., and C. Arden Pope III. “Lung Cancer and Air Pollution.” Environmental Health Perspectives 103, suppl. 8 (1995): 219-224. Jacobson, M. Z. Atmospheric Pollution. New York: Cambridge University Press, 2002. Krzyzanowski, M., B. Kunnadibbert, and J. Schneider, eds. Health Effects of Transport-Related Air Pollution. Geneva, Switzerland: World Health Organization, 2005. McGranahan, G., and F. Murray. Air Pollution and Health in Developing Countries. London: Earthscan, 2003. Pluschke, P., ed. Indoor Air Pollution. New York: Springer, 2004. Pope, C. Arden, III, et al. “Lung Cancer, Cardiopulmonary Mortality, and Long-Term Exposure to Fine Particulate Air Pollution.” Journal of the American Medical Association 287 (2002): 1132-1141. Ramachandran, G. Occupational Exposure Assessment for Air Contaminants. New York: CRC Press, 2005. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
U.S. Environmental Protection Agency Pollutants/Toxics: Air Pollutants http://www.epa.gov/ebtpages/pollairpollutants.html World Health Organization Air Pollution http://www.who.int/topics/air_pollution/en/ See also Arsenic compounds; Bronchoalveolar lung cancer; 1,3-Butadiene; Cigarettes and cigars; Coke oven emis41
Alcohol, alcoholism, and cancer sions; Dioxins; Lung cancers; Occupational exposures and cancer; Polycyclic aromatic hydrocarbons; Radon; Smoking cessation; Soots; Tobacco-related cancers; Wood dust.
u Alcohol, alcoholism, and
cancer Category: Carcinogens and suspected carcinogens Definition: Alcohol is a chemical that is generated during fermentation of sugar. Ethyl alcohol is the specific chemical that is generally referred to as alcohol. Alcohol is the most commonly used intoxicating agent around the world. Alcoholism (also called alcohol-dependence syndrome) is a phenomenon of continuous intake of alcohol, with a compulsive need to consume it. Alcohol has been linked to several cancers but a direct causal relationship between the two has not been established. Alcohol as carcinogen: Intake of alcohol is considered a risk factor for developing various kinds of cancers, and therefore, alcohol has been classified as a carcinogen. Ethyl alcohol, the form in which alcohol is commonly consumed, undergoes an array of metabolic changes when ingested. The main enzymes that are involved in metabolism of alcohol are alcohol dehydrogenase and aldehyde dehydrogenase. A small amount (approximately 10 percent) is metabolized by microsomal cytochrome P4502E1 (CYP2E1). Alcohol dehydrogenase converts about 80 percent of ethanol to acetaldehyde. Acetaldehyde is a mutagen and a carcinogen and is considered a risk factor in many cancers of the upper gastrointestinal tract. Acetaldehyde is implicated in a variety of processes such as inflammation of the tracheal epithelium, delaying of cell cycle progression, induction of apoptosis, chromosomal damages and aberrations, and sister chromatid exchanges. Much of the carcinogenic effect of alcohol is attributed to this single metabolite. Direct association between the concentration of acetaldehyde in saliva and development of cancer has been reported. Acetaldehyde covalently bonds with deoxyribonucleic acid (DNA) and forms structures called DNA-adducts. The most common DNA-acetaldehyde adduct is N2-ethyl-dG, which is not mutagenic. Acetaldehyde also induces the formation of the mutagenic DNA adduct called Cr-PdG (alpha-methylgamma-hydroxy-1, N2-propano-2′-deoxyguanosine). Polyamines are one of the basic molecules essential for cells and are implicated in cell growth and differentiation, nucleic acid synthesis, and protection against oxidative 42
Salem Health: Cancer damage. Polyamines facilitate acetaldehyde-induced formation of Cr-PdG adducts. Cr-PdG adducts are highly mutagenic and interfere with DNA replication and repair, inducing cancer formation. Polyamines also react with acetaldehyde and form crotonaldehyde, which is highly carcinogenic. Response to alcohol is individualistic and differs among people and races. This is because of polymorphisms in the genes for the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Presence of the ALDH2*1/2 allele significantly increases the risk of upper aerodigestive tract cancer. In addition to these enzymes, oral bacteria also generate acetaldehyde. High amounts of acetaldehyde are detected in saliva after alcohol consumption. Saliva is directly in contact with the upper aerodigestive tract, and this contact is considered a possible mechanism for its carcinogenic effects. Alcohol and breast cancer: Alcohol is one of the most ancient intoxicants known to humankind. Consuming one or two drinks a day is not just common but is also a social custom in many cultures. However, research suggests that even one or two drinks a day could put women at a greater risk for developing breast cancer. A study conducted at the
Alcohol has been linked to several cancers, although a direct causal relationship has not been established. (PhotoDisc)
Salem Health: Cancer
How Much Is Too Much? The risk for cancers of the mouth, esophagus, pharynx, larynx, and liver in men and women and breast cancer in women increases after about two drinks per day for men and one per day for women. One drink is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80proof liquor. The risk for liver cancer goes up significantly after five or more drinks per day. Source: National Cancer Institute
National Cancer Institute tested postmenopausal women for differences in hormone levels after alcohol consumption (15 or 30 grams of alcohol per day) for eight weeks. Results showed a significant elevation of estrone sulfate (an estrogen metabolite) and the hormone DHEAS (dehydroepiandrosterone sulfate). DHEAS is secreted by the adrenal glands, and increased levels of DHEAS indicate induction of a process called adrenal steroidogenesis, reflecting stimulation of the hypothalamic-pituitaryadrenal axis in the brain as a response to alcohol consumption. Alcohol and liver cancers: Excessive consumption of alcohol leads to alcohol liver disease. One type of alcohol liver disease is called alcoholic cirrhosis of the liver, a condition in which normal liver tissue is completely destroyed. Cirrhosis of the liver is considered the primary risk factor for development of hepatocellular carcinoma (liver cancer). Even though alcohol does not seem to cause liver cancer directly, there is a strong association between alcohol and liver cancer.
Aleukemia all cancer-related deaths are caused by chronic alcohol consumption. Education to make people aware of the link between alcohol consumption and cancer should aid in prevention of such cancers. Geetha Yadav, Ph.D. u
For Further Information Cho, Chi Hin, and Vishnudutt Purohit, eds. Alcohol, Tobacco, and Cancer. New York: Karger, 2006. Dorgan, J. F., et al. “Serum Hormones and the AlcoholBreast Cancer Association in Postmenopausal Women.” Journal of the National Cancer Institute 93 (2001): 710-715. Seitz, H. K., B. Maurer, and F. Stickel. “Alcohol Consumption and Cancer of the Gastrointestinal Tract.” Digestive Diseases 23 (2005): 297-303. Seitz, H. K., and F. Stickel. “Molecular Mechanisms of Alcohol-Mediated Carcinogenesis.” Nature Reviews 7 (2007): 599-612. Yirmiya, Raz, and Anna N. Taylor, eds. Alcohol, Immunity, and Cancer. Boca Raton, Fla.: CRC Press, 1993.
u
Other Resources
American Cancer Society Alcohol and Cancer http://www.cancer.org/docroot/PRO/content/ PRO_1_1x_Alcohol.pdf.asp?sitearea=PRO National Cancer Institute Alcohol Consumption http://progressreport.cancer.gov/doc_detail .asp?pid=1&did=2007&chid=71&coid=706&mid= See also Esophageal cancer; Gastrinomas; Gastrointestinal cancers; Hepatomegaly; Laryngeal cancer; Liver cancers; Pancreatic cancers; Pancreatitis.
Alcohol and other cancers: Drinking two or more drinks per day increases the risk of oral and upper gastrointestinal tract (GI) cancers in both men and women. Alcoholrelated cancers include those of the mouth, esophagus, and larynx. Drinking alcohol together with smoking increases the risk of developing cancer more than drinking alone. Alcohol is addictive, and alcoholism leads to enhanced tolerance levels, loss of control, cravings for alcohol, and an inability to stop drinking even when people wish to stop or need to stop for their health. Evidence shows that the nutritional status of the body is also negatively affected by alcohol.
Related conditions: Acute and chronic myelogenous leukemia (AML and CML), acute and chronic lymphatic leukemia (ALL and CLL)
Perspectives and progress: According to World Health Organization statistics, alcohol is responsible for about 1.8 million deaths a year, and alcohol-related cancer is the most common cause of these deaths. Some 3.6 percent of
Definition: Aleukemia describes a condition in which a patient has a normal or reduced white blood cell count. Leukemia cells are present in the bone marrow. Leukemia cells may also be present in the blood. Aleukemia may be
u Aleukemia Category: Diseases, symptoms, and conditions Also known as: Aleukemic myelosis, aleukemic leukemia
43
Alkaline phosphatase test (ALP)
Salem Health: Cancer
present in any of the four major types of leukemia: AML, CML, ALL, and CLL.
u Alkaline phosphatase test
Risk factors: The risk factors are the same as those for leukemia. The risks include age, genetic diseases, prolonged exposure to some chemicals such as benzene, chemotherapies used to treat other forms of cancer, and exposure to high doses of radiation or tobacco smoke.
Category: Procedures Also known as: ALKP, alk phos, alkaline phosphatase total
Etiology and the disease process: Aleukemias start when there is damage to the deoxyribonucleic acid (DNA) of blood cells. Normal cell development is interrupted, causing a decrease of mature cells and an increase in immature cells. Incidence: Aleukemia is present at the start of about 25 to 30 percent of acute leukemias. It is more prevalent in hairy cell leukemia, which is a slow-growing subtype of CLL. Symptoms: There may be no symptoms present. Patients may experience fatigue, weight loss, easy bruising, fever, and infections. Screening and diagnosis: No specific screening test exists for aleukemia. A low white blood cell count found when a complete blood count (CBC) is done as part of a routine exam or in response to symptoms may lead to further testing and diagnosis. Diagnosis is made by the examination of blood smears and bone marrow for the presence of leukemia cells. Staging is not done for any of the leukemias except CLL. The staging of CLL is based on imaging studies, blood tests, and bone marrow examination. The stages, ranging from Stage 0 to IV, are based on the involvement of lymph nodes, spleen, and liver, and decreasing numbers of red blood cells. The other forms of leukemia are classified by cell type. Treatment and therapy: Treatment depends on the type of cell involved and the classification or staging level. In leukemias that progress slowly, treatment may not start until the disease is more advanced. Prognosis, prevention, and outcomes: Prognosis depends on the type of cell involved and the rate of progression. No method of prevention exists. Treatment may slow the progress of the disease or cause complete remission. Some types of leukemia may not respond to treatment. Wanda E. Clark, M.T. (ASCP) See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Anemia; Antiandrogens; Blood cancers; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Eosinophilic leukemia; Fanconi anemia; Leukemias. 44
(ALP)
Definition: Alkaline phosphatase (ALP) is an enzyme that helps in the process of digestion and bone development. All tissues contain ALP. Higher concentrations are found in the liver, bone, kidney, and intestines. Various processes within the tissues release ALP into the blood. By measuring ALP blood levels, doctors can determine the presence of liver and bone disease, including cancer. ALP levels are determined by testing serum or plasma on an automated chemistry analyzer. Cancers diagnosed: Cancers of the bone, renal cells, liver, gallbladder, and bile ducts Why performed: The test is done as a part of a chemistry or liver panel to detect liver or bone disease. Once a diagnosis has been made and treatment started, the test may be done to determine if treatment is effective or if disease has progressed or returned. Patient preparation: The patient may be asked not to eat or drink or take certain medications for six to twelve hours prior to the test. Steps of the procedure: A small sample of blood is collected from a vein and placed in a tube. In children, blood may be obtained from a capillary in the heel or finger. After the procedure: A small gauze or cotton ball is applied at the site of needle insertion. The patient is asked to apply pressure. The person collecting the blood observes the site for bleeding and may apply a bandage. The bandage may usually be removed in thirty to sixty minutes. Risks: Risks from the procedure include bleeding, bruising, hematoma (bleeding under the skin), fainting, lightheadedness, or the need for multiple needle sticks to obtain a sample. Results: Normal ALP levels vary by the patient’s sex and age and by the analyzer used. Each laboratory establishes a set of normal ranges based on this information. The physician receives a report of the test results with the normal values established by the testing laboratory. Elevated levels indicate the possibility of liver or bone disease, including the presence of a tumor. The test does not distinguish from which tissue the increased amount of alkaline phosphatase comes. The physician may order
Salem Health: Cancer
Alkylating agents in chemotherapy reactive compounds containing alkyl groups. They are employed as antineoplastics, drugs that kill neoplasms (cancerous tumor cells) by interfering with their deoxyribonucleic acid (DNA) and cell division.
other blood tests, including an alkaline phosphatase isoenzyme test that determines if the increased ALP comes from bone, liver, or intestine. Other procedures such as X rays may also be ordered. Following cancer treatment, ALP levels are expected to decrease. If levels remain high or increase, then some cancer may remain or has returned. Wanda E. Clark, M.T. (ASCP)
Cancers treated: Various, especially slow-growing cancers such as solid tumors and leukemias Subclasses of this group: Alkyl sulfonates, ethyleneimines and methylmelamines, nitrogen mustards, nitrosoureas, platinum compounds, triazenes
See also Immunocytochemistry and immunohistochemistry; Paget disease of bone; Placental alkaline phosphatase (PALP).
Delivery routes: These drugs are administered both intravenously and orally in capsule and tablet form, on an inpatient, outpatient, and at-home basis, depending on the specific drug, type of cancer, and its location and aggressiveness. When possible, these drugs are best delivered to the tumor site to limit damage to normal cells.
u Alkylating agents in
chemotherapy Category: Chemotherapy and other drugs ATC code: 101A
How these drugs work: One of the oldest classes of chemotherapeutic drugs, alkylating agents were discovered during World War II when physician Cornelius P. Rhoads drew a connection between the lowered white
Definition: Alkylating neoplastic agents form a class of chemotherapeutic drugs, all of which consist of highly
Common Alkylating Agents Subclass
Delivery Mode
Cancers Treated
Altretamine Hexalen (hexamethylmelamine)
Ethylenimines
Oral
Ovarian cancer
Busulfan
Alkyl sulfonates
Oral, IV
Chronic myelogenous leukemia, other blood cancers
Platinum compounds
IV
Ovarian carcinoma
Drug
Brands
Carboplatin (CBDCA)
Paraplatin
Carmustine (BCNU)
BiCNU, Nitrosoureas Gliadel Wafer
IV
Brain tumors, multiple myeloma, Hodgkin disease, non-Hodgkin lymphoma, malignant melanoma, breast cancer, gastrointestinal cancers, Ewing sarcoma, and Burkitt lymphoma; applied topically for mycosis fungoides
Chlorambucil
Leukeran
Nitrogen mustards
Oral
Chronic lymphocytic leukemia, some non-Hodgkin lymphomas, advanced Hodgkin disease
Cisplatin (CDDP)
Platinol-AQ
Platinum compounds
IV
Metastatic testicular tumors, metastatic ovarian tumors, advanced bladder carcinoma
Cyclophosphamide (CTX)
Cytoxan
Nitrogen mustards
Oral, IV
Lymphomas, multiple myelomas, leukemias, mycosis fungoides, neuroblastoma, ovarian carcinoma, retinoblastoma, breast cancer
Dacarbazine (DTIC)
DTIC-Dome
Triazenes
IV
Melanoma, Hodgkin disease
Ifosfamide (isophosphamide)
Ifex
Nitrogen mustards
IV
Germ cell testicular cancer, sarcomas
(continued on page 46)
45
Alkylating agents in chemotherapy
Salem Health: Cancer Side effects: Although alkylating agents are more toxic to cancer cells than to normal cells, these drugs are nonspecific. That is, they target normal as well as cancerous tissue, so they exhibit the “Janus effect”: They kill both bad and good cells. Therefore they have toxic side effects, depending on the specific drug, its dosage, the duration of administration, and the individual patient’s physical condition and attitude. Common side effects include depressed blood cell counts, tiredness and fatigue, diarrhea, alopecia (hair loss), nausea and vomiting, infertility (both amenorrhea in women and impaired spermatogenesis in men), damage to intestinal mucosa, exfoliation of the bladder epithelium resulting in fluid retention, and in extreme cases cardiotoxicity, which would mitigate the chemotherapy regimen. In addition, some alkylating agents increase the risk of future malignancies, such as acute myeloid leukemia, which may emerge years after treatment. Christina J. Moose, M.A.
blood cell counts in six hundred sailors (who had been exposed to mustard gas during the sinking of the Liberty in 1943) and the possibility that the nitrous mustards could be adopted for use in leukemia patients. It was later observed that alkylating agents substitute alkyl groups for the hydrogen groups in the DNA of tumor cells. The alkyl groups cross-link guanine nucleobases in the double-helix strands of DNA, which makes it impossible for the two DNA strands to uncoil and separate in preparation for replication. As a result, these drugs prevent tumor cells from dividing during mitosis, stopping the cells’ growth. They may also stimulate the natural process of cell death (apoptosis). Because DNA is more actively replicated and transcribed in rapidly dividing cancer cells than in normal cells, these drugs are more toxic to tumor tissue than to normal tissue. Alkylating agents are also known to add methyl or alkyl groups onto any of the four nitrogenous bases found in DNA(adenine, guanine, cytosine, thymine), frequently altering the base-pairing relationships and leading to new mutations.
Common Alkylating Agents (continued)
46
Drug
Brands
Subclass
Delivery Mode
Lomustine (CCNU)
CeeNU
Nitrosoureas
Oral
Brain tumors, Hodgkin disease, bronchogenic carcinoma, non-Hodgkin lymphomas, malignant melanoma, breast cancer, renal cell carcinoma, carcinoma of the GI tract
Mechlorethamine (nitrogen mustard)
Mustargen
Nitrogen mustards
IV
Hodgkin disease, lymphosarcoma, chronic myelocytic or chronic lymphocytic leukemia; polycythemia vera; mycosis fungoides, bronchogenic carcinoma, non-Hodgkin lymphomas, malignant melanoma, breast cancer, renal cell carcinoma, carcinoma of the GI tract; applied topically for mycosis fungoides
Melphalan (L-PAM)
Alkeran
Nitrogen mustards
Oral, IV
Multiple myeloma, ovarian carcinoma
Oxaliplatin (oxalatoplatin, oxalatoplatinum)
Eloxatin, Transplatine
Platinum compounds
IV
Advanced ovarian cancer; may be effective for head and neck cancers, skin cancer, lung cancers, and non-Hodgkin lymphomas
Procarbazine
Matulane, Natulane
Hydrazine derivatives
Oral
Hodgkin disease and other lymphomas, brain tumors, skin cancer, lung cancer, multiple myeloma, mycosis fungoides
Cancers Treated
Streptozocin
Zanosar
Nitrosoureas
IV
Pancreatic islet cell cancer
Temozolomide
Temodar
Triazenes
Oral
Brain tumors (astrocytomas)
Thiotepa
Thioplex
Ethylenimines
IV, spinal injection, bladder infusion
Bladder cancer, ovarian cancer, breast cancer, lymphomas, bronchogenic carcinoma, and metastatic pleural, pericardial, and peritoneal cancers
Salem Health: Cancer
Alopecia
u For Further Information Chabner, Bruce A., and Dan L. Longo, eds. Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2006. Fischer, David S., et al. The Cancer Chemotherapy Handbook. 6th ed. St. Louis: Mosby, 2003. Panasci, Lawrence C., and Moulay A. Alaoui-Jamali, eds. DNA Repair in Cancer Therapy. Totowa, N.J.: Humana Press, 2004. Podolsky, M. Lawrence. Cures out of Chaos. Newark, N.J.: Harwood Academic, 1997. Skeel, Roland T. Handbook of Cancer Chemotherapy. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. u
Other Resources
National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Antineoplastics in chemotherapy; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; 1,4-Butanediol dimethanesulfonate; Carcinogens, known; Carcinogens, reasonably anticipated; Chemotherapy; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Cyclophosphamide; Infertility and cancer; Mustard gas; Sterility; Thiotepa.
u Alopecia Category: Diseases, symptoms, and conditions Also known as: Alopecia disseminata, alopecia universalis, alopecia totalis, baldness, hair loss, acomia, pelade Related conditions: Anagen effluvium, telogen effluvium Definition: Alopecia is abnormal loss of hair, a common side effect of treatments for cancers, including chemotherapy and radiation therapy. There are many types of alopecia, with many causes, including certain skin cancers and other types of cancer that spread to the skin, although marked hair loss from skin cancer is extremely rare. Risk factors: Chemotherapy for any cancer greatly increases the risk of alopecia, and radiation therapy increases the risk of hair loss from the irradiated area. Etiology and the disease process: Each human hair grows from a hair follicle, an elongated pouch formed during fe-
Chemotherapy has caused this woman to lose her hair. (© Lisa F. Young/Dreamstime.com)
tal development by growth of the upper part of the skin, the epidermis, down into the lower part, the dermis. The lower part of the follicle, the hair bulb, contains the germinal matrix, the cells that form the hair. Each hair goes through a three-phase growth cycle: anagen, or active growth; catagen, or regression; and telogen, or resting. When the telogen phase for each hair is complete, a new anagen phase begins. Human hairs complete their recurring growth cycle, as old hairs are pushed out by new hairs, in random order. At any given time, about 85 percent of hairs are in the anagen, or active growth phase. Chemotherapeutic agents target rapidly reproducing cells, like cancer cells. Unfortunately, these agents do not know the difference between a cancer cell and the rapidly reproducing cells of the germinal matrix in a hair bulb. They stop cell division, or mitosis, in matrix cells, just as they do in cancer cells. The anagen phase comes to a stop, and in many cases, all the hair that is in the anagen phase is shed. Hair lost through chemotherapy almost always regrows, because the hair follicle is left intact. Radiation therapy also stops the reproduction of rapidly dividing cells, but in higher doses, 47
Alpha-fetoprotein (AFP) levels radiation can damage the hair follicles it touches, preventing regrowth of hair. Incidence: At least some degree of hair loss is likely with many forms of chemotherapy. Certain drugs or combinations of drugs are virtually certain to cause some degree of hair loss. A few drugs cause nearly complete hair loss. Symptoms: Symptoms of alopecia related to cancer range from temporary thinning or breakage of a small patch of hair to loss of hair all over the body (alopecia disseminata, alopecia universalis, alopecia totalis), and hair loss can be temporary or permanent, depending on the cause. Screening and diagnosis: Diagnosis of chemotherapyrelated alopecia follows visible hair loss within days or weeks of administration of chemotherapeutic drugs. Treatment and therapy: Therapies for alopecia caused by chemotherapy include administration of vitamins, minerals, or omega-3 and omega-6 fatty acids—substances that promote healthy hair. The benefit of these therapies on cancer-related hair loss is still being researched, and consumption of some vitamins and minerals may reduce the effectiveness of chemotherapy, so any treatment for hair loss during therapy should be approved by the treating physician. Treatment for cancer-caused alopecia includes treatment for the underlying cancer, which may include surgery or chemotherapy. Again, noticeable hair loss from cancer itself is extremely rare. Prognosis, prevention, and outcomes: The prognosis for alopecia caused by chemotherapy depends on the chemicals used, the dosage, and the frequency of treatment. More intensive treatment is likely to cause more extensive hair loss. Whatever the amount or type of hair loss from chemotherapy, the prognosis is eventual regrowth of hair. Patchy regrowth may begin before chemotherapy is completed, an average of three to five months after initial hair loss from the first treatment. Because chemotherapy disrupts the matrix from which the hair is formed, including the melanocytes, or cells that give hair its color, regrown hair may differ in color or texture from the original hair. There has been some limited success in preventing scalp hair loss from chemotherapy through use of scalp cooling or a hairline tourniquet during administration of the chemotherapy. These, however, have been successful with only certain chemical agents. Their use has been questioned by some oncologists because, while they protect scalp follicles from damage, they also protect any cancer cells present in the scalp. Research trials are being conducted on other treatments that may reduce hair loss from chemotherapy. The prognosis for alopecia caused by radi48
Salem Health: Cancer ation therapy depends on the dosage of radiation. High doses usually cause permanent hair loss to the irradiated area; low doses more often cause temporary, local hair loss. Cathy Anderson, R.N., B.A. u
For Further Information Bleiker, T. O., N. Nicolaou, J. Traulsen, and P. E. Hutchinson. “‘Atrophic Telogen Effluvium’ from Cytotoxic Drugs and a Randomized Controlled Trial to Investigate the Possible Protective Effect of Pretreatment with a Topical Vitamin D3 Analogue in Humans.” British Journal of Dermatology 153, no. 1 (2005): 103-112. Jothilakshmi, P. K., A. J. Watson, and E. Jude. “Acute Alopecia Due to Metformin Treatment for Polycystic Ovarian Syndrome.” Journal of Obstetrics and Gynaecology 26, no. 6 (2006): 584-585. Wang, J., Z. Lu, and J. L. Au. “Protection Against Chemotherapy-Induced Alopecia.” Pharmaceutical Research 23, no. 11 (2006): 2505-2514. Wyatt, A. J., G. D. Leonard, and D. L. Sachs. “Cutaneous Reactions to Chemotherapy and Their Management.” American Journal of Clinical Dermatology 7, no. 1 (2006): 45-63.
u
Other Resources
Chemotherapy.com http://www.chemotherapy.com Healthline http://www.healthline.com WebMD http://www.webmd.com See also Alkylating agents in chemotherapy; Chemotherapy; Cyclophosphamide; Paraneoplastic syndromes; Radiation therapies; Self-image and body image; Side effects.
u Alpha-fetoprotein (AFP) levels Category: Procedures Also known as: Total AFP, AFP-13 percent, alphafetoglobulin, αFP, AFP tumor marker Definition: Alpha fetoprotein (AFP) is a protein produced by fetal tissue and by tumors. There are several forms of AFP. The test for AFP generally measures total AFP. The test is performed on serum or plasma on an automated chemistry analyzer.
Salem Health: Cancer Cancers diagnosed: Cancers of the liver, testes, and ovaries Why performed: The AFP test is done to detect and monitor cancers of the liver, testes, and ovaries. Physicians may order the test for patients with chronic liver disease because of the high risk of developing liver cancer. Because AFP is also produced by a fetus, AFP levels are generally higher in pregnant women. A test for AFP done on pregnant women is not done to detect a tumor but is used with other data to detect possible abnormalities in the developing fetus. Patient preparation: No special preparation is necessary. Steps of the procedure: A small sample of blood is collected from a vein and placed in a tube. In children, blood may be obtained from a capillary in the heel or finger. After the procedure: A small gauze or cotton ball is applied at the site of needle insertion. The patient is asked to apply pressure. The person collecting the blood observes the site for bleeding and may apply a bandage. The bandage may usually be removed in thirty to sixty minutes. Risks: Risks include bleeding, bruising, hematoma (bleeding under the skin), fainting, light-headedness, or the need for multiple needle sticks to obtain a sample. Results: Normal AFP levels vary by the patient’s sex and age and by the analyzer used. Each laboratory establishes normal ranges based on this information. The physician receives a report of the test results with the normal values established by the testing laboratory. AFP decreases at birth, and adult levels are normally low. Elevated levels are present in liver cancer and in some cancers of the testes and ovaries. Generally, higher levels of AFP indicate a larger tumor. The test is not considered specific for diagnosis, but it is an indicator that a tumor may be present. Physicians may order imaging studies and additional laboratory tests to determine the presence of a tumor. Some physicians order a test called AFP-13 percent, as 13 is one of the forms of AFP that make up the total. An increased percentage of AFP-13 to total AFP indicates an increased risk of developing liver cancer or a poorer prognosis. AFP levels usually return to normal within a month of treatment. Wanda E. Clark, M.T. (ASCP) See also Ataxia telangiectasia (AT); Beckwith-Wiedemann syndrome (BWS); Germ-cell tumors; Pathology; Placental alkaline phosphatase (PALP); Proteomics and cancer research; Testicular cancer; Yolk sac carcinomas.
Alveolar soft-part sarcomas
u Alveolar soft-part sarcomas Category: Diseases, symptoms, and conditions Also known as: Nonrhabdomyosarcoma soft-tissue sarcomas, ASPS Related conditions: Soft-tissue sarcomas Definition: Alveolar soft-part sarcoma is a slow-growing, malignant tumor that develops in deep soft tissues and muscles, most often in the thighs and buttocks. It is also found in the arm, chest, bladder, abdomen, and—in children—the head and neck. It gets its name from the way the tumor cells are clustered, resembling alveoli, or the air sacs of the lungs. Risk factors: No risk factors are known, and alveolar softpart sarcoma is nonhereditary. Etiology and the disease process: The disease’s etiology is murky. Early development of alveolar soft-part sarcoma appears to be linked to a genetic mutation involving the separation of a gene from chromosome 17 and its attachment to the X chromosome. A wealth of blood vessels allows tumor cells to enter the bloodstream and spread to other areas, usually the lungs and brain. Childhood alveolar soft-part sarcoma appears to have a different, and generally less aggressive, biology. Incidence: Alveolar soft-part sarcoma is rare, with 40 to 80 new cases annually in the United States. About half of alveolar soft-part sarcoma patients are between the ages of fifteen and twenty-nine, and women generally outnumber men, especially among younger patients. Symptoms: Common symptoms include a soft, painless lump, soreness, reduced range of motion, and numbness. Because alveolar soft-part sarcoma grows slowly in deep, elastic tissues, patients often do not notice symptoms until the cancer is advanced or has spread. Screening and staging: Diagnostic procedures include laboratory tests and imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and bone scans. A biopsy is required, however, to confirm alveolar soft-part sarcoma. Tumors are staged based on size, grade, and degree of spread: • Stage I: Low grade, with little potential for spreading • Stages II and III: High grade, with increased potential for spreading • Stage IV: Metastasis to distant organs Other criteria are typically used for staging pediatric alveolar soft-part sarcoma. 49
Amenorrhea Treatment and therapy: Surgical removal of the tumor and surrounding tissue is the primary treatment. Radiation therapy may be used before to shrink the tumor and after to kill any remaining cells, although it is used in children only if surgery alone is ineffective. Chemotherapy is not generally beneficial. Other therapies are under study. Prognosis, prevention, and outcomes: The five-year survival rate for patients with localized tumors is around 80 percent. If the disease has metastasized, the rate drops to 20 percent. However, long-term survival is possible even with spread because alveolar soft-part sarcoma grows slowly. The prognosis for children is considerably better, as their tumors are generally smaller and localized. Alveolar soft-part sarcoma can recur more than ten years after initial diagnosis, so long-term follow-up is recommended. Judy Majewski, M.S. See also Dermatofibrosarcoma protuberans; Ewing sarcoma; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Liposarcomas; Mesenchymomas, malignant; Rhabdomyosarcomas; Sarcomas, soft-tissue; Synovial sarcomas.
u Amenorrhea Category: Diseases, symptoms, and conditions Also known as: Primary amenorrhea, secondary amenorrhea, absent periods, absent menses, absent menarche Related conditions: Pregnancy, menopause, pituitary or gynecologic tumors Definition: Amenorrhea is the absence of menstruation, whether temporary or permanent. Amenorrhea is normal prior to puberty, during pregnancy and lactation, and after menopause. Amenorrhea may also occur as the symptom of a variety of abnormal conditions, including pituitary or gynecologic tumors, and is an expected result of many chemotherapeutic cancer drugs. Primary amenorrhea is the absence of menarche, the initial menstrual period, in women age sixteen and older. Menarche occurs normally in women between the eleventh and seventeenth year. The average age of menarche in the United States is 12.8 years. Secondary amenorrhea is absence of menses for three months in a woman with previously normal menstruation and for nine months in a woman with oligomenorrhea, which is infrequent periods and fewer than the normal eleven to thirteen a year. 50
Salem Health: Cancer Risk factors: Both primary and secondary amenorrhea can be influenced by a host of other factors, some of which include immunodeficiency, anorexia nervosa, congenital abnormalities of the reproductive tract, obesity, diabetes, dietary restriction, starvation, metabolic disorders, drugs, and excessive physical exercise. Amenorrhea can also signal a pituitary or a gynecologic tumor, and it is a common and even expected result of chemotherapy or radiation treatment for cancer. Etiology and the disease process: Amenorrhea is often due to the absence or change in hormones produced in the hypothalamus, the pituitary gland, or the ovaries (the triad that directs reproduction), and it can result from an abnormality in the outflow tract. In primary amenorrhea, in the presence of secondary sex characteristics and a uterus, the most common cause is outflow tract obstruction with a transverse vaginal septum or imperforate hymen, both easily correctable. However, primary amenorrhea can also have a genetic cause. The most common cause of secondary amenorrhea is pregnancy during a woman’s reproductive years. Secondary amenorrhea may also be related to lifestyle choices. Athletes and ballet dancers who train vigorously often experience missed periods. Stress, obesity, and starvation can also result in secondary amenorrhea. In these cases, women stop menstruating because the ovaries do not produce enough estrogen in a cyclic manner to cause the uterine lining to thicken and shed normally. If pregnancy is not the cause, the physician may test the patient’s levels of hormones produced by the thyroid and the pituitary glands. When amenorrhea is accompanied by elevated levels of prolactin, galactorrhea, headaches, or visual disturbances, a pituitary tumor may be the cause. Adenomas are the most common cause of anterior pituitary dysfunction. Gynecological tumors such as ovarian cancer must also be ruled out in the presence of amenorrhea. Cancer treatments such chemotherapy and radiation are often associated with amenorrhea. The greater the dose of the chemotherapeutic agent, the greater the chance of amenorrhea. Studies linking particular cancer treatments to the incidence of amenorrhea remain incomplete, but two drugs particularly linked to amenorrhea are doxorubicin and cyclophosphamide. Incidence: In the United States, the incidence of primary amenorrhea is 2.5 percent. The incidence of secondary amenorrhea is between 1 and 4 percent. Rarely, the cause of amenorrhea is a tumor of the pituitary. The true incidence of pituitary adenomas is difficult
Salem Health: Cancer to know with certainty because they are often asymptomatic; autopsy estimates range from 2.7 to 27 percent. Symptoms: The first sign of primary amenorrhea is the absence of menses. If the cause of absence of flow is an anomaly of the outflow tract of the blood, the patient may experience cramping and severe abdominal pain. In the case of secondary amenorrhea, other that the absence of menstruation, symptoms may include: • galactorrhea, in which case the breasts produce milk in a woman who is not pregnant or breastfeeding • headache or reduced peripheral vision as a potential sign of an intracranial tumor • hirsutism, or increased hair growth in a male pattern caused by excess androgen • vaginal dryness, hot flashes, night sweats, or disordered sleep, suggesting ovarian insufficiency or premature ovarian failure (premature menopause) • excessive weight gain or loss • anxiety Screening and diagnosis: With primary amenorrhea and the absence of secondary sex characteristics, the physician may order an ultrasound to determine if a uterus is present and measure the levels of two hormones produced by the anterior pituitary: the follicle stimulating hormone (FSH), which stimulates growth of the follicle in the ovary, and luteinizing hormone (LH), which triggers ovulation. Very low levels suggest that the gonads, or sex glands, have failed to develop or begin functioning. Karyotyping to study the chromosome arrangement may reveal a genetic reason for the absence of menarche. An example is Turner syndrome, which is a congenital endocrine disorder caused by failure of the ovaries to respond to pituitary hormone stimulation. In addition to primary amenorrhea and failure of sexual maturation, the physical examination may note short stature. About onethird of the patients show webbing of the neck, marled cubitus valgus (a deformity of the arm in which the forearm deviates laterally), and developmental disabilities. Often genetic studies reveal the presence of only 45 chromosomes, the second X chromosome being absent. Treatment and therapy: A thorough medical history often reveals the cause of amenorrhea, which can then be corrected by surgery, medication, or lifestyle changes. Secondary amenorrhea may be caused by some medications such as phenothiazines, some narcotics, and any condition related to pituitary insufficiency or thyroid dysfunction. For cases due to lifestyle choices, reducing the amount or intensity of exercise and maintaining a healthy
Amenorrhea weight should correct hormone levels and result in a return to regular periods. If is determined to be a symptom of a pituitary or gyencologic tumor, the patient will undergo tests for malignancy and follow-up treatment and therapy indicated for the particular cancer diagnosed. Prognosis, prevention, and outcomes: Most cases of amenorrhea are treatable, although some resulting from genetic conditions cannot be corrected. In women with low thyroid-stimulating hormone (TSH), or hypothyroidism, which is more often associated with hypermenorrhea or oligomenorrhea, the menstrual cycle is often returned to normal following hormone replacement therapy. If a pituitary tumor is causing the amenorrhea, these tumors are rare and often asymptomatic, seldom resulting in death. They are typically slow growing and benign. However, the numerous hormones produced in the pituitary orchestrate many bodily functions, so patients with these tumors may face a lifetime of hormone replacement and long-term follow-up care. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) u
For Further Information Bell, Ruth, et al. Changing Bodies, Changing Lives: A Book for Teens on Sex and Relationships. 3d ed. New York: Times Books, 1998. Hobart, Julie A., and Douglas R. Smucker. “The Female Athlete Triad.” American Family Physician 61, no. 11 (June 1, 2000). Master-Hunter, Tarannum, and Diana L. Heiman. “Amenorrhea: Evaluation and Treatment. ” American Family Physician 73, no. 8 (April 15, 2006). Slap, Gail B. “Amenorrhea.” In The Gale Encyclopedia of Childhood and Adolescence, edited by Jerome Kagan. Detroit: Gale, 1998.
u
Other Resources
American College of Obstetricians and Gynecologists http://www.acog.org American Society for Reproductive Medicine http://www.asrm.org See also Alkylating agents in chemotherapy; Chemotherapy; Endometrial cancer; Infertility and cancer; Neuroendocrine tumors; Ovarian cysts; Sterility. 51
American Association for Cancer Research (AACR)
u American Association for
Cancer Research (AACR) Category: Organizations Definition: Founded in 1907, the American Association for Cancer Research (AACR) is a nongovernmental organization of physicians, scientists, and advocates seeking to overcome the burden of cancer through research and dissemination of information. With more than 24,000 members in more than sixty countries, it is one of the largest organizations of its kind. Funding research: The AACR does not conduct cancer research itself but instead acts as a base of financial support for researchers. There are two basic types of support provided by the organization: direct research funding and scholarly or travel grants. As of 2007, the annual budget of the AACR was approximately $3.65 million. Approximately 69 percent of that went to funding research, while 15 percent went to education programs, and the remaining 16 percent was required for operational expenses. The AACR has provided more than $16 million dollars in research funding since 1993. The AACR provides three major grants that directly fund cancer research. The Jeannik M. Littlefield-AACR Grants in Metastatic Colon Cancer Research provide awards ranging from $500,000 to $1 million; four of these grants were given in 2007. The BCRF-AACR Grants for Translational Breast Cancer Research provide awards up to $250,000; three of these grants were given in 2007. The Avon Foundation-AACR International Scholar Awards in Breast Cancer Research provide up to $100,000; twelve of these grants were awarded in 2007. The AACR also has four other grants that range from $30,000 to $50,000. All of these awards pay for expenses such as laboratory equipment, materials, salaries, and limited travel. The other type of grant that the AACR provides helps students and scientists attend the many workshops and conferences offered by the AACR and other cancer research organizations. These types of grants may cover travel expenses, housing, and registration fees. Without such grants, many researchers, especially those who are younger or are just beginning to build a reputation in the field, would not be able to attend these collaborative events. Publications: Because dissemination of information is of vital importance, both to researchers seeking to make scientific progress and to the doctors and patients seeking treatment options, the AACR publishes five journals and one magazine. Each of these journals is peer-reviewed, 52
Salem Health: Cancer and together they contain approximately 23,000 pages each year. The AACR’s earliest journal, Cancer Research, was first published in January of 1949. It is the most highly quoted cancer journal worldwide. It accepts work from all areas of cancer research and is published bimonthly. Clinical Cancer Research focuses specifically on innovative clinical research, especially that which bridges the gap between laboratory research and clinical application. It began in January of 1995 and is also published on a bimonthly basis. Cancer Epidemiology, Biomarkers and Prevention was first published in November of 1991 and is published monthly. The journal focuses on the causes of cancer and cancer prevention. The AACR’s newest journals, Molecular Cancer Therapeutics and Molecular Cancer Research, were first published in 2001 and 2002, respectively. These journals focus on cancer research developments in molecular biology and are published on a monthly basis. CR magazine, which stands for “collaborations, results,” is intended not only for research scientists and physicians but also for people who have cancer, survivors of cancer, and anyone who is affected by the disease. The AACR hopes to help create community and camaraderie among people affected by cancer, providing the emotional support that many patients and family members need. The editorial board for the magazine is made up of cancer research scientists, cancer advocates, and cancer survivors. It began publication in the spring of 2006 and is published quarterly. CR magazine also provides podcasts of cancer news stories on its Web site. Events: To facilitate communication among scientists, the AACR holds numerous workshops, meetings, and conferences. The Annual Meeting of the AACR is the largest annual meeting in the field and is regarded by many cancer researchers as the most important. In 2007, it hosted more than 16,000 cancer scientists at the Los Angeles Convention Center. For five days, these scientists attended forty-six symposia, twenty forums, sixty-nine sessions, and more than forty minisymposia. Almost six thousand abstracts were presented at the seven poster sessions. The AACR publishes the proceedings of its annual meeting and also makes them available on its Web site, along with audio recordings and Webcasts from the event. In addition to the annual meeting, the AACR holds several large conferences and around a dozen smaller conferences. The larger conferences usually have between 500 and 3,000 attendees and focus on such topics as racial and ethnic disparities in cancer, molecular diagnostics, and cancer prevention. Smaller conferences usually attract be-
Salem Health: Cancer tween 150 and 400 people, and the topics tend to cover a great variety of special subjects, such as oncogenomics or proteomics in cancer research. The AACR also aids younger cancer researchers by organizing educational workshops throughout the year. These workshops are designed to provide opportunities for young investigators to develop essential research skills. Robert Bockstiegel, B.S. u For Further Information Jeffries, Lee P., ed. Leading Topics in Cancer Research. New York: Nova Science, 2007. Martakis, Ignatius K., ed. Cancer Research at the Leading Edge. New York: Nova Science, 2007. Pereira, Larissa S., ed. Cancer Research Perspectives. New York: Nova Science, 2008. u
Other Resources
American Association for Cancer Research http://www.aacr.org American Society of Clinical Oncology http://www.asco.org Association of American Cancer Institutes http://www.aaci-cancer.org See also American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u American Cancer Society
(ACS) Category: Organizations Also known as: American Society for the Control of Cancer Definition: The American Cancer Society (ACS) is an organization that provides cancer information, aids cancer patients, and collects and contributes funds for cancer research. History: Several New York City physicians established the American Society for the Control of Cancer (ASCC),
American Cancer Society (ACS) the ACS’s predecessor, in 1913. At that time, approximately 75,000 people in the United States died of cancer each year. ASCC leaders strove to educate people, including medical professionals, regarding cancerous conditions and treatments. The ASCC published articles in both mainstream and professional periodicals. During the mid-1930’s, ASCC Women’s Field Army volunteers distributed cancer information directly to people and collected funds for the organization’s work. By 1938, approximately 150,000 people were affiliated with the ASCC. After World War II, the renamed American Cancer Society (ACS) embraced research to control cancer. The ACS introduced its list of seven cancer warnings in 1947. Services and procedures performed: The ACS emphasizes cancer prevention, mitigating physical and emotional pain, and survival. The society strives to decrease cancer occurrence and death rates. ACS funds from donors advance cancer research, create educational material, staff the National Cancer Information Center, provide such support services as housing near cancer centers for patients and people accompanying them, and publicize issues relevant to cancer control. The ACS Web site posts cancer information, and the organization distributes printed and visual media to individuals and health centers. The ACS’s Cancer Survivor Network enables people affected by cancer to communicate. The ACS seeks donors, ranging from individuals to corporations. Fund-raisers include the ACS’s Relay for Life. A board of directors oversees national ACS activities, including distribution of fellowships and grants. Divisions and local units also conduct ACS work. By 2006, about three million volunteers, representing both medical professionals and people from other walks of life, participated in providing ACS services. Research: The ACS invests the most private funds for oncology investigations in the United States. ACS leaders support innovative research seeking to identify causes of cancer and to improve prevention and treatment methods. By the early twenty-first century, the ACS had invested $3 billion for researchers to pursue investigations. As of 2007, the ACS awarded peer-evaluated projects $130 million yearly. ACS-supported achievements created better screening techniques such as the prostate-specific antigen (PSA) test. The ACS funded research evaluating the use of Pap smears to detect cervical cancer and mammograms to detect breast cancer. Treatment methods also benefited from ACS financial support. Funded by the ACS, Sidney Farber studied the use of aminopterin to accomplish remission of 53
American Institute for Cancer Research (AICR) cancer, enabling chemotherapy to become a viable method to treat many cancers. ACS-supported researchers focusing on pediatric oncology developed more effective methods to combat leukemia in children. Investigators used ACS research money to study genes associated with cancer. An ACS-financed study linked cigarettes and cancer. ACS research funds contributed to creation of anticancer pharmaceuticals. Education: The ACS creates and distributes educational information to enhance people’s awareness of cancer issues. The society stresses preventing cancers by embracing healthy behaviors. The ACS urges people to seek cancer screening to detect cancers and seek treatment expeditiously to aid survival. The society’s information is incorporated in health lessons taught in many U.S. schools. ACS advertisements in various media promote colorectal and breast cancer screening and stopping smoking. The ACS publishes three journals for medical professionals, educational guides devoted to specific cancers, and books for patients’ children and caregivers. The society’s cookbook has appeared in several editions as new information regarding nutritional aspects of cancer prevention is determined. The ACS distributes Cure: Cancer Updates, Research & Education. The society supports workshops and conferences where medical professionals learn about current oncology information and methods. Advocacy: In 2007, the ACS devoted $15 million to advertisements for print and television commercials stressing how lack of insurance affects cancer detection and treatment. The ACS allied with other health groups and the American Association of Retired Persons (AARP) to promote better health care access. The nonpartisan Cancer Action Network (CAN) complements the ACS, conducting lobbying, which the ACS cannot pursue. CAN’s political work includes securing nonsmoking areas, preparing voter guides, and sponsoring a hotline to contact politicians. Elizabeth D. Schafer, Ph.D. u For Further Information American Cancer Society. The American Cancer Society’s Healthy Eating Cookbook: A Celebration of Food, Friends, and Healthy Living. 3d ed. Atlanta: American Cancer Society, 2005. Herdman, Roger, and Leonard Lichtenfeld, eds. Fulfilling the Potential of Cancer Prevention and Early Detection: An American Cancer Society and Institute of Medicine Symposium. Washington, D.C.: National Academies Press, 2004.
54
Salem Health: Cancer Ross, Walter S. Crusade: The Official History of the American Cancer Society. New York: Arbor House, 1987. Stein, Kevin, et al. “The American Cancer Society’s Studies of Cancer Survivors.” American Journal of Nursing 106, no. 3 (March, 2006): 83-85. u
Other Resources
American Cancer Society http://www.cancer.org American Cancer Society Cancer Action Network http://www.acscan.org Cure: Cancer Updates, Research, and Education http://www.curetoday.com See also American Association for Cancer Research (AACR); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u American Institute for Cancer
Research (AICR) Category: Organizations Definition: The American Institute for Cancer Research (AICR) is a private charity that sponsors research into the relationship between diet and cancer and works to disseminate findings about that relationship. History: Before the 1980’s, most cancer research was focused on diagnosis and treatment of the disease. Many scientists believed that cancer operated like a virus that affected cell metabolism, and they focused on early intervention and chemotherapy as their main strategies. The AICR was established in 1982 around the principle that cancer is preventable and that the disease is not random but is affected by lifestyle choices. At the time of its founding, this principle was not widely accepted. Later that same year however, the National Academy of Sciences published a report entitled Diet, Nutrition, and Cancer, and this document became the initial basis for the AICR’s cancer education program. In 1997, the AICR collaborated with the World Cancer
Salem Health: Cancer
American Institute for Cancer Research (AICR)
Research Fund (WCRF), based in the United Kingdom, to publish a 670-page report called Food, Nutrition, and the Prevention of Cancer: A Global Perspective. The report was the work of sixteen scientists from eight countries, who spent three years reviewing studies on diet and cancer. It was developed with participation from experts at the National Cancer Institute and the World Health Organization and was peer-reviewed. The report indicated that between 30 and 40 percent of all cancers could be directly linked to lifestyle choices such as food, drink, exercise, and overall health. The AICR produced more than 30,000 copies of the report and freely distributed it to cancer researchers and politicians. In 1999 the AICR published Stopping Cancer Before It Starts, a book that brought the message of the report to the public. The AICR began to expand more rapidly after the publication of these works. Private donations, the primary source of funding for the organization, increased both in number and size. As of 2007, more than 12 million Americans had made a donation to the organization, which had a total annual revenue exceeding $38 million and had contributed more than $82 million to research projects.
AICR Recommendations for Cancer Prevention
Educating the public: Spreading the message that people can lower their risk of cancer is a major part of the AICR’s program. In 2006, approximately $20 million, over 50 percent of the organization’s annual budget, went to educational activities. One of the ways the AICR fulfills its mission is through a free quarterly newsletter, which the AICR sends to more than 1.5 million homes. The newsletter provides meal-planning suggestions, recipes, and basic nutritional health information. The organization also produces more than seventy brochures, covering a wide array of topics within the subject of nutrition and cancer. Its latest series, The New American Plate, encourages people to fill two-thirds of their plate with fruits, vegetables, and grains, and keep protein to one-third or less. The AICR has also produced public service announcements, which have been carried by hundreds of television stations across the United States. Newspapers and magazines have also been a resource for the AICR. The organization also maintains a Web site and a national nutrition hotline to provide more in-depth information about ways that people can reduce their risk of cancer. The institute also hosts educational seminars and an annual conference. These educational seminars are offered free of charge and presented by registered dieticians. As of 2007, more than 41,000 people had attended a seminar, and they had been offered in more than 133 cities. The AICR annual research conference is becoming a major event in the field of cancer research, as the 2005 con-
• • • •
Eat mostly plant-based foods, limit consumption of red meat (beef, pork, and lamb), and avoid processed meats. Engage in physical activity every day for at least thirty minutes. Maintain a healthy weight throughout life, preferably as lean as possible without being underweight. Do not smoke or chew tobacco.
ference hosted more than four hundred participants and speakers from twenty-five universities and research facilities. Research grants: The AICR works to contribute funding to scientists in the field of cancer research who focus on the connection between cancer and diet. Approximately 14 percent of the annual budget goes to funding proposed research. To decide which proposals to fund, the institute follows a set of grant review process standards, established by the National Cancer Institute. Proposals are reviewed by a panel of experts on the basis of scientific merit. Final decisions about funding are made by the AICR Board of Directors. The AICR Investigator Initiated Grants Program awards up to $75,000 per year for up to two years to be used for research into either diet and cancer or physical activity and cancer. The AICR Post Doctoral Awards Program is intended for less established researchers and provides up to $38,000 per year for up to two years. The AICR also provides matching funds grants. The institute also supports the Marilyn Gentry Fellowship Program at the University of North Carolina at Chapel Hill School for Public Health, department of nutrition. The fellowship is named after AICR president Marilyn Gentry and is intended to support researchers as they transition from postdoctoral work into assistant professorships. Robert Bockstiegel, B.S. u
For Further Information American Institute for Cancer Research. Diet and Health Recommendations for Cancer Prevention: Healthy Living and Lower Cancer Risk. Washington, D.C.: Author, 2006. _______. The New American Plate Cookbook: Recipes for a Healthy Weight and a Healthy Life. Berkeley: University of California Press, 2005. 55
4-Aminobiphenyl Weldon, Glen, ed. Dietary Options for Cancer Survivors: A Guide to Research on Foods, Food Substances, Herbals, and Dietary Regimens That May Influence Cancer. Washington, D.C.: American Institute for Cancer Research, 2002. u
Other Resources
American Institute for Cancer Research http://www.aicr.org American Society of Clinical Oncology Http://www.asco.org Association of American Cancer Institutes http://www.aaci-cancer.org See also American Association for Cancer Research (AACR); American Cancer Society (ACS); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u 4-Aminobiphenyl Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: 4-Biphenylamine, p-aminobiphenyl, para-aminobiphenyl, p-aminodiphenyl Related cancers: Bladder cancer, liver cancer Definition: 4-Aminobiphenyl, an aromatic amine, occurs as a colorless to yellowish brown crystalline solid that turns purple in air and has an floral odor. Exposure routes: When heated, 4-aminobiphenyl emits toxic fumes. For the general public, exposure to 4-aminobiphenyl comes from inhalation of tobacco smoke. Occupational exposure occurs from inhalation by laboratory personnel who are doing research with 4-aminobiphenyl. When most of the 4-aminobiphenyl was disposed of by injection into underground wells in the late 1980’s, small amounts of it were released into the air, subjecting some individuals to possible contamination. Where found: 4-Aminobiphenyl is a by-product of tobacco smoke and is found as a contaminant in diphenylamine. Its use is confined to laboratory research, although 56
Salem Health: Cancer it may still be found in some dyes, particularly in cosmetics and drugs that contain yellow dye number 1 and in rubber compounds that were manufactured before the mid1950’s. At risk: Scientists and laboratory technicians who work where 4-aminobiphenyl is used in research as a chemical antioxidant have a high risk for 4-aminobiphenyl contamination. Because 4-aminobiphenyl is generated in tobacco smoke, people who smoke are at high risk for contamination. The general public is at risk for contamination from secondhand tobacco smoke. Etiology and symptoms of associated cancers: Inhalation of 4-aminobiphenyl can produce headaches, lethargy, urinary burning, and blood in the urine (hematuria). When metabolized, it can be activated by liver enzymes to form adducts with blood serum proteins, particularly hemoglobin and albumin. Hemoglobin adducts are associated with an increased risk for liver cancer. In some cases, 4-aminobiphenyl can undergo additional metabolism to form reactive compounds that are transported to the bladder, where they bind to deoxyribonucleic acid (DNA) molecules. In laboratory tests on cultured human cells, 4-aminobiphenyl caused genetic damage that included cell transformation and inhibition of DNA repair. 4-aminobiphenyl can cross the human placenta and has been detected in fetal blood. History: 4-Aminobiphenyl was commercially produced in the United States from the early 1930’s until the mid1950’s. It was used in the detection of sulfates, in the production of azo dyes and yellow-dye stuffs, and as an antioxidant in the production of rubber. There are still a few companies in the United States that manufacture 4-aminobiphenyl for use in laboratory research. Alvin K. Benson, Ph.D. See also Bladder cancer; Cigarettes and cigars; Diethanolamine (DEA); Liver cancers; Tobacco-related cancers.
u Amputation Category: Procedures Definition: Surgical removal of all or part of a limb as a result of peripheral vascular disease, trauma, tumor, infection, or congenital anomaly. Cancers treated: Soft-issue neoplasias (malignant fibrous histiocytoma, fibrosarcoma, rhabdomyosarcoma, synovial sarcoma); bone malignancies (osteosarcoma, chondrosarcoma, adamantinoma, Ewing sarcoma)
Salem Health: Cancer
Amputation
Why performed: Amputations are performed to remove extremities that are severely diseased, injured, or no longer functional. Amputation has five goals: removal of all diseased tissue; relief of pain; proper wound healing; prevention of metastatic spread of tumor cells; and construction of a stump that will permit useful function. Amputation as a musculoskeletal procedure is often accomplished as an alternative to limb salvage and should be considered a reconstructive maneuver. Because of the psychological implications and the alteration of body self-image with amputation, a multidisciplinary team approach should be taken to return the patient to a maximum level of independent function. The process should be considered the first step in the rehabilitation of the patient rather than a failure of treatment. Epidemiologic data on the incidence of amputation in the United States from 1993 to 2003 show that the number of lower-extremity amputations increased 14 percent, from 99,522 to 123,379 cases. Average hospital charge for this procedure increased 40 percent, from $24,332 to $34,046. Nearly two-thirds of amputations are performed in individuals with diabetes, even though these individuals represent only 6 percent of the entire population. Patient preparation: Amputation and subsequent healing depend on several factors, including vascular inflow, nutrition, and an adequate immune system. Prior to surgery, patients should be evaluated regarding these parameters. Patients with malnutrition or immune deficiency have a high rate of wound breakdown or infection. A serum albumin level below 3.5 grams per deciliter (g/dl) indicates a malnourished patient. An absolute lymphocyte count below 1,500 cubic millimeters is a sign of immune deficiency. If possible, amputation should be delayed in patients until these values can be improved by nutritional support. In severely affected patients, nasogastric or percutaneous gastric feeding tubes are necessary. Oxygenated blood is a prerequisite for wound healing. A hemoglobin level of more than 10 g/dl is required. Doppler ultrasonography has been used to measure vascular inflow and to predict the success of wound healing. An absolute Doppler pressure of 70 millimeters of mercury (mm Hg) and an ischemic index of 0.5 or greater are necessary at the surgical site. The transcutaneous partial pressure of oxygen (Tcp02) is now regarded as the gold standard in the measurement of vascular inflow. Values greater than 40 mm Hg correlate with acceptable healing rates. Steps of the procedure: With regard to tumor stage and desired functional outcome, there are a variety of surgical procedures pertaining to upper-limb, lower-extremity, or
Treatment of some cancers involves amputation, which requires the patient to learn new living skills. (Digital Stock)
axial skeletal amputation. Patients with musculoskeletal neoplasms face new choices in treatment with the development of limb salvage techniques and adjuvant chemotherapy and radiation therapy. If an amputation is chosen, then the incision must be planned carefully to achieve the appropriate surgical margin. These surgical margins are characterized by the relationship of the surgical incision to the lesion, to the inflammatory zone surrounding the lesion, and to the anatomic compartment in which the lesion is located. The four types of surgical margins include the following: • intralesional: the surgical incision enters the lesion • marginal: the surgical incision enters the inflammatory zone but not the lesion • wide margin: the incision enters the same anatomic compartment of the lesion but is outside the inflammatory zone • radical: the incision remains outside the anatomic compartment 57
Amyloidosis After the procedure: A variety of wound care methods are used after amputation, including rigid dressings, soft dressings, controlled environment chambers, air splints, and skin traction. The use of an immediate postoperative prosthesis (IPOP) has been shown to be effective in decreasing the time to limb maturation and definitive prosthetic fitting. Rehabilitation and prosthetic fitting remain the primary postoperative goals. Risks: The amputee is at risk for deep vein thrombosis (15 percent) and pulmonary embolism (2 percent). Prolonged postoperative immobilization, stagnation of blood due to ligation of large veins, delayed prosthetic fitting, and inactivity increase the overall risk of thromboembolism (clot). Approximately 80 to 90 percent of amputees experience some episodes of phantom limb pain, which are often severe but infrequent. Other major complications include failure of wound healing, infection, postoperative edema, joint contractures, and dermatological problems such as skin irritation as a result of improper prosthetic fit, breakdown over stump margins, and episodes of contact dermatitis. Results: There is an ongoing controversy when comparing limb salvage to amputation with regard to energy expenditure to ambulate, quality-of-life measures, and the performance of activities of daily living. Studies suggest that functional outcomes are comparable with either limb salvage or amputation. Overall survival remains comparable with either treatment. With some tumors, amputation may achieve better local disease control. Both treatment groups report qualityof-life problems involving employment, health insurance, social isolation, and poor self-esteem. John L. Zeller, M.D., Ph.D. u
For Further Information Bone, M., P. Critchley, and D. Buggy. “Gabapentin in Postamputation Phantom Limb Pain: A Randomized, Double-Blind Placebo-Controlled, Cross-Over Study.” Regional Anesthesia and Pain Medicine 27, no. 5 (2002): 481. Doherty, Gerard M., and Lawrence W. Way, eds. Current Surgical Diagnosis and Treatment. 12th ed. New York: Lange Medical Books/McGraw-Hill, 2006. Menendez, L. R., ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, Ill.: American Academy of Orthopedic Surgeons, 2002. Peabody, T. D., et al. “Evaluation and Staging of Musculoskeletal Neoplasms.” The Journal of Bone and Joint Surgery: American Volume 80, no. 8 (1998): 1204. Skinner, Harry B., ed. Current Diagnosis and Treatment 58
Salem Health: Cancer in Orthopedics. 4th ed. New York: Lange Medical Books/McGraw-Hill, 2006. u
Other Resources
American Academy of Orthopedic Surgeons http://www.aaos.org American College of Surgeons http://www.acs.org See also Bone cancers; Fibrosarcomas, soft-tissue; Hyperthermic perfusion; Juvenile polyposis syndrome; Limb salvage; Liposarcomas; Lymphangiosarcomas; Mastectomy; Neuroectodermal tumors; Occupational therapy; Orthopedic surgery; Sarcomas, soft-tissue; Surgical oncology; Synovial sarcomas; Veterinary oncology.
u Amyloidosis Category: Diseases, symptoms, and conditions Also known as: AL amyloidosis, immunoglobulin lightchain amyloidosis, primary amyloidosis Related conditions: Multiple myeloma Definition: Amyloidoses are a class of illnesses in which fibrillar protein deposits form throughout the body. Immunoglobulin-related (AL) amyloidosis, a disorder sometimes caused by cancerous antibody-secreting plasma cells, results when misfolded antibody chains form deposits that impair function of the heart, kidneys, and other organs. Risk factors: There are no known risk factors. Etiology and the disease process: In a minority of patients with multiple myeloma, antibody fragments that are produced by malignant plasma cells form insoluble fibrillar protein deposits. Deposits can form in many organs but are most often found in the kidney, heart, liver, and peripheral and autonomous nervous systems. These deposits ultimately lead to death, most commonly via heart disease and renal failure. Incidence: The overall incidence of AL amyloidosis is approximately 1 in 100,000 people per year. Men are more likely than women to develop AL amyloidosis. Approximately 15 percent of patients with multiple myeloma develop AL amyloidosis, but cases of myeloma-associated amyloidosis make up a small fraction of AL amyloidosis cases. Symptoms: Symptoms depend on the organs involved and vary among patients. Common symptoms include periph-
Salem Health: Cancer eral edema, proteinuria, hepatomegaly, hypotension, shortness of breath, irregular heartbeat, purpura, macroglossia, carpal tunnel syndrome, and peripheral neuropathy. Screening and diagnosis: Many amyloidoses are diagnosed by Congo Red staining of tissues biopsied from subcutaneous fat pads, rectal mucosa, bone marrow, or other sources. Once diagnosis of amyloidosis is established, a free light chain blood test is performed to confirm immunoglobulin chains as the cause of amyloid deposits. Treatment and therapy: Current treatments for amyloidosis parallel those used for multiple myeloma. Melphalan plus predisone reduces the number of malignant plasma cells and levels of circulating immunoglobulin light chains. This is often followed by autologous stem cell transplantation, aimed at rebuilding healthy bone marrow. In some patients, treatment results in a temporary resorption of amyloid fibrils and improvement in organ function. The malignant plasma cells are not completely eradicated, however, and remission is the usual course. IDOX (4′deoxy-4′-iododoxorubicin), a drug that binds to amyloid fibrils and promotes their disassembly, has shown promise in early trials. Prognosis, prevention, and outcomes: Prognosis for patients with AL amyloidosis depends on which organs are affected. Patients with cardiac involvement have the worst prognosis, while patients with involvement limited to other organs have longer median survival times. There is no known way to prevent amyloidosis. Kyle J. McQuade, Ph.D. See also Bone marrow transplantation (BMT); Crohn disease; Orbit tumors; Paraneoplastic syndromes; Stem cell transplantation.
Anal cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Cancer of the Anus, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Individuals Diagnosed (%) Survival Rate (%) 49 32 10 10
81.7 61.1 2.8 57.6
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
Risk factors: There are several risk factors for anal cancer, including cigarette smoking and anal receptive sexual intercourse. Infection with the human papillomavirus (HPV16), the sexually transmitted disease that causes genital warts, can cause anal squamous intraepithelial lesions (ASIL), which may develop into anal cancer. People with a suppressed immune system from cancer, cancer treatments, organ transplantation, HIV, or AIDS have an increased risk of anal cancer. The number of people with both HIV and anal cancer is rising. Etiology and the disease process: Researchers do not know the exact cause of the genetic changes that make healthy cells turn into anal cancer cells, although multiple risk factors have been identified. The anal cancer cells multiply and form masses or tumors.
Related conditions: Anorectum cancer, anal squamous intraepithelial lesions (ASIL), human papillomavirus (HPV), human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS)
Incidence: Anal cancer is a rare form of cancer; however, the number of new cases began to increase in the early 1980’s. The incidence of anal cancer is 1 in 100,000 people. New cases in 2007 in the United States were estimated to reach 4,650. Anal cancer occurs more frequently in women than in men. Women are more likely to develop cancer in the anal canal. Men are more likely to develop cancer tumors on the outside of the anus. Anal cancer occurs most frequently in adults in their early sixties, at a median age of sixty-one years.
Definition: Anal cancer is a rare cancer that forms in the anus, which is at the end of the rectum. The anus is about 1.5 inches long and contains sphincter muscles that control bowel movements. Stool passes through the anus as it leaves the body.
Symptoms: Anal cancer may not cause symptoms. Bleeding from the anus is a common early sign. This type of cancer may cause pain, itching, abnormal anal discharge, and changes in the diameter of stools. A mass or growth may develop in the anus. Nearby lymph nodes may
u Anal cancer Category: Diseases, symptoms, and conditions Also known as: Cancer of the anus, anal canal cancer
59
Anal cancer
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be swollen. The anus may feel unusually full. Screening and diagnosis: Screening tests for anal cancer are recommended for people with a high risk of anal cancer. Women should receive anal cancer screening as part of a yearly exam. Annual anal cancer screening is recommended for men after the age of fifty. Anal cancer is diagnosed with a series of tests and procedures. A digital rectal exam (DRE) is used to check for lumps, masses, or growths in the anus. Endoscopy, using an anoscope or rigid protosigmoidoscopy, allows inspection of the interior anal canal. An anoscope is a thin tube with a viewing instrument and light that is inserted into the anus. A protosigmoidoscope is longer and allows sections of the colon to be viewed as well. Ultrasound, computed tomography (CT) scans, positron emission (PET) scans, and magnetic resonance imaging (MRI) scans are used to provide images of the anal structures and to help determine if the cancer has spread. Fine needle aspiration and sentinel lymph node biopsy are used to obtain cells for examination to confirm if cancer is present. Staging is used to identify cancer growth and metastasis, plan treatment, and predict recovery. Fortunately, anal cancer rarely metastasizes. • Stage I: Anal cancer is 2 centimeters (cm) or less. • Stage II: Anal cancer is larger than 2 cm, is confined to the anus, and has not spread beyond the anus. • Stage IIIA: Anal cancer is any size with spread to nearby lymph nodes or close areas, such as the bladder, urethra, or vagina. • Stage IIIB: Anal cancer is any size with spread to nearby lymph nodes and close areas, or it has spread to lymph nodes in the pelvis. • Stage IV: Anal cancer has spread to distant locations in the body. Treatment and therapy: Chemoradiation is the treatment of choice for anal cancer. External radiation, brachytherapy, or both may be used. Chemotherapy 5-FU and Mutamycin (mitomycin) may be used in combination with radiation or surgery. Surgery is used for patients with residual anal cancer and includes local resection or abdominoperineal resection (APR). Prognosis, prevention, and outcomes: Anal cancer screening, HPV testing, HIV testing, quitting smoking, 60
Cancer of the anus. (BSIP/Photo Researchers, Inc.)
knowing the STD status of sexual partners before intercourse, and not participating in anal sex may help prevent anal cancer. Condoms may reduce the risk of HPV and HIV, but they are not a guarantee. HPV vaccination is available for girls and women. Many cases of anal cancer that are detected and treated early can be cured. However, anal cancer may recur even with treatment. It was estimated that 690 men and women with anal cancer would die in the United States in 2007, a rate of 0.2 per 100,000 people. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Cranston, R. D., et al. “The Prevalence, and Predictive Value, of Abnormal Anal Cytology to Diagnose Anal Dysplasia in a Population of HIV-Positive Men Who Have Sex with Men.” International Journal of STD and AIDS 18, no. 2 (February, 2007): 77-80. Das, P., C. H. Crane, and J. A. Ajani. “Current Treatment for Localized Anal Carcinoma.” Current Opinions in Oncology 19, no. 4 (July, 2007): 396-400. Meyer, J., B. Czito, F. F. Yin, and C. Willett. “Advanced Radiation Therapy Technologies in the Treatment of Rectal and Anal Cancer: Intensity-Modulated Photon Therapy and Proton Therapy.” Clinical Colorectal Cancer 6, no. 5 (January, 2007): 348-356. Uronis, H. E., and J. C. Bendell. “Anal Cancer: An Overview.” Oncologist 12, no. 5 (May, 2007): 524-534.
Salem Health: Cancer u
Androgen drugs
Other Resources
American Cancer Society How Is Anal Cancer Diagnosed? Http://www.cancer.org/docroot/CRI/content/CRI_ 2_4_3X_How_Is_Anal_Cancer_Diagnosed_47.asp National Cancer Institute Anal Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ anal/patient See also Abdominoperineal resection (APR); Anoscopy; Colostomy; Computed tomography (CT) scan; Digital rectal exam (DRE); Endoscopy; Gastrointestinal cancers; Gastrointestinal oncology; Infectious cancers; Risks for cancer; Sexuality and cancer; Sigmoidoscopy.
u Androgen drugs Category: Chemotherapy and other drugs ATC code: G03B Definition: Androgens are steroid hormones produced by the adrenal glands and testes or ovaries, responsible for male sex characteristics in the body. Testosterone, an endogenous androgen, is converted to estrogen by the enzyme aromatase. Androgenic agents can be used in the treatment of breast cancer. Cancers treated: Metastatic hormone-responsive breast cancer in postmenopausal women, or in premenopausal women who have undergone ovary ablation Subclasses of this group: Anabolic steroids, alkylated androgens, testosterone esters Delivery routes: Administered orally as tablets or capsules, or by intramuscular injection How these drugs work: Testosterone esters are lipophilic compounds that, when dissolved in oil, are administered via intramuscular injection. Alkylated androgens can be
given orally as their metabolic deactivation is hindered by the alkyl group at the 17α position. The mechanism of action for androgenic agents in breast cancer has not been fully established, though they are believed to block the growth of estrogen-dependent tumors by inhibiting aromatase activity. Older drugs such as calusterone underwent clinical trials in the 1960’s and 1970’s, with response rates of approximately 20 percent. Androgen drugs are not considered first-line therapy for breast cancer, as they are more toxic than other hormonal agents in use and response rates remain low. Androgens, when used, are frequently given in combination with aromatase inhibitors to inhibit the production of estrogen in vivo. Side effects: Androgens are male sex hormones and can cause masculinizing effects in women, including deepening voice, hirsutism, acne, and clitoral enlargement. Alkylated androgens are less potent than testosterone and hence possess a lower risk of these side effects, but liver toxicity, cholestatic hepatitis, and jaundice can occur at relatively low doses. Androgen therapy should be discontinued following abnormal liver function tests until the cause has been determined. Androgen therapy in patients with preexisting cardiac, renal, or hepatic disease increases the risk of edema and progression to congestive heart failure. In such cases, dosing should be discontinued and administration of a diuretic considered. Breast cancer patients undergoing androgen therapy are at increased risk of bone breakdown and reabsorption, leading to hypercalcemia. If this occurs, then drug therapy should be discontinued and the patient evaluated, as hypercalcemia may also indicate the progression of bone metastases. Karen M. Nagel, Ph.D. See also Amenorrhea; Antiandrogens; Appetite loss; Bisphenol A (BPA); Breast cancer in men; Chemoprevention; Endocrine cancers; Fanconi anemia; Granulosa cell tumors; Hormonal therapies; Myelofibrosis; Receptor analysis; Tumor flare.
Androgen Drugs for Breast Cancer Treatment Drug
Brands
Subclass
Delivery Mode
Testolactone Testosterone enanthate Fluoxymesterone Methyltestosterone
Teslac Delatestryl Androxy, Halotestin, Ora-Testrylm Android-F, Hysterone Tested, Virilon, Android-10, Methitest
Anabolic steroid Testosterone ester Alkylated androgen Alkylated androgen
Oral Intramuscular Oral Oral
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Anemia
Salem Health: Cancer
u Anemia Category: Diseases, symptoms, and conditions Also known as: Low red blood cell count, erythropenia, iron-poor blood Related conditions: Cytopenia Definition: Anemia is a low number of red blood cells, decreased volume of red blood cells, or a reduced concentration of hemoglobin. Risk factors: For anemia of cancer, risk is associated with the type of cancer, stage of disease, and treatment regimen. Etiology and the disease process: Anemia may be caused by deficiencies of vitamin B12, folic acid, or iron; antibody formation; kidney failure; lead poisoning; bone-marrow dysfunction; chemotherapy; or radiation therapy. It can also result from infiltration of bone marrow by leukemia or lymphomas or from internal bleeding or excessive blood loss from repeated blood sampling. Anemias caused by deficiencies in folic acid, vitamin
B12, and iron are generally known as nutritional anemias. In these forms of anemia, the endogenous hormone erythropoietin, responsible for red blood cell production, appears to be present in adequate amounts. Patients with cancer, however, can be anemic because of deficiencies in these nutrients. The anemia of cancer, a subset of anemia of chronic disease, is marked by reduction in the amount of the hormone erythropoietin found in the circulation, suppression of bone marrow function, disturbances in iron metabolism, and activation of the inflammatory and immune systems in response to the insult of cancer that activates hormones, which in turn decrease the production of endogenous erythropoietin. Another form of anemia is aplastic anemia, which may be caused by chemotherapy, radiation therapy, or drugs. In the normal state of health, endogenous erythropoietin is released by peritubular cells in the kidney cortex when specialized cells sense hypoxia (low oxygen content of the blood). In the bone marrow, erythropoietin stimulates the proliferation and differentiation of primitive cells (that is, progenitor cells) that will mature and differentiate
Numerous types of anemia exist.
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Anemia
into red blood cells. As the cells mature and differentiate, they synthesize hemoglobin, the iron-containing pigment that is responsible for carrying oxygen to all cells in the body and carrying carbon dioxide away from cells.
sions. In cases of severe anemia, however, transfusions are routinely used because it takes several days for the erythropoiesis-stimulating proteins to increase red blood cell count and hemoglobin concentration.
Incidence: It is estimated that the frequency of severe anemia, marked by a hemoglobin concentration less than 8 grams per deciliter (g/dl) across a broad range of cancers, is 5 to 20 percent, and that of mild anemia, marked by a hemoglobin concentration of 8 to 11 g/dl, is 25 to 45 percent.
Prognosis, prevention, and outcomes: The prognosis for anemia depends greatly on the type of anemia. For anemia of cancer, anemia may be directly related to prognosis and survival. Research suggests that it may be important to maintain hemoglobin concentration at a high level to decrease the effects of hypoxia, especially during treatment. Because chemotherapy and radiation therapy target rapidly dividing cells, both cancer cells and bone marrow cells, it is difficult to prevent anemia due to treatment without reducing the efficacy of treatments. Also, the anemia of cancer involves endogenous inflammatory and immune functions, which cannot be prevented. Proper nutrition may be useful in preventing anemia caused by deficiencies in folic acid, iron, and vitamin B12. MaryAnn Foote, M.S., Ph.D.
Symptoms: Symptoms of anemia can include fatigue, pale skin (including nail beds and the lining of the eyelids), dizziness, chills, shortness of breath, rapid pulse, and chest pains. Screening and diagnosis: A blood test can measure the hemoglobin concentration, or hematocrit; hemoglobin concentration is generally used, as it is more accurate than hematocrit. Other tests that are often done at the same time are red blood cell indices, which include red blood cell count, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular hemoglobin (MCH). Iron parameters, which include serum iron, total iron-binding capacity, percent transferrin saturation, and serum ferritin, are measured. A test for occult blood in the stool as a possible source of blood loss is often done, particularly in the setting of gastrointestinal cancers. A normal red blood cell count is 3.5 to 5.0 × 1012/liter for women and 4.3 to 5.9 × 1012/liter for men. Hematocrit, the measure of the volume of red blood cells as a percentage of the total blood volume, is 37 to 47 percent for women and 45 to 57 percent for men. Normal concentration of hemoglobin is 14 to 17.5 g/dl for men and 12 to 16 g/dl for women. Treatment and therapy: While anemia of cancer can be treated with transfusions of packed red blood cells, the standard of care at most cancer treatment centers is the use of recombinant human erythropoiesis-stimulating proteins such as epoietin alfa (Epogen or Procrit) or darbepoietin alfa (Aranesp). The recombinant human erythropoiesisstimulating proteins are given as injections three times a week to once every three weeks depending on the patient’s needs and type of recombinant protein used. The use of these recombinant proteins allows oncologists the option of not using red blood cell transfusions, with their small but inherent risks of autoimmunization and infection. The possibility of failure of bone marrow or stem cell transplantation increases with the number of previous transfu-
u
For Further Information Crawford, C., et al. “Relationship Between Changes in Hemoglobin Level and Quality of Life During Chemotherapy in Anemic Cancer Patients Receiving Erythropoietin Therapy.” Cancer 95 (2002): 888-895. Molineux, G., M. A. Foote, and S. G. Elliott, eds. Erythropoietins and Erythropoiesis: Molecular, Cellular, Preclinical, and Clinical Biology. Basel, Switzerland: Birkhäuser, 2003.
u
Other Resources
Anemia.com http://www.anemia.com MedlinePlus Anemia http://www.nlm.nih.gov/medlineplus/anemia.html See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Angiogenesis inhibitors; Antifungal therapies; Aplastic anemia; Blood cancers; Bone marrow transplantation (BMT); Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Colony-stimulating factors (CSFs); Fanconi anemia; Hairy cell leukemia; Hematologic oncology; Hemolytic anemia; Stem cell transplantation; Thrombocytopenia; Transfusion therapy; Waldenström macroglobulinemia (WM); Young adult cancers. 63
Angiogenesis
u Angiogenesis Category: Cancer biology Also known as: Blood vessel formation Definition: Angiogenesis is the formation of new blood vessels. It is a perfectly normal process in a developing or growing body, and during a woman’s reproductive years, it enables the menses and pregnancy. In addition, angiogenesis maintains health by developing a new blood supply in injured tissue, controlling inflammation, and even healing fractures of the bone. In health, the body controls angiogenesis, but in cancer, the body loses control. Angiogenesis is thought to be a process by which a cancer obtains its blood supply from its host. Without vascularization—the provision of blood vessels—no tissue in the body can live. Nearly every cancer known is associated with pathological angiogenesis. Relation of angiogenesis to cancer. In one way, a cancerous tumor is like any other bodily structure: Its survival de-
Tumor angiogenesis. (©ISM/Phototake—All rights reserved)
64
Salem Health: Cancer pends on the provision of oxygen and nutrients and the removal of waste. Cancerous tumors differ from normal tissue in that they tend to spread, or metastasize, without regard to normal borders between different tissues such as muscle, cartilage, and bone. Blood supply to a tumor enables it to spread. For its support and ability to grow, in effect the cancer must persuade the body to build vessels to and throughout the tumor, something that seems counterintuitive. In fact, the body contains defenses against this. As cancer develops, however, these defenses are short-circuited. The way the tumor fools its host into cooperation is chemically—with proteins and enzymes found naturally in the body but used by the tumor to its advantage. Proteins that induce growth are known as growth factors. Researchers have shown evidence that one chemical secreted by tumors, vascular endothelial growth factor (VEGF), in effect attracts blood vessels. Induced by growth factors and possibly hormones, new blood vessels actually sprout from existing vascular tracts into and around the cancer. Researchers also report that breast cancer cells produce interleukin-8 (IL-8), a protein that normally attracts white blood cells to injuries and inflammation, but which is also known to be angiogenic. Other researchers, exploring the role of certain enzymes in regulating angiogenesis in breast cancer, are focusing on the extracellular matrix, noncellular material that surrounds any tissue (picture the stuffing around mattress springs) and common not only to normal tissues but also to tumor cells. In addition to taking up space between cells (including cartilage, tendon, ligament, and bone), the extracellular matrix performs a critical function. Under normal circumstances after adulthood, the extracellular matrix prevents unauthorized (non-injury-related) angiogenesis and cell movement. Cancer short-circuits that inhibitory function. Compared with normal breast cells, some breast cancer cells have higher levels of two enzymes that degrade heparin, an important component of the extracellular matrix. A weakened and degraded extracellular matrix might well enable abnormal cell movement and angiogenesis. Not every researcher, however, is convinced that tumors depend on angiogenesis. Citing the “immature” vasculature of some tumors—meaning that the blood vessels are not as well organized as in normal body tissues— and the lack of consistent evidence from clinical trials, they question cancer’s angiogenesis dependency. Those who support the connection counter that cancer growth is by its very nature not only disorganized—it is growing a tumor rather than a kidney or a pancreas—but also, relative to other tissues, new in origin. Because cancer’s
Salem Health: Cancer
Angiogenesis
Known Angiogenic Growth Factors
• • • • • • • • • • •
Angiogenin Angiopoietin-1 Del-1 Fibroblast growth factors: acidic (aFGF) and basic (bFGF) Follistatin Granulocyte colony-stimulating factor (G-CSF) Hepatocyte growth factor (HGF) /scatter factor (SF) Interleukin-8 (IL-8) Leptin Midkine Placental growth factor
• • • • • • • • •
Platelet-derived endothelial cell growth factor (PD-ECGF) Platelet-derived growth factor-BB (PDGF-BB) Pleiotrophin (PTN) Progranulin Proliferin Transforming growth factor-alpha (TGF-alpha) Transforming growth factor-beta (TGF-beta) Tumor necrosis factor-alpha (TNF-alpha) Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF)
Source: The Angiogenesis Foundation
growth, unlike that of healthy tissue, is continual, its vasculature might be expected to remain immature. Preventing cancer-related angiogenesis: If tumors do require angiogenesis to survive and spread, then it seems logical to discourage angiogenesis. Inhibitors of angiogenesis were first discovered in 1975 and since then have been detected in such diverse natural sources as tree bark, green tea, fungi, shark cartilage and muscle, sea coral, and various herbs. Ways to prevent or change the process of angiogenesis being investigated include blocking the chemical signals from the tumor, making these signals less effective; preventing the breaching of the extracellular matrix; and after a tumor has already been supplied with blood vessels, causing the vessels to normalize, or stop supplying the tumor. Another area being researched targets oncogenes, genes that cause normal cells to become cancerous and also, it is believed, activate the angiogenesis switch. Researchers are developing antioncogene drugs. Angiogenesis inhibitors, while promising, have yet to be proven as efficacious treatments, in part because of the complexity and diversity of the tumors themselves. What works for one tumor may not work for another. Another complication of agents that inhibit angiogenesis is the chaos they could produce in inflammation control and healing. Nevertheless, the possibility of inhibiting angiogenesis only where it is needed, with very targeted inhibitors and perhaps with the assistance of other drugs such as paclitaxel (Taxol) and cyclophosphamide (Cytoxan, Neosar) and such COX-2 inhibitors as celecoxib (Celebrex) and thalidomide, all of which interfere with angiogenesis, remains an attractive investigative path. Research and clinical trials are ongoing. Jackie Dial, Ph.D.
u
For Further Information Chan, David. Breast Cancer: Real Questions, Real Answers. New York: Marlowe & Company, 2006. Firedewald, Vincent, M. D. Buzdar, and Michael Bokulich. Ask the Doctor: Breast Cancer. Kansas City, Mo.: Andrews McMeel, 1997. Link, John. Breast Cancer Survival Manual: A Step-byStep Guide for the Woman with Newly Diagnosed Breast Cancer. 4th ed. New York: Holt, 2007.
u
Other Resources
American Cancer Society http://www.cancer.org Angiogenesis Foundation About Angiogenesis http://www.angio.org/understanding/ understanding.html MayoClinic.com Angiogenesis Inhibitors: New Cancer Drugs Stop Tumor Growth http://www.mayoclinic.com/health/angiogenesis/ CA00079 National Breast Cancer Foundation http://www.nationalbreastcancer.org See also Angiogenesis inhibitors; Bioflavonoids; Biological therapy; BRAF gene; Bronchoalveolar lung cancer; Cancer biology; Cartilage supplements; Chemotherapy; Gene therapy; Genetics of cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); HIV/AIDS-related cancers; Human growth factors and tumor growth; Im65
Angiogenesis inhibitors munotherapy; Kidney cancer; Matrix metalloproteinase inhibitors; Oral and oropharyngeal cancers; Phenolics; Robert H. Lurie Cancer Center; Sarcomas, soft-tissue.
u Angiogenesis inhibitors Category: Chemotherapy and other drugs Definition: Angiogenesis inhibitors prevent the formation of new blood capillaries formed by the process called angiogenesis. As a result, cancer tumors are starved and die. Cancers treated: Multiple myeloma, mantle cell lymphoma, metastatic colorectal cancer, advanced renal cancer, gastrointestinal stromal tumors Delivery routes: Delivered intravenously on an inpatient basis (Velcade, Avastin) or orally in tablet (Sutent, Nexavar) and capsule (Thalomid) forms on an at-home basis How these drugs work: Angiogenesis is critical to normal growth, providing a network of new blood capillaries
Salem Health: Cancer that deliver oxygen and nutrients to developing tissues. Once formed, capillaries do not increase in size or number, because the endothelial cells that line them do not divide. In some normal conditions (wound repair, menstruation), however, they do. Tumors require a constant supply of newly formed blood capillaries in order to grow. Early in the angiogenesis process, tumors secrete “growth factors,” which signal the endothelial cells to proliferate. The new capillaries attach themselves to the tumor and deliver oxygen and nutrients. This blood supply also allows tumor cells to spread to other areas of the body (metastasize), a process that is a major cause of cancer deaths. Some scientists have long hypothesized that attacking angiogenesis might be a powerful tool in preventing tumor growth. Removing the blood supply might prevent the growth of new tumor cells and cause the tumors to grow more slowly or become smaller. In 1971, Dr. Judah Folkman, of Children’s Hospital in Boston, published a paper proposing the hypothesis that all tumor growth is angiogenesis-dependent. This founded the field of angiogenesis research and its control, a field of investigation that is now studied by many scientists.
A mouse with lung cancer, left, was treated with angiogenesis inhibitors in an experiment by Judah Folkman. Twelve days later, the tumor in the mouse, right, showed substantial improvement. (AP/Wide World Photos)
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Salem Health: Cancer
Angiogenesis inhibitors
Angiogenesis Inhibitors Drug
Brands
Subclass
Delivery Mode
Cancers Treated
Bevacizumab
Avastin
Monoclonal antibody
IV
Metastatic colorectal cancer
Bortezomib
Velcade
Dipeptide boronic acid analogue
IV
Multiple myeloma, mantle cell lymphoma
Sorafenib tosylate
Nexavar
Bi aryl urea
Oral
Advanced renal cell carcinoma
Sunitinib malate
Sutent
Malate salt of an indolinone-based tyrosine kinase inhibitor
Oral
Advanced kidney cancer, gastrointestinal stromal tumors
Thalidomide
Thalomid
Glutamic acid derivative
Oral
Multiple myeloma
In December, 2006, the United States’ National Cancer Institute (NCI) listed thirty angiogenesis inhibitors undergoing clinical trials. By 2007, the U.S. Food and Drug Administration (FDA) had approved five angiogenesis inhibitors for use in cancer treatment: Velcade, Avastin, Nexavar, Sutent, and Thalomid. Velcade was approved in 2003 for the treatment of multiple myeloma patients who had received at least two prior therapies with anticancer drugs and had demonstrated disease progression on the last therapy. It was approved in 2005 for multiple myeloma patients who had received one prior therapy and in 2006 for mantle cell lymphoma in patients who had received one prior therapy. Velcade interrupts various cell-signaling pathways critical to angiogenesis. Avastin was approved in 2004 to treat metastatic colorectal cancer. It is believed to act by attaching to a protein growth factor active in angiogenesis. When the growth factor is bound to Avastin, it cannot carry out its function in the angiogenesis process. Avastin enhances the effects of standard chemotherapy but does not appear to be effective when given alone to patients with colorectal cancer. Nexavar was approved in 2005 to treat adults with advanced renal cell carcinoma, an aggressive form of the disease and the most common of kidney cancers. It has not been studied in children. Nexavar is a small molecule, and as such, it enters endothelial cells and inhibits enzymes involved in intercellular signaling linked to cell division; it also acts by binding to vascular endothelial growth factor. Sutent was approved in 2006 for the treatment of gastrointestinal stromal tumors and advanced kidney cancer. Sutent is also a small molecule that enters tumor cells and prevents angiogenesis and cell proliferation by blocking the signaling activity of several growth factors. Thalomid (thalidomide) was approved in 2006 for the treatment of newly diagnosed multiple myeloma, in combination with the chemotherapy drug dexamethasone.
Thalidomide’s activity depends on its ability to block the growth factor signals necessary for angiogenesis. In 1994, Folkman and coworkers published a paper providing evidence that thalidomide is an angiogenesis inhibitor. Its ability to block the development of new blood vessels likely caused the limb malformations in babies of mothers who took the drug as a sedative during pregnancy. Both men and women taking the drug for cancer treatment are required to use contraception to avoid pregnancy. Side effects: The side effects of angiogenesis inhibitors depend on the medication. Some of the more common angiogenesis inhibitors have the following side effects: • Velcade: Fatigue, nausea, diarrhea, anorexia, constipation, thrombocytopenia, peripheral neuropathy, pyrexia, vomiting, and anemia • Avastin: High blood pressure, fatigue, blood clots, diarrhea, decreased white blood cells, headache, appetite loss, and mouth sores • Nexavar: Rash, diarrhea, high blood pressure, and redness, pain, swelling, or blisters on the palms of the hands or soles of the feet • Sutent: Diarrhea, skin discoloration, mouth irritation, weakness, altered taste, fatigue, high blood pressure, bleeding, swelling, and hypothyroidism • Thalomid: Somnolence, constipation, neuropathy, venous thromboembolism, and rash Bernard Jacobson, Ph.D. u
For Further Information D’Amato, R. J., M. S. Loughnan, E. Flynn, and J. Folkman. “Thalidomide Is an Inhibitor of Angiogenesis.” Proceedings of the National Academy of Sciences 91 (1994): 4082-4085. Davis, D. W., R. S. Herbst, and J. L. Abbruzzese, eds. Antiangiogenic Cancer Therapy. New York: CRC Press, 2007. 67
Angiography Folkman, J. “Tumor Angiogenesis: Therapeutic Implications.” New England Journal of Medicine 285 (1971): 1182-1186. Forough, R., ed. New Frontiers in Angiogenesis. New York: Springer, 2006. Sieman, D. W., ed. Vascular-Targeted Therapies in Oncology. Hoboken, N.J.: Wiley, 2006. Skinard, E. T., ed. New Research on Angiogenesis Inhibitors. Hauppage, N.Y.: Nova Science, 2006. u
Other Resources
Food and Drug Administration http://www.fda.gov National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Angiogenesis; Biological therapy; Chemotherapy; Oral and oropharyngeal cancers; Sarcomas, softtissue.
u Angiography Category: Procedures Also known as: Arteriography, angiogram, arteriogram Definition: Angiography is a general term for a minimally invasive imaging technique that uses real-time X rays and a special dye to see inside blood vessels, lymph nodes, and certain glands deep inside the body. The dye, known as a contrast medium, is injected into the body to highlight the vessels, lymph nodes, glands—and cancerous tumors— and make them easier to see. The contrast medium is a low-dose radioactive compound known as a radioisotope. The image created by the X ray is called an angiogram. Cancers diagnosed or treated: Cancers of the lymphatic system, the digestive system, the lungs, the brain, and certain glands Why performed: Doctors use angiography to detect and directly examine cancerous tumors and to show the blood flow to a tumor. A direct real-time view of a tumor and blood flow helps doctors diagnose and treat the cancer. With angiography, doctors can determine a tumor’s size, appearance, and relationship to nearby organs and tissues; whether the tumor is growing or extending into nearby parts of the body; and whether cancer cells are spreading to other parts of the body. In some cases, doctors use the procedure to deliver medicine to a tumor. 68
Salem Health: Cancer Patient preparation: Patient preparation varies slightly depending on the part of the body to be examined and whether the patient is already in the hospital (inpatient) or having the procedure done and then returning home the same day (outpatient). Nurses help the inpatient prepare. Outpatients stay several hours in a recovery room before going home. Most outpatients receive a mild sedative to help them relax during the procedure. The test may take up to several hours. Generally, patients should not eat or drink anything for eight hours before the procedure. Patients should tell their doctors if they are pregnant or breast-feeding; which medications they are taking, including aspirin; if they have any bleeding problems or are taking blood-thinning medications; if they have allergies to any substances or medications; if they suffer from asthma; if they have a history of kidney problems or diabetes; if they have blockage of the blood vessels caused by atherosclerosis (hardening of the arteries), high blood pressure, or aging; and if they think they will find it difficult to lie still during the procedure. Steps of the procedure: A team of technicians and nurses led by a radiologist (a doctor who diagnoses diseases by studying X rays and other images) conducts the procedure. The procedure takes place in the radiology laboratory of a medical center. The patient wears a hospital gown and receives a mild sedative but remains awake. The patient lies supine on a table much like an operating table. The surgeon makes a small incision near a blood vessel in the neck, chest, groin, or arm. Using real-time X rays displayed on a video screen for guidance, the surgeon then inserts a thin, flexible tube called a catheter into the vessel. The surgeon guides the catheter through the blood vessels until the tip reaches the area to be studied. Once the catheter is placed in the exact spot, the radiologist injects the dye. The dye travels through the catheter and to the blood vessels, making the target easier to see in the X ray. A round cylinder or rectangular box, known as a fluoroscope, takes the pictures. It moves both above and beneath the patient. After the procedure: After the test, a nurse applies a pressure bandage at the site where the catheter was inserted. Some patients feel tenderness or soreness at the site. Depending on where the catheter was inserted, the patient may have to remain in bed—in the hospital or at home— from several hours up to a day. The patient receives pain medicine if needed. Some people experience a headache, flushing of the face, or a salty or metallic taste in the mouth after the dye is inserted, but these feelings disappear quickly. Doctors generally recommend that patients drink extra fluids to help pass the dye from the body.
Salem Health: Cancer
Angiosarcomas
Risks: Angiography is a very common test. Both the X ray and the dye are safe. The exposure to radiation is low. There are, nevertheless, some small risks. There is a remote chance that a person may react to the contrast agent, or dye. Common contrast agents are iodine, barium, and gadolinium. In addition, patients may feel a slight burning sensation when the doctor injects the dye or some discomfort at the site where the catheter is inserted. Patients do not feel the catheter inside the body. There is a small risk of bleeding, pain, or infection at the site where the catheter is inserted. Results: The angiogram shows that there are no problems if the dye flows smoothly through the blood vessels and no tumors appear in the lymph nodes or glands studied. If the angiogram reveals that blood vessels are not in their normal position or the blood is flowing in an abnormal pattern, then a tumor may be present. Doctors will then conduct additional tests. Wendell Anderson, B.A. u
For Further Information Icon Health. Angiogram: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004.
Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006. Welch, H. G. Should I Be Tested for Cancer? Maybe Not and Here’s Why. Berkeley: University of California Press, 2004. See also Bile duct cancer; Chemoembolization; Embolization; Endocrinology oncology; Exenteration; Eye cancers; Gallbladder cancer; Hemangioblastomas; Hematemesis; Hemoptysis; Imaging tests; Lymphadenectomy; Lymphangiography; Pancreatic cancers; Percutaneous transhepatic cholangiography (PTHC); Testicular cancer; X-ray tests.
u Angiosarcomas Category: Diseases, symptoms, and conditions Related conditions: Soft-tissue malignancy Definition: Angiosarcomas are cancers that develop from blood vessels. Although the most common sites where they occur are the arms, legs, neck, and head, these tumors can occur anywhere on the body, most frequently on the skin or in the soft tissue. Angiosarcomas are made up of
An angiosarcoma on the knee. (©Lester V. Bergman/Corbis)
69
Anoscopy malignant cells that are rapidly proliferating and capable of extensive infiltration. Risk factors: Some risk factors have been linked with the development of angiosarcoma. Primarily, these include previous exposure to radiation therapy or chemotherapy, as well as exposure to carcinogens such as certain polyester fibers or bone wax. Etiology and the disease process: In many cases, angiosarcoma develops as a complication of a preexisting condition. For example, a radical mastectomy can lead to the development of an angiosarcoma in the soft tissue and skin of the breast. Additionally, foreign materials in the body, such as shrapnel, have resulted in angiosarcomas. Incidence: Angiosarcoma is a very rare tumor type, occurring in only 2 to 3 patients out of 1 million individuals. Nearly half of all angiosarcomas develop in the head and neck regions, but they also can occur in the soft tissue of the lower and upper extremities. Least common of all angiosarcomas are those that occur in other areas of soft tissue, such as the breast, kidney, and liver. Symptoms: Angiosarcomas in the soft tissues of the extremities may be identified as growing masses, while those that occur on the skin generally appear as blue or black nodules. Angiosarcomas that develop in other areas of soft tissue, especially within the abdominal cavity, are capable of growing quite large and often are not diagnosed until the size of the tumor begins to affect the surrounding tissues and organs. Screening and diagnosis: Diagnosis occurs by recognizing the abnormal growths within the skin or extremities of the patient. Angiosarcomas within the abdominal cavity may remain undiagnosed until related symptoms become apparent, such as neuronal symptoms occurring from compression of the lumbar or pelvic nerves. Treatment and therapy: Surgery and radiation therapy are common methods to treat angiosarcomas. Depending on the location, chemotherapy may also be used in combination with these other strategies. The most common chemotherapeutic agent to treat angiosarcoma is Adriamycin (doxorubicin). Prognosis, prevention, and outcomes: Angiosarcomas are aggressive tumors that have a tendency to spread rapidly and frequently reoccur, even after treatment. The reported five-year survival rate for these patients is only 20 percent. Lisa M. Cockrell, B.S. 70
Salem Health: Cancer See also Accelerated partial breast irradiation (APBI); Endotheliomas; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Liver cancers; Lymphangiosarcomas; Sarcomas, soft-tissue; Veterinary oncology.
u Anoscopy Category: Procedures Definition: Anoscopy is the examination of the anus, anal canal, and lower end of the rectum with an endoscope. Cancers diagnosed: Anal cancer, rectal cancer, cancer of an unknown primary site Why performed: Anoscopy is a diagnostic procedure to evaluate the presence of hemorrhoids, anal fissures, abscess, inflammation, tumors (malignant and benign), foreign bodies, infection such as condyloma or warts caused by human papillomaviruses (HPV), and anal squamous skin lesions associated with the human immunodeficiency virus (HIV). Patient preparation: The patient is instructed to clear stool from the rectal vault. A laxative, enema, or other preparation may be necessary for complete emptying of the rectum. For pediatric patients, their parents should be counseled on proper preparations for the procedure so that the patients’ anxiety may be reduced. In emergency cases, preparation for the procedure may not be possible. Steps of the procedure: The patient is asked to use a medical examination gown and to remove underwear. The position during the examination is either bending forward over the examining table or lying on the examination table on the patient’s left or right side with both lower limbs drawn up to the chest. The doctor performs a digital rectal examination wherein a gloved, lubricated index finger is inserted into the rectum to check for abnormalities and structures that can block visualization; the prostate is also examined in male patients. The external area of the anus is examined prior to the anoscope insertion. The doctor then uses the anoscope, a tubular instrument with a light source, to view the anus, anal canal, and lower rectum. The anoscope is lubricated prior to its insertion into the anus and anal canal; the patient may be asked to “bear down” during the insertion, as during a bowel movement. During the procedure, the patient may feel some pressure and the urge to defecate. A biopsy may be obtained during the procedure, as needed. The doctor slowly withdraws the anoscope as the anal canal is viewed carefully.
Salem Health: Cancer After the procedure: Patients can return to normal activities. If a biopsy was taken, then the patient may be instructed to have a sitz bath daily to relieve mild pain. Risks: No significant risk is associated with anoscopy. A small amount of bleeding and mild pain may occur if the patient has hemorrhoids or if a biopsy was obtained. Results: Normal results will show no structural or color abnormalities. Abnormal findings include hemorrhoids, fissures, infections, abscess, inflammation, or tumors. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. See also Anal cancer; Hemorrhoids.
u Anthraquinones Categories: Complementary and alternative therapies; chemotherapy and other drugs Definition: Anthraquinones form a group of anticancer agents derived from plant products. Anthraquinones naturally occur in some plants, such as aloe, senna, rhubarb, Cascara buckthorn, and sheep sorrel. Indian rhubarb root (Rheum palmatum) contains several anthraquinones. Sheep sorrel (Rumex acetosella) contains several types of anthraquinones. Subclasses of this group are emodin, aloe emodin, and anthraquionone derivatives. A number of conventional chemotherapeutic agents, such as Adriamycin (doxorubicin), are derivatives of anthraquinones. Cancers treated or prevented: Prostate cancer, breast cancer, non-Hodgkin lymphoma, acute leukemia Delivery routes: Anthraquionones are typically consumed as a mixture of several botanicals, such as in a tea, although intravenous administration has been used in the past. How these drugs work: Anthraquionones are ingredients in herbal mixtures such as Essiac or Flor-Essence that are typically consumed as a tea. The primary herbs in these botanical mixtures, rhubarb and sheep sorrel, are thought to contain anthraquionones. Such herbal extracts have been in use as a cancer treatment since the 1920’s, when they were popularized by a Canadian nurse, Rene Caisse, who obtained the recipe from a woman who claimed that it cured her breast cancer. Caisse opened a clinic and treated patients for more than forty years. After her death, researchers at Memorial Sloan-Kettering in New York tested her product, with inconclusive results. Anthraquionones are alleged to have anti-inflamma-
Anthrax tory effects and cytotoxic effects against tumor cells. Proponents claim that they strengthen the immune system, reduce tumor size, and improve and prolong the lives of people with many types of cancer. Although they have been shown to have tumor inhibition properties, they have been shown to stimulate tumor cell growth as well. Anthraquinones have been shown to stimulate various cytokines that are important in tumor cell defense, including IL-1, IL-6, and TNF. In experimental settings, anthraquinones have been shown to potentiate the action of Adriamycin (doxorubicin), a widely used chemotherapy drug, but the clinical significance of this action is unknown. Anthraquionone derivatives, such as Adriamycin and mitoxantrone, have been shown to be effective as chemotherapeutics. Side effects: Natural anthraquinones and their derivatives have laxative properties. Therefore, a side effect associated with anthraquionones is diarrhea as well as hyperkalemia as a result of chronic diarrhea. They have also been reported to cause nausea, vomiting, and contact dermatitis. A principal danger of this and other unconventional therapies is that they may delay diagnosis and conventional treatment of serious disease. C. J. Walsh, Ph.D. See also Essiac; Green tea; Herbs as antioxidants.
u Anthrax Category: Chemotherapy and other drugs Definition: Anthrax (from the Greek word for coal, anthrako, for the characteristic black skin lesions seen in cutaneous anthrax) is an often fatal infectious disease caused by the bacterium Bacillus anthracis. This bacterium is particularly virulent because it is surrounded by a coating that prevents the immune system from killing it and it secretes a toxin lethal to certain white blood cells (macrophages). Anthrax toxin, the key virulent component of B. anthracis, is currently being studied for use as targeted biological therapy for drug-resistant tumors. B. anthracis is sensitive to a number of antibiotics, including doxicyclin, and fluoroquinolones. Most people, however, do not have preexisting immunity to anthrax because it is not a routine immunization—with the exception of some U.S. military personnel. Cancers treated: Melanoma, breast cancer, colon cancer Delivery routes: Injection 71
Antiandrogens
Salem Health: Cancer
How this substance works: Anthrax infection begins when the spores of the bacteria are inhaled or come into contact with the skin. Anthrax toxin, produced by the bacteria, is the primary virulent factor. The toxin is activated by furin, a protein found in all living cells. Anthrax toxin may be genetically engineered to eschew furin and instead target only cells with high levels of urokinase, a protein produced prolifically by human tumor cells. The anthrax toxin contains three proteins that are innocuous when separate but work together to create a lethal environment for cells. Protective antigen (PA) is an anthrax protein that adheres to a host cell surface and bores a hole into it. The other A number of Bacillus anthracis bacteria. (Centers for Disease Control and Prevention) two proteins released by the bacteria, edema factor (EF) and lethal factor (LF), are too large to penetrate the outside of the cell unblocking the effect of androgens, which are hormones reless PA chaperones them inside. For cellular intoxication, quired for the development and survival of both normal PA is always needed; once inside the cell, only EF or LF is and cancerous prostate cells. needed to speed up the reactions that ultimately lead to rendering inactive parts of the immune system and finally Cancers treated: Prostate cancer to cell suicide (apoptosis). The term “anthrax lethal toxin,” Subclasses of this group: Nonsteroidal antiandrogens when used in cancer therapy research, refers to the combiand synthetic steroids nation of PA and LF. PA is the substance in the anthrax vaccine. Delivery routes: Administered orally as either capsules or Cancer researchers hope to harness the cellular suicide tablets, can be taken on an at-home basis caused by the anthrax toxin to prevent tumors from growing and spreading. In animal studies, the toxin both destroyed How these drugs work: Androgens are male hormones, tumor cells and prevented vascularization of tumors— which include testosterone, dehydroepiandrosterone, and which typically need a lot of nutrients, via vascularization, dihydrotestosterone. Androgens bind to androgen recepto grow. The bioengineered anthrax toxin has not been tors on the surface of prostate cells and turn on signaling shown to damage deoxyribonucleic acid (DNA) or prepathways involved in cellular development and survival vent cell growth in normal cells, common occurrences in and normal prostate function. Most prostate cancers, howtraditional chemotherapy. ever, are also dependent on androgen signaling. Therefore, without it, tumors may stop growing. Side effects: The potential side effects of anthrax therapy Nonsteroidal antiandrogens and synthetic steroids comare not yet known. pete with natural androgens for binding sites on androgen Pamela Richardson, M.S. receptors, thereby blocking the activity of the natural anSee also Biological therapy; Clinical trials. drogens. Synthetic steroids can also act on the hypothalamus in the brain to reduce the production of testosterone. Although antiandrogens inhibit androgen activity, blood levels of testosterone and other androgens may still be u Antiandrogens high, which could promote cancer cell growth. Therefore, antiandrogens are commonly used in combination with Category: Chemotherapy and other drugs other drugs that lower androgen levels, such as luteinizing ATC code: 102BB, G03HA hormone-releasing hormone agonists, which can stop tesDefinition: Antiandrogens are a class of drugs used to tosterone production. Antiandrogens may also be combined with inhibitors of the 5-α reductase enzyme, which treat prostate cancer. They can cause tumor cell death by 72
Salem Health: Cancer
Antidiarrheal agents
Common Antiandrogens for Prostate Cancer Treatment Drug
Brands
Subclass
Delivery Mode
Bicalutamide Cyproterone acetate Flutamide Nilutamide
Casodex Androcur, Climen Eulexin Anandron, Nilandron
Nonsteroidal antiandrogen Synthetic steroid Nonsteroidal antiandrogen Nonsteroidal antiandrogen
Oral Oral Oral Oral
block the conversion of testosterone into dihydrotestosterone. Dihydrotestosterone is thought to be a more potent and active androgen than testosterone. Side effects: Because antiandrogens affect the prostate, they may cause low sperm counts or reduce fertility. Other common side effects include diarrhea, hot flashes, liver toxicity, constipation, decreased appetite, nausea or vomiting, and flulike symptoms. Long-term treatment may also cause osteoporosis, in which bones become weakened. There are also some drug-specific side effects. For example, nilutamide can temporarily cause the eyes to become light sensitive and take longer to adjust to changes in light and dark settings. Flutamide is also associated with the rare side effects of dizziness, fainting, and severe headaches. Elizabeth A. Manning, Ph.D. See also Antiestrogens; Breast cancer in men; Breast cancers; Chemoprevention; Hormonal therapies; Immunotherapy; Tumor flare.
u Antidiarrheal agents Category: Chemotherapy and other drugs ATC code: AO7DA Definition: Antidiarrheal agents are a class of drugs used for the treatment or symptomatic relief of diarrhea. Cancers treated: Antidiarrheal agents are typically used to treat diarrhea associated with carcinoid tumors, colon cancer, lymphoma, thyroid cancer, pancreatic cancer, and pheochromocytoma, as well as cancer treatment-induced diarrhea, caused by such treatments as chemotherapy, radiation therapy, surgery, and bone marrow transplantation. Other causes of diarrhea in patients with cancer include anxiety and stress associated with the diagnosis. For these patients, antidiarrheal agents may be used in combination with antianxiety drugs.
Patients who have diarrhea with a different underlying cause should receive treatment specific to the cause. For example, those who have diarrhea caused by Clostridium difficile should be treated with the antibiotic metronidazole. Antidiarrheal agents may be administered as adjunct therapy after the initiation of antibiotic therapy. Subclasses of this group: Adsorbents, bulk-forming agents, opioids, piperidine derivatives, synthetic octapeptides, mucosal prostaglandin inhibitors Delivery routes: Administered orally in tablet, caplet, capsule, suspension, and liquid form at home or in the hospital; octreotide is administered by subcutaneous injection or by continuous intravenous (IV) infusion while the patient is hospitalized How these drugs work: Adsorbents bind with intestinal contents, increasing their density. Adsorbents such as kaolin and charcoal may inhibit the absorption of other antidiarrheals, making them ineffective. Bulk-forming agents treat diarrhea by absorbing water within the bowel and producing a formed stool. Mucosal prostaglandin inhibitors stimulate the absorption of fluid and electrolytes through the intestinal wall. They also reduce intestinal inflammation and motility by inhibiting prostaglandin synthesis. Moreover the mucosal prostaglandin inhibitor bismuth subsalicylate is thought to have antimicrobial action against Escherichia coli, a bacterium that causes diarrhea. Opioids bind to receptor sites in the intestinal tract, slowing intestinal motility. Synthetic octapeptides inhibit the release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide, slowing intestinal motility. Piperidine derivatives reduce peristolic activity by acting directly on the intestinal wall muscles. The reduction in peristolic activity delays intestinal content transit time, increases fecal density, and reduces fluid and electrolyte loss. Side effects: Side effects vary according to the drug class. Adsorbents such as bismuth subsalicylate may cause temporary darkening of the tongue and stools. Bulk-forming agents such as polycarbophil may cause abdominal dis73
Antidiarrheal agents
Salem Health: Cancer
Common Antidiarrheal Agents Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Aspirin
Bayer aspirin, Ecotrin, Empirin, Halfprin, Norwich Extra Strength
Mucosal prostaglandin inhibitor
Oral
Radiation therapy-induced diarrhea
Bismuth subsalicylate
Bismatrol, Bismatrol Extra, Kaopectate, Extra strength Kaopectate, Pepto-Bismol, PeptoBismol Maximum Strength, Pink Bismuth
Adsorbent, mucosal prostaglandin inhibitor
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Charcoal
Charcoal Plus DS, CharcoCaps
Adsorbent
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Difenoxin hydrochloride and atropine sulfate
Motofen
Opioid
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Diphenoxylate hydrochloride and atropine sulfate
Logen, Lomanate, Lomotil, Lonox
Opioid
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
comfort, bloating, dependence (with prolonged use), increased flatus, and intestinal blockage. Mucosal prostaglandin inhibitors such as aspirin may cause allergic reaction, bruising, gastrointestinal bleeding, hearing loss, hepatitis, itching, low platelet count, nausea, prolonged bleeding time, ringing in the ears, and rash. Opioids such as diphenoxylate hydrochloride and atropine sulfate may cause abdominal discomfort, allergic reaction, blurred vision, confusion, dizziness, dry mouth, dry skin, euphoria, headache, inability to urinate, increased heart rate, itching, loss of appetite, nausea, pancreatitis, rash, respiratory depression, restlessness, sedation, swollen gums, and vomiting. Piperidine derivatives such as loperamide may cause abdominal pain, distention or discomfort; allergic reaction; constipation; dizziness; dry mouth; drowsiness; fatigue; nausea; rash; and vomiting. 74
The synthetic octapeptide, octreotide, may cause abdominal discomfort, arrhythmias, backache, blurred vision, burning or pain at the injection site, cold symptoms, fat malabsorption, flatulence, flulike symptoms, flushing, gallbladder problems, hair loss, hyperglycemia, hypoglycemia, hypothyroidism, joint pain, low heart rate, nausea, pancreatitis, redness at the injection site, swelling, urinary tract infection, and vomiting. Collette Bishop Hendler, R.N., M.S. u
For Further Information Drug Facts and Comparisons 2008. 62d ed. St. Louis: Wolters Kluwer Health, 2008. Karch, Amy M. 2008 Lippincott’s Nursing Drug Guide. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2008.
Salem Health: Cancer
Antiestrogens
Common Antidiarrheal Agents (continued) Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Kaolin and pectin
Kao-Spen, Kapectolin, KP
Adsorbent
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Loperamide
Imodium, Imodium A-D, Piperidine derivative Kaopectate II Caplets, Maalox Anti-Diarrheal Caplets, Pepto Diarrhea Control
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Octreotide
Sandostatin, Sandostatin LAR
Synthetic octapeptide
Subcutaneous injection, IV
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Paregoric
Camphorated Tincture of Opium
Opioid
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Polycarbophil
Equalactin, Fiberall, FiberCon, Fiber-Lax, Konsyl Fiber, Mitrolan, Phillips’ Fibercaps
Bulk-forming agent
Oral
Diarrhea associated with colon cancer; lymphoma; thyroid cancer; pancreatic cancer; pheochromocytoma; cancer treatment (antibiotic therapy, bone marrow transplantation, chemotherapy, radiation therapy)
Nursing 2008 Drug Handbook. Philadelphia: Lippincott Williams & Wilkins, 2008.
mone-sensitive breast cancers because of their ability to inhibit estrogen-stimulated cancer growth.
See also Antinausea medications; Chemotherapy; Colorectal cancer; Crohn disease; Diarrhea; Enteritis; Gastrointestinal complications of cancer treatment; Inflammatory bowel disease; Laxatives; Side effects; Symptoms and cancer.
Cancers treated: Breast cancer
u Antiestrogens Category: Chemotherapy and other drugs ATC code: 102BA Definition: Antiestrogens interfere with the function of estrogen receptors. They are used in the treatment of hor-
Subclasses of this group: Selective estrogen receptor modulators (SERMs), estrogen receptor downregulators Delivery routes: Administered either intramuscularly or orally in capsule, tablet, or solution form on an inpatient, outpatient, or at-home basis How these drugs work: In 1962, ICI Pharmaceuticals synthesized the antiestrogen tamoxifen, what they hoped to be a new oral contraceptive. Although tamoxifen did not prove effective as a contraceptive, the discovery of hormone receptors in breast tissue by Elwood V. Jensen in 1966 led some researchers to believe that tamoxifen could 75
Antifungal therapies
Salem Health: Cancer
Common Antiestrogens for Breast Cancer Treatment Drug
Brands
Subclass
Delivery Mode
Fulvestrant Raloxifene Tamoxifen Toremifene
Faslodex Evista Nolvadex, Soltamox Fareston
Estrogen receptor downregulators SERMs SERMs SERMs
Intramuscular Oral Oral Oral
be a therapeutic option in hormone-sensitive breast cancer. Clinical research in the early 1970’s produced evidence that tamoxifen was effective in advanced breast cancers, and by the 1980’s it became the treatment option of choice for hormone-sensitive breast cancers in pre- and postmenopausal women as well as men. Later it was approved for use in reducing the risk of breast cancer in patients who are susceptible to the disease. Tamoxifen is a selective estrogen receptor modulator (SERM), a subclass of antiestrogens that act by binding to and changing estrogen receptors, resulting in both estrogenic and antiestrogenic effects depending on cell type. Antiestrogenic effects result in a slowing of cancer cell cycling and impaired deoxyribonucleic acid (DNA) replication. Estrogen receptor downregulators are used as a second-line treatment in hormone-sensitive breast cancer and act similarly to SERMs in that they antagonize the estrogen receptors of breast cells. These drugs, however, are pure estrogen receptor antagonists: Independent of cell type, they completely degrade the estrogen receptor, resulting in a total loss of transcriptional activity in cancer cells.
u Antifungal therapies
Side effects: Common side effects of antiestrogens are menopausal symptoms (hot flashes, night sweats), vaginal discharge, vaginal irritation, vaginal bleeding, gastrointestinal (GI) symptoms (nausea and vomiting, constipation, diarrhea), fatigue, muscle cramps, joint pain, and thromboembolism. Although tamoxifen inhibits estrogen receptors in breast cells, it is a partial agonist in the endometrium and can cause endometrial changes, such as endometrial cancer, polyps, endometriosis, uterine fibroids, and ovarian cysts. Amber L. Fields, M.S.
Delivery routes: Antifungal agents can be administered orally in capsules, tablets, or liquid suspension or vaginally by vaginal tablet. The can be administered in the hospital or at home. Some antifungal agents are administered by intravenous (IV) infusion while the patient is hospitalized. As the patient’s condition improves, IV infusions may be administered at home or in an outpatient treatment center.
See also Antiandrogens; Breast cancer in men; Breast cancers; Chemoprevention; Ductal carcinoma in situ (DCIS); Estrogen receptor downregulator (ERD); Estrogenreceptor-sensitive breast cancer; Fertility drugs and cancer; Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Isoflavones; Mastectomy; Phytoestrogens; Progesterone receptor assay; Receptor analysis; Soy foods. 76
Category: Chemotherapy and other drugs ATC code: J02 Definition: Antifungal therapies form a class of antiinfective drugs that are effective against fungi such as Aspergillus, Candida, Cryptococcus, Fusarium, and Scedosporium apiospermum. Cancers treated: Antifungal agents are used to treat fungal infections that develop in patients with any type of cancer. Fungal infections commonly occur in patients with acute lymphoblastic leukemia and acute myelocytic and monocytic leukemia. Antifungal agents are also used to prevent fungal infections in patients who have undergone bone marrow or stem cell transplantation. Subclasses of this group: Polyene antibiotics, echinocandins, bis-triazole derivatives, fluorinated pyrimidines, synthetic triazoles, imidazole derivatives, polyene macrolides
How these drugs work: Polyene antibiotics bind to components of the fungal cell membrane and alter the cell’s permeability, causing fungal cell death. Echinocandins work by inhibiting an enzyme that is essential to the fungal cell wall. Bis-triazole derivatives inhibit the fungal cytochrome P-450 and weaken the fungal cell wall, causing fungal cell death. Fluorinated pyrimidines interfere with protein synthesis within the fungal cells, causing cell death. Synthetic triazoles inhibit fungal cell wall synthesis, causing cell wall instability and eventually cell death. Imidazole derivatives inhibit the formation of ergosterol, a
Salem Health: Cancer
Antifungal therapies
sterol necessary for fungal cell-wall synthesis. Without ergosterol, the fungal cell wall becomes permeable and unstable, causing cell death. Polyene macrolides bind to sterols, making the fungal cell wall permeable. This increased permeability allows intracellular components to leak from the fungal cell, causing fungal cell death. Side effects: Side effects vary according to the antifungal agent. The amphotericans are potent antifungals that have toxic side effects, including kidney and liver failure. Side effects that may occur with antifungal agents include abdominal pain, abnormal dreams, allergic reaction, anemia, anxiety, back pain, bacterial bloodstream infection, bloody nose, bloody urine, blurred vision, cardiac arrest, chest pain, chills, cholestatic jaundice, confusion, constipation, cough, cytomegalovirus (CMV) infection, diar-
rhea, dyspepsia, edema, elevated sodium levels, enlarged breasts with tenderness, epigastric pain, fatigue, flushing, hives, gum disease, gastrointestinal bleeding, hallucinations, headache, heart failure, herpes simplex infection, hypotension, hyperglycemia, hypertension, hyperventilation, infection, insomnia, impotence, itching, light sensitivity, low calcium levels, low magnesium levels, low phosphorus levels, low potassium levels, low white blood cell count, loss of appetite, mouth ulceration, muscle aches, nausea, nervousness, petechiae, pulmonary edema, rash, respiratory failure, rhinitis, rigors, severe depression, severe vaginal bleeding, shortness of breath, sinusitis, sore throat, suicidal tendencies, sweating, taste perversion, upper respiratory tract infection, urinary tract infection, vomiting, and weakness. Collette Bishop Hendler, R.N., M.S.
Common Antifungal Agents Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Amphotericin B cholesteryl sulfate complex
Amphotec
Polyene antibiotic
Continuous or Invasive aspergillosis in patients with cancer intermittent IV (especially those with acute leukemia) who cannot infusion tolerate amphotericin B deoxycholate
Amphotericin B desoxycholate
Polyene Amphocin, Amphotericin B antibiotic for injection, Fungizone
IV infusion
Prevention of fungal infection in bone marrow transplant patients; treatment of systemic infections caused by histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis, disseminated candidiasis, aspergillosis, phycomycosis, zygomycosis, or meningitis in patients with cancer
Amphotericin B lipid complex
Abelcet
Polyene antibiotic
IV infusion
Fungal infections including Aspergillus and Candida in cancer patients who cannot tolerate amphotericin B desoxycholate
Amphotericin B liposomal
AmBisome
Polyene antibiotic
IV infusion
Suspected fungal infections in patients with low white blood cell count and fever; fungal infections caused by Aspergillus, Candida, or Cryptococcus species in cancer patients who cannot tolerate amphotericin B desoxycholate
Anidulafungin
Eraxis
Echinocandin IV infusion
Bloodstream infection and intra-abdominal abscess or peritonitis caused by Candida in patients with cancer
Caspofungin
Cancidas
Echinocandin IV infusion
Bloodstream infection and intra-abdominal abscess or peritonitis or pleural space infections caused by Candida in patients with cancer; aspergillosis in cancer patients who cannot tolerate all forms of amphotericin B (continued on page 78)
77
Antimetabolites in chemotherapy
Salem Health: Cancer
Common Antifungal Agents (continued) Drug (Other Names) Brands
Subclass
Delivery Mode Conditions Treated
Fluconazole
Diflucan
Bis-triazole derivative
Oral, IV infusion
Prevention of candidiasis in bone marrow transplant patients; cryptococcal meningitis or oropharyngeal, vulvovaginal, or systemic candidiasis
Flucytosine (5-FC, 5-fluorocytosine)
Ancobon
Fluorinated pyrimidine
Oral
Bloodstream infection, endocarditis, urinary tract infection, or lung infection caused by Candida or Cryptococcus in patients with cancer; meningitis caused by Cryptococcus in patients with cancer
Itraconazole
Sporanox
Synthetic triazole
Oral, IV infusion
Aspergillosis, oropharyngeal and esophageal candidiasis, blastomycosis, or nonmeningeal histoplasmosis in patients with cancer
Ketoconazole
Nizoral
Imidazole derivative
Oral
Oral candidiasis, systemic candidiasis, coccidioidomycosis, blastomycosis, histoplasmosis, chromomycosis, paracoccidioidomycosis, and severe dermatophyte infections that do not respond to other therapy in patients with cancer
Micafungin sodium
Mycamine
Echinocandin IV
Prevention of Candida infection in stem cell transplant patients and treatment of esophageal candidiasis
Nystatin
Mycostatin, Nilstat, Nystex
Polyene macrolide
Oral, vaginal
Intestinal, oral, or vaginal candidiasis in patients with cancer
Posaconazole
Noxafil
Triazole derivative
Oral
Prevention of Aspergillus and Candida infections in cancer patients
Voriconazole
Vfend
Synthetic triazole derivative
Oral, IV infusion
Candida infections of the bloodstream, esophagus, kidney, abdomen, bladder wall, wound, and skin in patients with cancer. Aspergillosis and serious infections caused by Fusarium and Scedosporium apiospermum in patients with cancer who cannot tolerate other antifungal therapy.
u For Further Information Drug Facts and Comparisons 2008. 62d ed. St. Louis: Wolters Kluwer Health, 2008. Karch, Amy M. 2008 Lippincott’s Nursing Drug Guide. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2008. Nursing 2008 Drug Handbook. Philadelphia: Lippincott Williams & Wilkins, 2008.
See also Aflatoxins; Candidiasis; Infection and sepsis; Neutropenia; Side effects.
78
u Antimetabolites in
chemotherapy Category: Chemotherapy and other drugs ATC code: 101B Definition: Antimetabolites are drugs that interfere with deoxyribonucleic acid (DNA) replication processes in cells. These agents have a structure very similar to that of some of the components involved in the synthesis of nucleotides, the structural units of DNA. This similarity causes the cell to mistake the antimetabolite for a natural component, allowing the drug to effectively inhibit nucleotide synthesis. Nucleotide synthesis and subsequent DNA replication are processes that a cell must undergo before it can divide, and therefore quickly growing tumor cells are
Salem Health: Cancer particularly susceptible to interference with DNA replication. Further, inhibiting DNA replication triggers the activation of death-promoting pathways in these cells, causing the antimetabolite to decrease the tumor size. Cancers treated: Many solid tumors, including breast, colon, lung (small-cell and non-small-cell), ovarian, and head and neck cancers; several leukemias and lymphomas, including acute lymphocytic leukemia, indolent B-cell lymphoma, and non-Hodgkin lymphoma Subclasses of this group: Folic acid antagonists, pyrimidine antagonists, purine antagonists, sugar-modified analogs, ribonucleotide reductase inhibitors Delivery routes: Intravenous (IV), oral, intra-arterial (into an artery), intrathecal (into the spinal canal) How these drugs work: The development of antimetabolite therapy was based on the understanding of the importance of DNA replication in cell division and proliferation. Antimetabolites inhibit DNA replication through one or both of two mechanisms. First, these drugs can inhibit the synthesis of nucleotides, the structural molecules that make up the DNA strand. The four nucleotides that are used to replicate DNA are divided into two categories. The two purine nucleotides are adenine and guanine, while the two pyrimidines are cytosine and thymine. With the exception of thymine, these nucleotides also serve as the structural units for ribonucleic acid (RNA). In RNA, thymine is replaced with another nucleotide, uracil. When the synthesis of these molecules is inhibited, the cellular pool of nucleotides is reduced, limiting the ability of the cell to synthesize new DNA strands. The second mechanism of action is the actual incorporation of the antimetabolite into the DNA itself. It is known that the enzymes responsible for DNA replication can mistake the agents for DNA nucleotides, but the direct consequences of this mistaken identity are as of yet unknown. There are four main subclasses of antimetabolites: folic acid antagonists, pyrimidine and purine antagonists, sugar-modified analogs, and ribonucleotide reductase inhibitors. Folic acid (folate) antagonists are thought to act primarily through inhibition of the dihydrofolate reductase (DHFR) enzyme. DHFR functions to change the structure of folic acid, also known as vitamin B9, allowing it to be used in various metabolic processes that result in the formation of nucleotides. Inhibition of DHFR therefore reduces the production of many of the nucleotides essential for DNA replication. Methotrexate is the prototypical folate antagonist, and it has been successfully used as an anticancer drug in the clinic for decades. One of the reasons that methotrexate is so efficacious is that once it en-
Antimetabolites in chemotherapy ters the cell, it is chemically modified in such a way that it is unable to exit the cell. This causes the intracellular concentration of methotrexate to remain very high. Pyrimidine and purine antagonists target tumor cells via a dual mechanism of action-inhibition of nucleotide synthesis and incorporation into DNA. To inhibit nucleotide synthesis, pyrimidine antagonists can directly inhibit the thymidylate synthase protein, a critical enzyme in the formation of the thymine nucleotide. When thymidylate synthase mistakes pyrimidine antagonists for their natural substrate, the agent inhibits and traps the enzyme in the middle of the catalysis reaction. A stable complex of the enzyme and drug are formed, decreasing the number of enzymes available for the further formation of thymine. Because there is a relatively small concentration of thymine normally in the cell, reducing these pools can drastically inhibit DNA synthesis. The most common pyrimidine antagonists, fluoropyrimidines, have also been found to incorporate into DNA and RNA, replacing the nucleic acids thymine and uracil, respectively. This incorporation occurs at a relatively low level, however, and is not thought to be the primary cause for cell death. Fluoropyrimidines, especially 5-fluorouracil, are used to treat many commonly occurring cancers, including colorectal, breast, gastric, pancreatic, and head and neck tumors. Compared with pyrimidine antagonists, purine antagonists incorporate more readily into nucleic acids. Purine antagonists also inhibit the synthesis of nucleic acids. Each purine antagonist may inhibit purine synthesis at different points along the metabolic pathway, but their effects are perhaps most notable on the enzymes PRPP amidotransferase and IMP dehydrogenase. Purine antagonists are considered to be self-limiting, meaning that the biochemical effects produced by the agent can antagonize each other. For example, when purine synthesis is inhibited, total DNA replication is reduced, thereby diminishing the potential for incorporation of the drug into the DNA. The main purine antagonists are mercaptopurine and thioguanine, and they are used primarily to treat leukemia, especially in children. Sugar-modified analogs were discovered in screening programs established after the clinical success of pyrimidine and purine antagonists was established. Widely used in leukemia therapy, the sugar-modified analog cytarabine was isolated from a species of sponge from the Caribbean Sea. It is characterized by a modification of the sugar moiety, not the base portion, of the nucleotide analog. Unlike the other pyrimidine and purine antagonists, which can affect both DNA and RNA, cytarabine almost exclusively affects DNA. The primary mechanism of action of cytarabine is incorporation into the DNA in place of the 79
Antimetabolites in chemotherapy
Salem Health: Cancer
cytosine nucleotide. The other main sugar-modified analog, fludarabine, has a modification in both the base and sugar moiety. Hydroxyurea is the prototypical ribonucleotide reduc-
tase inhibitor. The enzyme ribonucleotide reductase has a global effect on all DNA synthesis, as it is the enzyme responsible for converting the precursor ribonucleoside diphosphates to deoxyribonucleotide diphosphates.
Common Antimetabolites
80
Drug (Other Names)
Brands
Subclass
Delivery Mode
Cancers Treated
Azacytidine (Aza-C, 5-AC)
Vidaza
Pyrimidine antagonist
IV
Chronic myelocytic leukemia
Capecitabine Xeloda (prodrug of fluorouracil)
Pyrimidine antagonist
Oral
Metastatic colorectal cancer, metastatic breast cancer
Chlorodeoxyadenosine (CdA)
Cladribine, Leustatin
Purine antagonist
IV
Indolent B-cell lymphocytic leukemia (especially hairy cell leukemia); may have activity in chronic lymphocytic leukemia and non-Hodgkin lymphoma
Cytarabine (ara-C)
Cytosar-U, DepoCyt
Sugar-modified analog
IV, intrathecal, subcutaneous
Acute nonlymphocytic leukemia, advanced non-Hodgkin lymphoma, chronic myelocytic leukemia, meningeal leukemia
Fludarabine (F-ara-A)
Fludara
Sugar-modified analog
IV, oral
Refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma
Fluorodeoxyuridine (FdUrd, 5-FUdR, FdUMP)
FUDR, Floxuridine
Pyrimidine antagonist
Hepatic arterial infusion
Cancer of the gastrointestinal tract, especially tumors that have metastasized to the liver
Fluorouracil (FUra, 5-FU)
Adrucil
Pyrimidine antagonist
IV
Many solid cancers, including colorectal, breast, head and neck, gastric, and pancreatic tumors
Gemcitabine
Gemzar
Pyrimidine antagonist
IV
Locally advanced or metastatic lung cancer, pancreatic cancer, ovarian cancer, metastatic breast cancer
Hydroxyurea (HU, hydroxycarbamide)
Droxia, Hydrea
Ribonucleotide reductase inhibitors
oral
Chronic myelocytic leukemia, head and neck cancer, cervical cancer, ovarian cancer, melanoma
Mercaptopurine (MP, 6-MP)
Purinethol
Purine antagonist
Oral
Acute lymphocytic leukemia
Methotrexate (MTX, amethopterin)
Trexall, Rheumatrex
Folic acid antagonist
Oral, IV, intra-arterial, intrathecal
Breast cancer, bone cancers including osteogenic sarcoma, acute lymphocytic leukemia, head and neck cancer, bladder cancer, and several other solid tumors including lung, uterine, and cervical cancer
Pentostatin (2′-deoxycoformycin, dCF)
Nipent
Purine antagonist
IV
Indolent B-cell lymphocytic leukemia (especially hairy cell leukemia); may have activity in chronic lymphocytic leukemia
Thioguanine (TG, 6-TG)
Thioguanine Tabloid
Purine antagonist
Oral
Acute nonlymphocytic leukemia
Tiazofurin
Riboxamide
Purine antagonist
IV
Currently in clinical testing for several leukemias, especially chronic myelocytic leukemia
Salem Health: Cancer Side effects: In general, antimetabolites are more toxic to cells that are actively dividing, compared to cells that are not. Because tumor cells rapidly proliferate, antimetabolites can target these cells quite effectively. The drugs cannot differentiate, however, between cancer cells and rapidly dividing healthy cells, such as those that occur in the bone marrow, the lining of the gastrointestinal tract, and hair follicles. Therefore, most side effects induced by these drugs are dependent on which normal cells are affected. Methotrexate toxicity is mainly confined to the bone marrow and the gastrointestinal tissue lining. The side effects that can result in systemic therapy with pyrimidine and purine antagonists are mainly bone marrow suppression, although gastrointestinal toxicity can occur. Fluoropyrimidines, in particular, induce nausea, vomiting, anorexia, and diarrhea. Lisa M. Cockrell, B.S. u For Further Information Jackman, Ann L., ed. Antifolate Drugs in Cancer Therapy. Totowa, N.J.: Humana Press, 1999. Kantarjian, Hagop M., et al. The MD Anderson Manual of Medical Oncology. New York: McGraw-Hill, 2006. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. Pratt, William B., et al. The Anticancer Drugs. 2d ed. New York: Oxford University Press, 1994. Rustum, Youcef M., ed. Fluoropyrimidines in Cancer Therapy. Totowa, N.J.: Humana Press, 2003. Skeel, Roland T. Handbook of Cancer Chemotherapy. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007. u
Other Resources
National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Antineoplastics in chemotherapy; Chemotherapy.
u Antinausea medications Category: Chemotherapy and other drugs ATC code: A04A Definition: Antinausea agents, or antiemetics, encompass a range of drug classes that act on the peripheral and central nervous systems to prevent nausea and vomiting. In patients with cancer, antiemetics are used to control acute, delayed, and anticipatory nausea and vomiting that result from chemotherapy.
Antinausea medications Cancers treated: Indirectly used in the treatment of many cancers to control nausea and vomiting associated with many chemotherapy regimens Subclasses of this group: Serotonin-3 antagonists, substituted benzamides, corticosteroids, pheothiazines, benzodiazepines, butyrophenones, cannabinoids, neurokinin-1 antagonists Delivery routes: Administered to inpatients and outpatients as oral tablets, capsules, or liquids; as intravenous or intramuscular solutions; or as rectal suppositories How these drugs work: Nausea and vomiting, or emesis, are the most common chemotherapy-associated toxicities, affecting more than 75 percent of patients, especially with the development of combination regimens. The effective use of antinausea agents to improve chemotherapy tolerance is one of the most important advances of supportive cancer care. Among the first of agents to deter emesis was metoclopramide, a substituted benzamide that acts as a dopamine receptor antagonist and, at higher doses, as an additional serotonin receptor antagonist. Although the exact mechanisms of nausea and vomiting reflexes have not been determined, neurotransmitter blockade at dopaminergic, serotonergic, neurokinin-1, and other receptors in the central nervous system or peripherally in the gastrointestinal tract successfully controls the reactions. Like metoclopramide, phenothiazines such as chlorpromazine and butyrophenones such as haloperidol also prevent nausea and vomiting by dopaminergic blockade. Dopamine antagonism from these three subclasses provides relief of moderate emesis. The more newly developed serotonin-3 (5HT-3) receptor antagonists work peripherally, especially in the small intestine, and are extremely effective for the treatment and prevention of acute emesis. Ondansetron, granisetron, and dolasetron are equivalent in efficacy and may provide total receptor blockade, as evidenced by their dose-related efficacy plateaus. Palonsetron, a newer agent, is longer acting than others in the subclass. Because acute emesis is associated with peripheral control and delayed emesis is associated with central control, 5HT-3 antagonists are more effective in treating acute nausea and vomiting, which occurs in the first twenty-four hours after chemotherapy is administered. Benzodiazepines such as lorazepam have some antiemetic activity by blocking cortical input to the emetic center but are more useful for their sedative and anxiolytic effects, which make the agents ideal for combination regimens. In addition, these drugs induce retrograde amnesia, which is successful in preventing anticipatory nausea and 81
Antinausea medications
Salem Health: Cancer
Common Antinausea Agents Drug
Brands
Subclass
Delivery Mode
Type of Nausea Treated
Aprepitant
Emend
Neurokinin-1 receptor antagonist
Oral
Delayed prophylaxis, primarily (combined with corticosteroid)
Chlorpromazine, prochlorperazine, promethazine
Thorazine, Compazine, Phenergan
Phenothiazines
Oral, IV, rectal
Mild-to-moderate acute (combined with corticosteroid or 5HT-3 antagonist); breakthrough
Dexamethasone, methylprednisolone
Decadron, Medrol, MethaPred
Corticosteroids
Oral, IV
Mild-to-moderate acute as monotherapy; moderate-to-severe acute when combined with 5HT-3 antagonist; delayed prophylaxis when combined with NK-1 inhibitor; delayed postchemotherapy when combined with substituted benzamide; anticipatory
Cannabinoids
Oral
Anticipatory, breakthrough, or refractory nausea and vomiting
Dronabinol Haolperidol, droperidol
Haldol, Inapsine
Butyrophenones
Oral, IV, intramuscular
Mild-to-moderate acute (not recommended agents because of toxicities)
Lorazepam
Ativan
Benzodiazepine
Oral, IV, intramuscular
Anticipatory or breakthrough
Metoclopramide
Reglan
Substituted benzamide
Oral, IV
Acute or anticipatory (not as first-line agent); delayed when combined with corticosteroid
Ondansetron, granisetron, dolasetron, palonosetron
Zofran, Kytril, Anzemet,
Serotonin-3 receptor antagonists
Oral, IV
Uncontrolled mild, moderate, or severe acute; Moderate-to-severe acute (combined with corticosteroid); Delayed (less effective than NK-1 inhibitor)
vomiting that may occur with repeat chemotherapy administration. Neurokinin-1 (NK-1) receptors are more recently studied targets of nausea mechanisms; the only currently approved agent in the NK-1 antagonist class is aprepitant. Because NK-1 mediates substance P activation of NK-1 receptors in the brainstem, aprepitant’s NK-1 receptor antagonism is useful for the treatment of delayed emesis, which is more centrally mediated. Although its efficacy alone is not yet confirmed, aprepitant successfully prevents acute and delayed nausea and vomiting when combined with serotonin antagonists and corticosteroids. Corticosteroids, especially dexamethasone, methylprednisolone, and prednisone, have a confirmed effect, alone or in combination, against moderate nausea and vomiting, despite an unknown mechanism of action and a lack of receptor blockade. Corticosteroids are often the second drug in a combination regimen with dopamine, serotonin, or NK-1 receptor antagonists. Lastly, cannabinoids such as dronabinol act centrally 82
with psychotropic activity to provide limited but affirmed antinausea activity. They can be used for patients with moderate emesis and poor tolerance or response to other agents or for patients who need control of breakthrough pain. Side effects: Each subclass of antinausea agents is associated with different side effects; successful combination regimens provide greater efficacy without overlapping drug toxicities. Metoclopramide side effects are primarily related to dopamine antagonism and include extrapyramidal reactions, including acute dystonic reactions. Akathisia, or restlessness, is common and may persist for hours. Drowsiness and diarrhea are also possible. Phenothiazines and butyrophenones also cause dopaminerelated drowsiness, diarrhea, and extrapyramidal reactions. In addition, constipation, dizziness, and hypotension have been noted. Lorazepam is associated with sedation in addition to amnesia, confusion, transient enuresis, and blurred vision. Serotonin antagonists all have similar side effects
Salem Health: Cancer of mild to moderate headache in 20 to 30 percent of patients and mild, uncommon occurrences of constipation or diarrhea. Corticosteroids may cause insomnia, hyperglycemia, gastrointestinal upset, and, rarely, psychosis. NK-1 antagonism leads to fatigue, dizziness, headache, and gastrointestinal disturbances. Side effects of dronabinol include dysphoria, hallucinations, dizziness, dry mouth, sedation, and disorientation. Nicole M. Van Hoey, Pharm.D. u For Further Information Grunberg, S. M. “Antiemetic Activity of Corticosteroids in Patients Receiving Cancer Chemotherapy: Dosing, Efficacy, and Tolerability Analysis.” Annals of Oncology 18, no. 2 (February, 2007): 233-240. Jordan, K., H. J. Schmoll, and M. S. Aapro. “Comparative Activity of Antiemetic Drugs.” Critical Reviews in Oncology/Hematology 61, no. 2 (February, 2007): 162175. Roila, F., S. Fatigoni, and G. Ciccarese. “Daily Challenges in Oncology Practice: What Do We Need to Know About Antiemetics?” Annals of Oncology 17, suppl. 10 (September, 2006): 90-94.
See also Chemotherapy; Gastrointestinal complications of cancer treatment; Nausea and vomiting; Topoisomerase inhibitors.
u Antineoplastics in
chemotherapy Category: Chemotherapy and other drugs ATC code: 101 Also known as: Chemotherapeutic agents, antitumor compounds, cytotoxic antibiotics Definition: Antineoplastics are anticancer drugs used to treat malignancies and cancerous growths. Cancers treated: Various types of cancers Subclasses of this group: Alkylating agents, antimetabolites, mitotic inhibitors, topoisomerase inhibitors, cytotoxic antibiotics Delivery routes: Oral, intravenous, intramuscular, or subcutaneous injection How these drugs work: Antineoplastics are chemicals used to treat cancer and inhibit tumor cell growth. The term “neoplastic” refers to cancer cells, so the term “antineoplastic” literally means “anticancer cell.” Antineo-
Antineoplastics in chemotherapy plastic agents are used to stop tumor development or prevent the spread of cancer and to relieve some symptoms associated with cancer or to prolong patient survival. Antineoplastics are also sometimes referred to as chemotherapeutic agents, antitumor compounds, or cytotoxic antibiotics. The first antineoplastic agents were used in the 1940’s and either were made from synthetic chemicals or were derived from natural plants. More than fifty antineoplastic agents are approved by the Food and Drug Administration (FDA) for use in the United States. There are several major categories of antineoplastic agents based on their origins, chemical structures, and the how they work. These classifications include alkylating agents, antimetabolites, cytotoxic antibiotics, mitotic inhibitors, and topoisomerase inhibitors. Antineoplastic agents inhibit tumor cell growth using different mechanisms, with many affecting deoxyribonucleic acid (DNA) synthesis and interfering with cell division. Others work by altering immune function or affecting hormonal status of tumors. Antineoplastic drugs are either cycle specific or non-cycle specific, with cycle specific drugs acting only during certain phases of the cell cycle while non-cycle specific drugs may act during any cell cycle phase. The largest group of antineoplastic compounds is the alkylating agents, which were among the first anticancer drugs used. These compounds are the most commonly used agents in chemotherapy. Alkylating agents work by cross-linking DNA and preventing DNA bases from pairing up correctly, which interferes with DNA synthesis. Categories of alkylating agents include busulfans, alkylating-like drugs, nitrogen mustards, ethylenimines, and nitrosureas. Nitrogen mustards comprise the largest group of alkylating drugs and are particularly useful for treating neoplasms that increase white blood cells, such as lymphomas and leukemias, because they result in leukopenia. Unlike most other types of antineoplastic agents, nitrosureas can cross the blood-brain barrier and thus are useful for treating brain tumors. Also included among the alkylating agents are the metal salts, such as carboplatin and cisplatin. Other examples of alkylating agents include chlorambucil, cyclophosamide, and thiotepa. Antimetabolites work by interfering with cancer cell metabolism. Antimetabolites are analogs of normal metabolites (nucleic acids) and act by replacing natural substances. Since these compounds structurally resemble DNA base pairs, they become incorporated into DNA, thus interfering with DNA synthesis. Antimetabolites are cell-cycle specific and attack cells only during certain cell cycle phases. Most antimetabolites are preferentially effective against cells that are actively synthesizing DNA. 83
Antineoplastics in chemotherapy
Salem Health: Cancer
Antimetabolites are classified by the metabolite that they affect and include folic acid, purine, and pyrimidine analogs. All these compounds function by interfering with DNA synthesis in some way, either by directly inhibiting important enzymes or by being converted into substances that impair DNA synthesis. Methotrexate, a folic acid analog, inhibits an enzyme necessary for regeneration of intermediates required for DNA synthesis. Pyrimidine and purine analogs are converted into compounds that inhibit enzymes involved in DNA synthesis. 5-Fluorouracil and cytarabine are examples of pyrimidine analogs. Purine analogs include 6-mercaptopurine and pentostatin. Some antineoplastic drugs are considered antimitotics or mitotic inhibitors and bind to tubulin, preventing polymerization of microtubules necessary for mitotic spindle formation. This prevents mitosis and arrests cells during metaphase. Many of the vinca alkaloids function as mitotic inhibitors. Topoisomerase inhibitors interfere with
DNA synthesis by disrupting the function of the enzymes topoisomerases I and II, which are important in tubulin formation. Topoisomerases control the structure of DNA necessary for replication, and compounds that inhibit these enzymes work by preventing DNA from being unwound, a step required for DNA synthesis. Topoisomerase inhibitors include ironotecan, topotecan, etoposide, and teniposide. Many antineoplastic compounds are derived from plants and are known as natural products. They vary mechanistically, with some functioning as alkylating agents, some inhibiting mitosis, and some affecting enzymes important in DNA synthesis. The vinca alkaloids, made from the periwinkle plant (Catharanthus rosea), and the taxanes, made from the Pacific yew tree (Taxus), work as mitotic inhibitors by disrupting microtubule formation. Podophyllotoxins, derived from the mayapple plant (Podophyllum peltatum), and camptothecans, from the Asian “Happy
Common Antineoplastic Agents
84
Drug (Other Names)
Brands
Subclass
Delivery Mode
Cancers Treated
Asparaginase
Elspar
Miscellaneous
IV, intramuscular, subcutaneous
Acute lymphoblastic leukemia
Bleomycin
Blenoxane
Cytotoxic antibiotic
IV
Testicular cancer, squamous cell carcinoma, Hodgkin disease
Busulfan
Busulfex
Alkylating agent
Oral, IV
Chronic myelogenous leukemia, other blood cancers
Carboplatin (CBDCA)
Paraplatin
Alkylating agent
IV
Ovarian carcinoma
Cisplatin (CDDP)
Platinol-AQ Alkylating agent
IV
Testicular, ovarian, and bladder cancers
Chlorambucil
Leukeran
Alkylating agent
IV, oral
Leukemias, lymphomas, various cancers, Hodgkin disease
Cyclophosphamide (CTX)
Cytoxan
Alkylating agent
IV, oral
Leukemias, lymphomas, ovarian and breast cancers
Cytarabine (Ara C)
Cytostar-U
Antimetabolite
IV, subcutaneous
Leukemias, non-Hodgkin lymphoma
Dactinomycin (actinomycin D)
Cosmogen
Cytotoxic antibiotic
IV
Testicular carcinomas, sarcomas, other solid tumors
Doxorubicin Adriamycin, Cytotoxic (hydroxyldaunorubicin) Rubex antibiotic
IV
Leukemias, Hodgkin lymphoma, bladder cancer, breast cancer, other solid tumors
Etoposide
Etophos, Vepesid
Mitotic inhibitor
Oral, IV
Leukemias, lymphomas, lung, ovarian, and testicular cancers
5-fluorouracil (5-FU)
Adrucil
Antimetabolite
IV
Colon, rectal, breast, stomach, pancreatic cancers
Ifosfamide (isophosphamide)
Ifex
Alkylating agent
IV
Germ-cell testicular cancer, sarcomas
Salem Health: Cancer
Antineoplastics in chemotherapy
Tree” (Camptotheca acuminate), function as topoisomerase inhibitors. Most of these compounds are effective against tumor cells during various cell cycle phases. Another category of antineoplastics includes the antitumor or cytotoxic antibiotics, many of which are produced by species of the soil fungus Streptomyces. There are several cytotoxic antibiotics, such as Dactinomycin (actinomycin D), bleomycin, and doxorubicin. Cytotoxic antibiotics generally act during various phases of the cell cycle. Dactinomycin works by binding to DNA and preventing ribonucleic acid (RNA) synthesis, an important step in making proteins. Doxorubicin works by causing DNA to uncoil, which prevents the cell from reproducing. Bleomycin acts by fragmenting DNA. There are also many compounds that do not fit into these categories but are still useful antineoplastic agents, such as hormones, enzymes, and reagents used in immunotherapy. Hormones work by altering the cellular envi-
ronment, making it unfavorable for tumor growth. Enzymes, such as L-asparaginase, break down substances such as asparagine that tumor cells need for survival. Mitotane is a chemical related to the insecticide dichlorodiphenyl-trichloroethane (DDT) and interferes with the formation of adrenocortical steroids, with selective cyototoxic effects toward cells of the adrenal cortex. Other compounds include retinoids, such as bexarotene and tretinoid. Side effects: Antineoplastic compounds can destroy normal cells as well as neoplastic cells, although generally antineoplastic agents have greater effects on tumor cells because they grow rapidly. Many side effects associated with antineoplastic agents occur because of their effects on normal cells, especially those that divide rapidly, such as the cells of hair follicles, ovaries, testes, and blood-forming organs. Hair loss is common as a result of effects on
Common Antineoplastic Agents (continued) Drug (Other Names)
Brands
Subclass
Delivery Mode
Cancers Treated
Irinotecan
CPT-11
Topoisomerase inhibitor
IV
Metastatic colorectal cancer, bowel cancer
Mercaptopurine (6-MP)
Purinethol
Antimetabolite
Oral
Leukemia
Methotrexate (amethopterin)
Rheumatrex Antimetabolite
Oral, IV, subcutaneous
Acute lymphoblastic leukemia
Mitomycin (mitomycin C)
Mutamycin
Cytotoxic antibiotic
IV
GI, bladder, and breast cancers
Mitotane (o,p’-DDD)
Lysodren
Miscellaneous
Oral
Adrenocortical carcinoma
Oxaliplatin (oxalatoplatin)
Eloxatin, Alkylating agent Transplatine
IV
Advanced ovarian cancer, head and neck cancers
Pentostatin (deoxycoformycin)
Nipent
Antimetabolite
IV
Leukemias
Tenisopide
Vumon, VM-26
Mitotic inhibitor
IV
Leukemias, lymphomas, neuroblastoma
Thiotepa
Thioplex
Alkylating agent
IV, spinal injection
Bladder cancer, ovarian cancer, breast cancer, lymphomas
Topotecan
Hycamtin
Topoisomerase inhibitor
IV
Ovarian, small-cell lung cancers
Vincristine
Mitotic inhibitor Oncovin, Cytocristin, Vincristine sulfate
IV
Non-Hodgkin lymphoma, leukemias, smallcell lung cancer, cervical and breast cancers
Vinorelbine
Navelbine
IV
Leukemia, lymphoma, melanoma, breast and lung cancers
Mitotic inhibitor
85
Antioxidants hair follicles. Anemia, immune system impairment, and clotting problems result from adverse effects on bloodforming organs, which lead to decreased red blood cell, white blood cell, and platelet numbers. Nausea and vomiting are among the most common adverse side effects. Other side effects may include blood in the urine, diarrhea, fever or chills, cough, wheezing, shortness of breath, unusual bruising, problems with urination, dizziness, irregular heartbeat, skin rash, fatigue, loss of taste, headache, swelling, allergic reactions, or body aches. C. J. Walsh, Ph.D. u
For Further Information Clinical Pharmacology Made Incredibly Easy. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2008. Dawson, James S., Magali N. F. Taylor, and Peter J. W. Reide. Pharmacology. Philadelphia: Elsevier Health Sciences, 2002. Portable Pathophysiology. Philadelphia: Lippincott Williams & Wilkins, 2007. Skidmore-Roth, Linda. Mosby’s 2007 Nursing Drugs Reference. St. Louis: C. V. Mosby, 2006. Vardanyan, Ruben, and Victor Hruby. Synthesis of Essential Drugs. Philadelphia: Elsevier, 2006. u
Other Resources
Cancer Backup General Information on Chemotherapy http://www.cancerbackup.org.uk/Treatments/ Chemotherapy/Generalinformation/Overview MedlinePlus http://www.nlm.nih.gov/medlineplus/ druginformation.html National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Alkylating agents in chemotherapy; Chemotherapy; Immunotherapy; Proteasome inhibitors.
u Antioxidants Category: Lifestyle and prevention; complementary and alternative therapies Definition: Antioxidants are a class of compounds that help prevent damage to deoxyribonucleic acid (DNA), cellular proteins, and cell membranes by combining with 86
Salem Health: Cancer potentially damaging molecules called free radicals and neutralizing them. The body naturally makes many antioxidants, while others are found in fruits, vegetables, and grains. Antioxidants are also produced synthetically as dietary supplements. Cancers treated or prevented: Antioxidants are used to treat most types of cancer, although their effectiveness is questionable. They are usually taken for cancer prevention, although the link between antioxidant consumption and cancer prevention in humans is not proven. Delivery routes: Oral, as tablets, caplets, capsules, powder, or tea; some fruits and vegetables are high in antioxidants How these compounds work: Free radicals are formed during normal cellular metabolism. Free radicals are compounds that are unstable because they contain an unpaired electron. This unpaired electron causes the free radical to react with other molecules in order to gain another electron, creating an electron pair and a more stable molecule. The process of gaining an electron is called oxidation. Antioxidants in the body react with free radicals and make them harmless to cells. Cells naturally make many antioxidants such as glutathione and coenzyme Q10 (ubiquinone). When the number of free radicals exceeds the antioxidants available to neutralize them, however, the body develops a condition called oxidative stress. Oxidative stress appears to make cells especially susceptible to damage. Free radical formation and oxidation are normal processes. Oxidation and oxidative stress, however, are thought to contribute to aging, as well as to cancer, cardiovascular disease, and other chronic diseases. In the absence of adequate antioxidant compounds, free radicals most often combine with and damage DNA, cellular proteins, and molecules in cell membranes. This damage can cause gene mutations and change cellular metabolism, which may lead to cancer and other diseases. Exposure to ultraviolet (UV) light, radiation, cigarette smoke, and other known carcinogens increases the number of free radicals that are formed, suggesting another link between free radicals, oxidative stress, and cancer. In theory, increasing the amount of antioxidants in the body should decrease the amount of damage to DNA and cells and reduce the risk of cancer. Antioxidants have been shown to prevent or slow the development of some cancers in cell cultures grown in the laboratory and in some animal studies. The results in human studies have been mixed. Despite claims by some manufacturers of antioxidant dietary supplements, no clear link between antioxidant
Salem Health: Cancer
Antioxidants
consumption and cancer prevention or treatment has been established in humans. The role of antioxidants in the prevention and treatment of cancer is of high interest to research scientists. Many clinical trials are being conducted, and there is no cost for qualified individuals to participate in a clinical trial. The body makes some antioxidants, but others must be acquired through diet. Common antioxidants that the body does not make include vitamins A, C, and E, carotenoids, and flavonoids. Selenium is a mineral that is not strictly an antioxidant but is essential to many antioxidant reactions and often classed with the antioxidants. Coenzyme Q10 and glutathione are antioxidants naturally produced by the body that are also manufactured sold as high-dose supplements. Vitamin A (retinol) is a fat-soluble vitamin found in liver, egg yolks, whole milk, and dairy products made with whole milk. It is also sold as a dietary supplement and is included in most multivitamin tablets and in special antioxidant formulations such as ACE, a combination of vitamins A, C, and E. Vitamin Ais essential to health, but its role in cancer prevention and treatment is unclear. All-trans-retinoic acid (ATRA, Vesanoid) is a pharmaceutical drug that is a derivative of vitamin A. It is successfully used to treat promyelocytic leukemia and is being studied in Berries contain flavonoids, a group of antioxidant compounds. (U.S. Deindividuals with breast and skin cancers. To date, partment of Agriculture) however, vitamin A alone has not shown the same cancer-reducing effects as ATRA. min C has very strong antioxidant activities. Nevertheless, Alpha-carotene, beta-carotene, beta-cryptoxanthin, lumultiple human studies have failed to find a significant tein, zeaxanthin, and lycopene are all carotenoids that link between cancer prevention and vitamin C intake. show antioxidant activity in laboratory tests. These comVitamin E is a group of related compounds, the most pounds are found in red, yellow, and orange plants such as active of which is alpha-tocopherol. Vitamin E is a fatcarrots, cantaloupe, mango, and tomato. Beta-carotene soluble vitamin with antioxidant properties. It is found in and lycopene are also sold as dietary supplements either olive, sunflower, and safflower oils and in many nuts. The individually or in combination with other antioxidants. In role of vitamin E in cancer prevention is controversial. In the body, carotenoids are converted into vitamin A. An ex2004, researchers at The Johns Hopkins University Mediamination of twenty-one studies relating lycopene concal School did a meta-analysis of nineteen clinical trials sumption and prostate cancer found that men with the that included more than 136,000 individuals. This analysis highest lycopene intake had a modest decrease in the incishowed that taking more than 400 international units (IU) dence of prostate cancer. The role of carotenoids in cancer prevention is actively being studied. of synthetic vitamin E daily increased the chance of dying Vitamin C (ascorbic acid) is a water-soluble vitamin by about 4 percent. This amount is less than the safe daily found in citrus fruits. For centuries, it has been known that upper limit of 1,500 IU recommended by the United States vitamin C is essential for preventing the disease scurvy. Institute of Medicine for adults age nineteen and older. Dietary supplements of vitamin C are often promoted as a The Johns Hopkins analysis has been criticized because it preventive or treatment for the common cold, although did not differentiate between individuals taking different clinical studies have not proved its effectiveness. Vitaforms of vitamin E, such as the dietary supplement alpha87
Antiperspirants and breast cancer tocopherol acetate. This is a significant criticism because different forms of vitamin E have different activity levels in the body. Flavonoids are a group of antioxidant compounds found primarily in brewed tea, red wine, dark chocolate, apples, berries, and citrus fruits. These compounds have antioxidant activity. Traditional Chinese medicine has promoted the health effects of green tea for centuries, and recent studies show that dark (bitter) chocolate in small quantities may promote heart health, but the role of flavonoids in cancer prevention is unclear. Selenium is a mineral found in fish, shellfish, grains, Brazil nuts, and many vegetables that are grown in selenium-rich soils. By itself, selenium is not an antioxidant, but it plays a critical role in antioxidant activity and is often classified with the antioxidants that must be acquired through diet. Selenium deficiency has been linked to increases in colorectal, lung, and prostate cancers. Increased selenium intake in people who are not selenium deficient, however, does not decrease the risk of developing cancer. Additionally, selenium is toxic in large doses. Coenzyme Q10 and glutathione are the main antioxidants made by the body. They are also sold as dietary supplements. Studies of individuals who supplemented their diet with synthetic coenzyme Q10 or glutathione found no evidence that these supplements protected against cancer. Individuals who maintain a healthy weight and eat a diet low in fats and high in fruits, vegetables, and whole grains develop cancer at a lower rate than individuals who eat a more traditional American diet high in fat and low in fruits and vegetables. The American Cancer Society and the National Cancer Institute recommend that individuals meet as many of their vitamin, mineral, and antioxidant needs as possible by eating a healthy, varied diet rather than by taking dietary supplements. As of 2008, neither organization recommended the use of antioxidant supplements to treat or prevent cancer. Side effects: In 2007, a peer-reviewed meta-analysis of antioxidant studies was published in the Journal of the American Medical Association. Researchers looked at the data from sixty-eight clinical trials involving 232,606 individuals. They found that taking dietary supplements of vitamin A, beta-carotene, and vitamin E increased the risk of death from all causes by 5 percent. This increase was not seen in individuals who took vitamin C dietary supplements. The study did not look at individuals who increased their intake of these antioxidants through diet. Martiscia Davidson, A.M.
88
Salem Health: Cancer u
For Further Information DeCava, Judith A. The Real Truth About Vitamins and Antioxidants. 2d ed. Fort Collins, Colo.: Selene River Press, 2006. Frei, Balz, ed. Natural Antioxidants in Human Health and Disease. San Diego, Calif.: Academic Press, 2006. Panglossi, Harold V., ed. Antioxidants: New Research. New York: Nova Science, 2006. Quillin, Patrick. Beating Cancer with Nutrition. 4th ed. Tulsa, Okla.: Nutrition Times Press, 2005.
u
Other Resources
American Cancer Society Antioxidants and Cancer: The Jury’s Still Out http://www.cancer.org/docroot/NWS/content/ NWS_2_1x_Antioxidants_and_Cancer_The_ Jurys_Still_Out.asp MedlinePlus Antioxidants http://www.nlm.nih.gov/medlineplus/ antioxidants.html National Cancer Institute Antioxidants and Cancer Prevention: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ antioxidantsprevention See also Beta-carotene; Bioflavonoids; Carotenoids; Chemoprevention; Coenzyme Q10; Complementary and alternative therapies; Curcumin; Dietary supplements; Essiac; Free radicals; Fruits; Garlic and allicin; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Phenolics; Phytoestrogens; Resveratrol; Wine and cancer.
u Antiperspirants and breast
cancer Category: Social and personal issues Definition: Breast cancer is a cancer of the breast tissue, more common among women than men. In the United States, breast cancer is the third most common cause of death in women. Antiperspirants have been studied for a possible link to breast cancer. Looking at the link: Antiperspirants and deodorants are common over-the-counter cosmetics that are used to significantly reduce perspiration and to control body odor. Most commercially available antiperspirants contain alu-
Salem Health: Cancer
Antiperspirants and breast cancer
minum or aluminum-zirconium salts or complexes. These aluminum complexes react with salts in the sweat and form a plug that blocks the sweat duct. As a result, the duct cannot release liquid sweat. Blockage of a number of sweat ducts minimizes the sweat produced by underarms. The plugs are removed over time when the skin sloughs them off naturally. During the past decade, there have been numerous reports on the Internet and in the news claiming that underarm deodorant or antiperspirant use increases the risk of breast cancer, especially in women. However, there is no conclusive scientific evidence linking underarm antiperspirant use and subsequent development of breast cancer. Although there are no published scientific reports delineating a possible mechanism by which the use of underarm antiperspirants could cause breast cancer, public concern regarding this issue persists. Studies that looked at the correlation between antiperspirant use and the development of breast cancer have not been conclusive. The results of a 2002 study investigating the relationship between underarm antiperspirant use and breast cancer did not show an increased risk for women who reported regularly using underarm antiperspirants or deodorant. However, a 2003 study that examined the frequency of underarm shaving and antiperspirant or deodorant use among 437 breast cancer survivors found that those who shaved frequently and used these products were diagnosed with breast cancer at an earlier age. In addition, the study found that those who started the shaving and antiperspirant or deodorant use earlier than sixteen years of age were diagnosed at an earlier age with breast cancer than those who started these habits later in life. These results suggest, though not conclusively, that there could be a link between underarm hygiene habits and breast cancer.
More research is needed in this area to enable women to make informed choices.
Aluminum: Aluminum salts or complexes are one of the major constituents of many commercial antiperspirants and deodorants. Estrogen is a naturally occurring female hormone that is known to promote the growth and division of breast cells. Aluminum salts are classified as metalloestrogens (metals with estrogen hormone-like properties). Research studies have shown that aluminum salts cause an increase in estrogen-related gene expression in human breast cancer cells grown in the laboratory. However, this result has not yet been translated into human breast cancer cells in the body. Aluminum was detected at varying concentrations in human breast cancer tissue from one study of women with breast cancer. The source of the aluminum was not conclusively established, and hence a definite correlation between aluminum from antiperspirants and breast cancer cannot be made from this study.
u
Parabens: Esters of the chemical p-hydroxybenzoic acid are commonly called parabens and are used as preservatives in antiperspirants and many other skin-care cosmetics. Research has demonstrated that parabens possess estrogenic properties both in laboratory-grown cells and in cells within the body (in vitro and in vivo). Scientists have put forth the hypothesis that parabens can be absorbed by breast tissue from topical application of cosmetics such as antiperspirants and could accumulate there, causing the development and spread of breast cancer. A 2004 study that detected parabens in breast tumor tissue partially proved the hypothesis that parabens can accumulate in breast tissue. However, the study did not prove that the accumulated parabens caused breast cancer. Moreover, the study did not prove that the parabens originated from the antiperspirants. It also did not involve an analysis of healthy breast tissue for parabens and hence did not prove that parabens were found only in cancerous tissue and not in healthy tissue. More specific well-designed research is needed to address the absorption of parabens by the skin and objectively evaluate whether they increase the risk of breast cancer. The rising incidence of breast cancer in younger women combined with the fact that it is a major killer of women in the United States makes it a major public health issue. Considering the fact that a majority of young women use antiperspirants and deodorants, the importance of wellfunded, case-controlled research investigations to conclusively establish the proposed link between their use and breast cancer development cannot be overemphasized. Lalitha Krishnan, Ph.D. For Further Information “Antiperspirants Don’t Cause Breast Cancer.” Harvard Women’s Health Watch 10, no. 5 (2003): 7. Harvey, P. W., and D. J. Everett. “Significance of the Detection of Esters of P-hydroxybenzoic Acid (Parabens) in Human Breast Tumours.” Journal of Applied Toxicology 24 (2004): 1-4. McGrath, K. G. “An Earlier Age of Breast Cancer Diagnosis Related to More Frequent Use of Antiperspirants/ Deodorants and Underarm Shaving.” European Journal of Cancer Prevention 12, no. 6 (2003): 479-485. Mirick, D. K., S. Davis, and D. B. Thomas. “Antiperspirant Use and the Risk of Breast Cancer.” Journal of the National Cancer Institute 94, no. 20 (2002): 15781580. Surendran, A. “Studies Linking Breast Cancer to Deodor89
Antiviral therapies
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ants Smell Rotten, Experts Say.” Nature Medicine 10, no. 3 (2004): 216.
u Antiviral therapies
Other Resources
Category: Chemotherapy and other drugs ATC code: J05
American Cancer Society Antiperspirants and Breast Cancer Risk http://www.cancer.org/docroot/MED/content/ MED_6_1x_Antiperspirants.asp?sitearea=PED National Cancer Institute Antiperspirants/Deodorants and Breast Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ AP-Deo See also Carcinogens, known; Carcinogens, reasonably anticipated; Diethanolamine (DEA).
Definition: Antiviral agents are used to treat infections caused by viruses. In patients with cancer, they are also used in combination with other medications to treat human papillomavirus (HPV)-positive cervical cancer and head and neck squamous cell cancer. Antiviral agents known as protease inhibitors, nucleoside reverse transcriptase inhibitors, and nonnucleoside reverse transcriptase inhibitors are indicated for human immunodeficiency virus (HIV) infection. Cancers treated: Cervical cancer, head and neck cancers, HIV infection and opportunistic viral infections associated with all types of cancer. (continued on page 92)
Common Antiviral Agents Drug (Other Names)
Brands
Subclass
Delivery Mode Conditions Treated
Abacavir sulfate
Ziagen
Nucleoside reverse transcriptase inhibitor
Oral
Human immunodeficiency (HIV) infection in patients with Kaposi sarcoma, other opportunistic cancers
Acyclovir, acyclovir sodium
Zovirax
Synthetic purine nucleoside
Oral, IV
Varicella and herpes zoster in cancer patients
Adefovir dipivoxil
Hepsera
Acyclic nucleotide analog Oral
Chronic hepatitis in cancer patients
Amantadine hydrochloride
Symmetrel
Synthetic cyclic primary amine
Oral
Prevention or treatment of influenza A in cancer patients
Amprenavir
Agenerase
Protease inhibitor
Oral
Kaposi sarcoma for treatment of HIV infection
Atazanavir sulfate
Reyataz
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Cidofovir
Vistide
Nucleotide analog
IV
Cytomegalovirus (CMV) retinitis
Darunavir ethanolate
Prezista
Protease inhibitor
Oral
Kaposi sarcoma for treatment of HIV infection
Delavirdine mesylate
Resciptor
Nonnucleoside reverse transcriptase inhibitor
Oral
Kaposi sarcoma for treatment of HIV infection
Didanosine (ddl)
Videx, Videx EC
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Efavirenz
Sustiva
Nonnucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers (continued)
90
Salem Health: Cancer
Antiviral therapies
Common Antiviral Agents (continued) Drug (Other Names)
Brands
Subclass
Delivery Mode Conditions Treated
Emtricitabine
Emtriva
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Enfuvirtide
Fuzeon
Fusion inhibitor
Subcutaneous injection
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Entecavir
Baraclude
Guanosine nucleoside analog
Oral
Chronic hepatitis B in patients with cancer
Famciclovir
Famvir
Synthetic acyclic guanine Oral derivative
Acute herpes zoster infection and recurrent genital herpes in patients with cancer
Fosamprenavir calcium Lexiva
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Foscarnet sodium Foscavir (phosphonoformic acid)
Pyrophosphate analog
IV
CMV retinitis in patients with cancer
Gangciclovir
Cytovene
Synthetic purine Oral, IV nucleoside guanine analog
CMV retinitis in patients with cancer
Indinavir sulfate
Crixivan
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Lamivudine
Epivir
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma and other opportunistic cancers; chronic hepatitis B infection in cancer patients
Lopinavir and ritonavir
Kaletra
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Nelfinavir mesylate
Viracept
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Nevirapine
Viramune
Nonnucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Oseltamivir phosphate
Tamiflu
Selective neuraminidase inhibitor
Oral
Prevention and treatment of influenza infection
Ribavirin
Copegus, Rebetol, Synthetic nucleoside Ribaspheres, Virazole
Oral, inhalation
Chronic hepatitis infection
Ritonavir
Norvir
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Protease inhibitor
(continued on page 92)
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Antiviral therapies
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Common Antiviral Agents (continued) Drug (Other Names)
Brands
Subclass
Delivery Mode Conditions Treated
Saquinavir mesylate
Invirase
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Stavudine (2,3 didehydro3deoxythymidine, d4T)
Zerit, Zerit XR
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Tenofovir disoproxil fumarate
Viread
Nucleoside reverse transcriptase inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Tipranavir
Aptivus
Protease inhibitor
Oral
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Valacyclovir hydrochloride
Valtrex
Synthetic purine nucleoside
Oral
Herpes zoster and genital herpes in cancer patients
Valganciclovir
Valcyte
Synthetic nucleoside
Oral
CMV retinitis in cancer patients
Zanamivir
Relenza
Selective neuraminidase inhibitor
Inhalation
Prevention and treatment of influenza virus A and B
Zidovudine (azidothymidine, AZT)
Retrovir
Nucleoside reverse transcriptase inhibitor
Oral, IV
HIV infection in patients with Kaposi sarcoma, other opportunistic cancers
Subclasses of this group: Nucleotide analogs, purine nucleoside analogs, acyclic guanine derivatives, pyrophosphate analogs, purine nucleoside guanine derivatives, protease inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors Delivery routes: Administered orally in the form of capsules, tablets, and solutions at home or in the hospital; some also administered in the hospital by intravenous (IV) infusion or subcutaneous injection How these drugs work: The first successful antiviral drug, acyclovir, was discovered in the 1960’s for the treatment of herpesvirus infection. The increased incidence of HIV infection in the 1980’s initiated the development of a variety of antiviral agents that are available today. Antiviral agents work in a variety of ways depending on the drug type. Some competitively inhibit an enzyme located on the viral deoxyribonucleic acid (DNA) chain, halting growth of the viral DNA. Some work on viral ribonucleic acid (RNA), preventing the virus from penetrating healthy cells. Others inhibit viral nucleic acid synthesis by interacting directly with the DNA enzymes. Protease inhibitors 92
inhibit the enzyme needed for viral replication. Reverse transcriptase inhibitors also inhibit viral replication after incorporating themselves into the viral DNA. Side effects: The most common side effects associated with antiviral therapy include gastrointestinal symptoms such as anorexia, abdominal pain, diarrhea, dyspepsia, flatulence, nausea, and vomiting. Other side effects that may occur with antiviral therapy include headache, dizziness, insomnia, depression, suicidal ideation, peripheral neuropathy, weakness, rash, sweating, back pain, chest pain, fever, muscle ache, pneumonia, weight loss, anxiety, elevated or decreased blood pressure, pancreatitis, tremor, cough, shortness of breath, chills, low white blood cell count, low platelet count, anemia, hypoglycemia, seizures, hepatitis, and liver toxicity. Collette Bishop Hendler, R.N., M.S. u
For Further Information Drug Facts and Comparisons 2008. St. Louis: Wolters Kluwer Health, 2008. Lorigan, Paul, ed. Lung Cancer. Dana-Farber Cancer Institute Handbook. New York: Mosby Elsevier, 2007.
Salem Health: Cancer Nursing 2008 Drug Handbook. Philadelphia: Lippincott Williams & Wilkins 2008. See also Antidiarrheal agents; Antifungal therapies; Aplastic anemia; Herpes simplex virus; Herpes zoster virus; Infection and sepsis; Leukoencephalopathy; Viral oncology; Virus-related cancers.
u Anxiety Category: Social and personal issues Definition: Anxiety encompasses a complex set of behavioral, cognitive, and physiological responses to a perceived threat. Symptoms of anxiety include apprehension or fearfulness toward a future event or outcome, physical signs (such as muscle tension, elevated heart rate, breathing changes, and sweating), and often concern about the meaning or implications of the anxious reaction itself. Description of the problem: A key feature of anxiety is the perception of an imminent or future threat, regardless of the accuracy of the perception. Although it is easy to imagine exaggerated or unrealistic appraisals of threat in many circumstances, in the case of cancer, anxiety is a normal and expected reaction to a true threat—a serious and often life-threatening disease. Therefore, distinguishing a normal anxious reaction from a pathological one is difficult in cancer patients as well as in their caregivers and loved ones. Excessive anxiety is a marker of poor coping among cancer patients and warrants further evaluation. Vital to the assessment of clinically significant anxiety is the extent to which anxiety meaningfully impairs the ability to function. For example, extreme anxiety may prevent an otherwise able patient or loved one from continuing to work, or it may interfere with medical care when a patient’s fearful avoidance prevents or delays receipt of tests or treatments. The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-R (4th rev. ed., 2000) recognizes several distinct types of anxiety disorders, including generalized anxiety disorder, panic disorder, specific phobia, social phobia, obsessivecompulsive disorder, and post-traumatic stress disorder. Anxiety may also be a prominent feature of depression or an adjustment disorder (a short-term psychological reaction to a stressful event), both of which are common among cancer patients. The experience of being a cancer patient can contribute to the development of anxiety disorders in several ways.
Anxiety For example, a patient may develop a phobia of particular objects or procedures such as needles or diagnostic tests that were associated with highly stressful experiences. After cancer care, some patients may experience symptoms of post-traumatic stress disorder, characterized by recurrent intrusive memories and flashbacks, avoidance of reminders of stressful events, and hyperarousal symptoms such as sleep difficulties and irritability. Anxiety may also have origins in medical causes such as certain types of tumors or physiological side effects from some treatments. Prevalence: Not surprisingly, research suggests that the vast majority of cancer patients experience anxiety at some point during their illness. Far fewer develop clinical anxiety disorders. Although several studies have suggested an increased prevalence of anxiety disorders among cancer patients, others suggest little or no difference in this prevalence when cancer patients are compared with the
While receiving chemotherapy, a young boy plays a virtual reality game in an effort to distract him from the treatment and relieve his anxiety. (AP/Wide World Photos)
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APC gene testing general population. Reported rates of anxiety disorders are usually lower when assessed using formal diagnostic criteria and range from 10 to 30 percent. Assessment: In the clinical setting, anxiety is most commonly assessed face to face by a primary care provider or by a provider with special expertise in mental health, such as a psychiatrist or a clinical psychologist. The assessment is usually in the form of an interview to establish the nature, duration, and severity of symptoms according to established criteria, whether according to the diagnostic standards set out by the American Psychiatric Association or some other diagnostic system. Numerous standardized questionnaires are also available to measure anxiety in clinical and research settings. These questionnaires ask respondents to self-report the frequency or severity of various symptoms commonly associated with anxiety. Examples of anxiety assessment questionnaires that have been used with cancer patients include the Beck Anxiety Inventory, the State-Trait Anxiety Inventory, and the Hospital Anxiety and Depression Scale. Treatment and therapy: Anxiety related to medication or disease is usually first treated by managing the underlying condition causing symptoms. However, in many cases, anxiety is treated as a condition in its own right. Effective interventions for anxiety include both medical and psychological treatment options. Medical management of anxiety usually entails treatment with an anxiolytic (antianxiety) or antidepressant medication, the latter particularly when signs of a depressed mood are present. The most commonly prescribed anxiolytic medications belong to the class of drugs known as benzodiazepines, which includes clonazepam (Klonopin), alprazolam (Xanax), and diazepam (Valium). Commonly prescribed antidepressants include selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and sertraline (Zoloft), serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta), and to a lesser extent tricyclic antidepressants such as imipramine (Tofranil) and clomipramine (Anafranil). Psychological treatments include individual psychotherapy (talk therapy), group therapy, family therapy, and certain mind-body interventions. In particular, research heavily supports the efficacy of cognitive-behavioral therapy, which encompasses a variety of therapeutic techniques. Broadly speaking, the goals of cognitive-behavioral therapy for anxiety are to guide patients toward a more balanced and rational appraisal of their concerns and to encourage behaviors that reduce or neutralize anxieties rather than exacerbate them. Other frequently used thera94
Salem Health: Cancer peutic approaches include training in relaxation techniques, mindfulness meditation, and hypnosis. Biofeedback may also be effective in helping patients recognize and manage physical symptoms of anxiety by, for example, reducing muscle tension and cardiovascular reactivity to stress. Andrea Bradford, M.A. u
For Further Information American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR. 4th rev. ed. Washington, D.C.: Author, 2000. Antony, Martin M., Susan M. Orsillo, and Lizabeth Roemer, eds. Practitioner’s Guide to Empirically Based Measures of Anxiety. New York: Kluwer Academic/Plenum, 2001. Baum, Andrew, and Barbara L. Andersen, eds. Psychosocial Interventions for Cancer. Washington, D.C.: American Psychological Association, 2001.
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Other Resources
American Psychiatric Association http://www.psych.org American Psychological Association http://www.apa.org Anxiety Disorders Association of America http://www.adaa.org National Cancer Institute Anxiety Disorder http://www.cancer.gov/cancertopics/pdq/ supportivecare/anxiety See also Counseling for cancer patients and survivors; Depression; End-of-life care; Grief and bereavement; Living with cancer; Medical marijuana; Pain management medications; Palliative treatment; Psycho-oncology; Psychosocial aspects of cancer; Relationships; Self-image and body image; Sexuality and cancer; Side effects; Stress management; Support groups; Survivorship issues.
u APC gene testing Category: Procedures Also known as: Adenomatosis polyposis coli gene testing Definition: The APC gene is a tumor-suppressor gene that is often mutated in colorectal and other cancers. Most mutations leading to colorectal cancer occur spontaneously in
Salem Health: Cancer
Aplastic anemia
the digestive tracts of affected individuals, but approximately 5 percent of cases result from inherited mutations in APC. Testing for mutations in APC usually involves determining the deoxyribonucleic acid (DNA) sequence of a patient’s APC gene, but other screens are sometimes used.
See also Adenomatous polyps; Colorectal cancer; Desmoid tumors; Gardner syndrome; Genetic counseling; Genetic testing; Hereditary cancer syndromes; Hereditary polyposis syndromes; Tumor markers; Turcot syndrome.
Cancers diagnosed: Familial adenomatous polyposis, familial colon cancer
u Aplastic anemia
Why performed: Testing for mutations in the APC gene is performed to diagnose familial adenomatous polyposis (FAP), an inherited condition in which precancerous polyps form in the colon. Although these polyps are initially benign, they may develop into cancer if untreated. The DNA of patients exhibiting symptoms of FAP is sequenced to confirm diagnosis and to characterize the mutation in APC. Because FAP is an inherited disorder, genetic testing is often done in relatives of those afflicted with FAP in order to determine whether prophylactic treatment is required.
Category: Diseases, symptoms, and conditions Also known as: Bone marrow failure
Patient preparation: Patients considering genetic testing may meet with a genetic counselor to discuss the benefits and risks of the test and the significance of negative, positive, and inconclusive tests. The material required for genetic testing is obtained from a blood sample. Steps of the procedure: Blood samples are sent to a clinical laboratory that offers APC screening. DNA is purified from the blood sample, and the DNA that encodes for APC is amplified by polymerase chain reaction (PCR) and sequenced using standard, automated methods. After the procedure: The patient may consult with a physician or genetic counselor to discuss the implications of the test results.
Related conditions: Thrombocytopenia (low platelet count), neutropenia (low white count) Definition: The bone marrow is responsible for producing all of the blood cells in the body. Aplastic anemia is a lifethreatening condition caused when the bone marrow stops producing enough new cells to create new blood cells. The typical life span of red blood cells is 120 days, platelets about 6 days, and white blood cells about 1 day. The bone marrow needs to produce cells continuously to replace the dying cells. Aplastic anemia can be acquired or hereditary. The more common acquired aplastic anemia can be a temporary condition caused by exposure to toxic chemicals, pesticides, and benzenes. Common causes for the cancer patient are chemotherapy and radiation. Hereditary aplastic anemia is rare and can be associated with Fanconi anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita. Etiology and the disease process: Although the cause of most aplastic anemia is unknown, those cases induced by chemotherapy and radiation result from the therapy’s suppression of bone marrow function. The bone marrow is not able to manufacture the cells that are needed to create red blood cells, platelets, and white blood cells.
Risks: Complications from drawing blood are rare but may include pain, bleeding, hematoma, or infection. Because the information obtained from APC screening may have dramatic psychological effects, it is essential that patients be offered genetic counseling.
Incidence: Aplastic anemia is a rare condition with only about 500 to 1,000 new cases each year in the United States. Of patients who are diagnosed with aplastic anemia, 20 percent have an inherited disorder as well.
Results: Sequence analysis allows clinicians to identify the specific DNA mutation(s) present in a FAP patient. Once the mutation has been identified, close relatives can be screened to determine if they share the FAP-causing mutation. Patients who do not carry the mutation are at no greater risk for colon cancer than the general population. Colectomy (surgical resection of the colon) and other prophylactic treatment are recommended for individuals who carry cancer-causing mutations in the APC gene. Kyle J. McQuade, Ph.D.
Symptoms: The signs and symptoms of aplastic anemia may be seen immediately or can be slow to develop and be dependent on the blood counts themselves. Common symptoms include fatigue, dizziness, an irregular heart rate, fevers, frequent infections, frequent nose bleeds, oozing gums, blood in the stool, bruising, difficulty in stopping bleeding from a cut, and petechiae (similar to a red pinpoint rash, located on the arms, legs, and trunk). Patients may also complain of severe shortness of breath even while at rest. 95
Aplastic anemia
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can be given to help the bone marrow release immature red blood cells from the bone marrow to mature and become functioning red cells. Not all forms of aplastic anemia will respond to growth factors. Platelet transfusions will help the patient be able to form clots to stop bleeding. White blood cells are not typically transfused because of their short life span; however, they may be given to patients who have a severe infection. Patients with a low white blood cell count may receive filgrastim, a white blood cell growth factor, to stimulate the release of the immature white blood cells so that they can mature and fight off infections. Like the red cell growth factor, filgrastim may not be applicable for all forms of aplastic anemia. This pinpoint rash on the palm of the hand is a symptom of aplastic anemia. (Custom Patients may receive medications such Medical Stock Photo) as antithymocyte globulin (ATG), cyclosporine, and methylprednisolone. TradiScreening and diagnosis: Aplastic anemia is typically tional therapy consists of the patient taking all three medifound when patients complain of fatigue to their physications. It may take a few months before an improvement cians. The physical assessment includes looking for pale in blood counts is apparent. Patients may say that they are or yellow-tinted skin; listening to the heart, lungs, and feeling better before their counts actually reflect an imbreathing patterns; feeling the liver and spleen for enlargeprovement. Antibiotics and antivirals may also be given to ment; and checking for signs of bleeding. The physician prevent infection. may also assess the patient’s environment to determine Bone marrow transplants are more commonly used whether exposure to toxic chemicals or other triggers has with younger patients to replace damaged bone marrow. occurred. Diagnostic testing includes analysis of blood, Research is ongoing to develop additional treatments for urine, and stool samples, and bone marrow aspiration and aplastic anemia. biopsy. The patient may also have images taken (X rays, Prognosis, prevention, and outcomes: Historically computed tomography scans, and ultrasound) to look for aplastic anemia has had a poor prognosis. However, great enlarged organs. Once testing is complete, the aplastic strides have been made on the treatments available for anemia is staged according to how many cells are seen in aplastic anemia, and modern therapy has cured or manthe bone marrow. The three stages are moderate, severe, or aged the disease in many patients. Treatment can be effecvery severe. tive but may take months before results are seen. Patients may also need to try different therapies to find one that Treatment and therapy: The treatment for aplastic aneworks for them. Some forms of aplastic anemia can be premia depends on the severity and the patient’s symptoms. vented by avoiding exposure to toxins, radiation, and medThe patient’s overall health also determines what type of ication, but other forms cannot be prevented. treatment can be tolerated. Moderate aplastic anemia is not Katrina Green, R.N., B.S.N., O.C.N. treated, but the physician keeps a close eye on the blood counts and the patient’s symptoms. If the aplastic anemia is caused by chemotherapy or radiation, the patient is treated with transfusions and growth factors. Transfusions of red blood cells and platelets are the most common. Red blood cell transfusions help raise the hematocrit and hemoglobin, which improves the anemia symptoms. Epoietin alfa, a red blood cell growth factor, 96
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For Further Information Klag, Michael J, ed. Johns Hopkins Family Health Book. New York: HarperCollins, 1999. Schrezenmeier, Hubert, and Andrea Bacigalupo, eds. Aplastic Anemia: Pathophysiology and Treatment. New York: Cambridge University Press, 2000.
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Other Resources
Aplastic Anemia & MDS International Foundation http://www.aplastic.org National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov See also Anemia; Bone marrow transplantation (BMT); Fanconi anemia; Hairy cell leukemia; Hematologic oncology; Leukemias; Leukopenia; Myelodysplastic syndromes; Neutropenia; Transfusion therapy.
u Appendix cancer Category: Diseases, symptoms, and conditions Also known as: Carcinoid tumor, colonic adenocarcinoma, mucinous cyst adenocarcinoma, signet-ring cell adenocarcinoma Related conditions: Appendicitis, peritoneal carcinomatosis, disseminated peritoneal adenomucinosis Definition: Appendix cancer is a cancerous tumor in the appendix, the pouchlike, thin tube with a closed end that is located in the lower right quadrant of the abdomen. The appendix, also called the vermiform appendix because its appearance is wormlike, is attached to the cecum, the first section of the large intestine, close to where it joins with the small intestine. It is not known to have a significant function in the body but may play a role in the immune system. Cancerous tumors that originate in the appendix are part of the larger grouping of colorectal or gastrointestinal cancers. Types of appendix cancer include carcinoid tumor, mucinous cyst adenocarcinoma, colonic-type adenocarcinoma, and signet-ring cell adenocarcinoma. Risk factors: Because appendix cancer is not common, no specific risk factors have been identified. However, risk factors for colorectal cancers in general include a diet high in red meat, lack of exercise, obesity, and cigarette smoking. Etiology and the disease process: The cause of appendix cancer is unknown. It often goes undiagnosed until it causes appendicitis or the appendix ruptures. In a majority of patients, appendix tumors spread in a process called peritoneal seeding, in which multiple, initially small, tumors are produced throughout the abdominal cavity. Lowgrade tumors grow more slowly and are generally less invasive, whereas high-grade tumors are faster growing and considerably more invasive.
Appendix cancer Incidence: Cancer that starts in the appendix, or primary appendix cancer, is uncommon. Therefore, these cancers are usually included in the statistical data for colorectal cancer. and actual incidence rates are not available. One estimate is that about 1 percent of colorectal cancer cases in the United States are primary appendix cancer, with about 1,100 new cases diagnosed in 2007. About 66 percent of appendix tumors are carcinoid tumors, 20 percent are mucinous cyst adenocarcinoma, and 10 percent are colonic-type adenocarcinoma. Signet-ring cell adenocarcinoma, which is very rare, is an aggressive cancer that is more difficult to treat than other adenocarcinomas. Symptoms: People with appendix cancer may not experience symptoms until the disease is far advanced. The first reported symptoms are typically those of appendicitis, which include fever, pain in the lower right quadrant of the abdomen, nausea, and vomiting. Other symptoms may include bowel changes, abdominal bloating, pelvic pain, infertility, and an increase in waistline size, with possible navel protrusion. Some people experience no symptoms at all, and the cancer is found incidentally during surgery for another condition such as ovarian tumors. Screening and diagnosis: There are no screening tests for appendix cancer. Most often it is found during surgery for another abdominal condition, either when a biopsy is performed on the tissue that has been removed or when the surgeon observes abnormalities or tumors in the abdomen. Computed tomography scanning, magnetic resonance imaging, and ultrasound can be performed if appendix cancer is suspected or to determine the extent of the cancer’s spread. Radionuclide scanning is performed to determine the spread of a carcinoid tumor. No standard staging system exists for appendix cancer. Instead, appendix tumors are usually classified by whether the cancer is confined to the appendix or has spread and how far: to distant organs or only to nearby tissues. Treatment and therapy: The treatment of appendix cancer depends on the type of tumor, its size, and whether the cancer has spread. Surgery to remove the tumor along with nearby blood vessels, lymph nodes, and part of the large bowel is the most common treatment for tumors that are low grade and slow growing. Currently, the most effective treatment for higher-grade, more aggressive tumors and tumors that have seeded the abdomen is a procedure called cytoreductive or debulking surgery. During this procedure, the surgeon removes as much of the cancer in the abdomen as possible. When complete, it means that all visible tumors were removed; when incomplete, it means 97
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Stage at Diagnosis and Relative Survival Rates for Appendix Cancer, 1988-2001 Survival Rates (%) Stage Stage I Stage II Stage III Stage IV
1-Year
5-Year
10-Year
97.4 92.6 87.2 65.9
89.9 73.9 48.3 25.4
83.2 63.9 37.0 16.2
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
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Other Resources
American Cancer Society http://www.cancer.org Appendix Cancer (Appendiceal Carcinoma) & Peritoneal Surface Malignancy http://www.appendix-cancer.com Cancer.Net http://www.cancer.net/portal/site/patient See also Carcinoid tumors and carcinoid syndrome; Continuous hyperthermic peritoneal perfusion (CHPP); Small intestine cancer; Stomach cancers.
u Appetite loss that some tumors could not be removed. This surgery is typically combined with intraoperative hyperthermic intraperitoneal chemotherapy; a high concentration of a chemotherapy solution is instilled in the abdomen during surgery. The solution, heated to just above normal body temperature, has been found to be effective because it destroys cancer cells and tumors that are too small to be seen and also because it can reach all surfaces in the abdomen. Postoperative intraperitoneal chemotherapy is also used in some cases. Prognosis, prevention, and outcomes: The prognosis for appendix cancer varies greatly and depends on several factors, including the type of tumor, whether it has spread, and how it is treated. Complete cytoreductive surgery combined with intraoperative hyperthermic intraperitoneal chemotherapy has been found to be effective in increasing survival rates, especially with mucinous cyst adenocarcinoma. Appendix cancer has no known method of prevention. Dorothy P. Terry, R.N. u
For Further Information Carmignani, C. P., and P. H. Sugarbaker. “Synchronous Extraperitoneal and Intraperitoneal Dissemination of Appendix Cancer.” European Journal of Surgical Oncology 30, no. 8 (October, 2004): 864-868. Holland, Jimmie C., and Sheldon Lewis. The Human Side of Cancer. New York: HarperCollins, 2000. Sugarbaker, Paul H. “New Standard of Care for Appendiceal Epithelial Neoplasms and Pseudomyxoma Peritonei Syndrome?” Lancet Oncology 7, no. 1 (January, 2006): 69-76. 98
Category: Diseases, symptoms, and conditions Also known as: Anorexia Related conditions: Cachexia Definition: Loss of appetite in cancer patients, referred to by medical professionals as anorexia, may result from either the cancer itself or the treatments used to combat the disease. Cancer-related anorexia is associated with weight loss and has been shown to correlate with a poorer outcome and a lower quality of life. Risk factors: Those with cancer and undergoing chemotherapy for cancer are at risk. Etiology and the disease process: Because many cancer treatments affect not only cancer cells but also healthy cells, several unwanted side effects may result. For instance, chemotherapy may reduce the turnover of taste receptor cells in the tongue, which may alter the flavor of food. Additional damage to other cell types in the mouth may result in sores, gum disease, dry mouth, and sore throat. Cells in the digestive tract may also be injured, resulting in abnormal gut motility and difficulty swallowing. Together, these effects may change the way food tastes and decrease the desire to eat. Emotional side effects, such as fear and depression, as well as psychological effects, such as food aversion, can also contribute to the loss of appetite. Furthermore, many cancer patients with anorexia report early satiety, meaning that they feel full after eating only a small amount of food. Biological causes for cancer-related anorexia also exist. Cytokines released by tumor cells or produced by immune cells in response to cancer may affect the central nervous system and the gastrointestinal tract to promote
Salem Health: Cancer appetite loss. Specifically, the central nervous system is responsible for controlling food intake and energy homeostasis, while effects on the gastrointestinal tract can influence feelings of fullness. Examples of cytokines that may affect appetite include tumor necrosis factor-alpha (TNF-α), C-reactive protein, interleukin-1 beta (IL-1 beta), IL-6, and tumor-derived lipid mobilizing factor (LMF). However, there is some conflicting data as to whether blood levels of these cytokines correlate with, or are responsible for, the loss of appetite. Incidence: In general, approximately 25 percent of cancer patients report loss of appetite. The incidence can be as high as 90 percent for patients with advanced cancers. However, different types of cancers tend to have different rates of anorexia. For example, approximately 60 to 80 percent of patients with cancers of the lung, stomach, pancreas, or esophagus have significant weight loss caused, in part, by anorexia. However, loss of appetite is not as frequent in patients with breast or prostate cancer. Treatment and therapy: Cancer-related anorexia may be managed by either changing eating habits or taking medication. There are several dietary suggestions for cancer patients who struggle with loss of appetite. Liquid or powdered meal replacements as well as juice, soups, and milkbased drinks or shakes may be used in place of solid food to provide nutrients. Eating several small meals or snacks instead of three large meals per day may also be more feasible for patients with cancer-related anorexia. Additionally, drinking a glass of wine or exercising regularly may also stimulate the appetite. However, patients should consult with their doctors before consuming alcohol or beginning an exercise regimen. The pharmacological treatment of cancer-related anorexia can be broadly divided into three groups: appetite stimulants, anticatabolic agents, and anabolic agents. Examples of appetite stimulants include progestational agents (such as megestrol acetate and medroxyprogesterone), which can improve caloric intake. Corticosteroids (such as prednisolone and methylprednisolone) may improve appetite because of their inhibition of prostaglandin metabolism and IL-1 signaling. Cyproheptadine, an antihistamine, is also a serotonin antagonist, and its effects on this neurotransmitter in the brain can also promote an increase in appetite. A more controversial appetite stimulant is cannabis (marijuana), as it can stimulate CB1 receptors in the brain to enhance appetite. Anticatabolic agents, which inhibit the production or activity of appetite-decreasing cytokines, are also important in combating cancer-related anorexia. Examples include thalidomide (a potent inhibitor of TNF-α produc-
Appetite loss tion) and eicosapentaenoic acid (an inhibitor of adenylate cyclase activity and tumor-derived LMF activity). Anabolic agents such as oxandrolone and fluoxymesterone have been studied as well, and they may build lean tissue mass by increasing muscle protein synthesis. The hormone androgen may also be useful in cancer patients (except for those with hormone-dependent tumors) as it can promote muscle growth and strength and may also induce the secretion of leptin, a hormone produced by adipose tissue to stimulate appetite. Prognosis, prevention, and outcomes: Generally appetite loss resolves itself when its underlying cause is remedied. Although appetite loss can interfere with the healing process, it does not usually cause death in patients with early-stage cancers. However, cancer-related anorexia is often associated with cachexia, a wasting syndrome characterized by not only the loss of appetite but also weight loss, breakdown of muscle tissues, depletion of reserves within fat (adipose) tissue, fatigue, and weakness. In advanced-stage cancer, the cancer anorexia-cachexia syndrome is observed in about 80 percent of patients and is one of the most frequent causes of death. u
For Further Information Behl, D., and A. Jatoi. “Pharmacological Options for Advanced Cancer Patients with Loss of Appetite and Weight.” Expert Opinion on Pharmacotherapy 8, no. 8 (June, 2007): 1085-1090. Perboni, S., and A. Inui. “Anorexia in Cancer: Role of Feeding-Regulatory Peptides.” Philosophical Transactions of the Royal Society B: Biolocial Sciences 361, no. 1471 (July 29, 2006): 1281-1289. Poole, K., and K. Froggatt. “Loss of Weight and Loss of Appetite in Advanced Cancer: A Problem for the Patient, the Carer, or the Health Professional?” Palliative Medicine 16, no. 6 (November, 2002): 499-506. Rubin, H. “Cancer Cachexia: Its Correlations and Causes.” Proceedings of the National Academy of Sciences of the United States of America 100, no. 9 (April 29, 2003): 5384-5389.
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Cancer.Net Appetite Loss http://www.ascocancerfoundation.org/patient/ Diagnosis+and+Treatment/Treating+Cancer/ Managing+Side+Effects/Appetite+Loss 99
Arsenic compounds National Cancer Institute Eating Hints for Cancer Patients: Before, During, and After Treatment http://cancer.gov/cancertopics/eatinghints/page3 Elizabeth A. Manning, Ph.D. See also Antidiarrheal agents; Cachexia; End-of-life care; Gastrointestinal cancers; Gerson therapy; Living with cancer; Medical marijuana; Pain management medications; Palliative treatment; Side effects; Taste alteration; Weight loss.
u Arsenic compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Arsenic pentoxide, arsenic trioxide, arsenic acid Related cancers: Lung cancer, bladder cancer, liver cancer, kidney cancer, prostate cancer, colon cancer, certain types of skin cancer Definition: Arsenic occurs in small concentrations in earth and minerals. Leaching effects of water and wind erosion continuously release trace amounts, which can be transported over long distances via windblown dust, surface water, and groundwater flow. Inorganic arsenic compounds are naturally occurring combinations of arsenic and oxygen, sulfur, or chlorine. These and the complex minerals they are associated with are generally water soluble and occur as white, odorless solids. They typically have high melting and boiling points and can be extremely toxic, even fatal, if inhaled or ingested in large quantities. Exposure routes: Arsenic compounds in the form of dust and fumes can be absorbed through dermal layers of the skin or can be inhaled and absorbed in respiratory passageways. Arsenic can be ingested orally as a contaminant in food or water. Where found: Arsenic is a naturally occurring material in soil and water and also in various ores, especially copper and lead. Therefore, arsenic compounds are found throughout the environment. Arsenic naturally combines with other naturally occurring elements including sulfur, oxygen, and chlorine to create relatively stable inorganic arsenic compounds. Often the most concentrated environmental forms of arsenic are released into the atmosphere via volcanoes and mineral and ore erosion. Because arsenic compounds cannot be destroyed, a fairly constant 100
Salem Health: Cancer level of toxic inorganic compounds of arsenic always exists in the environment, either in soil, water, or as airborne particulate matter. Because most arsenic compounds are soluble in water, airborne arsenic may be transported great distances before being removed via precipitation to return to soil and water. At risk: Compounds of inorganic arsenic are used in the manufacture of semiconductors and as a wood preservative. They are also used in making special glass. People involved in these industries are especially at risk because of direct occupational exposure. Because many arsenic compounds occur in ores, people who work in metal smelters are often exposed to higher levels of arsenic. Similarly, carpenters and contractors and others may be exposed to the fumes of burning wood treated with an arsenic preservative or inhale sawdust from treated wood. The most common arsenic poisoning incidents occur among workers involved in the production of arsine, an extremely toxic gas produced by combining arsenic and hydrogen. Finally, people who live in areas with high levels of arsenic in rock or in water are at greater risk. Etiology and symptoms of associated cancers: Studies conducted on humans testing positive for high levels of inorganic arsenic compounds show significant correlations with various cancers, including skin, liver, lung, and bladder cancer. Studies show an especially strong positive correlation between an increase in toxicity levels of arsenic in air, soil, and water and an increase in nonmelanoma skin cancer. Internal cancers, including liver, kidney, and bladder cancer, probably result from exposure to arsenic via ingestion of food and liquid contaminated with high levels of inorganic arsenic and its compounds. As plants fairly readily absorb inorganic arsenic and its compounds, plants in habitats with high levels of arsenic will be contaminated with higher than normal amounts of this highly toxic mineral. Digestion of plant food in the gastrointestinal tract increases exposure to and absorption of certain arsenic compounds, which then are carried to the liver, kidney, aorta, and skin before they are transferred to the bladder for excretion. Note that this list of exposed organs equates to the more common types of arsenic-induced cancers. The two most common types of nonmelanoma skin cancers associated with toxic arsenic levels are basal cell carcinoma and squamous cell carcinoma. Basal cell carcinoma begins in the lowest layer of the epidermis, called the basal cell layer. It is highly unusual for a basal cell cancer to spread to lymph nodes or to distant parts of the body. However, if a basal cell cancer is left untreated, it can grow into nearby areas and invade the bone or other tissues be-
Salem Health: Cancer neath the skin. Squamous cell carcinomas tend to be more aggressive than basal cell cancers. They are more likely to invade fatty tissues just beneath the skin, and slightly more likely to spread to lymph nodes or distant parts of the body, although this is still uncommon. Symptoms include changes in skin texture, size, or color, and the area may become sore or ooze. Very high levels of arsenic exposure and absorption via all routes may lead to a decrease in blood cell production, lymphatic cancer, brain damage, and, in women, infertility and miscarriages. History: In industry, inorganic arsenic compounds were used as pesticides as early as the middle of the nineteenth century. Within the next century, however, use of such compounds was curbed because of noticeable environmental effects. The most common use for inorganic arsenic since the 1980’s is in wood preservation. Pressuretreated wood is made by immersing wood in chromated copper arsenate (CCA) or applying it to the wood under pressure. The arsenic component helps protect the treated wood from weather damage, insects, and decay. CCA is no longer used for residential projects but is used for industrial building. Although the United States has not produced arsenic since 1985, it is still the world’s leading arsenic consumer. This puts people at risk in nontraditional ways. For example, people with decks and other housing structures constructed with preserved wood are automatically at increased risk of arsenic exposure, as are farmers who used arsenic-containing pesticides. In medicine, diseases such as syphilis and psoriasis, leukemia, and asthma were commonly treated with inorganic arsenic solutions until the 1970’s. Even in the twenty-first century, it is still used as an antiparasitic agent in veterinary medicine, especially in many countries outside the United States. Continued use of arsenic in all its forms has actually increased environmental levels in soil, water, and air—-a trend that is likely to continue with increased industrial demands for this highly valuable but also highly toxic mineral. Dwight G. Smith, Ph.D. u
For Further Information Battacharyua, Prosun, et al., eds. Biogeochemical Interactions, Health Effects, and Remediation. Vol. 9 in Arsenic in Soil and Groundwater Environment. Cambridge, Mass.: Elsevier, 2007. Frost, Floyd J. Cancer Risks Associated with Elevated Levels of Drinking Water Arsenic Exposure. Washington, D.C.: AWWA Research Foundation and U.S. Environmental Protection Agency, 2004.
Arterial embolization Naidu, R., et al., eds. Managing Arsenic in the Environment: From Soil to Human Health. Enfield, N.H.: CSIRO and Science, 2006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
National Library of Medicine Environmental Health and Toxicology: Enviro-Health Links—Arsenic and Human Health http://sis.nlm.nih.gov/enviro/arsenicandhumanhealth .html See also Basal cell carcinomas; Bowen disease; Chewing tobacco; Cigarettes and cigars; Coke oven emissions; Fibrosarcomas, soft-tissue; Free radicals; Hemangiosarcomas; Hepatomegaly; Liver cancers; Lung cancers; Melanomas; Nickel compounds and metallic nickel; Occupational exposures and cancer; Pesticides and the food chain; Soots; Squamous cell carcinomas.
u Arterial embolization Category: Procedures Also known as: Transarterial bland embolization, transarterial chemotherapy, transarterial chemo embolization (TACE) Definition: Arterial embolization is the intentional blockage of an artery, thus depriving a tumor of a blood supply, oxygen, and nutrients. In some cases, embolization is used to deliver drugs or other chemotherapeutic agents via blood vessels to induce the cytotoxicity of tumors. Cancers treated: Hepatocellular carcinoma, tongue carcinoma Why performed: In patients whose cancer is significantly advanced and for whom surgical options cannot be considered, or in conditions of metastasis outside the liver and inadequate hepatic reserves, arterial embolization is preferred as a viable alternative. This option is generally chosen when the tumor is greater than 4 centimeters in size and there are multiple lesions. Arterial embolization takes advantage of the fact that the liver receives its blood supply from two main sources, the hepatic artery and hepatic portal vein, and that the major supplier of blood to liver is the hepatic artery. During the embolization procedure, the hepatic artery is blocked. Embolization may be combined 101
Artificial sweeteners with chemotherapy or radiotherapy to enhance the effects of treatments. Patient preparation: Patients are briefed on all the steps and options involved in the procedure. A hospital stay is generally required. Patients receive intravenous sedation to cause numbness and to mitigate pain. Steps of the procedure: During the procedure, an angiographic catheter is introduced in the branches of the hepatic artery. Usually a dye is injected for contrast and to acquire images. The hepatic artery is then blocked with occluding agents such as polyvinyl alcohol beads, which are transported to terminal hepatic arteries and occlude the vessels. The liver can still be healthy and functional using a blood supply derived from the alternative route of portal veins. In cases where arterial embolization is combined with chemotherapy (as in transarterial chemo embolization, or TACE), an anticancer drug (such as doxorubicin) is injected through the catheter and then the artery is blocked. Pressure is applied to prevent bleeding after the procedure is performed. Sometimes radiotherapy is combined with arterial embolization. After the procedure: An overnight stay in the hospital may be required. Generally, patients are advised to take adequate rest and avoid strenuous activities for at least twenty-four hours. The procedure may be repeated every six to eight weeks. Risks: Total liver failure, although not common, is a risk associated with this procedure. Side effects termed “embolization syndrome,” including nausea, abdominal pain, and mild fever, may ensue. Results: Increasing evidence shows that this procedure increases the rates of survival in liver cancer patients. In cases where it is combined with chemotherapy, recovery is expedited as a result of the presence of increased and prolonged concentrations of drugs around tumors. Geetha Yadav, Ph.D. See also Carcinoid tumors and carcinoid syndrome; Chemoembolization; Embolization; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary nonVHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Leiomyomas; Living will; Urinary system cancers; Virus-related cancers.
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u Artificial sweeteners Category: Lifestyle and prevention Also known as: Aspartame, saccharin Definition: Artificial sweeteners are nonnutritive chemical substances that have virtually no or very low caloric value and are used as substitutes in food products for natural sweeteners such as sugar and honey. Artificial sweeteners are commonly used for controlling weight and insulin levels. Government-approved artificial sweeteners: Artificial sweeteners are nonnutritive in nature since they provide no calories or energy to the body. There are five artificial sweeteners—aspartame (NutraSweet, Equal), saccharin (Sweet’N Low, Sweet Twin, Necta Sweet), acesulfame K (Sunnet, Sweet One), neotame, and sucralose (Splenda)— approved for use in the United States by the U.S. Food and Drug Administration (FDA). Two artificial sweeteners that the FDAhas not approved are alitame and cyclamate. Aspartame is two hundred times sweeter than sugar and was approved for use as a general-purpose sweetener in all foods and drinks in 1996. Saccharin is two hundred to seven hundred times sweeter than sugar. It is used as a tabletop sweetener and in soft drinks and chewing gum. Acesulfame K was first approved by the FDA as a tabletop sweetener and is about two hundred times sweeter than sugar. Neotame, which is about seven thousand to fourteen thousand times sweeter than sugar, was approved in 2002 as a general-purpose sweetener in a wide variety of food products. Sucralose is the only artificial sweetener that has three chlorine atoms in its chemical structure and is six hundred times sweeter than sugar. It was approved in 1998 for use in food products, such as beverages, chewing gum, and frozen desserts. Sucralose was approved by the FDAas a general-purpose sweetener in all foods in 1999. Metabolism: Sucrose, the chemical entity in natural table sugar, binds to special receptor proteins in the taste buds. This binding initiates a cascade of events that finally results in a signal sent to the brain that causes the sensation of sweet taste. Additionally, sugar is a carbohydrate that is metabolized by the body to provide calories. Artificial sweeteners have a greater affinity for the receptor proteins and work by binding two hundred to fourteen hundred times more strongly to the receptor proteins than sucrose. As a result of their stronger binding capacity, the artificial sweeteners are needed in much lower quantities than sugar to produce the same degree of sweetness. The artificial sweeteners are either excreted by the body or converted to by-products with little or no caloric
Salem Health: Cancer output. Saccharin, sucralose, and acesulfame K are excreted unchanged by the body and do not provide any calories. The enzymes in the body hydrolyze neotame and produce methanol as a by-product. Aspartame is broken down in the body to produce methanol and the amino acids aspartic acid and phenylalanine and very few calories compared with sugar. Methanol is further degraded to formaldehyde in the body. Both methanol and formaldehyde are toxic to human beings at high doses. People with the genetic disease phenylketonuria (PKU) lack the enzyme that breaks down phenylalanine. Because phenylalanine is produced as a by-product of aspartame digestion, people with PKU should not ingest aspartame. Foods containing aspartame must carry a label warning consumers with PKU that the product is a source of phenylalanine. Cancer risk: Questions regarding the risk of cancer associated with the consumption of artificial sweeteners arose when early studies indicated that saccharin caused bladder cancer in test animals. Subsequent epidemiological studies of groups of people did not find a definitive correlation between saccharin use and bladder cancer. There are two more controversial reports on the correlation between aspartame use and cancer. One study found more lymphomas and leukemias in rats fed very high doses of aspartame while the other study did not find a link between aspartame use and cancer. Artificial sweeteners are regulated by the Food and Drug Administration. Before artificial sweeteners can be launched in the U.S. market, the FDA reviews numerous safety studies conducted with them, including the studies that assess their potential cancer risk. The reviews have not conclusively demonstrated any strong positive correlation between various cancers and artificial sweetener use. Studies continue to be conducted, and the FDA will continue to review and evaluate the results. Artificial sweeteners are beneficial for people with diabetes and for people on weight-loss plans. The effects of their long-term use on weight-maintenance and cancer risk are controversial because they are not clearly understood. In the light of insufficient experimental data and all the controversy swirling around the use of artificial sweeteners, moderation should be the watchword for everyone using them. Lalitha Krishnan, Ph.D. u
For Further Information Abegaz, E. M. “Aspartame Not Linked to Cancer.” Environmental Health Perspectives 115, no. 1 (January, 2007): A16-17. Gallus, S., et al. “Artificial Sweeteners and Cancer Risk in
Asbestos a Network of Case-Control Studies.” Annals of Oncology 18, no. 1 (January, 2007): 40-44. Lim, U., et al. “Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies.” Cancer Epidemiology Biomarkers and Prevention 15 (September, 2006): 1654-1659. Soffritti, Morando, et al. “First Experimental Demonstration of the Multi-potential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats.” Environmental Health Perspectives 114, no. 3 (March, 2006): 379-385. u
Other Resources
Green Facts http://www.greenfacts.org/en/aspartame/artificialsweeteners.htm MayoClinic.com Artificial Sweeteners: A Safe Alternative to Sugar http://www.mayoclinic.com/health/diabetes-diet/ NU00592 National Cancer Institute Artificial Sweeteners and Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ artificial-sweeteners See also Dietary supplements; Nutrition and cancer prevention; Obesity-associated cancers; Weight loss.
u Asbestos Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Chrysotile, actinolite, amosite, anthophyllite, crocidolite, tremolite Related cancers: Pleural and peritoneal mesothelioma, gastrointestinal cancers, laryngeal cancer, possibly kidney and other cancers Definition: Asbestos refers to six naturally occurring fibrous silicate minerals: the serpentine mineral chrysotile and the amphibole minerals actinolite, amosite, anthophyllite, crocidolite, and tremolite. The fire-resistant properties of these minerals have been known since antiquity. Their fibers are released into the environment from both natural and human sources and are found in indoor and outdoor air, soil, drinking water, food, and even some medicines. Although there are a variety of forms of asbes103
Asbestos tos, some more associated with cancer than others, all forms of asbestos share a common characteristic: Because asbestos consists of silica crystals, the fibers are inherently irritating to human tissue. Exposure routes: Inhalation and ingestion Where found: Materials for roofing, thermal and electrical insulation, cement pipe and sheets, flooring, gaskets, friction materials, coatings, plastics, textiles, paper, and other products At risk: Workers in asbestos mining and milling, shipyards, building demolition, insulation, brake repair, and asbestos abatement, and their families Etiology and symptoms of associated cancers: Several asbestos-related conditions are nonmalignant, including asbestos warts (callus-like growths that form when asbestos fibers become embedded in the skin), asbestosis, pleural plaques, pleural thickening, and pleural effusions (the collection of fluid around the lung a few years after asbestos exposure). Inhaled or ingested asbestos fibers lead to the two most serious asbestos-related disorders: the noncancerous asbestosis, in which scarred and increasingly stiff lung tissue progressively reduces breathing capacity, and the cancer known as malignant mesothelioma. These diseases may take years or decades to develop, although there have been cases of adolescents developing mesothelioma within only a few months of initial asbestos exposure.
Salem Health: Cancer Malignant mesothelioma takes two main forms: pleural mesothelioma, in which tumors form on the outer lining of the lungs, and peritoneal mesothelioma, in which tumors form on the peritoneum, the sac containing the abdominal organs. Both have a high mortality rate because mesothelioma is rarely detected in its early stages; the average age of diagnosis is sixty. Symptoms—chest pain, cough, weight loss, and shortness of breath—are often attributed to more common diseases such as asthma. As the cancer spreads, lung capacity is diminished, and the patient eventually succumbs to the inability to take in sufficient oxygen, if not to the failure of other organs after the cancer metastasizes. Asbestos exposure has also been associated with cancers of the stomach, liver, and other organs. Researchers have observed digestive-tract cancers in workers exposed to crocidolite, amosite, and chrysotile, although study results are inconsistent. An excess of laryngeal cancer has been reported in shipyard workers, chrysotile miners, insulation workers, and others exposed to asbestos. People living near asbestos factories or mines or living with asbestos workers have also developed mesothelioma; however, there is no clear association between cancer risk and exposure to asbestos in drinking water. Smokers who are also exposed to asbestos are at a synergistically (rather than additively) greater risk of developing lung cancer.
History: In the 1930’s, researchers established that asbestos presented especially high risks of causing lung diseases in miners, shipyard workers, and others who either manufactured or worked with materials incorporating asbestos, such Asbestosis: Most Frequently Recorded Occupations as insulation. It soon became evident on Death Certificate that exposure to minute amounts of asbestos could lead to asbestos-related Occupation Number of Deaths Percent disorders. Miners’ spouses developed Plumbers, pipefitters, and steamfitters 238 8.3 mesothelioma after being exposed to Managers and administrators 129 4.5 asbestos through doing laundry, for exElectricians 125 4.4 ample, while children became victims Carpenters 120 4.2 through exposure to their parents’ work Insulation workers 108 3.8 clothes in the home. Laborers, except construction 95 3.3 In the United States, asbestos was Supervisors, production occupations 85 3.0 one of the first hazardous air pollutants Welders and cutters 78 2.7 regulated by the Clean Air Act of 1970. Janitors and cleaners 74 2.6 The first lawsuits resulting from occuTruck drivers 66 2.3 All other occupations 1,639 57.3 pational exposures began in the late Occupation not reported 102 3.6 1960’s and increased in 1973 when the Total 2,859 100.0 Fifth Circuit Court of Appeals applied strict liability in Borel v. Fibreboard Source: Multiple cause of death data from the National Center for Health Statistics Paper Prods. Corp. (493 F.2d 1076). In Note: U.S. residents age fifteen and over, selected states and years, 1990-1999. 1976, Congress passed the Toxic Sub-
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Ascites Bowker, Michael. Fatal Deception: The Untold Story of Asbestos—Why It Is Still Legal and Still Killing Us. Emmaus, Pa.: Rodale, 2003. Harris, L. V., and I. A. Kahwa. “Asbestos: Old Foe in Twenty-First Century Developing Countries.” Science of the Total Environment 307, nos. 1-3 (2003): 1-9. Institute of Medicine of the National Academies. Board on Population Health and Public Health Practices. Committee on Asbestos: Selected Health Effects. Asbestosis: Selected Cancers. Washington, D.C.: National Academies Press, 2006. Pass, Harvey I. One Hundred Questions and Answers About Mesothelioma. Sudbury, Mass.: Jones & Bartlett, 2004. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. u
Other Resources
’Lectric Law Library A History of Asbestos Use and Asbestos Litigation http://www.lectlaw.com/files/med40.htm National Toxicology Program http://ntp.niehs.nih.gov An X ray of a lung showing cancer caused by asbestos. (James Cavallini/Photo Researchers, Inc.)
stances Control Act, which imposed regulations regarding asbestos, including a requirement that asbestos abatement occur in schools. The International Labour Organization’s Asbestos Convention of 1986 mandated that national laws should “prescribe the measures to be taken for the prevention and control of, and protection of workers against, health hazards due to occupational exposure to asbestos.” The widespread use of asbestos fibers in multiple applications means that exposure remains a concern in the twenty-first century. Although asbestos is no longer as widely used in industry, which has reduced exposure in the workplace, people still risk asbestos exposure when engaging in home improvement projects as they rip out old flooring or replace ceiling tiles. Christina J. Moose, M.A. u
For Further Information Bartrip, Peter. Beyond the Factory Gates: Asbestos and Health in Twentieth Century America. New York: Continuum, 2006.
See also Air pollution; Bronchoalveolar lung cancer; Cancer clusters; Carcinomatosis; Epidermoid cancers of mucous membranes; Free radicals; Head and neck cancers; Kidney cancer; Laryngeal cancer; Lung cancers; Mesothelioma; Occupational exposures and cancer; Risks for cancer; Sarcomas, soft-tissue; Statistics of cancer; Throat cancer; Urinary system cancers.
u Ascites Category: Diseases, symptoms, and conditions Also known as: Peritoneal cavity fluid or peritoneal fluid excess, hydroperitoneum, abdominal dropsy, peritoneal carcinomatosis, malignant ascites Related conditions: Late-stage cancer or liver disease, associated with ovarian, endometrial, breast, gastrointestinal (stomach, colon, pancreatic) cancer Definition: Ascites is an abnormal accumulation of excess fluid in the abdominal (peritoneal) cavity that causes swelling or bloating. In late-stage cancer, tumor cells may be isolated from the fluid. Ascites can also occur with liver disease. 105
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Risk factors: Ascites is not uncommon in cancer patients; 15 to 50 percent develop this condition at some time during their illness. Ascites is most common in patients with ovarian cancer but may also be present in patients with uterine, breast, colon, stomach, and pancreatic cancers. Liver involvement with cancer can increase the problem with ascites. Noncancerous conditions that can result in ascites include hepatitis, kidney failure, heart failure, and constrictive pericarditis (inflammation of the sac around the heart). Etiology and the disease process: A lining of tissue, the peritoneum, supports the organs in the abdomen and covers the peritoneal cavity. Normally a small amount of body fluid lubricates this cavity and is kept in correct proportion by a pressure gradient. The liver stores blood and fluid depending on the pressure in the venous and arterial blood system. Under normal conditions, the lymphatic system drains 80 percent of the peritoneal fluid, so minimal accumulation occurs. When pathological or disease conditions
occur, the fluid accumulates and edema settles in the peritoneal cavity. In malignant ascites, a tumor may obstruct the lymphatic system so that drainage cannot occur. Liver involvement can cause a backup of fluid into the peritoneal cavity. In severe cases of ascites, gallons of liquid can fill the peritoneal cavity, pressing on the diaphragm (the muscles that separate the chest from the abdomen and allow a person to breathe). Ascites is not actually a disease but a symptom of some pathological condition within the body. Some of the conditions that can result in ascites include cirrhosis of the liver (80 percent of ascites cases), pancreatic ascites, chylous ascites (a symptom of lymphoma), and cancer. Renal and endocrine ascites occur in rare instances. Incidence: Approximately 10 percent of all cases of ascites occur in cancer patients. As many as half of all cancer patients will experience ascites. About 30 percent of all ovarian cancer patients have ascites, with as many as 60 per-
Abdomen distended by ascites. (Custom Medical Stock Photo)
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Salem Health: Cancer cent presenting with ascites at death. Most cases result from disease that starts in the peritoneum or spreads from other body organs (metastasis). Symptoms: Mild ascites may not be noticeable or present any symptoms. As the disease progresses, the abdomen can become more distended and swollen to the point of discomfort and pain. The patient may experience a feeling of heaviness. The patient may have trouble sitting, walking, or moving around. Fluid buildup may cause indigestion, nausea, or vomiting. The patient may experience diminished appetite with weight loss and general fatigue. When the fluid becomes excessive, the patient may have weight gain and shortness of breath. Some patients complain of swelling in the legs and ankles or experience hemorrhoids. Changes may occur in the navel as fluid collects. The severity of symptoms depends on the progression of the disease.
Ashkenazi Jews and cancer the problem. Generally, unless the cause is corrected, the fluid will return after draining with paracentesis. In fact, rapid reduction through the draining of fluid can result in rapid reaccumulation of fluid. Removing more than five liters at one time can result in hypotension, shock, and death. Robert W. Koch, D.N.S., R.N. u
For Further Information Ginès, Pere, et al., eds. Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. 2d ed. Malden, Mass.: Blackwell Publishing, 2005. Hawkins, Rebecca. “Clinical Focus: Ascites.” Clinical Journal of Oncology Nursing 5, no. 1 (January/February, 2001).
u
Other Resources
Screening and diagnosis: Diagnosis is confirmed using a physical exam and patient history along with X rays, ultrasound, computed tomography, or paracentesis with fluid analysis (removing fluid through a thin needle into the abdomen). Simple measuring of abdominal girth can provide a baseline for continued assessment.
Cancer.Net Fluid in the Abdomen or Ascites http://www.cancer.net/patient/Diagnosis+and+ Treatment/Treating+Cancer/Managing+Side+Effects/ Fluid+in+the+Abdomen+or+Ascites+-+ASCO+ curriculum#mainContent idmainContent
Treatment and therapy: Treatment is targeted to the symptoms and to improve quality of life. One approach is to reduce sodium and fluid intake to decrease fluid buildup. Another is the use of diuretic drugs that promote removal of fluid through the kidneys as urination. Caution must be taken in the use of diuretics as the patient may experience hypovolemia (a drop in circulating blood volume through large loss of blood or fluid) with a severe drop in blood pressure or a potassium imbalance that can threaten the regular beat of the heart. If discomfort is severe, a therapeutic paracentesis can be performed by the health care provider. This procedure drains fluid from the abdomen through a thin needle inserted into the peritoneal cavity. This procedure is generally performed with a local anesthesia. Rarely, surgery to shunt the fluid away from the abdominal cavity (peritoneovenous shunt) or specific chemotherapy may help. Repeated paracentesis as can be tolerated by the patient may be the only effective approach long term. Few alternative or complementary approaches are effective for ascites. Diet can be modified to minimize sodium intake. The patient should consume potassium-rich foods such as low-fat yogurt, cantaloupe, or baked potatoes to assist with proper heart function.
MedlinePlus Ascites http://www.nlm.nih.gov/medlineplus/ency/article/ 000286.htm
Prognosis, prevention, and outcomes: The prognosis for ascites depends on the underlying cause and intensity of
See also Cytology; Gallbladder cancer; Gastrointestinal cancers; Hepatomegaly; Krukenberg tumors; Mesothelioma; Paracentesis; Peritoneovenous shunts; Ultrasound tests.
u Ashkenazi Jews and cancer Category: Social and personal issues Also known as: German or Eastern European Jews Definition: Although the major cancer risk factors in all populations are socioeconomic status, diet, lifestyles, and environment (which Jews in general share with other ethnic and racial groups), Ashkenazi Jews, originally from central, northern, and Eastern Europe, have some specific gene mutations that increase their susceptibility to certain forms of cancer. Description of the population: In the ninth or tenth century, Ashkenazi (meaning “German” in Hebrew) Jews began settling in northern France and western Germany. Toward the beginning of the sixteenth century, their com107
Ashkenazi Jews and cancer munity became centered in Poland-Lithuania. For centuries the religious and political isolation of the Ashkenazim (plural of Ashkenazi) within the larger host communities ensured their genetic purity, all the more so as they tended to intermarry. This means that the term “Jewish,” in addition to religious and cultural denotations, can also refer to a common biological background distinct from that of others. There are about 10 million Jews in the world, the majority of whom are Ashkenazi rather than Sephardic Jews. Sephardic Jews, also known as Spanish or Oriental Jews, hail from Spain, Portugal, and North Africa and are in a minority in the United States as in most parts of the world. Although American Jews, mostly Ashkenazim, are generally health conscious and respect medical science and its providers so that they tend to practice preventive health care, they are nevertheless more affected by certain disorders than members of other ethnic groups. Cancer researchers, starting in the 1990’s, began to discover that specific gene mutations leading to cancers of the breast, ovaries, colon, and rectum were more prevalent among Ashkenazi Jews than in the population at large. This suggested a genetic origin. Cancers of genetic origin: Ashkenazi Jews can trace their roots back to a small number of founders—several hundreds or thousands of them—who originally lived in a confined environment and tended to intermarry. Geneticists theorize that if even just a few of these founders had a gene mutation, this mutation would have been amplified in later generations of Ashkenazim, largely because of intermarriage. This theory is confirmed by the fact that people of Ashkenazi Jewish descent have a higher incidence of a number of specific mutations, including those that increase the risk of developing certain types of cancer. Such childhood neurological dysfunctions as Tay-Sachs disease and Bloom syndrome are caused by gene mutations and are more prevalent among Ashkenazi Jews. Breast and ovarian cancer: Isolated in 1994, BRCA1 is a major gene that, when one of its two copies is inherited in an altered form, predisposes individuals to breast (and ovarian) cancer. BRCA1 (for breast cancer 1) was found in 1 percent of the general Jewish population (mostly Ashkenazim) in the United States compared with 0.1 to 0.6 percent in Americans at large. Soon another breast cancer gene, BRCA2 (for breast cancer 2), was also discovered to have greater prevalence among the Ashkenazim, bringing the overall risk factor among them even higher. Three distinct mutations in the BRCA1 and BRCA2 genes were found in 1 out of 40 Ashkenazi Jewish women, increasing their odds of getting breast or ovarian cancer. When these 108
Salem Health: Cancer mutated genes are inherited from both parents rather than one, the risk of the disease is increased even further. Astudy by the Journal of the American Medical Association (JAMA) published in June, 2007, pointed out that in the case of breast cancer, the gene mutation may have originated from a woman’s father rather than from her female antecedents. Half of genetic mutations for breast cancer are inherited from a father, not a mother. However, unless the father has female relatives with breast cancer, the faulty gene may have passed down unnoticed and without causing cancer (because breast cancer among men is rare). Accordingly, when a woman has few aunts or older sisters, a gene mutation can hide in a family tree so that it appears that her breast or ovarian cancer struck out of nowhere when it really originated from a mutation handed down by her father. A woman with breast cancer who has a BRCA1 or BRCA2 gene mutation has a four times greater chance of developing cancer in the other breast and a ten times greater risk of developing ovarian cancer than a woman with breast cancer who has no BRCA gene alteration. This finding argues that women at greater risk, such as the Ashkenazim, should have genetic testing because three commonly used predictive methods do not accurately estimate the genetic breast cancer risk without a family history of such carcinomas. However, Orthodox Jewish rabbis may oppose genetic testing on the grounds that it might cause couples to refrain from marriage and procreation. It must be borne in mind, too, that the Ashkenazim, like others, are subject to breast cancer risks independent of genetic causes. Colorectal cancer: Ashkenazi Jews have a lifetime risk of colorectal cancer of 9 to 15 percent, one of the highest in the world, compared with 5 to 6 percent for non-Ashkenazi populations. Although rare in the general population, the A636P mutation is detected in up to 7 percent of Ashkenazi Jews with early-onset colorectal cancer. Hereditary nonpolyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome attributable to mutations in one of several deoxyribonucleic acid (DNA) mismatch repair genes, most commonly MLH1 and MSH2. Although rare in the general population, among Ashkenazi Jews, the MSH2 mutation is found to a greater degree with early-onset colorectal cancer and may account for up to one-third of HNPCC. Pancreatic and other cancers: Pancreatic cancer is the most fatal of all gastrointestinal cancers. Its survival rate of only 1 to 3 percent in the West disproportionately affects the Ashkenazim. Approximately 5 to 10 percent of this cancer shows familial clustering, and there are no pan-
Salem Health: Cancer creatic cancer screening programs with acceptable sensitivity and specificity. Men who inherit the altered BRCA1 gene are slightly more at risk to experience prostate cancer as well. Similarly, carcinomas of the stomach and nonHodgkin lymphoma have a higher incidence among the Ashkenazim. Interpreting statistics: Although Ashkenazi Jews have one of the highest lifetime colorectal cancer risks of any ethnic group in the world, carcinoma of the uterine cervix occurs very infrequently among them, and lung cancer among the Ashkenazim is also low, probably because of decreased tobacco use. The interpretation of statistics that portray variations in the incidence of cancer in any ethnic or religious group, including Ashkenazi Jews, must be carefully evaluated in view of the greater picture. Peter B. Heller, Ph.D. u
For Further Information Brandt-Rauf, Sherry I., et al. “Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease.” American Journal of Public Health 96, no. 11 (2006): 1979-1988. Goodman, Richard, and Arno G. Motulsky, eds. Genetic Diseases Among Ashkenazi Jews. New York: Raven Press, 1979. Kedar-Barnes, I., and P. Rozen. “The Jewish People: Their Ethnic History, Genetic Disorders, and Specific Cancer Susceptibility.” Familial Cancer 3, nos. 3/4 (2004): 193-199. Kolata, Gina. “Using Genetic Tests: Ashkenazi Jews Vanquish a Disease.” The New York Times, February 18, 2003, Sec. F, pp. 1, 6. Lippe, Scott D. “Ashkenazi Jews and Colon Cancer.” American Journal of Gastroenterology 94, no. 10 (1999): 3085. Locker, G. Y., and H. T. Lynch. “Genetic Factors and Colorectal Cancer in Ashkenazi Jews.” Familial Cancer 3, nos. 3/4 (2004): 215-221. Lynch, H. T., et al. “Cancer in Jews: Introduction and Overview.” Familial Cancer 3, nos. 3/4 (2004): 177192. _______. “Familial Pancreatic Carcinoma in Jews.” Familial Cancer 3, nos. 3/4 (2004): 233-240. Mahowald, Mary B. “Ethnicity, Cultural Differences, and Sex Selection.” In Genes, Women, Equality. New York: Oxford University Press, 2000. Vadlamani, Lalit, et al. “Colorectal Cancer in RussianSpeaking Jewish Emigrés: Community-Based Screening.” American Journal of Gastroenterology 96, no. 9 (2001): 2755-2760.
Asian Americans and cancer u
Other Resources
Genetics Home Reference http://ghr.nlm.nih.gov National Cancer Institute Cancer Risk in Ashkenazi Jews Who Carry a Specific Mutation in a Gene Previously Associated with Colon Cancer http://www.cancer.gov/newscenter/Ashkenaziestimating-risk-colon-QA See also BRCA1 and BRCA2 genes; Ethnicity and cancer; Family history and risk assessment; Fanconi anemia; Geography and cancer; Hairy cell leukemia; Pancreatic cancers; Rectal cancer.
u Asian Americans and cancer Category: Social and personal issues Definition: Cancer is one of the leading causes of death in Asian Americans. Cancer kills more Asian American women than women of any other ethnicity in the United States. Asian Americans have higher incidence and mortality rates for certain cancers, with wide disparities between Asian ethnic groups. Overall, there are disproportionately high rates of liver, breast, cervical, and lung cancer in the largest Asian American and Pacific Islander groups. Description of the population: There are approximately 11.9 million Asian Americans living in the United States, and more than twenty-five Asian ethnicities are represented. Asian Americans and Pacific Islanders refer to people who originate in many countries and represent myriad ethnicities. Major ethnic groups included by the U.S Census Bureau are Chinese, Japanese, Korean, Malayan, Mien, Cambodian, Indonesian, Burmese, Bhutanese, Bangladeshi, Filipino, Hmong, Sikh, Sri Lankan, Laotian, Pakistani, Nepalese, Thai, Vietnamese, Tongan, Samoan, Marianan, Guamanian, and Chuukese. Cancer statistics are very limited in some Asian American and Pacific Islander ethnic subgroups. In fact, many of the statistics represent cancer incidence and mortality only in Chinese, Vietnamese, Filipino, Korean, Japanese, Tongan, and Samoan peoples; national statistics on Mien and Hmong are scarce. Asian Americans and Pacific Islanders are considered a health disparity population, which is defined as “a population displaying a significant disparity in the overall rate of disease incidence, prevalence, morbidity, mortality or sur109
Asian Americans and cancer vival rates in the population as compared to the health status of the general population,” according to the Minority Health and Health Disparities Research and Education Act of 2000. Incidence, death, and survival statistics: Asian Americans and Pacific Islanders have the fourth highest incidence rates of cancer of all ethnicities (329.3 per 100,000 people for men and 263.9 per 100,000 for women). The most common cancers in Asian American and Pacific Islander women are breast (79.7 per 100,000), colorectal (32.1 per 100,000), and lung (26.9 per 100,000). The highest cancer incidences in Asian American and Pacific Islander men are prostate (79.8 per 100,000), lung (49.7 per 100,000), and colorectal (42.0 per 100,000). Vietnamese women have the highest rates of cervical cancer. The rates are not only the highest of all Asian American and Pacific Islander groups, but five times higher than the rates for white women. Vietnamese men
Cancer kills more Asian American women than women of any other ethnicity in the United States. (PhotoDisc)
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Salem Health: Cancer have incidence and death rates from liver cancer that are seven times higher than those of white men. Native Hawaiians have the second highest all-site cancer mortality (207.2 per 100,000), while African Americans have the highest rates (209.8 per 100,000). Asian American and Pacific Islander men and women have the highest incidence rates of stomach cancer (9.3 per 100,000 for women and 17.5 per 100,000 for men) and intrahepatic bile duct cancer (11.0 per 100,000 for women and 20.1 per 100,000 for men) of all ethnicities. Breast cancer is the leading cause of cancer deaths in Asian American and Pacific Islander women, and Koreans have the highest incidence and mortality from stomach cancer. Lung cancer rates are 18 percent higher for Southeast Asians than whites. Japanese have the highest incidence and mortality rates for stomach and uterine cancers, while Koreans have the lowest colorectal cancer screening rates. Hmong have elevated rates of multiple cancers, including liver, cervical, nasopharyngeal, leukemia, and nonHodgkin lymphoma. Risk statistics: Socioeconomic status, hepatitis B infection, tobacco use, language barriers, and low rates of participation in cancer screening are major challenges. Recent immigrants who are monolingual have difficulty accessing medical care. Further, the concept of disease prevention is alien to many who had limited or no access to medical care in their native countries. Most Asian American subgroups are diagnosed with cancer at a more advanced stage than whites. A cancer diagnosis is frightening for most people, regardless of ethnicity. Adding to the challenge in Asian American and Pacific Islander groups are cultural beliefs promoting fear of cancer. A cancer diagnosis can result in ostracism, loss of friendships, and being regarded as the carrier of bad luck. These common occurrences prevent many Asian Americans from seeking early medical attention and participating in cancer prevention screening. Smoking is relatively common in Asian Americans and Pacific Islanders (17.8 percent of men and 4.8 percent of women). Immigrants arrive in the United States with smoking habits in place. Social and work formalities override concerns about lung cancer. Also, commercial advertising for tobacco products is great in stores that serve a large Asian American and Pacific Islander customer base. Hepatitis B infection is widespread in China and Southeast Asia, so it is also present in immigrants from these areas. An infected person might not have symptoms for decades. Infection is most commonly transmitted at childbirth, when the infant is exposed to the infected mother’s
Salem Health: Cancer
Asian Americans and cancer
Top Ten Cancer Sites: Incidence and Death Rates for Asian Americans and Pacific Islanders, 2004 Incidence Cancer Site Prostate Female breast Lung and brochus Colon and rectum Corpus and uterus Liver and intrahepatic bile duct Stomach Non-Hodgkin lymphoma Thyroid Ovary
Rate per 100,000 People 79.8 79.7 36.7 36.4 15.6 13.5 12.8 11.9 9.1 8.7
Death Cancer Site Lung and brochus Female breast Prostate Colon and rectum Liver and intrahepatic bile duct Pancreas Stomach Ovary Non-Hodgkin lymphoma Leukemias
Rate per 100,000 People 26.3 12.6 11.4 11.2 10.2 7.7 7.0 4.6 4.5 3.8
Source: U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2004 Incidence and Mortality Web-Based Report (Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, 2007)
blood. Other routes of transmission include drug use (sharing needles) and tattoos. Although the hepatitis B vaccine is effective in preventing infection, in many Asian countries the vaccine is expensive and not always available at rural clinics. Very limited public health education exists in many Asian countries. People are unaware of the association between chronic hepatitis B infection and liver cancer and do not know that infection can be asymptomatic and that treatment is available. Asian American and Pacific Islander women have very low participation rates for mammography, Pap smears, and performance of breast self-exams. Participation has increased with awareness based on language-appropriate information regarding availability of Medicare coverage for screening, centers where native languages are spoken, and ways to prevent and detect cancer in its early stages. Perspective and prospects: Screening, early detection of cancer, and treatment are the core approach to dealing effectively with cancer, regardless of the person’s race or ethnicity. However, achieving this goal within myriad Asian American and Pacific Islander groups involves enormous complexity. Asian Americans born in the United States and those with higher levels of education and jobs providing medical insurance are more likely to be aware of and participate in prevention and early cancer screening practices. Hawaiians and Pacific Islanders have more dietary and obesity-related medical issues than Vietnamese and Chinese. Hmong and Mien communities maintain health beliefs that do not easily blend with West-
ern medicine. Physical isolation and language barriers among immigrants are persistent challenges. Modifiable behaviors and factors that lead to higher rates of certain cancers in Asian American and Pacific Islander communities include hepatitis B infection (liver cancer), tobacco use (lung and bronchial cancers), and low participation in cancer screenings such as Pap smears (cervical cancer), mammography testing (breast cancer), and fecal occult blood testing, colonoscopy, and bariumcontrast X ray (colorectal cancer). High-fat diets, certain environmental exposures including radiation, and genetic factors also are known to increase the risk of certain cancers. Organizations such as the Asian American Network for Cancer Awareness, Research and Training (AANCART), have been major sources of data on cancer incidence and mortality in specific Asian American communities. Clearly, health education that is culture- and languageappropriate plays a major role in prevention and early detection of cancer in all Asian American communities. Distrust of Western medicine is a major barrier in Hmong and some other groups. Language-appropriate materials stressing mammograms, fecal occult blood tests, prostatespecific antigen (PSA) tests, and Pap testing must be widely distributed within Asian American communities, followed up by health workers who are able to explain the role of screening and early detection. There are no studies indicating that Asian Americans have a genetic predisposition for any particular cancer. Therefore, economic and cultural disparities are the main issues facing anyone 111
Astrocytomas
Salem Health: Cancer
intent on lowering cancer rates in these communities. Bilingual community health workers have had success in reaching many immigrant populations. University medical centers and public health departments in cities with large Asian American communities have been addressing specific issues such as hepatitis B antigen/antibody screening, identification and treatment of individuals with chronic hepatitis B, Vietnamese-language cervical cancer screening programs, and antismoking programs. The greatest challenge continues within monolingual communities. Janet R. Green, M.S.P.H. u
For Further Information Haynes, M. Alfred, and Brian D. Smedley, eds. The Unequal Burden of Cancer: An Assessment of NIH and Research Programs for Ethnic Minorities and the Medically Underserved. Washington, D.C.: National Academy Press, 1999. Smedley, Brian D., Adrienne Y. Steth, and Alan P. Nelson eds. Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care. Washington D.C.: National Academy Press, 2003. Wong, S. T., et al. “Disparities in Colorectal Cancer Screening Rates Among Asian Americans and NonLatino Whites.” Cancer 104, no. 12 (2005): S2,940S2,947. u
Stanford School of Medicine—Asian Liver Center http://liver.stanford.edu Vietnamese Community Health Promotion Project— University of California, San Francisco http://www.suckhoelavang.org/main.html See also Chewing tobacco; Choriocarcinomas; Ethnicity and cancer; Krukenberg tumors; Statistics of cancer; Stomach cancers.
u Astrocytomas Category: Diseases, symptoms, and conditions Also known as: Gliomas Related conditions: Primary brain tumors Definition: Astrocytomas, the most common gliomas, are primary malignant brain tumors that can occur in most parts of the brain and occasionally in the spinal cord. As the name implies, astrocytomas are derived from astrocytes—nonneural support cells of the central nervous system. The types of astrocytomas based on clinical pathology include pilocytic astrocytoma, fibrillary astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Because astrocytomas are primary brain tumors formed in the brain, they rarely spread to other parts of the body;
Other Resources
American Cancer Society http://www.cancer.org Asian American Cancer Support Network http://www.aacsn.org Asian American Network for Cancer Awareness, Research and Training (AANCART). http://www.aancart.org Asian American Pacific Islander Health Foundation http://www.apiahf.org Centers for Disease Control and Prevention Highlights in Minority Health and Health Disparities http://www.cdc.gov/omhd National Cancer Institute SEER Cancer Statistics Review 1975-2005 http://seer.cancer.gov/csr/1975_2005 112
An MRI of the brain of a man with a cerebellar glioma. The tumor appears in bright contrast to the surrounding brain tissue. (Simon Fraser/Photo Researchers, Inc.)
Salem Health: Cancer however, they usually grow rapidly and invade surrounding normal brain tissue and therefore are life-threatening. Risk factors: Brain tumors are caused by mutated or missing genes that result in abnormal cells. High-dose ionizing radiation used over time to treat brain tumors may on occasion cause secondary tumors. Exposure to certain chemicals such as pesticides, petrochemicals, and formaldehyde, and to electromagnetic fields over time increase the risk of developing astrocytomas. Etiology and the disease process: Generally, malignant brain tumors are caused by changes in genetic structure due to inherited or environmental factors. It was thought that only 5 percent of primary brain tumors, including astrocytomas, are inherited; however, one study has shown that 80 percent of patients with grade IV astrocytoma (glioblastoma multiforme) had anomalous copies of chromosome 7. Familial clustering of gliomas is also associated with defined inherited tumor syndrome, including Li-Fraumeni syndrome, Turcot syndrome, and the neurofibromatosis I syndrome. Incidence: Gliomas of both benign and malignant tumors account for 45 to 50 percent of all primary brain tumors; grade I and II astrocytomas account for 25 to 30 percent of all gliomas. Approximately 13,000 people in the United States die of malignant brain tumors every year, which represents about 2 percent of all cancer-related deaths. Symptoms: Various symptoms may occur with astrocytomas, which depend largely on the location and size of the tumor. Seizure, focal neurologic deficits such as weakness or speech problems, and headaches are common symptoms. The headaches that are associated with brain tumors are typically worse in the morning and accompanied by vomiting. Sometimes increased pressure on the brain tissue can cause blurred, double, or even loss of vision. Behavioral changes may also follow with changes in mood and general state of well-being. Screening and diagnosis: Methods of screening and diagnosing astrocytomas include computed tomography (CT) scans, magnetic resonance imaging (MRI), angiograms, X rays of the head and skull, and biopsies. Other brain scans, such as magnetic resonance spectroscopy (MRS), single-photon emission computed tomography (SPECT), or positron emission tomography (PET), provide a gauge of brain activity and blood flow. Brain tumors are graded based on the following criteria: mitotic index (growth rate), vascularity (blood supply), presence of necrotic center, invasive potential (border distinctness), and similarity to normal cells.
Astrocytomas
Relative Survival Rates for Astrocytomas, 1988-2001 Years 1 2 3 5 8 10
Survival Rate (%) 62.3 48.4 42.7 35.8 30.7 27.8
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Accordingly, astrocytomas can be graded into four levels. Pilocytic astrocytoma are grade I tumors that are slow growing and do not invade the surrounding normal tissue, and are commonly diagnosed in children and young adults. Low-grade astrocytomas, including fibrillary or protoplasmic astrocytomas, are grade II tumors that grow slightly faster than grade I tumors and are invasive, with high incidence in the cerebrums of young adults and in the brain stems of children. Anaplastic astrocytomas are grade III, malignant and invasive tumors that occur in the same location as the low-grade astrocytomas and have a high recurrence rate. Glioblastomas multiforme are grade IV, a malignant type that is by far the most common glioma: Approximately 50 percent of astrocytomas are glioblastomas. The common sites of tumors are cerebral hemispheres in adults and the brain stem in children, and they typically contain more than one cell type. Treatment and therapy: Treatment options differ according to size, grade, and location of the tumor. Tumors may be removed by craniotomy, an open-skull procedure. They may also be removed by ultrasonic aspiration, in which ultrasonic waves fragment the tumors, which are then aspirated. Alternatively, stereotactic radiosurgery may be performed with a Gamma Knife on benign, malignant, or metastatic tumors that are around 4 centimeters (cm) in size. Chemotherapy may be used as a primary therapy in young children or as an adjuvant after tumor removal with radiosurgery. For pilocytic and fibrillary astrocytomas, complete resection of the tumor is achieved; however, if excision is not possible because of the tumor’s location, chemotherapy is indicated in young children and radiotherapy in adults. The treatment options for anaplastic astrocytoma and glioblastoma multiforme include total re113
Ataxia telangiectasia (AT) section followed by radiotherapy and chemotherapy after surgery. Prognosis, prevention, and outcomes: The prognosis and outcome of astrocytomas largely depend on the age of the patient, histological features of the tumor, and degree of neurologic or functional impairment. In low-grade astrocytomas, the mean survival time after surgery is six to eight years with the prognosis depending on whether the tumor undergoes progression to a malignant phenotype. Complete recovery is possible in pilocytic astrocytoma if total resection is achieved, while fibrillary astrocytomas show frequent recurrence. In patients with anaplastic astrocytomas and glioblastoma multiforme, the extent of resection is a prognostic factor; generally, younger patients below the age of forty-five have a better prognosis. Bagirathy Ravishankar, Ph.D. u For Further Information Arjona, D., et al. “Early Genetic Changes Involved in Low-Grade Astrocytic Tumor Development.” Current Molecular Medicine 6 (September, 2006): 645-650. Compostella, A., et al. “Prognostic Factors for Anaplastic Astrocytomas.” Journal of Neuro-Oncology 81 (February, 2007): 295-303. Miller, C. R., and A. Perry. “Glioblastoma.” Archives of Pathology and Laboratory Medicine 131 (March, 2007): 397-406. Robins, H. Ian, et al. “Therapeutic Advances for Glioblastoma Multiforme: Current Status and Future Prospects.” Current Oncology Reports 9, no. 1 (2007): 66-70. Szeifert, G., et al. “The Role of the Gamma Knife in the Management of Cerebral Astrocytomas.” Progress in Neurological Surgery 20 (2007): 150-163. u
Other Resources
Mayo Clinic Gliomas http://www.mayoclinic.org/glioma/astrocytomas.html Neurosurgery Today Astrocytoma Tumors http://www.neurosurgerytoday.org/what/patient_e/ tumors.asp See also Brain and central nervous system cancers; Cell phones; Craniotomy; Gamma Knife; Gliomas; Oligodendrogliomas; Spinal axis tumors.
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u Ataxia telangiectasia (AT) Category: Diseases, symptoms, and conditions Also known as: A-T, Louis-Bar syndrome, BoderSedgwick syndrome Related conditions: Nijmegen breakage syndrome Definition: Ataxia telangiectasia (AT) is a rare primary immunodeficiency disease that causes ataxia (Greek for “lack of order”), or uncoordinated movements. This symptom is caused by dysfunction of the central nervous system that coordinates movement. Telangiectasias are small, red spider veins caused by dilation of blood vessels. In AT these appear in the eyes, cheeks, and other skin surfaces. Risk factors: AT is caused by mutations in the ATM gene (ataxia telangiectasia, mutated) located on chromosome 11q22-23, which codes for a 370kDa protein kinase. The ATM gene is 150kb with 66 exons. Etiology and the disease process: The ATM protein kinase responds to double-stranded deoxyribonucleic acid (DNA) breaks, by autophosphorylation to an active form. This active ATM kinase is involved in the assembly of a multiprotein complex that helps the cell respond to DNA damage. ATM is also involved in triggering the accumulation of the tumor-suppressor protein p53 that is a master control switch to prevent cells from dividing. If the ATM protein is lacking, there is a delay in the accumulation of p53, so the cell continues to divide without DNA repair and increases the chances of mutations leading to cancer. Incidence: AT is a rare recessive genetic disease with an incidence of 1 in 40,000 to 1 in 100,000. Symptoms: AT symptoms include neurodegeneration, causing uncoordinated movements; immunodeficiency, such as a lack or reduced level of immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin G2 (IgG2); extreme sensitivity to ionizing radiation; and an increased risk of cancer. Telangiectasias are not always present. Those with AT have frequent sinus and respiratory infections and can have recurring severe lung infections. The neurological problems result in delayed development of motor skills and poor balance, which are typically noted by two years of age. As the neurological degeneration continues, with progressive loss of muscle control, patients usually require a wheelchair for mobility in their teenage years. Slurred speech is generally present by age ten. AT patients also may have mild diabetes mellitus, premature gray hair, difficulty swallowing, and de-
Salem Health: Cancer layed physical and sexual development. Their intelligence quotient (IQ) is normal. People with AT have an increased risk of developing cancer, especially leukemia and lymphoma. Other cancers, such as stomach, brain, ovary, skin, liver, larynx, and breast, are also associated with AT. Screening and diagnosis: Ataxia, uncoordinated movements, is typically the symptom noted first. Telangiectasia may or may not be observed. Lab tests show a low lymphocyte count, especially of T and B lymphocytes. A screen of serum immunoglobulins may show low levels of IgA, IgG2, immunoglobulin G4 (IgG4), and IgE. Magnetic resonance imaging (MRI) and computed tomography (CT) scans may show cerebellar atrophy. Those with AT also have elevated levels of alpha-fetoprotein and carcinoembryonic antigen in the serum. The size of the thymus may be examined by X rays. A molecular diagnosis of AT includes sequencing of the ATM gene or examining closely linked markers if there is a family history of the disease. A test of protein function or a cytogenetic test to look for specific breakpoints can also be done. Treatment and therapy: There is no specific treatment for AT; rather the specific symptoms are treated. Antibiotics are given to control infections. Gamma-globulin injections can help the dysfunctional immune system. Physical, occupational, and speech therapy can be of benefit. Because of the sensitivity to ionizing radiation, AT patients with cancer should not receive radiation therapy. They should not have unnecessary X rays for screening tests. Prognosis, prevention, and outcomes: There is no cure for ataxia telangiectasia. Life expectancy varies, but often those with AT die in their twenties, although some live to their forties. Almost half of AT deaths are due to lung infections. If the frequent infections can be controlled, about 20 percent of those with AT die from cancer. About 28 percent of AT deaths are due to both pulmonary infections and malignancies. The parents of an AT child can have molecular diagnoses to assess their risk of having another child with AT. If both parents are carriers of a mutated ATM gene, there is a 25 percent risk of having a child with AT. Prenatal testing can be done to determine if the fetus has AT. There are suggestions that those who are carriers of a mutant ATM gene may be at a greater risk of developing cancers, especially leukemia and lymphoma, so more frequent cancer screenings may be beneficial to carriers. There is evidence that ATM mutations are breast cancer susceptibility alleles. AT is a rare disease, but the study of the ATM gene has led to a better understanding of how the cell responds to double-stranded DNA damage. Susan J. Karcher, Ph.D.
Autologous blood transfusion u
For Further Information Ahmed, M., and N. Rahman. “ATM and Breast Cancer Susceptibility.” Oncogene 25 (2006): 5906-5911. Andreassen, C. N. “Can Risk of Radiotherapy-Induced Normal Tissue Complications Be Predicted from Genetic Profiles?” Acta Oncologica 44 (2005): 801-815. Lavin, M. F., and S. Kozlov. “ATM Activation and DNA Damage Response.” Cell Cycle 6, no. 8 (2007): 931942. Lee, Y., and P. J. McKinnon. “Responding to DNA Double Strand Breaks in the Nervous System.” Neuroscience 145 (2007): 1365-1374. McKinnon, P. J. “ATM and Ataxia Telangiectasia.” EMBO Reports 5 (2004): 772-776. Niida, H., and M. Nakanishi. “DNA Damage Checkpoints in Mammals.” Mutagenesis 21 (2006): 3-9. Shiloh, Y. “The ATM-Mediated DNA-Damage Response: Taking Shape.” Trends in Biochemical Sciences 31 (2006): 402-410. u
Other Resources
National Cancer Institute Ataxia Telangiectasia: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ ataxiaqa National Institute of Neurological Disorders and Stroke Ataxia Telangiectasia Information Page http://www.ninds.nih.gov/disorders/a_t/a-t.htm See also Family history and risk assessment; Genetic testing; Nijmegen breakage syndrome.
u Autologous blood transfusion Category: Procedures Also known as: Preoperative autologous blood donation (PABD), intraoperative blood salvage, postoperative blood salvage, acute normovolemic hemodilution (ANH) Definition: Autologous blood transfusion is the collecting and reinfusing of a patient’s own blood. Collection is done before surgery and/or during or after the surgical procedure. Cancers treated: All types of cancer, based on the physician’s decision Why performed: Autologous blood transfusion is performed to replace blood lost as a result of surgery. 115
Axillary dissection Patient preparation: A physician evaluates the patient to determine whether autologous transfusion is appropriate. The decision is based on established standards. The criteria that the physician uses include the likelihood of the patient needing blood during or after surgery, the type of cancer, and other medical conditions that the patient has. There must also be an autologous donor/transfusion program available to the patient, adequate time to collect blood prior to surgery, and equipment available for the collection and reinfusion of blood during surgery. Steps of the procedure: The physician writes an order for autologous transfusion. For preoperative autologous blood donation (PABD), the patient donates one or more units of blood at a blood donor center. The donor center staff attaches special labels to the unit of blood indicating it is for a specific patient. Blood collected prior to surgery is stored for up to forty-two days, separately from other blood. Two systems are available for the collection and reinfusion of blood during surgery. One system is semiautomated: Blood is collected, washed, and transfused to the patient. The other system is a suction system that collects the blood and returns it to the patient without washing. The patient is constantly monitored by anesthesia staff. In acute normovolemic hemodilution, blood is removed, and, at the same time, a solution to maintain fluid volume is infused. The blood is collected into blood bags and may be stored for up to twenty-four hours if properly refrigerated. The patient is monitored by anesthesia staff during surgery and by nursing staff after surgery. Postoperative blood salvage is not usually used for cancer patients. After the procedure: Following the donation of blood prior to surgery, the donor center staff gives the patient refreshments and observes the patient for any signs of an adverse reaction. During and following the transfusion of autologous blood, anesthesia staff or a nurse monitors the patient for any signs of an adverse reaction. Risks: The risks of PABD are infusion of the wrong unit of blood, which is very low. The risks of intraoperative blood salvage include reinfusing cancer cells and the reduction of platelets and other clotting factors. The risks of acute normovolemic hemodilution include a reduction of hemoglobin and oxygen-carrying capacity and the dilution of clotting factors. Results: Ideally, autologous blood transfusion results in a decrease in blood loss and a better surgical outcome. Wanda E. Clark, M.T. (ASCP) See also Transfusion therapy. 116
Salem Health: Cancer
u Axillary dissection Category: Procedures Also known as: Axillary lymph node dissection Definition: Axillary dissection is a surgical procedure carried out to remove and examine underarm lymph nodes through an incision in the armpit region (axilla). Cancers treated: Carcinoma of the breast, melanoma Why performed: For persons with operable breast cancer or melanoma, axillary dissection is used to determine whether cancer has spread beyond the primary tumor. Because these primary tumor cells usually infiltrate axillary lymph nodes before invading distant organs, physicians recommend that nodes be removed and examined histologically for the absence or presence of malignant cells. The results will guide the treatment course. Patient preparation: A few days before surgery, the patient undergoes a blood test, chest X ray, and electrocardiogram in order to assess general health. To avoid excessive bleeding, any blood-thinning medications are usually suspended at this time. Patients are cautioned not to eat or drink in the eight hours before surgery and, on admission to the hospital, are asked to sign an informed consent form. Steps of the procedure: The operation, performed under general anesthesia, lasts up to two hours. The surgeon makes an incision under the arm and removes a section of fat that contains a cluster of lymph nodes. The incision is sutured, and a drain is generally inserted to remove excess fluid. After the procedure: Most patients remain in the hospital overnight, longer if complications develop. Nurses monitor the patient until the anesthetic wears off and vital signs stabilize. The drain may be left in place until the first follow-up visit. Postoperative measures include medication to relieve pain, preventive care to avoid infection at the incision site, the use of compression bandages to reduce fluid retention, and stretching exercises to rehabilitate arm movement. No heavy lifting is allowed during the recovery period of up to six weeks. Risks: The most common complications of axillary dissection are numbness under the arm, swelling of the arm (lymphedema) with feelings of tightness and reduced range of motion, and infection at the incision site. Results: Before proceeding with an axillary dissection, the surgeon may decide to biopsy the sentinel lymph node (the very first node that drains fluid from the tumor). If no cancer cells are found, then no other nodes or only a few
Salem Health: Cancer adjacent key nodes are removed. If tumor cells are detected, however, then a more extensive axillary dissection is performed to excise six to ten nodes or more. The greater the number of cancerous nodes, the less favorable is the prognosis for survival. Anna Binda, Ph.D. See also Breast cancers; Cutaneous breast cancer; Lobular carcinoma in situ (LCIS); Lumpectomy; Lymphedema; Mastectomy; Melanomas; Mucinous carcinomas; Sentinel lymph node (SNL) biopsy and mapping.
u Azathioprine Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1985 Also known as: Azasan, Imuran Related cancers: Non-Hodgkin lymphoma, cancers of the skin and liver Definition: Azathioprine is a drug prescribed for transplant patients and those whose immune systems attack their own tissues, but long-term usage causes cancer. Exposure routes: Ingestion, intravenous injection, and inhalation Where found: The drug is found in hospitals, used for transplant and autoimmune disease patients, and in manufacturing plants that make and package the drug. At risk: Patients who take azathioprine and workers who manufacture it. Etiology and symptoms of associated cancers: In the liver, azathioprine is converted to 6-mercaptopurine, which inhibits deoxyribonucleic acid (DNA) synthesis. This suppresses the immune system but can also cause a dangerous decrease in the number of white blood cells (leukopenia)
Azathioprine and platelets (thrombocytopenia), increased risk of infection and bleeding, gastrointestinal disturbances, and liver damage. The substance 6-mercaptopurine also inserts between adjacent nucleotide bases in DNA molecules and causes mutations that lead to various types of cancer. Azathioprine increases the risk of developing squamous cell carcinoma, a type of skin cancer that appears as persistent wartlike growths, scaly patches, or open sores that crust over and bleed; non-Hodgkin lymphoma, a blood-based cancer of white blood cells called T cells, the most common symptoms of which are painless swelling of the neck, or underarm lymph nodes, unexplained fever, loss of weight and appetite, itchy skin with reddened patches, and constant fatigue; and cancer of the bile ducts or hepatobiliary carcinomas, whose symptoms include jaundice, itching, stomach pain, weight loss, and fever. History: The pioneer of liver transplantation, Sir Roy Yorke Calne, first used azathioprine to prevent organ rejection in liver transplant patients. Azathioprine was the standard antirejection drug in the 1970’s for organ transplants and was later enlisted to treat patients who suffer from diseases that result when the immune system attacks the patient’s own body (autoimmune diseases). Several epidemiological studies have shown that transplant patients who took azathioprine were at a high risk for different types of tumors. Other patients who took azathioprine but were not transplant patients, including those with rheumatoid arthritis, systemic lupus, inflammatory bowel disease, and certain skin and renal diseases, have also shown higher incidences of such malignancies, but not as high as those observed in transplant patients, since the dosages to treat autoimmune diseases are lower than those used for transplant patients. Mycophenolate mofetil, which is not as carcinogenic, is gradually replacing azathioprine as the antirejection drug of choice. Michael A. Buratovich, Ph.D. See also Crohn disease; Myasthenia gravis; Pancolitis.
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Bacillus Calmette Guérin (BCG)
u Bacillus Calmette Guérin
(BCG) Category: Chemotherapy and other drugs ATC code: 103AX03 Also known as: BCG Live, Pacis BCG Live, TICE BCG Definition: Bacillus or bacille Calmette Guérin (BCG) solution is an immunotherapeutic agent containing live, weakened bacteria. It is currently approved by the U.S. Food and Drug Administration (FDA) as a primary therapy for carcinoma in situ of the urinary bladder. The BCG solution for bladder cancer contains water, saline, and a freeze-dried and live (but avirulent) strain of Mycobacterium bovis, an organism that causes tuberculosis in cattle. The BCG vaccine is used throughout the world to immunize humans against tuberculosis, with varying rates of efficacy; the BCG vaccine is not routinely administered in the United States. BCG is named for the two Pasteur Institute researchers who discovered the vaccine against human tuberculosis: physician Léon Charles Albert Calmette (1863-1933) and bacteriologist Jean-Marie Camille Guérin (1872-1961). Cancers treated: Superficial or early-stage bladder cancer in which tumors have not entered the muscle layer of the bladder wall Delivery routes: Instillation How this substance works: Generally BCG treatment follows surgery to remove tumors from the surface (epithelium) of the inside of the bladder (lumen). A health care provider inserts a catheter to deliver the BCG solution to the bladder. The solution remains in the bladder for at least two hours. The millions of M. bovis bacteria in BCG solution stimulate the immune system to seek out and destroy cancer cells. Patients usually have a series of weekly instillations over a number of months followed by maintenance instillations, depending on the treatment plan. The exact mechanism of action of the BCG solution is unknown. It is thought that certain proteins in the bacteria adhere to the urothelium or lining of the bladder wall. The urothelium then releases a number of cytokines or inflammatory substances that alert the immune system that a pathogen is present. The bacteria may also enter the cancer cells and break down proteins to display on the cancer cell surface, thus flagging it for destruction by the immune system. Approximately 70 percent of patients respond to initial treatment, and 75 percent of those patients remain free of 118
Salem Health: Cancer bladder cancer for more than five years. Because BCG contains live bacteria, patients with compromised immune systems should not be treated with BCG solution. Patients should also not take antibiotics, which would kill the live bacteria and prevent effective treatment. Side effects: Most patients (80 to 90 percent) who receive successive treatments with BCG solution experience one or more side effects, including the urgent need to urinate, blood in the urine, pain during urination, fatigue, nausea, chills, and a low-grade fever that lasts twenty-four to seventy-two hours. Pamela Richardson, M.S. See also Biological therapy; Bladder cancer; Immunocytochemistry and immunohistochemistry; Immunotherapy.
u Bacteria as causes of cancer Category: Carcinogens and suspected carcinogens Also known as: Helicobacter pylori, Salmonella typhi, Streptococcus bovis, Chlamydophila (previously Chlamydia) pneumoniae Related cancers: Gastrointestinal cancers, lung cancer Definition: Although no bacterium has been shown to be absolutely responsible for causing cancer, very strong evidence implicates two types of bacteria in the process of cancer formation, and less convincing evidence implicates others. Each of these types of bacteria has been shown to cause a persistent (chronic) infection in which the organisms are in contact with the tissue over a long period of time. During that time, genes for cell division and other cell maintenance functions, the same ones that are damaged by other known chemical and physical carcinogens, are damaged by the metabolic and toxic products produced by these bacteria. Equally important are immune system defenses and additional genetic and environmental factors that make only certain individuals susceptible to these organisms. The two types of bacteria are Helicobacter (associated with gastric cancer) and Salmonella typhi (gallbladder cancer). Additional bacteria probably associated with different cancers include Streptococcus bovis (colorectal cancer), Chlamydophilia pneumoniae (lung cancer), strains of Escherichia coli (colorectal cancer associated with Crohn disease and ulcerative colitis), and different types of oral streptococci (oral cancers). Exposure routes: Ingestion and inhalation Where found: Infected and uninfected persons carrying certain bacteria; contaminated water, air, and surfaces
Salem Health: Cancer At risk: Genetically susceptible individuals specific to each type of bacteria Etiology and symptoms of associated cancers: Cancer caused by H. pylori is characterized by tumors in the protective layer of mucus in the stomach, including the immune tissue. Continued high incidence of stomach cancer in areas of Asia suggests that a diet high in salted, smoked, and pickled foods is a contributory factor. Transmission of H. pylori is thought to be by the fecal-oral route. The second strongest case for bacterial causation of cancer involves S. typhi and its role in causing cancer of the gallbladder. It has been known since the famous case of Typhoid Mary that survivors (or carriers without symptoms) of typhoid fever carry S. typhi for at least a year and can transmit the pathogen in their feces. The organism resides in the gallbladder during that entire time, thus fulfilling one of the conditions necessary to cause cancer (long exposure). Cancer formation in the gallbladder is frequently associated with gallstone formation (solid deposits of cholesterol or calcium salts). Symptoms that may indicate a diseased gallbladder include chronic indigestion, upper abdominal pain, nausea and vomiting, and fever. All of these symptoms may also be associated with additional gastrointestinal problems, so they are not definitive for gallbladder problems, including gallbladder cancer. Associated risk factors include cholelithiasis (especially untreated symptomatic chronic gallstones), obesity, reproductive factors, environmental exposure to toxic chemicals, congenital malformation of bile ducts, and chronic infections affecting the gallbladder. The most significant risk factor for those cancers associated with S. typhi appears to be chronic infection of the gallbladder. Data show that patients with chronic infections with this organism are eight times more likely to have cancer of the gallbladder than those who had acute infections in which the organisms were cleared from their body. Genetic susceptibility of American Indians and Mexican Americans, especially women (in all populations), to gallbladder cancer suggest that these groups are predisposed to develop it primarily or secondarily due to an increased incidence of cholesterol gallstones. A secondary pathway of cancer development revolves around congenital malformation of the bile duct, and is seen primarily in people from Japan, Korea, and possibly China. History: The first indication that a relationship existed between bacteria and cancer occurred in 1951, when researchers found that patients frequently had both infective endocarditis (infection of the heart) and colonic carcinoma. It took until 1974 to identify S. bovis as the bacte-
Bacteria as causes of cancer rium associated with the colonic cancer and bacteremia (bacteria in blood). It is known today that S. bovis is a natural inhabitant of the human gastrointestinal tract and causes both endocarditis and bacteremia. Patients having colon carcinoma frequently also harbor S. bovis, and these cancerous lesions may develop years after having endocarditis or bacteremia. Further research has focused on the bacteria naturally found in the gastrointestinal tract and their ability to metabolize nutrients into carcinogens. Experiments done using gastrointestinal flora from rats determined that metabolic products are mutagenic (cause mistakes in deoxyribonucleic acid, or DNA). The fact that germ-free rats did not develop tumors as frequently as normal animals was also significant in defining the relationship between diet and gastrointestinal flora. Data from later experiments have suggested that the presence of microorganisms as a causative agent for cancer formation may be more complicated than first thought. Conflicting reports suggest that the presence of H. pylori is both detrimental and beneficial in the development of esophageal cancer. The ability to use the presence of microorganisms as an indication that cancer may also be present (in situations in which the cancer is not easily diagnosed at an early stage) is being examined. This is the case with oral tumors and specific oral bacteria. Therefore, the precise relationship between microorganisms and different types of cancer is still unclear and remains to be determined. Steven A. Kuhl, Ph.D. u
For Further Information Hope, Mari, et al. “Sporadic Colorectal Cancer: Role of the Commensal Microbiota.” FEMS Microbiology Letters 244 (2005): 1-7. Lax, Alistair, and Warren Thomas. “How Bacteria Could Cause Cancer: One Step at a Time.” Trends in Microbiology 10 (2002): 293-299. Mager, Dixie. “Bacteria and Cancer: Cause, Coincidence, or Cure? A Review.” Journal of Translational Medicine 4 (2006): 14.
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Other Resources
Centers for Disease Control and Prevention Helicobacter pylori http://www.cdc.gov/ncidod/aip/research/hp.html National Cancer Institute H. pylori and Cancer: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ HPylori 119
Barium enema
Salem Health: Cancer
See also Achlorhydria; Alcohol, alcoholism, and cancer; Diverticulosis and diverticulitis; Esophagitis; Ethnicity and cancer; Helicobacter pylori; Infectious cancers; Mucosa-associated lymphoid tissue (MALT) lymphomas; Poverty and cancer; Prostatitis; Risks for cancer; Stomach cancers; Virus-related cancers.
u Barium enema Category: Procedures Also known as: Lower gastrointestinal (GI) series, single-contrast barium enema, double-contrast barium enema, air contrast barium enema Definition: A barium enema involves the insertion of barium sulfate, a radiopaque contrast medium, into the colon, the first section of the large intestine. This procedure is used with X rays as a diagnostic and screening test for colon cancer, colorectal cancer, and colon polyps, growths that are sometimes a precursor to colon cancer.
A barium enema is an outpatient procedure that is performed at a hospital radiology department or an outpatient radiology center. A barium enema does not require anesthesia, and patients are awake. A single-contrast barium enema takes about forty-five minutes, and a doublecontrast study takes about an hour to complete. Patients disrobe and wear an examination gown for the procedure. Steps of the procedure: Patients lie on an X-ray table. An X ray is taken before the barium is inserted. Patients lie on their side for the barium insertion process. Awell-lubricated plastic tube is gently inserted through the anus and into the rectum. Barium is slowly poured through the tube to fill the colon. The barium is monitored on a barium fluoroscope monitor. A balloon at the end of the enema tube is inflated to keep the barium in the colon. Patients may receive medication to relieve cramping. X rays are taken from a variety of angles. Patients are asked to change positions, and the X-ray table may be tilted. Pressure may be applied to the patient’s abdomen to help move the barium through the colon.
Cancers diagnosed: Colon cancer, colorectal cancer, colon polyps Why performed: A barium enema with X rays is used to screen for and help diagnose colon cancer, colorectal cancer, and colon polyps. The American Cancer Society recommends screening beginning at the age of fifty, earlier for people with risk factors. Barium sulfate shows up on X rays and highlights the shape of the colon better than X rays alone. A single-contrast barium enema uses barium sulfate that is inserted into the colon. A double-contrast barium enema involves inserting barium into the colon, emptying the colon, and then expanding the colon with air. The barium remains on the lining of the colon, and the air expands the folds of the colon to allow a better view. Patient preparation: Patients consume a clear liquid diet for one to three days before the test. Patients are instructed to consume large amounts of water and to use laxatives and enemas on the day before the test. An enema may be repeated on the day of the test to make sure the bowel is clear of stool and gas. For women, a pregnancy test may be used to ensure that the patient is not pregnant. Patients should tell their doctor if they have a latex allergy. 120
An X ray of the abdomen (frontal view), showing cancer of the left descending colon, after a barium enema. (©ISM/Phototake—All rights reserved)
Salem Health: Cancer At the end of the procedure, the enema tube is gently removed. Patients empty the barium from the colon by using a bedpan or going to the bathroom. After the barium is removed, a few final X rays are taken. For a double-contrast barium enema, the colon is drained of barium. The colon is then filled with air, and X rays are taken. When the procedure is complete, the enema tube is removed, and patients empty the colon of barium. Afew final X rays are taken. After the procedure: Patients should drink plenty of fluids to help remove the barium from their bodies. Bowel movements will contain barium for one to two days following the tests. The barium may make bowel movements appear pink or white in color.
Barium swallow European Journal of Radiology 61, no. 3 (March, 2007): 382-387. Rosman, A. S., and M. A. Korsten. “Meta-analysis Comparing CT Colonography, Air Contrast Barium Enema, and Colonoscopy.” American Journal of Medicine 120, no. 3 (March, 2007): 203-210. See also Adenomatous polyps; Barium swallow; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Crohn disease; Diverticulosis and diverticulitis; Gallium scan; Imaging tests; Medicare and cancer; Ovarian cancers; Pancolitis; Premalignancies; Small intestine cancer; X-ray tests.
Risks: A barium enema is a low-risk procedure. Occasionally, the barium may harden, resulting in constipation. Drinking extra fluids and using a laxative may relieve constipation. In rare cases, the bowel may become inflamed or perforated. Patients should contact their doctor if they experience bleeding, severe pain, fever, or no bowel movements within two days of the procedure.
u Barium swallow
Results: The X-ray films are read by a radiologist. The ordering doctor may review the films as well. A healthy colon and rectum are free of abnormal growths or polyps. Any abnormalities, such as cancer or precancerous tissues, are visible on the films. Abnormal results are followed with colonoscopy. Mary Car-Blanchard, O.T.D., B.S.O.T.
Definition: A barium swallow is a diagnostic test in which the patient ingests barium sulfate, a radiopaque contrast medium. It is used with X rays to detect mouth, throat, vocal cords, esophagus, stomach, and small intestine cancers.
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For Further Information Etzioni, D. A., et al. “Measuring the Quality of Colorectal Cancer Screening: The Importance of Follow-Up.” Diseases of the Colon and Rectum 49, no. 7 (July, 2006): 1002-1010. Fenton, J. J., et al. “Delivery of Cancer Screening: How Important Is the Preventive Health Examination?” Archives of Internal Medicine 167, no. 6 (March 26, 2007): 580-585. Jimbo, M., et al. “Effectiveness of Complete Diagnostic Examination in Clinical Practice Settings.” Cancer Detection and Prevention 30, no. 6 (2006): 545-551. Pickhardt, P. J. “The Natural History of Colorectal Polyps and Masses: Rediscovered Truths from the Barium Enema Era.” American Journal of Roentgenology 188, no. 3 (March, 2007): 619-621. Rollandi, G. A., E. Biscaldi, and E. DeCicco. “Double Contrast Barium Enema: Technique, Indications, Results, and Limitations of a Conventional Imaging Methodology in the MDCT Virtual Endoscopy Era.”
Category: Procedures Also known as: Barium swallow X ray, barium swallow exam, barium swallow test, barium meal, doublecontrast barium swallow, upper gastrointestinal (GI) series, esophagraphy, esophagogram, esophagram
Cancers diagnosed: Oral cavity (mouth) cancer; oropharyngeal (throat) cancer; vocal cord cancer, including laryngeal and hypopharyngeal cancer, glottic cancer, supraglottic cancer, subglottic cancer; esophageal cancer; stomach cancer; stomach polyps, which may precede stomach cancer; small intestine cancer, including carcinoid tumors, gastrointestinal stromal tumors, lymphomas, and adenocarcinoma Why performed: A barium swallow with X rays is performed to help diagnose cancer of the mouth, throat, vocal cords, esophagus, stomach, and small intestine. When swallowed, barium sulfate shows up on X rays and highlights the linings of the above-mentioned structures. A double-contrast barium swallow involves swallowing substances that create air in the stomach to expand it, allowing a better view. Patient preparation: Patients may be placed on a restricted diet a few days before the test. Patients should not eat, drink, chew gum, or smoke after midnight before the test. Patients receive instructions from their doctors about swallowing medications. The stomach needs to be empty for the procedure. In some cases, the stomach contents are removed through a tube placed in the nose. For women, a 121
Barium swallow
Salem Health: Cancer taken. Then, patients drink sixteen to twenty ounces of barium sulfate. The barium sulfate is mixed in a thick drink that may have flavor added to it; otherwise, the drink is described as tasting chalky. The examination table may be tilted or pressure may be applied to the patient’s abdomen to help spread the barium. The barium is viewed on a barium fluoroscope monitor as it travels through the upper digestive tract. Still X-ray images can be taken at any time. Patients may need to drink more barium sulfate as the test progresses. For a double-contrast barium swallow, the patient swallows baking soda crystals. The baking soda creates gas, and the air expands the stomach. Additional images are taken, and the patient is repositioned or the examination table is tilted as necessary. After the procedure: Patients should drink plenty of fluids to help remove the barium from their bodies. Patients can eat a regular diet unless instructed otherwise. Bowel movements will contain barium for one to two days following the tests. The barium may make bowel movements appear white, gray, or pink in color.
Extended, infiltrating, and mild stenosing esophageal cancer are revealed by a barium X ray. (©ISM/Phototake—All rights reserved)
pregnancy test may be performed to ensure that the patient is not pregnant. Abarium swallow is an outpatient procedure that is performed at a hospital radiology department, outpatient radiology center, or doctor’s office. The test does not require anesthesia, and patients are awake. A barium swallow usually takes from thirty to sixty minutes, depending on the extent of the procedure. Patients disrobe and wear a gown for the test. Patients need to remove metal objects that may interfere with the X rays, including glasses, dentures, and jewelry. Steps of the procedure: The patient’s vital signs are taken before the test and monitored during the test. Patients may sit, stand, or lie on an X-ray table for the procedure. Patients may be secured to the X-ray table if it is tilted to allow images to be taken from various angles. X rays of the patient’s heart, lungs, and abdomen are 122
Risks: A barium swallow is considered a low-risk procedure. The radiation exposure is low, but it carries a small risk of cancer. Patients may be allergic to the flavorings that are mixed with the barium drink. Occasionally, the barium may harden, resulting in intestinal blockage or constipation. Patients should contact their doctor if they have not had a bowel movement within one to two days of the procedure. Results: The X-ray films are read by a radiologist. The ordering doctor may review the films as well. The linings of healthy structures are free of abnormal growths or polyps. Any abnormalities, such as cancer or precancerous tissues, appear as growths or polyps. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Drop, A., et al. “The Modern Methods of Gastric Imaging.” Annales Universitatis Mariae Curie-Skuodowska 59, no. 1 (2004): 373-381. Gore, R. M., et al. “Upper Gastrointestinal Tumours: Diagnosis and Staging.” Cancer Imaging 29, no. 6 (December, 2006): 213-217. Hosaka, K. “Radiological Investigation of the Mucosae Around Early Gastric Cancers.” Journal of Gastroenterology 41, no. 10 (October, 2006): 943-953. Kunisaki, C., et al. “Outcomes of Mass Screening for Gastric Carcinoma.” Annuals Surgical Oncology 13, no. 2 (February, 2006): 221-228.
Salem Health: Cancer Levine, M. S., and S. E. Rubesin. “Diseases of the Esophagus: Diagnosis with Esophagography.” Radiology 237, no. 2 (November, 2005): 414-427. Pasuawski, M., J. Zuomaniec, E. Ruci½ska, and W. Koutyk. “Synchronous Primary Esophageal and Gastric Cancers.” Annales Universitatis Mariae Curie-Skuodowska 59, no. 1 (2004): 406-410. Summers, D. S., M. D. Roger, P. L. Allan, and J. T. Murchison. “Accelerating the Transit Time of Barium Sulphate Suspensions in Small Bowel Examinations.” European Journal of Radiology 62, no. 1 (April, 2007): 122-125. See also Diarrhea; Esophageal cancer; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Imaging tests; Laryngeal cancer; Laryngectomy; Small intestine cancer; Stomach cancers; Throat cancer; Upper gastrointestinal (GI) series; X-ray tests.
u Barrett esophagus Category: Diseases, symptoms, and conditions Also known as: Barrett’s esophagus, Barrett’s metaplasia, Barrett’s mucosa, Barrett’s syndrome, columnar epithelium lined lower oesophagus (CELLO), columnar-lined esophagus Related conditions: Esophageal adenocarcinoma, gastroesophageal reflux disease (GERD), hiatal hernia
Barrett esophagus people with GERD, some of the acid of the stomach leaks into the esophagus, possibly because of a weakness in the sphincter. In about 10 to 15 percent of these people, the acid changes the color and makeup of the cells lining the esophagus. These cells are much like cells in the intestines; they are darker than the normal esophagus tissue and more resistant to stomach acid. Rarely, Barrett esophagus cells develop into a precancerous state called dysplasia. Dysplasia, in some cases, then develops into esophageal cancer. Incidence: About 700,000 adults in the United States have Barrett esophagus. It is very uncommon in children; the average age of diagnosis is sixty. It is twice as common in men as in women. Caucasians and Hispanics are more likely to develop this condition than those of other ethnic backgrounds. Symptoms: Symptoms include chronic heartburn, chronic acid reflux, trouble swallowing or a feeling that something is stuck in the throat, weight loss, spitting up food, excessive burping, hoarseness, sore throat, and bleeding. Sometimes people with chronic heartburn will get some relief from their symptoms when they develop Barrett esophagus. The intestinal metaplasia may help protect the esophagus from the stomach acid because those cells are normally found in the intestines and are better able to withstand stomach acid. Screening and diagnosis: Adults over the age of forty who have had chronic heartburn or acid reflux may be
Definition: Barrett esophagus is a condition in which some of the cells lining the esophagus (tube that carries food to the stomach) are replaced with a different type of cell similar to those lining the intestines, a process called intestinal metaplasia. Rarely, these cells develop into cancer of the esophagus (esophageal adenocarcinoma). This condition is named after Norman Barrett, who first described it in 1957. Risk factors: Developing Barrett esophagus is linked to chronic heartburn and another common condition called gastroesophageal reflux disease (GERD). However, the chances of heartburn or GERD developing into Barrett esophagus are very small. Sometimes people who develop GERD have a part of the stomach that bulges through the diaphragm (hiatal hernia). This kind of hernia may trap acid in the esophagus and cause more damage, eventually leading to GERD and progressing into Barrett esophagus. Etiology and the disease process: Normally, a round muscle (sphincter) near the bottom of the esophagus keeps stomach acid from washing back up into the esophagus. In
Barrett esophagus has produced two areas of dysplasia. (Custom Medical Stock Photo)
123
Basal cell carcinomas screened with an endoscopy to see whether they have Barrett esophagus. However, screening for this disease is not commonly recommended as an endoscopy is expensive and the rate of discovering the condition is very low. People who have no symptoms should not have an endoscopy just to see if they have this condition. Barrett esophagus can be diagnosed only by performing a biopsy on suspected tissue. There is no staging for Barrett esophagus. Treatment and therapy: Treatment for Barrett esophagus involves avoiding further damage. Therapies that keep the acid in the stomach from moving up into the esophagus may include antacid-type medications or other medications that stop stomach acid production. Lifestyle changes, such as losing weight, stopping smoking, and avoiding certain foods, also help. Other ways to keep the acid in the stomach include eating smaller meals more often, wearing loose-fitting clothing, waiting two to three hours after eating before lying down, and elevating the head of the bed 8 to 10 inches. A type of surgery that reinforces the sphincter that keeps acid in the stomach may also help. There is no cure for Barrett esophagus other than surgically removing the esophagus. This type of surgery is only performed on those who have already developed esophageal adenocarcinoma or are at very high risk for developing it. With this surgery, the affected part of the esophagus is removed, and the stomach is brought up and attached to the nonaffected part of the esophagus. Possible treatments for removing Barrett esophagus cells are being investigated. These include various ways of destroying those cells with lasers or chemicals. However, removing the cells has not yet been proven to reduce the risk of Barrett esophagus recurring or developing into esophageal cancer. Removing the Barrett esophagus cells is usually recommended only when a patient has highly developed precancerous or already cancerous cells. Prognosis, prevention, and outcomes: Barrett esophagus may not cause any problems or symptoms in those who have it. It is only significant because it is a precursor to esophageal adenocarcinoma, but even those who have Barrett esophagus have a less than 1 percent chance of developing this type of cancer. Those who have been diagnosed with Barrett esophagus should be screened regularly, every one to three years, to ensure that the cells are not developing into cancer. Some ways of attempting to prevent further damage to the esophagus are to eat a diet low in fat and high in fruits, vegetables, and fiber. Avoiding smoking and maintaining a healthy weight may also help. Marianne M. Madsen, M.S. 124
Salem Health: Cancer u
For Further Information Parker, James, and Philip M. Parker, eds. The Official Patient’s Sourcebook on Barrett’s Esophagus: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2004. Shalauta, Saad R. “Barrett’s Esophagus.” American Family Physician 69, no. 9 (May 1, 2004): 2113-2118. Sharma, Prateek, and Richard E. Sampliner, eds. Barrett’s Esophagus and Esophageal Adenocarcinoma. 2d ed. Malden, Mass.: Blackwell, 2006. u
Other Resources
Barrett’s Oesophagus Foundation http://www.barrettsfoundation.org.uk MedicineNet.com Barrett’s Esophagus http://www.medicinenet.com/barretts_esophagus/ article.htm National Digestive Diseases Information Clearinghouse Barrett’s Esophagus http://digestive.niddk.nih.gov/ddiseases/pubs/barretts See also Esophageal cancer; Esophagectomy; Esophagitis; Histamine 2 antagonists; Premalignancies; Upper gastrointestinal (GI) endoscopy.
u Basal cell carcinomas Category: Diseases, symptoms, and conditions Also known as: Basal cell cancer, BCC Related conditions: Basal cell epitheliomas Definition: Basal cell carcinoma is a cancer in which the cancerous cells resemble the basal cells of the epidermis, the outer layer of the skin. It is the most common type of skin cancer. Risk factors: Exposure to ultraviolet light is the primary risk factor. People with light skin and eyes are more susceptible because they have less melanin, the pigment that colors skin and blocks the sun’s radiation. People who are exposed to more ultraviolet light because they work outdoors or use tanning booths are also at greater risk. Children are particularly susceptible to skin damage from the sun because they burn more readily. Arsenic exposure, usually from contaminated drinking water, is another risk factor.
Salem Health: Cancer
Basal cell carcinomas
Etiology and the disease process: Basal cell carcinomas are thought to begin in the upper part of the skin, the epidermis, or in a hair follicle. The basal cell layer forms the base of the epidermis. Basal cells continually divide to form new cells of skin, hair, or glands. They become cancerous when something disrupts their deoxyribonucleic acid (DNA) instructions for making normal new cells. The most common cause is ultraviolet radiation, probably UVB. These rays can hit the nuclei of skin cells and damage chromosomes or DNA. The body repairs most of the damage to chromosomes, but cells that are not repaired can begin to divide wildly and become cancer cells, which destroy surrounding cells or tissues. Basal cell carcinomas are slow growing and rarely spread to other parts of the body. If left untreated, however, they can do extensive damage to surrounding tissue. Incidence: Basal cell carcinoma is the most common skin cancer in the United States, making up about 75 percent of skin cancers. Nearly a million new cases are reported each year, and about 90 percent of those are attributed to solar radiation, although some cases occur in skin rarely exposed to the sun. Men are at higher risk than women, probably because they have, in the past, worked outdoors more. Basal cell carcinoma is more common in adults than in children, and the elderly are the most likely candidates, as these cancers can take twenty to fifty years to manifest after radiation exposure. Symptoms: The most common symptom of basal cell carcinoma is a skin lesion, which is a superficial growth or a sore that does not heal. There are many types of basal cell carcinoma and nearly as many types of lesions. Lesion size varies from a few millimeters to several centimeters, and some lesions are larger than they appear on the skin because they invade underlying tissues. The lesions are usually painless, though the surrounding skin can become irritated and tender. Some lesions are flat, reddish or crusty patches that can be mistaken for psoriasis or eczema. The color and appearance of lesions varies widely, from white or yellow and scarlike to pink, red, tan, brown, or black. Lesions are often waxy or translucent in appearance, and many are described as pearly. Some lesions are smooth and symmetrical, while others have irregular borders or a bumpy surface with superficial blood vessels. Other lesions have rolled edges with a crater in the middle. Many lesions bleed easily. Screening and diagnosis: The U.S. Preventive Services Task Force evaluated routine screening for skin cancers in 2001 and did not find evidence to recommend whole-body
A patient with basal cell carcinoma. (Custom Medical Stock Photo)
skin examination for skin cancer, so health care providers look for skin cancers as circumstances allow or warrant. The diagnosis of basal cell carcinoma is made by histologic, or microscopic, examination of lesional cells from a sample of the lesion or from examination of the entire lesion. The type and variety of cancer are determined by the makeup and differentiation of cells. Treatment and therapy: The most common treatment for basal cell carcinoma is surgical excision, or removal, of the lesion. Some normal tissue is taken all around the lesion so that the physician can be sure no cancer cells are left. Mohs surgery, which allows for better margin control, is the treatment of choice for sclerosing basal cell carcinoma. Other treatments include curettage and electrodesiccation, or scraping of the lesion and destroying the remaining tissue with electric current; cryosurgery, or freezing with liquid nitrogen; topical chemotherapy; radiation; laser surgery; and photodynamic therapy, in which a 125
Beckwith-Wiedemann syndrome (BWS) sensitizer is absorbed into the lesion, which is then exposed to a laser beam. Prognosis, prevention, and outcomes: The cure rate is about 85 to 99 percent for primary tumors. One variant of basal cell carcinoma, called sclerosing, morpheaform, or infiltrating, is more likely to recur after treatment. This variant, which usually resembles a scar, is more difficult to treat because it grows in thin strands that may be missed in the tissue sample. Though death from basal cell carcinoma is extremely rare, untreated lesions can cause extensive damage and disfigurement, sometimes requiring skin grafts or reconstructive surgery. Early detection and treatment give the best outcomes. Basal cell carcinoma is also highly preventable through avoidance of excessive sun exposure, particularly in childhood. Childhood exposure to ultraviolet radiation can result in skin cancer that appears decades later. Limiting sun exposure, using sunscreen, and wearing sun-protective clothing and hats are useful methods of preventing damage to the skin from ultraviolet light. Cathy Anderson, R.N., B.A. u For Further Information Burns, C. A., and M. D. Brown. “Imiquimod for the Treatment of Skin Cancer.” Dermatology Clinics 23, no. 1 (2005): 151-164. Neale, R. E., et al. “Basal Cell Carcinoma on the Trunk Is Associated with Excessive Sun Exposure.” Journal of the American Academy of Dermatology 56, no. 3 (2007): 380-386. Noble, J. Textbook of Primary Care Medicine. 3d ed. St. Louis: Mosby, 2001.
u
Other Resources
Medem Medical Library http://www.medem.com Skin Cancer Foundation http://www.skincancer.org See also Arsenic compounds; Bowen disease; Choriocarcinomas; Dermatology oncology; Electroporation therapy; Exenteration; Eye cancers; Eyelid cancer; Lip cancers; Medulloblastomas; Melanomas; Mohs surgery; Moles; Neuroectodermal tumors; Radical neck dissection; Skin cancers; Squamous cell carcinomas; Sunlamps; Turcot syndrome; Vulvar cancer. 126
Salem Health: Cancer
u Beckwith-Wiedemann
syndrome (BWS) Category: Diseases, symptoms, and conditions Also known as: Wiedemann-Beckwith syndrome, exomphalos-macroglossia-gigantism (EMG) syndrome Related conditions: Hemihypertrophy (enlargement of one side of the body); hypoglycemia (low blood sugar); exomphalos (a protrusion of the umbilicus) or other abdominal wall defects such as umbilical hernia, omphalocele, and diastasis recti; visceromegaly (enlarged organs) or enlarged tongue or skeleton; adrenal gland abnormalities such as adrenocortical cytomegaly (enlarged cells of the adrenal cortex); dysplasia of the renal medulla; and embryonal cancerous tumors (tumors that arise from embryonic or fetal tissue) such as nephroblastoma (Wilms’ tumor affecting the kidney, about 75 percent), hepatoblastoma (liver malignancy, about 1 to 11 percent), rhabdomyosarcoma (a soft-tissue tumor most commonly found in the head and neck, arms, and legs, and the renal and genital tracts, about 5 percent), and neuroblastoma (affecting primitive neuronal cells in the adrenal gland and behind the peritoneum, the serous tissue that lines the abdomen, about 4 percent) Definition: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder caused by abnormalities in the 11p15.5 region of chromosome 11. The expression of the involved chromosome is variable and the penetrance (the degree to which features or characteristics resulting from the person’s genetic makeup are seen by others) is incomplete. Penetrance is affected by either paternal or maternal transmission of information and gene control. Risk factors: De novo mutations and inheritance through familial linkage are the primary risk factors. Analysis of the chromosomes is diagnostic in familial heritance, and all show transmission through the mother. Analysis of paternally derived BWS shows duplication or trisomy of the 11p15.5 region. These multiple copies result in a varying phenotype. Thus, different patterns of inheritance have been documented. Etiology and the disease process: The overexpression of insulin-like growth factor-2 (IGF-2) is a key determinant of BWS. This overexpression occurs in the following manner. One set of chromosomes is inherited from the father, and the other is inherited from the mother. Each set of
Salem Health: Cancer chromosomes contains a gene or a set of genes responsible for the characteristics of the new individual. Often, a gene on either the maternal or paternal chromosome is expressed, while the corresponding gene on the other parent’s chromosome is silent. The expression of a gene on one parent’s chromosome and the silence of the corresponding gene on the other parent’s chromosome is termed imprinting. BWS develops when the normally expressed maternal gene is overactive. Deregulation of imprinted growth regulatory genes on chromosome 11, region 11p15.5, results in an imbalance between maternal and paternal allele expression. This region contains the genes for insulin and insulin-like growth factor-2 (IGF-2), both potent stimulators of fetal growth. This genetic aberration triggers exaggerated growth in the fetus, both in overall size as well as the enlargement of various structures and organs. Other tissues sensitive to abnormal growth factors respond by producing a high incidence of embryonal tumors and other anomalies. The loss of IGF-2 imprinting results in an overexpression of IGF-2 and leads to an enlarged body, organs, and overstimulation of embryonic tissues, which are the basis for various tumors affecting the kidneys, liver, and adrenal glands. Incidence: BWS occurs in approximately 1 in 14,000 live births in the regular population in the United States. The incidence is higher with in vitro births (assisted reproductive technology). Because of phenotypic variation, many individuals with BWS may go undiagnosed, especially if the penetrance is mild or subtle. Symptoms: Major symptoms include macroglossia (large tongue), pre- or postnatal growth greater than the ninetieth percentile, and abdominal wall defects. Minor symptoms include hypoglycemia, ear creases or helical indentations, facial nevus flammeus (port-wine stain), a large placenta at birth, and polyhydramnios (excessive amniotic fluid). Abnormalities in all body systems have been reported in association with BWS. Screening and diagnosis: Because of the high incidence of embryonal tumor formation, abdominal ultrasonographic examinations are necessary every three months, especially in the first six years of life (the period when most embryonal tumors manifest). Wilms’ tumor is rapidly progressive, and even individuals who have been examined every six months have been found to have latestage disease. Diagnosis is by imaging studies (ultrasound, magnetic resonance imaging, computed tomography, bone scans), biopsy, laboratory tests (complete blood count, blood smear, alpha-fetoprotein, tests to evaluate functioning of the involved organs).
Beckwith-Wiedemann syndrome (BWS) Staging is a process to determine whether the cancer has spread (metastasized) to other sites. Classification includes: • Stage I: The cancer can be completely removed by surgery. • Stage II: A majority of the cancer is removed by surgery with a small amount remaining at the primary site. • Stage III: The cancer has spread to the lymph nodes. • Stage IV: The cancer has spread to distant sites in the body. • Recurrent: The cancer has returned after it has been treated. Treatment and therapy: Hypoglycemia must be prevented and, if present, rapidly treated to prevent central nervous system abnormalities, especially mental retardation. Embryonic tumors require treatment (surgery, radiation, chemotherapeutic drug administration). Macroglossia is treated with surgery to ensure a patent (open) airway and normal mouth and speech development. Other anomalies are given standard treatment for the problem. Prognosis, prevention, and outcomes: Prevention requires a decision by affected individuals not to reproduce. Prenatal genetic testing is currently not available. Prenatal ultrasound examination may lead to early detection of an affected fetus. If the pregnancy is continued, medical personnel can be alerted, thus allowing prompt attention to the infant at birth to detect problems and intervene in a timely manner, hopefully preventing some complications. Prognosis depends on the range of morbidities and their management. Wanda Todd Bradshaw, R.N.C., M.S.N. u
For Further Information Cohen, M. Michael. “Beckwith-Wiedemann Syndrome: Historical, Clinicopathological, and Etiopathogenetic Perspectives.” Pediatric and Developmental Pathology 8 (2005): 287-304. Smith, Adam C., Sanaa Choufani, José C. Ferreira, and Rosanna Weksberg. “Growth Regulation, Imprinted Genes, and Chromosome 11p15.5.” Pediatric Research 61, no. 5 (2007): 43R-47R. Weksberg, Rosanna, Cheryl Shuman, and Adam C. Smith. “Beckwith-Wiedemann Syndrome.” American Journal of Medical Genetics, Part C 137C (2005): 12-23.
u
Other Resources
Beckwith-Wiedemann Syndrome Family Forum http://www.beckwith-wiedemann.info 127
Benign prostatic hyperplasia (BPH) Online Mendelian Inheritance in Man http://www.ncbi.nlm.nih.gov/sites/entrez?db=OMIM See also Adrenal gland cancers; Adrenocortical cancer; Nephroblastomas; Rhabdomyosarcomas; Wilms’ tumor.
u Benign prostatic hyperplasia
(BPH) Category: Diseases, symptoms, and conditions Also known as: Benign enlargement of the prostate (BEP), lower urinary tract symptoms (LUTS) Related conditions: Prostate cancer, urinary retention Definition: Benign prostatic hyperplasia (BPH) refers to an enlarged prostate gland. The prostate is a reproductive gland in men that produces semen, the fluid that nourishes and transports sperm. It is about the size and shape of a walnut and is located below the bladder. The gland surrounds the urethra, the tube that carries urine outside the body. The prostate grows in size in most men as they age. Risk factors: Increasing age and a family history of BPH contribute to the risk of developing this condition. Etiology and the disease process: The exact cause of BPH is unknown. It is not cancerous, nor does it increase the risk of developing prostate cancer. Incidence: Approximately 50 percent of men between the ages of fifty-one and sixty and 90 percent over age eighty develop BPH. About half of all men diagnosed with BPH have moderate to severe symptoms. Symptoms: The enlarged prostate presses down on the urethra and irritates or obstructs the bladder. Common symptoms include frequent urination two or more times per night, a sudden urge to urinate, a weak urine stream, dribbling after urinating, straining to urinate, the inability to prevent urine leakage, or the sensation that the bladder is not empty even after urinating. In extreme cases, urinary retention, the complete inability to urinate, is a problem. Screening and diagnosis: The evaluation typically consists of a complete medical history, a digital rectal exam to feel the size of the prostate, a urinalysis to check for blood or infection in the urine, a prostate-specific antigen (PSA) blood test to screen for prostate cancer, and questions to assess the severity of symptoms. Additionally, urine flow rate, a post-void residual urine test, a pressure-flow study, 128
Salem Health: Cancer an X ray of the urinary tract, or cystoscopy (a test using a scope inserted into the urethra and bladder) may be recommended. Treatment and therapy: Depending on the severity of symptoms, treatment can include lifestyle modifications, such as decreasing the intake of fluid before bedtime and limiting the consumption of alcohol and caffeine, or medication to increase urine flow. In extreme cases, surgery to remove part of the prostate may be recommended. Prognosis, prevention, and outcomes: Many men with BPH have only minor symptoms and are able to manage their discomfort with lifestyle modifications. A yearly exam is recommended to monitor symptoms and the impact of BPH on daily life. Vonne Sieve, M.A. See also Digital rectal exam (DRE); Prostate cancer; Prostate-specific antigen (PSA) test; Prostatectomy; Prostatitis; Saw palmetto; Transrectal ultrasound; Urologic oncology.
u Benign tumors Category: Diseases, symptoms, and conditions Also known as: Mass, benign neoplasm, noncancerous tumor Related conditions: Lipoma, chondroma, adenoma, hemangioma Definition: A benign tumor is a noncancerous growth that does not invade nearby tissue or spread to other parts of the body. Benign tumors are caused by cell overgrowth and are thus distinct from other tissue formations, such as cysts or abscesses. A tumor is a mass of tissue that serves no useful purpose and exists at the expense of healthy tissues. Benign tumors do not exhibit any of the three characteristics of malignant tumors: Benign tumors do not invade nearby tissues, do not metastasize, and do not grow in an unlimited, accelerated manner. Risk factors: The specific risk factors for benign tumors vary depending on the location of the tumor and the tissue type. For example, risk factors for benign breast tumors include such factors as body mass index, height, and breast size. Problems with the body’s immune system can cause tumors, both malignant and benign. Certain viruses can also play a role in tumor formation, as in cervical cancer and hepatocellular carcinoma. Exposure to loud sounds or music can increase the risk of developing benign tumors in
Salem Health: Cancer
Benign tumors
the ears, as can repeated exposure to cold water. Smoking can cause benign tumors to appear in the lower lip. Etiology and the disease process: The source of most benign tumors is a discrete population of cells that have been altered through acquired genetic defects. Such abnormal tissue masses are termed benign neoplasms. Benign tumors are usually encapsulated, meaning that they are confined to a specific, localized area and surrounded by a thin layer of tissue. This limits the growth rate and invasive potential of the tumor. In the liver, the most common benign tumors are hemangiomas. These tumors are made of abnormal blood vessels, most likely present at birth but only detected later when they cause symptoms or are identified on an ultrasound or computed tomography (CT) imBenign tumor nevus pigmented lesions. (Custom Medical Stock Photo) age obtained for another reason. Hemangiomas occur more frequently in women. Screening and diagnosis: When a tumor is found, a biInfections can cause benign tumors to appear in the larynx, opsy is performed to determine whether the tumor is bewhich can be detected by symptoms of hoarseness. nign or malignant. Although usually not life-threatening, Incidence: Benign tumors are common and usually not once diagnosed, benign tumors should be monitored regulife-threatening. However, benign tumors cause more than larly, as a benign tumor may progress and become a malig13,000 deaths annually, compared with more than 500,000 nant tumor. For instance, a colon polyp is a type of benign annual deaths due to malignant tumors. Benign tumors can tumor, but most incidences of colon cancer develop from cause serious injury or death by pressing on vital organs colon polyps. The most common benign tumors of the ear (such as the brain), tissues, or nerves in the vicinity of the occur behind the ear. They can also occur within the ear growth. Benign tumors in the kidneys can range in size canal or on the scalp and can be discovered during a roufrom 1 millimeter to several centimeters without causing tine ear examination, which includes audiometry (hearing any symptoms or requiring treatment. Benign tumors in tests) and tympanometry (middle ear testing). When lookthe lungs are relatively rare, making up only 7 to 10 pering into the ear, the doctor may observe cysts or benign tucent of all tumors in the lungs. Benign tumors in the stommors within the ear canal. ach account for 5 to 10 percent of all stomach tumors, afTreatment and therapy: Often a benign tumor will reflicting many people between the ages of forty and fifty. quire no treatment if it is located in a low-risk area where it Men are two to four times more likely to develop benign will not cause symptoms or disturb proper function of an stomach tumors compared with women. organ. If causing symptoms, benign tumors are usually Symptoms: Benign tumors may be asymptomatic or may treated by surgery. Benign tumors may also be removed cause one or more of the following symptoms depending for cosmetic reasons. The incidence of recurrence after on their location and their specific tissue type: itching, obsurgery is typically low. Chemotherapy and radiation therstruction of the intestines, bleeding or occult blood loss reapy are usually ineffective in the treatment of benign tusulting in anemia, cosmetic changes, hormonal syndromes mors. Benign tumors of the brain may be surgically recaused by hormones secreted by the tumor, compression moved to prevent harmful effects on the surrounding of the blood vessels or vital organs, and pain or dysfuncnormal brain tissue. tion induced by pressure. Benign tumors in the nose have Prognosis, prevention, and outcomes: Benign tumors the following symptoms: hard breathing, bleeding, headache, or severe eye pain and blurring. tend to grow more slowly than malignant tumors and are 129
Benzene less likely to threaten health. If a tumor is benign, the prognosis is generally very good. The situation can be more serious if the tumor is located in the brain. Michael R. King, Ph.D. u For Further Information Black, Peter McL. Living with a Brain Tumor: Dr. Peter Black’s Guide to Taking Control of Your Treatment. New York: Henry Holt, 2006. DeMonte, Franco, et al., eds. Tumors of the Brain and Spine. New York: Springer, 2007. Moore, Stephen W. Griffith’s Instructions for Patients. 7th ed. Philadelphia: Elsevier Saunders, 2005. u
Other Resources
Genetics Home Reference Benign Tumors http://ghr.nlm.nih.gov/conditionGroup=benigntumors Medline Plus Benign Tumors http://www.nlm.nih.gov/medlineplus/ benigntumors.html See also Acoustic neuromas; Adenomatoid tumors; BirtHogg-Dubé syndrome (BHDS); Brachytherapy; BRAF gene; Carcinogens, known; Carney complex; Castleman disease; Chemoprevention; Cowden syndrome; Craniopharyngiomas; Endotheliomas; Fibroadenomas; Gastrointestinal stromal tumors (GISTs); Gestational trophoblastic tumors (GTTs); Glomus tumors; Hemangioblastomas; Hystero-oophorectomy; Lacrimal gland tumors; Leiomyomas; Metastasis; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Phyllodes tumors; Pineoblastomas; Radical neck dissection; Sertoli cell tumors; Tuberous sclerosis.
u Benzene Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Benzol, phenyl hydride, 1,3,5cyclohexatriene Related cancers: Cancers of the blood and blood-forming organs, including acute myelogenous, monocytic, erythroblastic and lymphocytic leukemias, lymphomas, and Zymbal gland carcinomas Definition: Benzene (chemical formula C6H6) is a clear, colorless to light yellow, volatile and flammable liquid 130
Salem Health: Cancer that has an aromatic odor. It is slightly soluble in water, is sensitive to heat, and mixes easily with alcohol, ether, chloroform, acetone, carbon tetrachloride, carbon disulfide, oils, and glacial acetic acid. It forms a solid below 42 degrees Fahrenheit. In the United States, the Safe Drinking Water Act (1976) has legal control over benzene levels in drinking water, which cannot exceed 5 parts per billion (ppb). Exposure at 19,000-20,000 parts per million for five to ten minutes is fatal. Exposure routes: Inhalation, skin contact, and oral ingestion are the most toxic and dangerous routes. Where found: Benzene is an industrial chemical that is widely used as a solvent and used in inks, rubber, lacquers, paint removers, gas additives, glue backing for carpeting, high solvent paints, some furniture wax, automobile exhaust, tobacco smoke, secondhand smoke, taxidermy, firefighting, metal preparation and pouring, petroleum refining, industrial cleaning, drinking water, and closed processes to synthesize organic chemicals. It is also used to make dyes and insecticides and in the processing of numerous chemicals. At risk: Children and pregnant woman are at higher risk. However, anyone exposed to benzene is at risk. For example, the presence of benzene in gasoline makes exposure to it a risk for anyone filling an automobile gas tank. Etiology and symptoms of associated cancers: It is not clear how benzene causes damage to the blood-forming organs, which then leads to leukemias and lymphomas. Interaction between breakdown products (metabolites) is being studied as a likely cause. Exposure to as little as 1 part per million lowers white cell counts. Symptoms of leukemias and lymphomas include fever, night sweats, fatigue, bleeding and easy bruising, bone pain, frequent infections, swollen lymph nodes, and weight loss. History: Benzene is a natural component of crude oil. In 1825 Michael Faraday performed distillation experiments and extracted a gas from the oil. The gas burned, and he named it “bicarburet of hydrogen.” The chemical structure of benzene remained elusive until 1865, when Friedrich August Kekulé von Stradonitz hypothesized a hexagonal structure. Benzene was derived from the distillation of coal by A. W. Hoffman in 1846. The uses of and demand for benzene increased along with oil exploration as its usefulness in many industrial applications became apparent. Linus Pauling, the Nobel Prize-winning physicist, was
Salem Health: Cancer one of many scientists to attempt to elucidate the unique hybrid structure of benzene that was confirmed in 1931. The main use of benzene prior to World War I was in gasoline blending, as it increased octane. It was used extensively in industry in World War II, and almost all organic-chemistry-related industry involves petroleum (benzene-containing) products. Janet R. Green, M.S.P.H. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Air pollution; Aleukemia; Aplastic anemia; Bioflavonoids; Blood cancers; 1,3-Butadiene; Carcinogens, known; Carcinogens, reasonably anticipated; Chlorambucil; Cigarettes and cigars; Coal tars and coal tar pitches; Coke oven emissions; Dioxins; Free radicals; Leukemias; Myelodysplastic syndromes; Myelofibrosis; Organochlorines (OCs); Phenolics; Urinary system cancers.
u Benzidine and dyes
metabolized to benzidine Category: Carcinogens and suspected carcinogens RoC status: Benzidine, known human carcinogen since 1980; dyes metabolized to benzidine, known human carcinogens since 2000 Also known as: Direct Blue 6, Direct Black 38, Direct Brown 95 Related cancers: Bladder cancer, and less frequently cancer of the stomach, liver, kidney, central nervous system, and pancreas Definition: Benzidine is an organic compound used to make dyes. It is usually found in the form of a powder that is white, reddish gray, or grayish yellow. Exposure routes: Benzidine can enter into the human body in many ways. If air containing molecules of benzidine is inhaled, the benzidine can enter into a person’s system. Benzidine can also be ingested, either directly or in contaminated drinking water. It is also possible for benzidine to enter the human body through the skin if direct contact is made with benzidine or a benzidine-based dye. Where found: For many years, benzidine was used in the production of dyes and dyeing compounds. It was also used occasionally in some clinical and laboratory settings, for example, in blood detection. Dyes that metabolize to benzidine were used in many different dyeing applica-
Benzidine and dyes metabolized to benzidine tions. Benzidine was used especially often to dye paper products, textiles, and leather goods. Plants manufacturing dyes were likely to contain large quantities of benzidine or dyes that metabolize to benzidine, as were plants that produced goods using such dyes. Beginning in the late 1970’s use of these dyes was phased out. Because of long usage, there remains the possibility of benzidine contamination in areas around plants and factories that once used benzidine or related dyes. Benzidine that is released into or makes its way into rivers or streams generally settles quickly on the bottom of the riverbed or streambed. Benzidine that was released into the environment through accidental contamination or as a waste product that ends up in the soil bonds strongly to particles found in the soil. It is not likely to seep into the groundwater and contaminate drinking water sources because of these strong bonds. Because its use in dyeing was phased out, benzidine and related dyes are used in only very small quantities in mostly research and laboratory settings in the United States. At risk: People who worked in industries that manufactured dyes or regularly used dyes in the production of other goods before the late 1970’s were at risk of exposure to high levels of benzidine and dyes that metabolize to benzidine. According to the Occupational Health and Safety Administration, in 1979 there were sixty-three separate occupations in which workers were at risk for benzidine exposure. Also at risk are people living near factories or plants that manufactured or used benzidine or benzidinebased dyes, especially if by-products of the plant were released into the air or water. Some residual benzidine may continue to exist at such locations. Benzidine and related dyes have also been identified as existing at many hazardous waste disposal sites and people who live near such areas may be at risk of exposure. Etiology and symptoms of associated cancers: Benzidine and related dyes have been shown to cause cancer in laboratory animals. Studies of humans who have a history of working with benzidine or related dyes have also shown that prolonged benzidine exposure is a significant risk factor for developing bladder cancer. Scientists do not clearly understand all the complex mechanisms involved in how benzidine causes cancer, but benzidine is believed to interfere with normal cellular processes. Bladder cancer is the cancer most commonly associated with benzidine exposure. The first signs and symptoms of bladder cancer are usually changes in bladder function or habits. This may include a person’s often feeling the urge to urinate without actually being able to do so. Needing to urinate much more frequently than usual is also 131
Benzodiazepines a possible symptom of bladder cancer, as is blood in the urine. History: Benzidine has a long history as an important industrial dye. It was first made in 1845. Its first use as a dye was in 1884, when a dye named Congo Red was created for the first time. Benzidine and related dyes were extremely useful in dyeing because of the way they adhere to cotton and cotton products. In the 1920’s some physicians and researchers began to suspect a relationship between exposure to benzidine and the development of bladder cancer. It was not until 1976, however, that major commercial production of benzidine and benzidine-based dyes ceased in the United States. There are no major manufacturers of benzidine for the purposes of dyeing or of benzidine-based dyes in the United States; however, there are still some small manufacturers of benzidine because it has some research and laboratory applications. It is considered a possible occupational carcinogen by the Occupational Safety and Health Administration. Personal protection is required for work with benzidine and related products, and it is necessary to take precautions to ensure that no benzidine is released into the environment. Benzidine is also considered a hazardous substance that requires special labeling and precautions when it is transported. Robert Bockstiegel, B.S. u For Further Information Bozzone, Donna M. Causes of Cancer. New York: Chelsea House, 2007. Pohanish, Richard P. Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens. 5th ed. Norwich, N.Y.: William Andrew, 2008. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Williams, Nerys R. Atlas of Occupational Health and Disease. New York: Oxford University Press, 2004. u
Other Resources
International Agency for Research on Cancer http://www.iarc.fr/index.html Occupational Safety and Health Administration http://www.osha.gov See also Carcinogens, known; Carcinogens, reasonably anticipated; Immunocytochemistry and immunohistochemistry. 132
Salem Health: Cancer
u Benzodiazepines Category: Chemotherapy and other drugs ATC code: N05BA Also known as: Alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan) Definition: Benzodiazepines are a class of drugs with antianxiety, sedative, and muscle-relaxing properties. Cancers treated: Adjuvant therapy for many types of cancer Delivery routes: Orally by capsule or tablet, intramuscularly by injection How these drugs work: Benzodiazepines are a class of medications that act primarily on the gamma aminobutyric acid-α (GABA-A) receptors in the brain. Medications within the class vary according to their rapidness of onset, potency, frequency of dosing, length of effect, and halflife. They are typically used in the general medical population to alleviate anxiety or treat insomnia. Benzodiazepines are put to similar uses with cancer patients, as well as directed toward disease-specific conditions. When choosing among benzodiazepines, physicians consider the unique properties of specific medications (such as speed of onset, duration of effect, side effects), as well as patient characteristics (age, vigor, pain tolerance,
Common Benzodiazepines The following common benzodiazepines are used to treat acute mania, alcohol dependence, seizures, anxiety, insomnia, and muscular disorders. Trade Name
Generic Name
Ativan Dalmane Dormicum Halcion Klonopin Lexotanil Librium Loramet Mogadon ProSom Restoril Rohypnol Sedoxil Serax Valium Xanax
lorazepam flurazepam midazolam triazolam clonazepam bromazepam chlordiazepoxide lormetazepam nitrazepam estazolam temazepam flunitrazepam mexazolam oxazepam diazepam alprazolam
Salem Health: Cancer coping skills) and the types of cancer and treatments involved. Short-acting medications with rapid onset are often employed to treat acute anxiety, panic, and phobic responses to therapy. Longer-acting medications may be selected to assist patients engaging in painful or aversive cancer treatments (such as chemotherapy) to promote relaxation, reduce anticipatory anxiety, suppress recall of treatment, and alleviate nausea and restlessness (akisthisia). Long-acting benzodiazepines may also be employed to treat generalized anxiety and grief reactions stemming from cancer. Highly sedating benzodiazepines are often used to treat anxiety-related insomnia. Side effects: A number of side effects are associated with benzodiazepines. Long-term use can lead to drowsiness and deficits in memory, concentration, and motor coordination. Though safe for most in recommended dosages, benzodiazepines can potentially cause respiratory depression, and patients should be monitored closely as they initiate treatment. All benzodiazepines, especially those with rapid onsets and short durations of action, have the potential to cause dependence and, in rare cases in the cancer patient population, abuse. Consequently, physicians must closely supervise patients’ use of these medications. Abrupt discontinuation of benzodiazepines may cause withdrawal symptoms that, while severe, are usually managed with appropriate medical intervention. These symptoms include “rebound” anxiety, confusion, agitation, seizures, and, rarely, death. Paul F. Bell, Ph.D. See also Antinausea medications; Anxiety; Pain management medications.
u Beryllium and beryllium
compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2002 Also known as: Glucinium. Glucinium is a rarely used term, but it is noteworthy because, although the name describes beryllium’s tempting, sugary flavor, it does not warn of its poisonous nature, and those working with the alkaline earth metal should be cautioned. Related cancers: Lung cancer Definition: Beryllium is an alkaline earth metal found in ore deposits and in some precious stones. It was discovered in 1798 in emeralds and beryl and isolated in 1828.
Beryllium and beryllium compounds The metal did not see large-scale industrial use until the late 1950’s. In the twenty-first century, however, because of its high melting point, great elasticity, exceptional thermal conductivity, high permeability to X rays, and resistance to oxidation, beryllium finds uses across a wide range of products. Exposure routes: Inhalation of beryllium compounds that are found in dust and fumes combined with prolonged exposure elevate the risk of pulmonary disease and lung cancer. Beryllium can also enter the body through food and drinking water, but these routes seem less harmful because of its poor absorption. However, contact through abraded skin may result in local irritation, ulceration, or granulomatous growths. Where found: Beryllium has found uses across a variety of industries due to its properties as a light, high-strength metal combined with great elasticity and high melting point. A brief list includes uses in X-ray diagnostics; as a lightweight structural material required by the aerospace and missile industries; and as an alloying agent found in applications requiring high strength and first-rate electrical conductivity. Additionally, beryllium and its compounds find use in nonsparking tools, telecommunication devices, electrical contacts, nuclear reactors, ceramics, microwave equipment, communication satellites, space vehicles, aircraft, semiconductors, electrical insulators, everyday items such as golf clubs and bicycle frames, and many other applications requiring a hardening agent found in alloys such as beryllium copper. At risk: Workers experiencing chronic exposure to beryllium compounds are most at risk. This would include beryllium miners (the United States is the world’s largest producer); workers involved with beryllium alloys, ceramics, nuclear reactors, phosphorus manufacture, electronic equipment, and missiles; and garment workers exposed to beryllium dust. According to Environmental Protection Agency (EPA) estimates, work facilities in the United States release approximately 1 million pounds of beryllium and beryllium compounds into the environment annually, but the risk to the general population remains poorly understood. What is understood is that lung cancer risk rises with exposure time and beryllium dust concentration. Etiology and symptoms of associated cancers: The nonmalignant disease associated with beryllium and its compounds is called berylliosis. When exposed to high levels of beryllium, the immediate response is characterized by inflammation of the nose, larynx, trachea, bronchioles, 133
Beryllium and beryllium compounds and lungs. This is the acute form of beryllium disease and requires air levels of the metal on the order of 100 micrograms/cubic meter (mcg/m3) or more. Normally, ambient air levels are thousands of times less. As the exposure becomes more chronic, and typically from contact at much lower levels just exceeding 0.02 mcg/m3 over ten or more years, berylliosis takes the form of a granulomatous disease of the lungs and possibly other organs. Granulomas are nodular inflammatory lesions packed with immune cells (macrophages). Both the acute and chronic forms of berylliosis are usually not fatal. The beryllium lymphocyte proliferation test (BeLPT) is an effective blood test that measures beryllium sensitization. Although most people with beryllium sensitization will eventually develop berylliosis, further testing must be done to establish the individual’s disease status. This is an important diagnostic tool because chronic berylliosis is not only a serious illness but also a significant pathway to malignancy. The progression to chronic berylliosis follows a continuing, overzealous, and ultimately destructive immune response that leads to lung scarring and loss of respiratory capacity. This cascade of events is triggered by chemical messengers called cytokines, which repeatedly call in more immune cells than the lungs can process. This overzealous immune response leads to severe lung damage. The terrible number of deaths from the 1918 flu epidemic was a result of just such a cytokine storm and not from the destructive properties of the virus itself. The progression to lung cancer is not completely understood, and there is some debate over just how lung cancer arises from berylliosis, but most experts accept that chronic berylliosis is a strong marker for events leading to malignancy. History: Cancer arising from beryllium or its compounds depends on length and level of exposure. In general these exposure risks have been significantly reduced since the 1950’s, when workers might have been exposed to hundreds of times the levels found in twenty-first century working conditions. In 1991 researchers confirmed the carcinogenicity of beryllium and its compounds, and in 2002 the Department of Health and Human Services officially recognized beryllium as a carcinogen. The Occupational Safety and Health Administration (OSHA) sets permissible peak exposure limits for beryllium at 0.025 mcg/ m3; however, independent occupational health organizations are urging the reduction of these limits even further. To confuse the issue, there is even some minor debate on just how well previous data support the connection between cancer risk and beryllium exposure. 134
Salem Health: Cancer What is known is that certain factors may affect the progression of chronic beryllium disease (CBD). These factors include the individual’s work environment, the duration and intensity of exposure, and the particle size and solubility of the beryllium dust. Also the individual’s genetic makeup, lifestyle habits, and general health are contributing issues. Richard S. Spira, D.V.M. u
For Further Information American Conference of Governmental Industrial Hygienists. 1999 TLVs and BEIs: Threshold Limit Values for Chemical Substances and Physical Agents—Biological Exposure Indices. Cincinnati, Ohio: Author, 1999. American Industrial Hygiene Association. The AIHA 1998 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook. Fairfax, Va.: Author, 1998. Kelleher, P. C., et al. “Beryllium Particulate Exposure and Disease Relations in a Beryllium Machining Plant.” Journal of Occupational and Environmental Medicine 43 (2001): 238-249. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. U.S. Environmental Protection Agency. Integrated Risk Information System (IRIS) on Beryllium. Washington, D.C.: National Center for Environmental Assessment, Office of Research and Development, 1999. _______. Toxicological Review of Beryllium and Compounds. Washington, D.C.: Author, 1998. U.S. Occupational Safety and Health Administration. Occupational Safety and Health Standards, Toxic and Hazardous Substances. Code of Federal Regulations 29 CFR 1910.1000. Washington, D.C.: Author, 1998.
u
Other Resources
Agency for Toxic Substances and Disease Registry ToxFAQS for Beryllium http://www.atsdr.cdc.gov/tfacts4.html U.S. Environmental Protection Agency CICAD Report on Beryllium and Beryllium Compounds http://www.inchem.org/documents/cicads/cicads/ cicad32.htm See also Carcinogens, known; Cytokines; Lung cancers.
Salem Health: Cancer
u Beta-carotene Category: Lifestyle and prevention ATC code: A11CA02 Also known as: A-Caro-25, betacarotene, carotene, carotenoid, Lumitene, retinal, retinol Definition: Beta-carotene is a member of a family of nutrients called carotenoids, which are found in many red, orange, yellow, and green fruits and vegetables (such as carrots, sweet potatoes, squash, spinach, apricots, and broccoli). The body converts beta-carotene into vitamin A, which plays a role in vision, bone development, cell division, and cell differentiation. Cancers treated or prevented: Studies have found that a diet high in fruits and vegetables containing beta-carotene reduces the risk of certain types of cancer, including those of the prostate and lung. Researchers believe that betacarotene and other antioxidants in fruits and vegetables work together to lower cancer risk.
Bethesda criteria It was thought that beta-carotene supplements might reduce the risk of certain cancers, especially lung cancer, but there is no evidence of any cancer preventive benefit when beta-carotene is taken alone in supplement form. In fact, studies have found that smokers and people who have been exposed to asbestos who take beta-carotene supplements have a significantly higher risk of developing lung cancer and of dying from their cancer than those who do not take the supplements. In addition, the National Cancer Institute’s Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1992-2001) found that men with the highest levels of beta-carotene in their blood were at increased risk for developing more aggressive and deadly prostate cancer. Delivery routes: Oral in capsule and tablet forms. Eating five servings of fruits and vegetables daily provides 6 to 8 milligrams of beta-carotene. How this substance works: Beta-carotene is an antioxidant. It protects cells and deoxyribonucleic acid (DNA) from damage caused by unstable molecules called free radicals, which are produced during metabolic processes as cells burn up oxygen for energy. Free radicals are believed to contribute to cancer and other diseases. Vitamin A, which the body produces from beta-carotene, helps prevent the uncontrolled cell growth that occurs with cancer. Side effects: Beta-carotene may increase the risk of lung cancer or prostate cancer in people who smoke or drink alcohol heavily or who have been exposed to asbestos. It also may increase the risk of more aggressive prostate cancers. In high doses, beta-carotene may interact with some types of chemotherapy drugs or radiation. Stephanie Watson, B.S. See also Antioxidants; Carotenoids; Chemoprevention; Free radicals; Fruits; Nutrition and cancer prevention; Stomach cancers.
u Bethesda criteria Category: Procedures Definition: Bethesda criteria are a standardized set of criteria that are used to identify potential cases of hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome. Carrots contain beta-carotene, among other nutrients. (U.S. Department of Agriculture)
Hereditary nonpolyposis colorectal cancer: HNPCC is an autosomal dominant disease that is characterized by early age of onset (average is before the age of forty-five), 135
Bile duct cancer tumor formation in a variety of tissues (endometrial, gastric, renal, ovarian, and skin), and microsatellite instability. HNPCC accounts for only about 3 to 5 percent of the cases of colorectal cancer, and the molecular and genetic testing that is required to diagnose this form of cancer can be quite time-consuming and costly. Therefore, it became important to set down a standardized set of criteria for identifying potential cases of HNPCC and to separate them from sporadic, noninherited forms of colorectal cancer. History: In 1997, a group of experts met at the National Institutes of Health to discuss the state of research on HNPCC. They came up with a set of criteria, the Bethesda criteria, which expanded the previous Amsterdam criteria to include extracolonic tumor formation as well as more specific histological characterization. In 2002, the criteria were further revised to define tumors that should be tested for microsatellite instability (MSI), which is the frequent mutation of repetitive deoxyribonucleic acid (DNA) sequences due to defects in the mismatch repair machinery in the cell. Criteria: Currently, the criteria for identifying a potential case of HNPCC are as follows: • Colorectal cancer diagnosed prior to age fifty • Presence of synchronous or metachronous HNPCCassociated tumors • High microsatellite instability (MSI-H) histology diagnosed prior to age sixty • One or more first-degree relatives diagnosed with an HNPCC-related tumor prior to age fifty • Colorectal cancer diagnosed in two or more first- or second-degree relatives Testing: If a patient meets the Bethesda criteria, a number of molecular and genetic tests are recommended. The ideal set of tests would include evaluation of microsatellite instability status as well as immunohistochemical analysis of tumors. In patients who show high levels of microsatellite instability and loss of expression of one or more of the DNA mismatch repair proteins, DNA sequencing of MSH2 and MLH1, the two genes most commonly mutated in HNPCC, should be performed. Patients who have mutations in either of these genes show an increased risk of developing cancer, and they should therefore undergo frequent screening. Lindsay Lewellyn, B.S. See also Ashkenazi Jews and cancer; Endometrial cancer; Ethnicity and cancer; Family history and risk assessment; MLH1 gene; MSH genes; Pancreatic cancers; PMS genes; Turcot syndrome. 136
Salem Health: Cancer
u Bile duct cancer Category: Diseases, symptoms, and conditions Also known as: Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, perihilar cancer, Klatskin tumors Related conditions: Sclerosing cholangitis, liver cancer Definition: Bile is a fluid produced by the liver that aids in the digestion of fats. Bile is transported from the liver through a series of tubes, called bile ducts, to either the gallbladder, which stores and concentrates the bile, or directly to the small intestine. Bile duct cancer forms in the inner layer of these ducts. It can develop in the smaller ducts within the liver, where it is called intrahepatic cholangiocarcinoma, or in ducts outside the liver, where it is called extrahepatic cholangiocarcinoma. Extrahepatic cholangiocarcinoma is divided into two types, depending on where the cancer originates. Perihilar cancer develops in the bile duct close to its exit point from the liver. Distal bile duct cancer develops close to where the bile duct empties into the small intestine. Approximately 95 percent of cholangiocarcinomas are adenocarcinomas. Risk factors: Conditions that irritate the bile ducts have been linked to an increased risk of developing cholangiocarcinoma. These disorders include bile duct stones, congenital bile duct cysts, viral hepatitis, sclerosing cholangitis (especially in people who smoke), and nonviral cirrhosis. Other risk factors include ulcerative colitis, liver flukes (parasites found in Asian countries), and obesity. Exposure to some chemicals, including polychlorinated biphenyls, dioxin, and Thorotrast (previously used in X-ray diagnosis), also increase the risk of developing this cancer. Etiology and the disease process: The exact cause of most cholangiocarcinomas is unknown. Patients with no known risk factors often develop this cancer. Cholangiocarcinoma is a slow-growing cancer that can remain undetected until it has reached an advanced stage. It originates in the mucosal cells that line the ducts and spreads throughout the layers of the ducts. Eventually, the ducts become blocked, preventing the flow of bile. When the cancer grows through the walls of the ducts, it can invade the liver, gallbladder, small and large intestines, and blood vessels that serve the liver. Incidence: Primary cholangiocarcinoma is a rare disease that is most common in Asian countries because of its association with liver flukes. Approximately 90 percent of cholangiocarcinomas are extrahepatic, with about 65 percent perihilar tumors and 25 percent distal cancers. About
Salem Health: Cancer
Bile duct cancer
4,000 people in the United States develop this cancer each year, most of whom are men, and about 70 percent of them are older than age sixty-five. The American Cancer Society has noted an increase in the incidence of intrahepatic cholangiocarcinoma, possibly because of improved diagnostic testing.
Relative Survival Rates for Bile Duct Cancer, 1988-2001 Survival Rates (%)
Symptoms: Most cholangiocarcinomas do not produce symptoms until they are in the advanced stages. Jaundiced and itchy skin, dark urine, and pale bowel movements may occur if the ducts become blocked and bilirubin, a chemical in bile, is forced into the blood vessels. Other symptoms include fever, bloating, loss of appetite, weight loss, and fatigue. Screening and diagnosis: There are no screening tests for cholangiocarcinoma. Diagnosis typically is made during surgery for a gallbladder disorder or during diagnostic tests for other conditions. Blood chemistry and liver function tests, though not specific for this cancer, may show abnormal results. Tumor-marker studies may show the presence of carcinoembryonic antigen and cancer antigen 19-9 (CA 19-9). Ultrasound, computed tomography scanning, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, positron emission tomography, and percutaneous transhepatic cholangiography are imaging studies used to diagnose cholangiocarcinoma, determine treatment options, and assess the spread of the disease. Biopsy and biliary brushing may be performed to obtain cells for differential testing. Staging is based on the number of tumors present and the extent of their spread to other organs. Treatment and therapy: Traditional treatment for cholangiocarcinoma includes surgery, chemotherapy, and radiation therapy. Surgery for intrahepatic cholangiocarcinoma always involves the removal of part of the liver and is a difficult procedure. In many cases, the cancer is too far advanced at the time of diagnosis for surgery to be successful or safe for the patient. Surgery for extrahepatic cholangiocarcinoma usually involves the removal of the bile duct, gallbladder, and parts of the liver and small intestine. It may also include the resection of part or all of the pancreas. When the cancer cannot be removed, symptoms may be relieved by creating a bypass around the tumor blocking the bile duct or inserting a biliary drain. Chemotherapy and radiation therapy may be used before surgery to shrink a tumor, in place of surgery when the tumor is inoperable, and after surgery to destroy cells that may have spread. Common chemotherapeutic agents used include fluorouracil, cisplatin, doxorubicin, and gemcitabine. Radiation is commonly administered in the form of
Years
Intrahepatic
Extrahepatic
1 2 3 5 8 10
27.9 19.5 8.5 4.8 3.4 3.2
43.7 25.4 17.5 12.8 9.8 9.7
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) Note: The median survival time for bile duct cancer is 5.6 months, for extrahepatic bile duct cancer, 9.4 months.
tiny seeds that are implanted into the duct, delivering highdose radiation directly to the tumor. Other forms of treatment that are being tested include using a person’s own immune system to fight the cancer, introducing viruses that seek out and destroy cancer cells, and photodynamic therapy, in which a special light is used to activate a drug that has been administered for the purpose of destroying cancer cells. Prognosis, prevention, and outcomes: The overall survival rate for cholangiocarcinoma is poor, with fewer than 20 percent surviving five years after diagnosis. Although there is no definitive way to prevent this disease, reducing exposure to its risk factors may prevent its development. Dorothy P. Terry, R.N. u
For Further Information Holland, Jimmie C., and Sheldon Lewis. The Human Side of Cancer. New York: HarperCollins, 2000. Souhami, Robert, and Jeffrey Tobias. Cancer and Its Management. Malden, Mass.: Blackwell, 2005. Stern, Theodore A., and Mikkael A. Sekeres. Facing Cancer: A Complete Guide for People with Cancer, Their Families, and Caregivers. New York: McGraw-Hill, 2004. u
Other Resources
American Cancer Society http://www.cancer.org 137
Bilobectomy
Salem Health: Cancer
Cancer.Net http://www.cancer.net/portal/site/patient
to be kept clean, and a gradual return to physical activity is recommended.
See also Afterloading radiation therapy; Alkaline phosphatase test (ALP); Carcinoid tumors and carcinoid syndrome; Cholecystectomy; Computed tomography (CT) scan; Endoscopic retrograde cholangiopancreatography (ERCP); Endoscopy; Gallbladder cancer; Gastrointestinal cancers; Infection and sepsis; Infectious cancers; Iridium seeds; Klinefelter syndrome and cancer; Liver cancers; Pancreatectomy; Pancreatic cancers; Percutaneous transhepatic cholangiography (PTHC).
Risks: The risks of a bilobectomy procedure are a narrowing of the bronchi (the large air passages leading from the windpipe to the lungs), scar formation, injury to nerves during surgery that may cause numbness and tingling in the chest area, and leakage of air from the surgical site with partial or complete collapse of the lung.
u Bilobectomy Category: Procedures Also known as: Lobectomy, thoracotomy Definition: A bilobectomy is a surgical procedure to remove two lobes of the lung.
Results: Surgery, including bilobectomy, is most effective for Stage I and Stage II non-small-cell lung cancer. Smoking cessation is of utmost importance to maximize surgical treatment as it improves wound healing and allows for the best outcome when additional therapies, such as radiation and chemotherapy, are used. Vicki Miskovsky, B.S., R.D. See also Bronchoalveolar lung cancer; Esophagectomy; Lobectomy; Lung cancers; Mesothelioma; Pleural effusion; Pleurodesis; Pneumonectomy; Surgical biopsies; Thoracoscopy; Thoracotomy.
Cancers treated: Various types of lung cancer Why performed: A bilobectomy is performed to remove diseased lung tissue. Patient preparation: Bilobectomy is performed under general anesthesia in a hospital with the usual preoperative preparation, such as physical examination, blood testing, and consultation with an anesthesiologist. In addition, an examination and additional lung tests will be done by a pulmonologist (a lung specialist). Steps of the procedure: The surgical procedure is performed by a thoracic surgeon making a cut in the side; the rib cage is separated or cut away to allow the lungs to be seen, and the pleura (a membrane around the lungs) is also cut away. The lung being operated on may be deflated, and the other lung continues to work with the help of a breathing tube. The lobes of the lung are pulled apart and separated, and the diseased lobes are cut free and removed. Arteries and veins that have been cut are sealed or reconnected. A drainage tube is left in the chest wall to drain or suction out fluid and air. The procedure may take from two to five hours. After the procedure: Pain medication will be used to make the patient more comfortable after the surgery. A hospital stay of about one week is to be expected; during hospitalization, breathing exercises as well as exercises for movement (range of motion) will be taught. Recovery at home can take several weeks, during which time pain medications may be used, the surgical incision site needs 138
u Bioflavonoids Category: Lifestyle and prevention Also known as: Flavonoids Definition: Flavonoids are the most common plant phenolic compounds. Their basic chemical structure consists of two benzene rings linked by a chain of three carbon atoms that can itself form a heterocyclic ring with oxygen. Variations of this chemical theme give rise to thousands of different bioflavonoids, which can be grouped in several families. Six families include bioflavonoids particularly common in the diet: flavonols, flavanols, flavonones (or flavanones), isoflavones, flavones, and anthocyanidines. Examples of bioflavonoids from each of these families are quercetin, cathechin, hesperitin, genistein, apigenin, and cyanidine, respectively. Most of the plant bioflavonoids occur as glycosides, that is, they have a sugar attached. Nutrition: The principal food sources of bioflavonoids are apples, celery, onions, green and black tea, citrus fruits, berries, soy, red wine, and cocoa. Although bioflavonoids are resistant to heat, certain food manipulations, such as the peeling of fruits or boiling, can cause some loss of their content or bioavailability. After the sugar moiety is removed by enzymes of the gastrointestinal tract, a variable portion of the ingested bioflavonoids is readily absorbed. The absorbed bioflavonoids are metabolized in the liver by conjugation with other chemical groups (for example,
Salem Health: Cancer
Biological therapy
glucuronic acid, sulfate, or methyl groups) and converted to smaller compounds.
eases, or to help lessen side effects from other cancer treatments such as chemotherapy.
Bioflavonoids and cancer: Numerous studies in experimental models, both in vivo and in vitro, have suggested that bioflavonoids have anticarcinogenic potential. As effective antioxidants, they prevent mutagenesis and tumor promotion by protecting deoxyribonucleic acid (DNA) and proteins from oxidative damage. By acting on signal transduction pathways that control the cell cycle, bioflavonoids inhibit proliferation and stimulate apoptosis, that is, programmed death, of human cancer cells. Cell cycle-related actions performed by bioflavonoids include suppressing nuclear factor kappa B activation, inhibiting mitogen-activated protein kinases, and blocking epidermal growth factor signaling. Bioflavonoids also stimulate detoxifying enzymes, such as cytochrome P450, which convert carcinogens into water-soluble compounds that can be eliminated from the body. In addition, they inhibit inflammation and angiogenesis. There is also strong scientific evidence that diets rich in fruits and vegetables protect against various forms of cancer. Some epidemiological studies have shown significant associations between high consumption of bioflavonoids and a reduced risk of certain forms of cancer, such as lung, rectal, and prostate cancers. However, several other epidemiological studies have failed to find such significant associations. Although bioflavonoids are gaining increasing acceptance as cancer-preventing agents, more consistent epidemiological data is needed before issuing specific public health guidelines. Reyniel Cruz-Aguado, Ph.D.
Cancers treated: A number of cancers, including melanoma, leukemia, breast, ovarian, colon, lung, and kidney cancers
See also Antioxidants; Beta-carotene; Carotenoids; Chemoprevention; Coenzyme Q10; Complementary and alternative therapies; Curcumin; Dietary supplements; Essiac; Free radicals; Fruits; Garlic and allicin; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Phenolics; Phytoestrogens; Resveratrol; Wine and cancer.
u Biological therapy Category: Chemotherapy and other drugs Also known as: Immunotherapy, biological response modifier therapy, biotherapy, biologic agents, biologic therapies, biologicals Definition: Biological therapy is an emerging, growing class of cancer drugs that work to help optimize the ability of the body’s immune system to fight cancer or other dis-
Subclasses of this group: Cytokines, monoclonal antibodies, colony-stimulating factors, antiangiogenesis agents, cancer vaccines Delivery routes: The delivery route varies depending on which biological therapy is being used. Various biological therapies may be given by mouth, by intravenous (IV) drip (infusion), by subcutaneous or intramuscular injection, or by delivery directly into a body cavity to treat a specific site. How these drugs work: The cells, antibodies, and organs of the immune system work to protect and defend the body against foreign invaders, such as bacteria or viruses. The immune system is a complex network of cells and organs that work together in a variety of ways. White blood cells are a very important part of the immune system. Lymphocytes are a type of white blood cell found in the blood and many other parts of the body that are intimately involved with the way that most biologic agents work. Types of lymphocytes include B cells, T cells, and natural killer (NK) cells. B cells mature into plasma cells that secrete proteins called antibodies, which recognize and attach to foreign substances known as antigens. Each type of B cell makes one specific antibody that recognizes one specific antigen. T cells produce proteins called cytokines, which include interferons, interleukins, and colony-stimulating factors. Cytokines are proteins that activate the immune system and that play an important role in communication between immune system cells. NK cells produce powerful cytokines that attach to and kill many foreign invaders, infected cells, and cancerous cells. Advances in techniques of molecular biology since the 1980’s have brought about a revolution in the understanding of many biological processes at a molecular level, including mechanisms involved in immunity and the pathogenesis of many diseases. In many cases, it has become possible to identify discrete specific molecular targets for therapeutic intervention and to design therapies to block or interact with those targets. At the same time, technological advances have made it possible to engineer and to produce these targeted therapeutic molecules for medical use. Physicians and researchers have found that, in addition to protecting the body against foreign invaders, the immune system might be able to differentiate between healthy 139
Biological therapy
Salem Health: Cancer
Common Biological Therapies Drug (Other Names)
Brands
Subclass
Delivery Mode Cancers Treated
Aldesleukin (interleukin-2)
Proleukin
Cytokine
Subcutaneous
Kidney cancer, melanoma
Alemtuzumab
Campath
Monoclonal antibody
IV
Chronic lymphocytic leukemia
Bacillus Calmette-Guérin vaccine
TheraCys BCG, TICE BCG
Vaccine
Introduction into bladder
Bladder cancer
Bevacizumab
Avastin
Monoclonal antibody
IV
Lung cancer, colorectal cancer
Cetuximab
Erbitux
Monoclonal antibody
IV
Head and neck cancers, colorectal cancer
Epoetin alfa, erythropoietin
Procrit
Colony-stimulating factor
Subcutaneous
Boosts red blood cell level during chemotherapy
Epratuzumab
LymphoCide
Monoclonal antibody
IV
B-cell leukemia
Filgrastim, granulocyte colony-stimulating factor
Neupogen
Colony-stimulating factor
Subcutaneous, Boosts white blood cell level during IV chemotherapy
Gemtuzumab ozogamicin
Mylotarg
Monoclonal antibody
IV
Acute myelogenous leukemia
Ibritumomab tiuxetan
Zevalin
Monoclonal antibody
IV
B-cell lymphoma
Interferon alpha-2a
Roferon-A
Cytokine
Subcutaneous
Hairy cell leukemia
Interferon alpha-2b
Intron-A
Cytokine
Subcutaneous
Melanoma, hairy cell leukemia, non-Hodgkin lymphoma, Kaposi sarcoma
Lym-1
Oncolym
Monoclonal antibody
IV
Lymphoma
Oprelvekin (interleukin-11)
Neumega
Cytokine
Subcutaneous
Boosts platelet level during chemotherapy
Panitumumab
Vectibix
Human monoclonal antibody
IV
Colorectal cancer
Quadrivalent human papillomavirus recombinant vaccine
Gardasil
Vaccine
Intramuscular
Cervical cancer
Rituximab
Rituxan
Monoclonal antibody
IV
Non-Hodgkin lymphoma
Tositumomab
Bexxar
Monoclonal antibody
IV
B-cell lymphoma
Trastuzumab
Herceptin
Monoclonal antibody
IV
Breast cancer
cells and cancer cells in the body and to eliminate cancerous ones. Biological therapies are designed to repair, stimulate, or enhance the immune system, either directly or indirectly, by assisting in the following ways: making cancer cells more recognizable by the immune system, boosting the killing power of immune system cells, changing the way in which cancer cells grow such that they act more like healthy cells, stopping the process that changes a normal cell into a cancerous cell, enhancing the body’s ability to repair or replace normal cells damaged or destroyed by other forms of cancer treatment such as chemotherapy or 140
radiation, and preventing cancer cells from spreading to other parts of the body. Biological therapies involve molecules that the body normally produces in small amounts in response to infection and disease and the use of modern recombinant deoxyribonucleic acid (DNA) technology to produce these molecules in large amounts for use in the treatment of cancers and other diseases. Molecular splicing of genes or portions of genes of interest to form DNA sequences that code for recombinant or fusion proteins is performed. These recombinant DNA sequences are spliced into plas-
Salem Health: Cancer mid vector molecules that can be introduced into host cells, which can be used in scaled-up production of large amounts of the purified recombinant or fusion protein. Important types of biological therapies are cytokines (interferons and interleukins), monoclonal antibodies, growth factors, colony-stimulating factors, antiangiogenesis agents, and cancer vaccines. Interferons were the first cytokines to be produced in the laboratory for use as biological therapies. Several types of inferons occur naturally in the body, of which interferon alpha is the most widely used in cancer treatment. Interferons can improve the immune system function against cancer cells and may in addition directly slow the growth of cancer cells or promote their development into cells with more normal behavior. There is some evidence that interferons may also stimulate NK cells and T cells, thereby boosting the immune system’s function against cancer cells. Intron A (interferon alpha) has been approved by the Food and Drug Administration (FDA) for cancer treatment; it is used for the treatment of hairy cell leukemia, melanoma, chronic myeloid leukemia, and AIDS-related Kaposi sarcoma and non-Hodgkin lymphoma. Interleukins are also cytokines that occur naturally in the body. Many types have been identified. Interleukin-2, which stimulates the growth and activity of many immune cells which can destroy cancer cells, has been the most widely studied in cancer treatment. Proleukin (interleukin-2) has been approved for use in the treatment of metastatic melanoma and metastatic renal cell carcinoma. Monoclonal antibodies are a single species of antibody that is produced in the laboratory from a single type of cell and is specific for a particular antigen. The production of monoclonal antibodies involves the creation of a hybrid cell line specific for that antibody molecule, called a hybridoma. Once produced, a hybridoma can be perpetuated in the laboratory to produce as much of the pure monoclonal antibody as desired. Monoclonal antibodies may be used in several ways. They may be used to boost the immune response to cancer cells, they may be designed to act against growth factors to inhibit the growth of cancer cells, and they may be linked to anticancer drugs, radioactive substances, or toxins to act as a vector to deliver these toxic agents directly to cancer cells. Rituxan (rituxamab) and Herceptin (trastuzumab) are examples of monoclonal antibodies that have been approved by the FDA, Rituxan for the treatment of non-Hodgkin lymphoma and Herceptin to treat metastatic breast cancer. Colony-stimulating factors (CSFs) stimulate bone marrow cells to divide and develop into white blood cells, red blood cells, and platelets. CSFs may be helpful for some patients undergoing treatment for cancer because many
Biological therapy anticancer drugs used in chemotherapy can damage the body’s ability to make these important cells in the bone marrow. Thus patients receiving chemotherapy have an increased risk of developing infections, anemia, and bleeding more easily. The dose of chemotherapy that a patient receives, and therefore the chemotherapy regimen’s effectiveness in fighting cancer, can sometimes be increased by using CSFs to eliminate or reduce the risk of infection or the need for transfusions. Neupogen (filgrastim) and Procrit (epoetin alfa) are colony-stimulating factors that the FDA has approved for use in cancer patients, Neupogen to boost the number of white blood cells during chemotherapy and Procrit to boost the number of red blood cells during chemotherapy. Antiangiogenesis agents, also called angiogenesis inhibitors, are an emerging type of biological therapy that show promise in fighting cancer. Cancer cells are rapidly dividing cells that depend on a rich network of small blood vessels to supply them with oxygen and nutrients. Tumors must generate this network of new blood vessels, a process called angiogenesis. Several types of molecules and antibodies have been shown to prevent angiogenesis and shrink tumors. Avastin (bevacizumab) is an antiangiogenic monoclonal antibody that has been approved for the treatment of lung and colorectal cancers. Cancer vaccines are another type of biological therapy being studied. Vaccines for infectious diseases work by exposing an uninfected individual to a weakened form of the infectious agent. The vaccine stimulates the immune system to mount an immune response to the agent but cannot cause the disease. The immune system produces antibodies specific to antigens present on the surface of the infectious agent. The immune system is also stimulated to produce certain types of T cells, which remember the exposure to the antigen. If the individual is subsequently challenged with the same infectious agent, then these T cells will orchestrate a quick and effective immune response, protecting the individual from contracting the disease. Cancer vaccines to treat existing cancers (therapeutic vaccines) or to protect healthy individuals from developing cancer (prophylactic vaccines) are being studied. Therapeutic vaccines may be effective in stopping the growth of existing cancer cells, in preventing cancer from recurring, or in killing existing cancer cells. Prophylactic vaccines are administered to healthy individuals to protect against cancers that are caused by viruses. Gardisil (quadrivalent human papillomavirus recombinant vaccine) is a prophylactic vaccine that has been approved by the FDA for the prevention of cervical cancer caused by human papillomavirus. Some biological therapies have been approved by the 141
Biopsy FDA for certain types of cancer, while many, still in development, are offered in clinical research studies to measure the effects of the treatment. In these cases, study results are often used as part of the FDA evaluation of the drug’s efficacy and safety. Side effects: The side effects of biological therapy regimens are variable from patient to patient. The most common side effects are a result of stimulation of the immune system and are similar to flulike symptoms, including fever, chills, body aches, nausea, vomiting, loss of appetite, and fatigue. Some patients may experience a rash or swelling at the injection site. Most side effects diminish one to two days after treatment. For patients who receive multiple doses of a biological therapy, the side effects usually lessen over time. Jill Ferguson, Ph.D. u For Further Information Kimura, F. “Molecular Target Drug Discovery.” Internal Medicine 46 (2007): 87-89. Old, L. J. “Immunotherapy for Cancer.” Scientific American 275 (1996): 136-143. Reang, P., M. Gupta, and K. Kohli. “Biological Response Modifiers in Cancer.” Medscape General Medicine 14 (2006): 33. Rosenberg, Steven A., ed. Principles and Practice of the Biologic Therapy of Cancer. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2000. Sorscher, S. M. “Biological Therapy Update in Colorectal Cancer.” Expert Opinion on Biological Therapy 7 (2007): 509-519. Zafir-Lavie, I., Y. Michaeli, and Y. Reiter. “Novel Antibodies as Anticancer Agents.” Oncogene 28 (2007): 3714-3733.
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Other Resources
American Cancer Society Immunotherapy http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Biological_Therapy_Immunotherapy_ 50.asp?sitearea= Emory Healthcare Biologic Therapies for Cancer Care http://healthlibrary.epnet.com/ GetContent.aspx?token=8482e079-8512-47c2-960ca403c77a5e4c&chunkiid=32583 142
Salem Health: Cancer National Cancer Institute Biological Therapy http://www.cancer.gov/cancertopics/ biologicaltherapy Stanford Comprehensive Cancer Center Biological Therapy for Cancer Treatment http://www.cancer.gov/cancertopics/ biologicaltherapy See also Anthrax; Antineoplastics in chemotherapy; Bacillus Calmette Guérin (BCG); Cancer biology; Chemotherapy; Cytokines; Gene therapy; Immune response to cancer; Immunotherapy; Medical oncology; Metastasis; Monoclonal antibodies; Nutrition and cancer treatment; Stem cell transplantation; Tumor necrosis factor (TNF); Tyrosine kinase inhibitors; Vaccines, therapeutic.
u Biopsy Category: Procedures Also known as: Tissue sampling, fine needle aspiration, needle biopsy, percutaneous biopsy, core biopsy, incisional biopsy, excisional biopsy, endoscopic or laparoscopic biopsy, surgical biopsy, open biopsy, transvenous biopsy Definition: A biopsy is the removal of a tissue sample for laboratory analysis to detect the presence of cancer cells. There are several types of biopsy procedures. The type of biopsy procedure performed is dependent on the type of cancer suspected and the area of the body being examined. In fine needle aspiration (also called needle biopsy or percutaneous biopsy), a very fine needle is inserted into the area and a sample of fluid or tissue is withdrawn through the needle into an attached syringe. This type of biopsy procedure may be used to remove tissue from an organ that is otherwise accessible only via surgery, such as the liver, pancreas, or lung. The advantage of fine needle aspiration is that it does not require a surgical incision. To place the needle accurately, ultrasound or computed tomography (CT) guidance may be used. Similar to fine needle aspiration, core biopsy uses a larger needle to withdraw a greater sample of fluid or tissue. Ultrasound or CT guidance may be used. In incisional biopsy, a scalpel or similar instrument is used to remove a portion of the suspected cancerous tissue via an incision made in the skin. Incisional biopsies are most commonly used to remove soft tissue, such as skin, connective tissue, muscle, and fat. For skin lesions, an in-
Salem Health: Cancer
Biopsy
In incisional biopsy, a scalpel is used to remove a sample of the suspected cancerous tissue through an incision made in the skin. (PhotoDisc)
cisional biopsy may be performed with a hollow, circularshaped instrument (punch biopsy), or a razor may be used (shave biopsy). Depending on the type of procedure, the patient may be under general or local anesthesia. In excisional biopsy (sometimes called open biopsy or surgical biopsy), a whole lump, tumor, or organ and a margin of normal tissue around it are removed. An excisional biopsy may be used to remove some types of tumors or suspected cancers that need to be removed entirely for an accurate diagnosis, such as the removal of lymph nodes to diagnose lymphoma accurately. General anesthesia is usually used for excisional biopsies. In endoscopic or laparoscopic biopsy, an endoscope (small camera on a thin tube) is used to view an internal area and to identify the tissue for removal. The endoscope transmits magnified images of the area onto a video monitor to guide the physician during the procedure. The endoscope can be inserted through a natural body opening, such as the throat to remove esophageal tissue, or it can be inserted through a small incision. Surgical instruments attached to the endoscope or inserted through other small in-
cisions can be used to remove the tissue. Endoscopic biopsy procedures are the most common type of biopsies. A laparoscopic biopsy procedure may be used when a tissue sample is needed from more than one area or when a larger tissue sample is needed. General or local anesthesia may be used, depending on the biopsy site. A capsule biopsy is a type of laparoscopic technique in which a patient swallows a capsule that is connected to a thin tube. X rays confirm the proper positioning of the capsule, and a syringe attached to the end of the tube is used to withdraw a tissue sample into the capsule. The capsule and tube are gently removed, and the tissue sample is taken to the laboratory for analysis. This type of biopsy procedure may be used to remove a sample of tissue from the lower gastrointestinal tract. Other biopsy procedures include colposcopic biopsies to identify and remove abnormal tissue from the cervix, transvenous biopsy to remove tissue via a catheter inserted into a vein in the neck, and bone marrow biopsy to remove a bone marrow sample through a needle inserted into the hip and withdrawn through a syringe. 143
Biopsy Cancers diagnosed: Various, including breast, bone, gynecological, liver, lung, lymph node, skin, thyroid, urological, and gastrointestional cancers Why performed: A biopsy is performed to diagnose and stage cancer when an abnormality is found during diagnostic tests. It also may be performed to determine the cause of unexplained symptoms or to match organ tissue before a transplant. Patient preparation: Tests before the procedure may include blood tests, urine tests, a chest X ray, an electrocardiogram, CT scanning, magnetic resonance imaging (MRI), and other imaging tests. The patient preparation for a biopsy procedure varies depending on the type of procedure and biopsy location. In some cases, no special preparation is required. In other cases, the patient must not eat or drink for eight hours beforehand and is required to stop taking anticoagulant medications for several days before the procedure. The patient will receive specific preparation instructions from the health care team. Steps of the procedure: Local or general anesthesia may be used, depending on the type of biopsy procedure and biopsy location. The biopsy site is cleansed, and a local anesthetic is injected into the area. In some cases, such as with sentinal node biopsy, a radioactive substance or dye is injected into the tumor and a scanner is used to locate the lymph node or tissue containing the radioactive substance or stained with the dye. The tissue sample or fluid is removed via one of the biopsy techniques. The sample is sent to a laboratory for microscopic analysis by a pathologist. There are a variety of methods for processing tissue samples. Histologic sections involve preparing stained, thin slices of tissue mounted on slides, a process that may take up to forty-eight hours. With the histologic method, the tissue sample is placed in a machine that replaces all water in the sample with paraffin wax. The sample is embedded into a larger block of paraffin, sliced into very thin sections, and stained with dye to aid microscopic analysis. Frozen tissue analysis involves freezing the tissue, slicing it into thin sections, and staining the sections to aid analysis. Smears are tissue samples that are spread onto a slide for examination. The results of smears can usually be obtained very quickly. After the procedure: The length of a patient’s recovery and the steps for recovery vary depending on the type of biopsy procedure and biopsy location. The patient may stay in a recovery room for a certain amount of time after the procedure. The biopsy site is usually covered with a bandage or dressing. Medication is prescribed as needed for relief of pain, which may include discomfort at the bi144
Salem Health: Cancer opsy site or muscle pain. An overnight hospital stay may be required for some fine needle aspiration, laparoscopic, and surgical biopsy procedures. Specific instructions for driving, activity, incision care, medications, nutrition, and follow-up care are provided to the patient, as applicable. In some cases, the patient is not permitted to drive home after the procedure. Depending on the physician’s instructions, the patient may be required to stay on bed rest at home for a certain amount of time after the procedure. Risks: The risks of biopsy procedures are dependent on the type of procedure performed and the biopsy location. Possible risks of all biopsy procedures include bleeding and infection. The risk of death associated with biopsy procedures is generally very low. The physician may discuss specific mortality rates and risks with the patient, depending on the type of procedure performed. Results: The tissue sample removed during the procedure is either normal, which means it is benign or noncancerous, or abnormal, which means it has unusual characteristics and may be malignant or cancerous. In some cases, the tissue that was obtained during the biopsy is not adequate to make a diagnosis, and a repeat biopsy procedure or a different type of biopsy procedure may be performed. The type of cancerous cells and extent of disease will help guide the patient’s treatment. Angela M. Costello, B.S. u
For Further Information DeVita, Vincent, Jr., Samuel Hellman, Steven A. Rosenberg, et al., eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. McPhee, Stephen J. Maxine A. Papadakis, and Lawrence M. Tierney, eds. Current Medical Diagnosis and Treatment 2008. New York: McGraw-Hill Medical, 2007. Ota, D. M. “What’s New in General Surgery: Surgical Oncology.” Journal of the American College of Surgeons 196, no. 6 (2003): 926-932.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov RadiologyInfo http://www.radiologyinfo.org
Salem Health: Cancer Society of Interventional Radiology http://www.sirweb.org See also Anoscopy; Axillary dissection; Bone marrow aspiration and biopsy; Breslow’s staging; Bronchoscopy; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Colposcopy; Computed tomography (CT)guided biopsy; Conization; Core needle biopsy; Culdoscopy; Cystoscopy; Cytology; Dilation and curettage (D&C); Dukes’ classification; Endoscopic retrograde cholangiopancreatography (ERCP); Endoscopy; Flow cytometry; Gastric polyps; Gleason grading system; Grading of tumors; Hormone receptor tests; Hysteroscopy; Immunocytochemistry and immunohistochemistry; Ki67 test; Laparoscopy and laparoscopic surgery; Laryngoscopy; Liver biopsy; Loop electrosurgical excisional procedure (LEEP); Lumpectomy; Lymphadenectomy; Mediastinoscopy; Needle biopsies; Needle localization; Pap test; Paracentesis; Pathology; Pleural biopsy; Polypectomy; Premalignancies; Progesterone receptor assay; Prostate-specific antigen (PSA) test; Receptor analysis; Screening for cancer; Sentinel lymph node (SLN) biopsy and mapping; Sigmoidoscopy; Staging of cancer; Stereotactic needle biopsy; Surgical biopsies; Thoracoscopy; Thoracotomy; TNM staging; Upper gastrointestinal (GI) endoscopy; Wire localization.
u Birt-Hogg-Dubé syndrome
(BHDS) Category: Diseases, symptoms, and conditions Related conditions: Renal cell carcinoma, pulmonary cysts Definition: Birt-Hogg-Dubé syndrome (BHDS) is a rare, genetically linked syndrome named after the three Canadian doctors who first identified it as a skin disorder. It consists of three types of benign skin growths: fibrofolliculomas, white or flesh-colored tumors that occur in hair follicles; trichodiscomas, overgrowths of tissues in hair disks; and acrochordons, commonly called skin tags. These growths are typically found on the face, neck, chest, and scalp. Since the identification of BHDS in 1977, further study of patients with the syndrome has revealed additional abnormal conditions that characteristically develop in affected individuals. The most common of these conditions include benign and cancerous kidney tumors, lung cysts, and spontaneous pneumothorax.
Birt-Hogg-Dubé syndrome (BHDS) Risk factors: BHDS is genetically linked, meaning that it is associated with a defect in one or more genes. Although in most cases the gene responsible for BHDS has been passed through families, evidence of genetic mutation in people with no familial link has also been identified. People with a defective gene and who also smoke have a higher risk of developing kidney cancer. Etiology and the disease process: BHDS is caused by a mutation in the gene that is responsible for the body’s production of folliculin, a protein that acts as a tumor suppressor. When folliculin is absent or not functioning properly, it cannot control cellular growth and division, which leads to tissue overgrowth and the formation of tumors. Folliculin is present in many types of tissues but is primarily found in skin, lung, and kidney cells. The folliculin gene, otherwise know as FCLN, is located on chromosome 17p11.2. Normally, during conception, the body receives two copies of every gene, one from the mother and one from the father. In BHDS, a single defective copy of the gene, from either the mother or the father, results in a person’s being affected by the disease. BHDS usually begins with the formation of skin growths. As the disease progresses, these growths increase in number and size. Slow-growing kidney tumors can develop as single or multiple tumors in one or both kidneys. Several types of tumors have been associated with BHDS, including benign tumors such as renal oncocytomas and cancerous tumors such as chromophobe renal carcinoma and clear cell carcinoma. Benign tumors often become cancerous as the disease progresses. Research into kidney tumors associated with BHDS indicates that a genetic mutation occurs in the second gene of affected kidney cells, producing two defective genes, which allows these tumors to grow. Incidence: BHDS is very rare, having been identified only in about sixty families worldwide. A precise incidence rate is unknown because people are not routinely tested for the presence of the FCLN gene. There is no indication that race or gender influences a person’s risk of having the gene or developing the disease. The typical age that a person begins to display signs of BHDS is between the late twenties and early forties. The incidence of kidney cancer in people with BHDS may be as low as 15 percent; however, the incidence of lung cysts is estimated to be about 90 percent. Symptoms: Although some people with BHDS have no noticeable symptoms of the disease, the development of fibrofolliculomas or acrochordons is usually the first indication that the person is affected. Initially looking like 145
Birth control pills and cancer small, white pimples, fibrofolliculomas typically become larger and more prolific as time passes. The development of polyps in the mouth or colon may also indicate BHDS and should be investigated further. Lung cysts, which usually do not cause respiratory problems, or lung cancer may be detected during routine examinations or testing for other conditions. Multiple or bilateral kidney tumors are often the first indication of BHDS. Screening and diagnosis: Several recurrent tests are recommended for people with BHDS and those with family members who have BHDS. Recommendations include an annual kidney ultrasound and chest X ray, computed tomography scanning or magnetic resonance imaging every two years, and biopsies of suspicious skin growths. DNA (deoxyribonucleic acid) testing to check for genetic alterations should be considered for individuals who have family members with the disease. Genetic counseling should precede any such testing. The disease is typically diagnosed after skin lesion biopsies are positive for fibrofolliculomas or when multiple kidney tumors and lung cysts are identified. Treatment and therapy: There is no specific medical treatment recommended for the skin tumors associated with BHDS. Surgical removal, electrodesiccation, and dermabrasion have been used without long-term success, as the growths recur. A relatively new procedure for BHDS-related skin tumors is laser skin resurfacing, which has been successful in several cases; however, long-term results are unknown. Both benign and cancerous kidney tumors are removed surgically. However, new tumors often form in place of the ones removed. When possible, only part of the kidney is removed to prolong the patient’s kidney function. Experimental treatments to destroy the cancer cells may be used on recurrent tumors. These include cryoablation, freezing the tumor, and radio frequency ablation, killing the tumor with heat. Prognosis, prevention, and outcomes: The prognosis for BHDS depends on whether kidney cancer develops and the success of its treatment. BHDS cannot be prevented. Dorothy P. Terry, R.N. u For Further Information Lindor, Noralane M., et al. “Birt-Hogg-Dubé Syndrome: An Autosomal Dominant Disorder with Predisposition to Cancers of the Kidney, Fibrofolliculomas, and Focal Cutaneous Mucinosis.” International Journal of Dermatology 40, no. 10 (October, 2001): 653-656. Pavlovich, C. P., et al. “Renal Tumors in the Birt-Hogg-
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Salem Health: Cancer Dubé Syndrome.” American Journal of Surgical Pathology 26 (2002): 1542-1552. Pomery, Chris. DNA and Family History. Toronto: Dundurn Press, 2004. u
Other Resources
Birt Hogg Dube Family Alliance What Is BHD? http://www.birthoggdube.org/id1.html Genetics Home Reference Birt-Hogg-Dubé Syndrome http://ghr.nlm.nih.gov/ condition=birthoggdubesyndrome See also Hereditary leiomyomatosis and renal cell cancer (HLRCC); Kidney cancer; Urinary system cancers.
u Birth control pills and cancer Category: Carcinogens and suspected carcinogens RoC status: Most birth control pills contain two active ingredients, a form of estrogen and a form of progesterone. Collectively, estrogens have been classified as a known human carcinogen since 1985. Progesterone has been listed as a reasonably anticipated human carcinogen since 1985. Also known as: Oral contraceptives Related cancers: Breast cancer, cervical cancer Definition: A birth control pill is a tablet containing a synthetic estrogen, such as ethinylestradiol; a synthetic progesterone, such as norethindrone; or both. These compounds mimic the action of naturally occurring sex hormones and are administered to alter the function of tissues that respond to these hormones. For example, a moderate, consistent dose of estrogen will prevent the typical spike in estrogen that occurs naturally during the middle of the menstrual cycle. This in turn prevents the ovary from releasing an egg. Estrogen and progesterone have different effects on reproductive tissues that, in combination, are highly effective in preventing pregnancy. Although the majority of birth control pills contain a dose of each hormone, minipills that contain only a progesterone are also available. Although contraception is the most common reason for using birth control pills, the pill is also commonly prescribed for other purposes, such as bothersome menstrual symptoms and acne.
Salem Health: Cancer
Birth control pills and cancer
Exposure routes: Birth control pills are tablets that are ingested orally. Several alternative delivery systems, such as transdermal patches, contain similar active ingredients that are taken into the body through other routes. Where found: Birth control pills are manufactured by drug makers and prescribed by health providers. The World Health Organization estimates that approximately 10 percent of all women of reproductive age worldwide use birth control pills. At risk: At highest risk are women of reproductive age, particularly in developed countries where the pill is more widely available and pill use is more prevalent. A small minority of pill users are women who take the pills to manage menopausal symptoms. Etiology and symptoms of associated cancers: The majority of breast cancers, though not all, involve the abnormal growth and proliferation of cells that are responsive to estrogen. Studies in mice and rats indicate that exposure to either synthetic estrogen alone or synthetic progesterone alone caused maligEstrogen, an essential ingredient in birth control pills, is a known human carnant tumors to develop in mammary tissue. cinogen. (Object Gear) Likewise, combinations of synthetic estrogen and progesterone appear to cause developthe risk of cervical cancer even when HPV status is taken ment of both benign and malignant mammary tumors in into account. animals. In humans, breast cancer risk increases with proConversely, the use of birth control pills appears to relonged exposure to estrogen from both internal and exterduce the risk of some types of cancer. There is abundant nal sources, although not all studies of birth control pill usevidence suggesting that birth control pill use reduces a ers have demonstrated an increased risk of breast cancer. woman’s risk of developing ovarian cancer, possibly due Research suggests that breast cancer risk related to pill use to fewer cycles of ovulation over her life span. Birth conis greatest among women who use the pill for several years trol pill use also appears to decrease the risk of cancer of or more before their first full-term pregnancy. After longthe endometrium (the uterine lining), with protective efterm cessation of pill use, the risk of breast cancer appears fects lingering long after cessation of pill use. to decrease to a level comparable to that of women who never used the pill. The risk of cervical cancer is also increased with birth History: The first birth control pill became available in the control pill use and appears to be related to the duration of United States in 1960, and birth control pills were widely pill use, although the risk most likely declines over time adopted in the decades that followed. Early concern about after cessation of use. Research to date has yet to fully exthe safety of birth control pills linked the high doses of plain the relationship between cervical cancer and birth estrogen in birth control pills with an increased risk of control pills. Some researchers have argued that pill users serious cardiovascular events, including heart attack and differ from nonusers in risk factors for human papillostroke. Over time, drug manufacturers lowered the dosmavirus (HPV) infection, which is closely linked to the ages of estrogen in birth control pills. development of cervical cancer. However, to date several By the 1980’s researchers had observed associations studies have suggested that birth control pill use increases between birth control pill use and cancer risk. However, 147
Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether
Salem Health: Cancer
studies were inconsistent in confirming this relationship, and a number of large population-based studies were undertaken to clarify the effect of pill use on cancer risk. After review of multiple such studies, the International Agency for Research on Cancer, a division of the World Health Organization, classified combined estrogenprogesterone birth control pills as carcinogenic to humans. Andrea Bradford, M.A.
u Bis(chloromethyl) ether and
u For Further Information Cerhan, James R. “Oral Contraceptive Use and Breast Cancer Risk: Current Status.” Mayo Clinic Proceedings 81, no. 10 (2006): 1287-1289. Parker, James M., and Philip M. Parker, eds. Birth Control Pills: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Icon Health, 2003. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Zonderman, Jon, and Laurel Shader. Birth Control Pills. New York: Chelsea House, 2006.
Related cancer: Lung cancer
u
Other Resources
Mayo Clinic Birth Control Pill Frequently Asked Questions: Benefits, Risks, and Choices http://www.mayoclinic.com/health/birth-control-pill/ WO00098 National Cancer Institute Oral Contraceptives and Cancer Risk: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ oral-contraceptives See also Antiestrogens; Cervical cancer; Endocrine cancers; Endometrial cancer; Endometrial hyperplasia; Estrogen-receptor-sensitive breast cancer; Fertility drugs and cancer; Fibrocystic breast changes; Gestational trophoblastic tumors (GTTs); Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Ovarian cancers; Ovarian cysts; Progesterone receptor assay; Receptor analysis; Screening for cancer; Vasectomy and cancer.
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technical-grade chloromethyl methyl ether Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: BCME, chloro(chloromethoxy) methane dichloromethyl ether, CMME, dimethylchloroether, methyl chloromethyl ether
Definition: Bis (chloromethyl) ether (BCME) and technicalgrade chloromethyl methyl ether (CMME) are chemicals known as chloroalkyl ethers. Both are clear, flammable liquids with strong, unpleasant odors. Exposure routes: After BCME and CMME are released into the air, humans can be exposed by inhalation, dermal contact, and oral exposure via contaminated water. Potential exposure by inhalation can occur to workers who are involved in the production of BCME and CMME. Where found: BCME and CMME are found at production sites where they have been released into the air and at landfill sites where they have been transferred for disposal. Both are found in chemical plants where they are manufactured and in research laboratories where they are used to make other chemicals. They can also be found in plants where they have been used to make several types of polymers, resins, plastics, and textiles. Small quantities of BCME can be formed as an impurity during the production of CMME. CMME can be converted to BCME through hydrolysis. At risk: The greatest risk for contamination from BCME and CMME is to chemical plant workers, laboratory workers, ion-exchange resin makers, and polymer producers. The general public experiences some risk from both chemicals around sites where they are produced or where they are discarded, such as landfills and surface impoundments. Etiology and symptoms of associated cancers: Individuals exposed to BCME and CMME show significant increases in the incidence of lung carcinomas, mostly of the oat-cell type, which is generally not associated with smoking tobacco. The number of lung carcinomas is much higher in people exposed to just BCME, as compared with individuals who are exposed to both BCME and CMME. When exposed to BCME or CMME, individuals have shown a slight increase of incidence of chromosomal aberrations in peripheral lymphocytes. Both chemicals can
Salem Health: Cancer
Bisphenol A (BPA)
induce unscheduled synthesis of deoxyribonucleic acid (DNA) in human fibroblasts in vitro. History: Although BCME and CMME were previously manufactured in the United States, use of both chemicals in the United States has dropped significantly since 1976. Since 1982, only CMME is produced in the United States. In the past, BCME was used to treat vulcanized rubber to increase adhesion and in the production of flame-retardant fabrics. CMME is used as an alkylating agent and solvent in manufacturing polymers, ion-exchange resins, and water repellants. Alvin K. Benson, Ph.D. See also Carcinogens, known; Carcinogens, reasonably anticipated; Occupational exposures and cancer.
u Bisphenol A (BPA) Category: Carcinogens and suspected carcinogens Also known as: 4, 4′-(1-Methylethylidene)bisphenol; 2, 2-bis (4-hydroxyphenyl) propane Related cancers: Prostate and breast cancer Definition: Bisphenol A (BPA) is an organic compound belonging to the aromatic class known as phenols. It is the main monomer used for the manufacture of polycarbonate plastics, which are essentially long chains of individual BPAmolecules linked together. All the BPAmonomers do not react to form the polymer, as a result of which small amounts of the unpolymerized free units leach into the contents of the plastic containers. Exposure routes: Exposure to BPA is mainly through direct contact or by ingesting food or drink that has been in contact with plastic material containing bisphenol A. BPA is known to leach into the contents of polycarbonate containers under certain conditions. It is also released from epoxy resins that are used in dental sealants, food container linings, polyvinyl chloride (PVC) pipes, and flooring materials. As plastics are used ubiquitously in modern society, bisphenol A has many plausible exposure routes for humans. Where found: Bisphenol A is a high-production-volume chemical used as the main building block for the manufacture of many polymers such as polycarbonates and epoxy resins. Polycarbonates are widely used for making food and drink containers, baby bottles, milk containers, and water pipes, and epoxy resins are used in the linings of metal food containers and in dental sealants.
BPA, a suspected carcinogen, is known to leach into the contents of plastic bottles. (©Sean Macdiarmid/Dreamstime.com)
At risk: Infants, children, and adults Etiology and symptoms of associated cancers: The safety data on bisphenol A are controversial. A hazard assessment study by the National Toxicology Program is ongoing. The final peer-reviewed assessment results will be used as a basis for federal regulation of the compound. If the assessment indicates concern about carcinogenicity and other health risks associated with BPA exposure, appropriate measures will be formulated to protect public health and safety. BPA is a known hormone disrupter, and many studies have confirmed this effect. Most research data on the adverse effects of BPA exposure have been collected in rodent studies. Low-level chronic exposure to BPA has been reported to cause endocrine disruption even at levels of 2.3 micrograms per kilogram (mcg/kg) per day, leading to aberrant growth of mammary tissue in mice, which is a pre149
Bisphenol A (BPA) cursor to breast cancer. Additionally it has been reported that prenatal exposure to low levels of BPA causes breast cancer in adult rats. Research reports indicate that BPA at low levels causes adverse effects on the development of the prostate in fetal mice. Studies also suggest that exposure to BPA in the womb alters gene behavior in such a way as to lead to development of prostate cancer in adult rats. A small study involving Japanese women found that the serum levels of BPA were three times higher in women with a recurrent history of miscarriages, providing indirect evidence for BPA as an endocrine-disrupting chemical. History: Bisphenol A was first synthesized in 1891. In the 1930’s it was demonstrated that BPA mimicked the action of estrogens in rats. Around that time, diethylstilbestrol, a more potent estrogen, was discovered, relegating BPA to the background in terms of pharmacological use. In the 1950’s polymer chemists discovered that BPA could be polymerized readily to make plastics such as polycarbonate. BPA thus became a large-volume chemical used in the plastics industry. It is also used as an inert ingredient in antioxidants, pesticides, and flame retardants. Additionally it is used in materials for making reinforced pipes, water-main filters, floorings, and enamels. Its ubiquitous use creates various exposure routes for humans. BPA has been measured in river water, reservoirs, streams, and estuaries. There is ongoing debate about the safety limit for this compound. In the 1980’s the Environmental Protection Agency (EPA) set a reference dose of up to 50 mcg/kg per day in the United States and considers intake below this dose to be safe for health. However, based on research in the late 1990’s and early 2000’s, scientists are of the consensus that exposure to BPA well below the EPA guideline induces adverse effects in rodents in the fetal stage, and these effects are precursors to breast cancer and prostate cancer in adulthood. The cause for concern is that the low levels inducing carcinogenicity in the rodent experiments are within the range of daily human exposure to BPA. European and American regulatory agencies have maintained that exposure to BPA from polycarbonates and epoxy resins does not pose a health risk. Bisphenol A is one of two hundred compounds selected by the Canadian regulatory agency for further safety assessment studies. The U.S. Food and Drug Administration is aware of the need for an objective assessment of the experimental data on the health risks of BPA exposure. The assessment, which will form the basis for regulation of bisphenol A by federal toxicology agencies, will affect the health of millions of people. Lalitha Krishnan, Ph.D. 150
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For Further Information Haighton, L. A., et al. “An Evaluation of the Possible Carcinogenicity of Bisphenol A to Humans.” Regulatory Toxicology and Pharmacology 35 (2002): 238-254. Mittelstaedt, Martin. “‘Inherently Toxic’ Chemical Faces Its Future.” Globe and Mail, April 7, 2007. Stowell, Cheri L., et al. “A Role for Sulfation-Desulfation in the Uptake of Bisphenol A into Breast Tumor Cells.” Chemistry and Biology 13, no. 8 (2006): 891-897. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Vom Saal, Frederick S., et al. “Chapel Hill Bisphenol A Expert Panel Consensus Statement: Integration of Mechanisms, Effects in Animals and Potential to Impact Human Health at Current Levels of Exposure.” Reproductive Toxicology 24, no. 2 (2007): 131-138. Wetherill, Y. B., et al. “Bisphenol A Facilitates Bypass of Androgen Ablation Therapy in Prostate Cancer.” Molecular Cancer Therapeutics 5 (2006): 3181-3190.
u
Other Resources
American Cancer Society Federal Report Looks at Risks from Plastics Chemical http://www.cancer.org/docroot/NWS/content/ NWS_1_1x_Federal_Report_Looks_at_Risks_from_ Plastics_Chemical.asp Breast Cancer Fund Bisphenol A http://www.breastcancerfund.org/site/ pp.asp?c=kwKXLdPaE&b=2638145 National Toxicology Program Bisphenol A http://ntp.niehs.nih.gov/ index.cfm?objectid=BC9825E3-123F-79087BF465F9E25681B0 Toxicology and Chemical Substances/European Chemical Bureau http://ecb.jrc.it See also Acrylamides; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; Cadmium and cadmium compounds; Carcinogens, known; Carcinogens, reasonably anticipated; Chromium hexavalent compounds; Di(2-ethylhexyl) phthalate (DEHP); Organochlorines (OCs); Pesticides and the food chain; Plasticizers; Vinyl chloride.
Salem Health: Cancer
Bladder cancer
u Bisphosphonates Category: Chemotherapy and other drugs ATC code: M05BA Definition: Bisphosphonates are medications that act primarily on bone to inhibit resorption or bone destruction resulting from cell-induced bone breakdown. They treat various bone-degenerating conditions. Cancers treated: Breast cancer, hypercalcemia of malignancy (HCM), metastatic bone cancer, multiple myeloma, bone pain, osteoporotic bone loss from cancer treatments Subclasses of this group: Aminobisphosphonates, nonaminobisphosphonates Delivery routes: Bisphosphonates are administered as oral tablets and as intravenous (IV) solutions to outpatients and inpatients. Bisphosphonates in any form are best administered without food to avoid decreased bioavailability. How these drugs work: Bone resorption is part of normal bone regeneration mediated by osteoclasts, or bone breakdown cells. Abnormal osteoclast activity results from lytic bone lesions of multiple myeloma, metastatic bone tumors from breast cancer or other solid tumors, or osteoporosis from glucocorticoids in chemotherapy regimens and from breast-cancer-induced menopause. Bisphosphonates inhibit resorption by decreasing osteoclast activity. This mechanism reduces further bone loss and fracture, minimizes pain associated with osteoclast lesions and weakened bone, and reverses hypercalcemia of malignancy (HCM), which can result when
bone breakdown releases calcium to the blood. Monthly bisphosphonate administration has been shown to reduce the incidence of bone metastases in women with breast cancer as well, and these drugs have substantially reduced the risk of bone loss and fracture in spinal vertebrae and the hip. Side effects: A major side effect of this drug class is irritation of the esophageal mucosa, which can be reduced by taking the drug with a full glass of water and by remaining in an upright position directly after drug ingestion. This side effect may occur even with IV administration. Other side effects include constipation, diarrhea, dyspnea, myalgia, fever, decreased calcium and phosphate, and altered magnesium. Impaired kidney function and renal failure are possible. IV administration causes fever, flulike syndrome, and local injection site reactions. Other side effects noted in trials of patients with cancer include anxiety, headache, insomnia, anorexia, and abdominal pain. Nicole M. Van Hoey, Pharm.D. See also Bone scan; Hypercalcemia; Paget disease of bone.
u Bladder cancer Category: Diseases, symptoms, and conditions Also known as: Transitional cell carcinoma Related conditions: Kidney cancer Definition: Bladder cancer is a cancer that forms in the inner lining of the bladder.
Common Bisphosphonate Agents Drug
Brands
Delivery Mode Cancers/Conditions Treated
Aledronate
Fosamax
Oral
Glucocorticoid-induced osteoporosis
Etidronate
Didronel
Oral, IV
Hypercalcemia of malignancy (HCM)
Ibandronate
Boniva
Oral, IV
Breast cancer bone metastases; menopause-induced osteoporosis
Pamidronate
Aredia
IV
HCM malignancy with or without bone metastases; breast cancer and multiple myeloma; off-label for pain associated with prostatic carcinoma; possible prevention of breast cancer-related bone loss
Risedronate
Actonel
Oral
Glucocorticoid-induced osteoporosis; possible prevention of breast cancer-related bone loss
Tiludronate
Skelid
Oral
Bone metastases
IV
Multiple myeloma; solid tumor bone metastases; HCM
Zoledronic acid Reclast, Zometa
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Bladder cancer Risk factors: Researchers do not completely understand the causes of bladder cancer; however, several carcinogens, family history, and prior diagnosis of bladder cancer remain the chief causes. Smokers are at greatest risk for developing bladder cancer as well as people with exposure to certain chemical dyes in the rubber- and leatherprocessing, textile, and printing industries. Etiology and the disease process: The wall of the bladder is lined with cells called transitional cells and squamous cells. More than 90 percent of bladder cancers begin in the transitional cells and are called transitional cell carcinomas. About 8 percent of bladder cancer patients have squamous cell carcinomas. Cancer that is only in cells in the lining of the bladder is called superficial bladder cancer and often recurs after treatment. Cancer that begins as a superficial tumor may grow through the lining and into the muscular wall of the bladder. This invasive cancer may extend through the bladder
An infiltrating tumor (upper right) in the muscular wall of the bladder. (John Bavosi/Photo Researchers, Inc.)
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Salem Health: Cancer wall into a nearby organ such as the uterus, vagina, or prostate gland or into nearby lymph nodes, in which case cancer cells may have spread to other lymph nodes or other organs such as the lungs and liver or to the bones. Incidence: Primarily occurring in men and women over the age of forty, bladder cancer is diagnosed in 38,000 men and 15,000 women each year in the United States. According to the National Cancer Institute, this is the fourth most common type of cancer in men, and the eighth most common in women. Caucasians get bladder cancer twice as often as African Americans and Hispanics. People with family members who have bladder cancer as well as people who have previously had bladder cancer are more likely to get the disease. Symptoms: Bladder cancer often causes no symptoms until it reaches an advanced state that is difficult to cure. The most common symptom of bladder cancer is blood in the urine (hematuria). Some patients experience pain or burning during urination, or a change in urinary habits, such as a frequent urge to urinate. Screening and diagnosis: Screening tests include a medical interview, a physical examination, urinalysis, urine cytology, and cystoscopy. The urinalysis determines if the urine contains abnormalities such as blood, protein, sugar, and solids. Urine cytology is a microscopic examination of urine to detect any abnormal cells that have sloughed off the bladder wall and have been released in the urine. If necessary, cytoscopy is performed with a very narrow tube with a light and camera inserted through the urethra to examine the inside of the bladder. If bladder cancer is suspected, a physician may order a computed tomography (CT) scan, pyelography, or biopsy. The CT scan is helpful for a three-dimensional view of the bladder and urinary tract to determine if any masses or tumors exist in the bladder or if the cancer has spread to other organs. Pyelography involves injecting a special dye into a vein or the urethra and examining a series of timed-interval X rays of the urinary system to determine if abnormalities exist. The biopsy is typically performed during cytoscopy, and abnormal cells can be detected with a microscope. Staging refers to the size of the cancer and the extent to which it has invaded the bladder wall and spread to other parts of the body. High-grade tumors are significantly more aggressive and life-threatening than low-grade tumors. Approximately 10 per-
Salem Health: Cancer cent of bladder cancer is found to be superficial bladder cancer in situ, which is a highly aggressive, early manifestation of bladder cancer.
Bladder cancer
Incidence of Bladder Cancer per 100,000 People, by Gender 45 Men
Women
40.5 Treatment and therapy: The physi40 cian may treat superficial bladder cancer with transurethral resection (TUR) 35 by inserting a cystoscope into the bladder through the urethra and using a tool 30 with a small wire loop on the end to remove the cancer and to burn away any remaining cancer cells with an electric 25 current. For invasive bladder cancer or 20.3 20.2 cancer involving a large portion of the 20 bladder, surgery is performed to remove 16.4 the entire bladder, nearby lymph nodes, 15 part of the urethra, and the nearby organs that may contain cancer cells. In 10.1 10 some cases of low-grade cancer, only 7.6 part of the bladder is removed in a pro5.5 cedure called segmental cystectomy. 5 3.9 Radiation therapy uses high-energy rays to kill localized cancer cells to 0 shrink the tumor before surgery or if White Black Hispanic Asian/Pacific surgery is not an option. Chemotherapy Islander uses one drug or a combination of drugs to kill cancer cells. Superficial bladder Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 cancer can be treated with local cheNote: Based on cases diagnosed in 2000-2004 motherapy; once per week for several weeks, a catheter is inserted through the urethra and remains in the bladder for several hours. If the cancer has deeply u For Further Information invaded the bladder or spread to lymph nodes or other orDunetz, Gary N. Bladder Cancer: A Resource Guide for gans, chemotherapy may be used to treat the entire body. Patients and Their Families. Bloomington, Ind.: Biological therapy, or immunotherapy, uses the body’s AuthorHouse, 2006. natural immune system to fight cancer by inserting a cathEllsworth, Pamela. One Hundred Questions and Answers eter with a solution containing live, weakened bacteria to About Bladder Cancer. Sudbury, Mass.: Jones & Bartkill cancer cells in the bladder. lett, 2005. Schoenberg, Mark P., et al. The Guide to Living with Prognosis, prevention, and outcomes: Bladder cancer Bladder Cancer. Baltimore: Johns Hopkins University has one of the highest recurrence rates of all cancers. If Press, 2000. treated once, patients must continue a course of follow-up screenings. The five-year survival rate for patients with early-stage bladder cancer is 85 percent. Most patients u Other Resources with bladder cancer (up to 80 percent) will be diagnosed with a superficial tumor. Patients with tumors invading Mayo Clinic the bladder wall have a five-year survival rate of 60 to 75 Bladder Cancer percent. http://www.mayoclinic.com/health/bladder-cancer/ Robert J. Amato, D.O. DS00177
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Blood cancers National Cancer Institute Bladder Cancer http://www.nci.nih.gov/cancertopics/types/bladder See also 4-Aminobiphenyl; Bacillus Calmette Guérin (BCG); Cystography; Cystoscopy; Gastrointestinal oncology; Kidney cancer; Squamous cell carcinomas; Transitional cell carcinomas; Urethral cancer; Urinary system cancers; Urography; Urostomy.
u Blood cancers Category: Diseases, symptoms, and conditions Also known as: Hematopoietic neoplasms, malignant neoplasms, bone marrow diseases Related conditions: Leukemia (acute myelogenous or myelocitic leukemia, or AML; acute lymphocytic or lymphoid leukemia, or ALL; chronic myelogenous or myelocitic leukemia, or CML; chronic lymphocytic or lymphoid leukemia, or CLL), lymphoma (Hodgkin disease, or HD; non-Hodgkin lymphoma, or NHL), and myeloma (plasma cell dyscrasia, plasma cell myeloma, multiple myeloma, myelomatosis) Definition: Blood cancers are those that arise from an abnormality in the production of any of the mature blood cells or their precursor stem cells. Not all bone marrow disorders, such as anemia, are cancers. The three main types of blood cancer are leukemia, lymphoma, and myeloma. Leukemia is a cancer of any of the five dominant types of white blood cells. It occurs when the bone marrow produces abnormal white blood cells, which replicate, limiting the ability of healthy cells to function. Chronic leukemia develops slowly, while acute leukemia develops quickly. Of the four subtypes of leukemia, the acute forms exhibit immature blood-forming cells or blasts, and the chronic forms exhibit few or no blast cells but changes in the presentation of marrow cells. Acute lymphocytic leukemia (ALL), also known as acute lymphoid leukemia, is the most common type of blood cancer among those under nineteen years of age. ALL is characterized by lymphoblasts replacing normal cells in the marrow and lymph nodes lowering the affected individual’s ability to fight infection. Chronic lymphocytic leukemia (CLL) is the most common type of blood cancer among those fifty years of age and older and the most prevalent type of leukemia. Acute myelogenous leukemia (AML), in which leukemic blast cells proliferate and block the production of normal marrow cells, results in a deficiency of red blood cells, 154
Salem Health: Cancer white cells, and platelets. Chronic myelogenous leukemia (CML) is seen mostly in adults and begins with a change in a single stem cell, a future red cell, white cell, or platelet. Lymphomas originate in malignant changes in the lymphatic or immune system. The primary types are Hodgkin disease and non-Hodgkin lymphoma. Hodgkin disease is characterized by abnormal T or B white blood cells. As the abnormal cells divide, they proliferate and can spread throughout the body. Non-Hodgkin lymphoma is a cancer of the lymphoid tissue, which is mostly made up of lymph nodes that manufacture and store lymphocytes, white blood cells that protect against infection. Myelomas are progressive blood cancers of plasma cells, which produce antibodies to fight against infections and regulate the immune system. Myeloma results from an overproduction of these antibodies, an impaired immune system, and invasive tumors. Risk factors: The risk factors and causes of many types of blood cancers are not well known, and most cases of blood cancer occur in individuals with no identifiable risk factors. However, for AML, which along with CLL is among the most common types of blood cancer seen in adults, these specific risk factors have been found: Down syndrome and other genetic disorders, chronic exposure to ionizing radiation and chemicals such as benzene in the workplace, high doses of radiation therapy and the chemotherapies used to treat lymphoma or other types of cancer, and tobacco smoke. Those who are immunosuppressed with certain human retroviruses and bacteria, such as the Epstein-Barr virus (EBV) in Africa; those with human immunodeficiency virus (HIV); and those with human T-cell leukemia virus (HTLV) are at greater risk of developing lymphomas. Familial clustering also has been associated with the development of lymphomas. Etiology and the disease process: Cancer develops as a result of a variety of factors and over a number of years. Blood cancers differ widely by group and within each subtype in their progression, causes, and molecular presentation. The leukemias begin in two types of white blood cells: neutrophils and monocytes, which are germ-ingesting cells, and lymphocytes, which are immune-defense cells. Abnormal white blood cells in the bone marrow multiply and enter the bloodstream, crowding out normal cells. Lymphomas develop when these immune-defense cells multiply and cause tumors in the lymph nodes or other parts of the immune system. Development of blood cells through the hematopoietic process is arrested, and abnormal blood cells proliferate. Every stage of hematopoietic development can result in a particular type of cancer. Non-Hodgkin lymphoma (NHL) is manifested by
Salem Health: Cancer well-differentiated cells with slow progression, while other forms are more aggressive with lymphocytes of limited differentiation. Tumors of the bone marrow are characteristic of myelomas. In myeloma, cells that are to become immune cells develop in the bone marrow from stem cells, as will all blood cells. A major type of white blood cells, B lymphocytes, which typically develop into plasma cells, undergo multiple genetic changes as they change into plasma cells, causing malignant plasma cells to develop. These myeloma cells travel throughout the bloodstream, reside in the bone marrow, and damage healthy tissue. The myeloma interferes with the plasma cell’s production of protective proteins called immunoglobulins or antibodies by producing M proteins or abnormal immunoglobulin, making those affected susceptible to infection.
Blood cancers for diagnosis of myeloma was seventy, with the majority, 28.1 percent, between the ages of seventy-five and eightyfour. Incidence rates for all types of leukemia are higher among men than women and higher among African Americans than those of European descent. New cases of multiple myeloma are estimated to be diagnosed at a rate of 5 to 6 per 100,000 people each year. The incidence rate of myeloma is higher for men than women across racial and ethnic groups. Symptoms: Signs and symptoms of blood cancers vary widely and may be similar to those of other, less severe illnesses. Symptoms vary based on the category and subtype of blood cancer; for example, symptoms of acute leukemia may include pallor, shortness of breath with exertion, lack of energy, night sweats or a mild fever, slow healing of cuts and bruises, unexplained weight loss, tiny red spots under the skin, bone and joint aches and pains, and low white blood cell count (especially neutrophils and mono-
Incidence: The most common forms of leukemia seen in adults aged fifty and over are chronic lymphocytic leukemia (CLL) and acute myelogenous leukemia (AML). The incidence of acute lymphocytic leukemia (ALL) increases in those over sixty years of age. In 2007, new cases of CLL were estimated at 15,340 and new cases of AML at 13,410. The National Cancer Institute (NCI) reports that between 2000 and 2004, the average median age at diagnosis for leukemia was sixty-seven, with 23.7 percent between the ages of seventy-five and eightyfour. Based on cases diagnosed during this period, the age-adjusted incidence rate for leukemia was 12.3 per 100,000 men and women per year. Chronic leukemias accounted for 7 percent more cases than acute leukemias. It was estimated that 71,380 cases of lymphoma would be diagnosed in the United States in 2007. The majority of these cases, 63,190, were projected to be of the non-Hodgkin type. Incidence rates of Hodgkin lymphoma tend to be higher among men than women. Non-Hodgkin lymphoma also is more commonly diagnosed among men, particularly those aged sixty to sixtyfour (52.3 in every 100,000 men in this age group). According to the NCI’s cancer surveillance data, the median age for diagnosis of lymphoma was sixty-four, with the majority of cases, 21.3 percent, diagnosed between the ages of seventy-five and eighty-four. Non-Hodgkin lymphoma is the fifth most common cancer among men and women. It was estimated that 19,900 new cases of myeloma would be diagnosed in the United States This X ray reveals a secondary tumor in the humerus; the primary is in the in 2007. NCI data indicated that the median age bronchus. (©Mediscan/Corbis)
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Blood cancers
Salem Health: Cancer
Estimated New Blood Cancer Cases and Deaths by Gender, 2007 New Cases Blood Cancer Type
Men Women
Deaths Total
Men Women
Total
Leukemias (all) Acute myeloid leukemia Chronic myeloid leukemia Acute lymphocytic leukemia Chronic lymphocytic leukemia Other leukemias
24,800 19,440 44,240 7,060 6,350 13,410 2,570 2,000 4,570 3,060 2,140 5,200 8,960 6,380 15,340 3,150 2,570 5,720
12,320 5,020 240 820 2,560 3,680
9,470 21,790 3,970 8,990 250 490 600 1,420 1,940 4,500 2,710 6,390
Lymphomas (all) Hodgkin disease Non-Hodgkin lymphoma
38,670 32,710 71,380 4,470 3,720 8,190 34,200 28,990 63,190
10,370 770 9,600
9,360 19,730 300 1,070 9,060 18,660
Multiple myeloma
10,960
5,550
5,240 10,790
8,940 19,900
Source: Data from American Cancer Society, Cancer Facts and Figures 2007 (Atlanta: Author, 2007)
cytes). Although specific bone marrow and blood tests are needed to diagnose any type of blood cancer, some of those affected with certain subtypes of leukemia may have enlarged lymph nodes in the neck, groin, or armpit, and they may suffer from frequent infections. Often individuals who have Hodgkin disease or nonHodgkin lymphoma experience painless, swollen lymph nodes, loss of appetite, vomiting, bloating, abdominal pain, fullness (due to enlargement of the liver, spleen or abdominal lymph nodes), pain in the lower back, bone pain, constant coughing, and unexplained lethargy. Early symptoms of myeloma are bone pain, particularly with movement, and infections involving the skin, the urinary tract, the bronchial tract, or lungs. These symptoms may also be accompanied by pallor resulting from anemia, weakness, and exaggerated fatigue. Screening and diagnosis: Blood tests and specific bone marrow tests are needed to diagnose blood cancer; however, individuals in early stages of the disease may not have symptoms suggesting cancer. Current evidence does not suggest that routine blood screening before the onset of symptoms will detect cases of blood cancer and lead to improved medical outcomes or be cost effective in those at average risk of developing cancer according to their medical, family, and occupational history. The first indication that a person has blood cancer may be the results of a blood test performed as part of an annual physical. The blood sample may reveal anemia or changes in white blood cells, a possible indicator of leukemia. If an individual has symptoms that suggest blood cancer, the physician will 156
take a medical history and check for swelling of the liver, spleen, or lymph nodes in the armpits, groin, or neck. Urinalysis will also be performed to detect substances or cellular material in the urine. Other tests include a blood test to assess blood cell count, a cytogenetic exam to analyze the number and shape of chromosomes to check for genetic abnormalities, a bone marrow aspirate to check for cancerous cells in liquid bone marrow, and a bone marrow biopsy to check for cancerous cells in the bone specimen. If cancerous cells are present, additional tests may be ordered to ascertain if the disease has spread and to organs or systems. These tests include tumor-marker tests (immunophenotyping, based on the type of antigen or marker on the surface of the cell), a spinal tap or lumbar puncture to obtain a sample of cerebrospinal fluid, chest X rays (for signs of infection or lymph node involvement), or ultrasound scans. Staging is used to assess the extent or severity of the disease, to plan treatment, and to predict the outcome or prognosis. Classification of each type of blood cancer into stages is based on the site that is affected, the progression of the disease, and the appearance of the affected cells. For example, CLL is staged according to the risk-based Rai classification system using symptoms such as blood lymphocyte count, presence of enlarged lymph nodes or organs, platelet count, and anemia. Other forms of leukemia, such as acute leukemia, are not staged because of acute onset, which typically means the cancer has spread to other organs at the time of diagnosis. Although leukemic cancerous cells circulate in the blood and bone marrow, in lymphomas cells form tumors
Salem Health: Cancer in lymphatic tissue. The Ann Arbor staging system is used for staging both Hodgkin disease and non-Hodgkin lymphomas on the basis of specificity of site of lymph node involvement. The TNM (tumor/lymph node/metastasis) system may be used to stage the size of a tumor, lymph node involvement, and existence or extent of spread through other parts of the body. The International Staging System (ISS) is used for staging multiple myelomas based on blood tests for two proteins, albumin and betamicroglobulin, which are markers for the disease. Treatment and therapy: Blood cancers are typically treated with one or more of the following: chemotherapy, radiation therapy, stem cell transplantation, and immunotherapy. A treatment plan is created using an anticancer agent such as chemotherapy, sometimes in combination with radiation therapy. The goal of chemotherapy, drugs given in combination and via different methods of delivery, is to destroy cancerous cells or to stop them from growing and multiplying, producing long-term remission or a cure. Radiation may be used to treat localized cancers such as lymphomas and certain types of leukemia, or it may be used to relieve symptoms when cancerous growths cause pain or pressure on bones, nerves, or organs. However, chemotherapy and radiation therapy can cause longterm or late effects, affecting fertility or growth and causing learning disabilities or illnesses secondary to the primary cancer such as leukemia. Chemotherapy doses considered tolerable by most patients may not be sufficient to arrest, cause remission in, or cure acute leukemia, myeloma, or lymphoma. In patients who may be at high risk of relapse, who relapse after a successful course of treatment, or who do not respond as expected to conventional treatment, stem cell transplantation (transplanting cells from which blood cells and immune cells arise) can enable production of normal blood cells such that intensive chemotherapy can bring about recovery. Immune treatments (using antibodies from the patient or a donor) may be used alone or in combination with other therapies to attack cells that remain after chemotherapy and that may attach to antigens on the malignant cells. They also are used as vaccines to suppress malignant cells that remain in the body following therapy. New chemotherapies, immunotherapies, vaccines, gene therapies, and types of bone marrow transplants to suppress the growth of cancerous cells and affect the course of the disease are always being developed and tested. Patients need to be reminded that pain and uncomfortable symptoms arising from the toxic effects of cancer treatments can be managed by consulting with their physicians. Supportive care to improve functioning and quality of life, transfusions,
Blood cancers antibiotics to protect against infection, and a healthy diet and lifestyle are critical for those undergoing cancer treatment. Prognosis, prevention, and outcomes: Many factors affect the outcome of a patient’s blood cancer, including the type, location, and stage of disease as well as individual and demographic factors such as the person’s general health, age, and response to treatment. A cancer survivor will undergo follow-up care, which includes frequent monitoring of blood counts, X rays, urine tests, imaging tests such as computed tomography (CT) or positron emission tomograph (PET) scans. Those whose remission lasts five years are considered cured. Survival rates for those with blood cancer have been rising since 1975 and the advent of more effective cancer treatments, according to the NCI’s Cancer Trend Report 2005 Update. No specific guidelines for preventing blood cancer exist, as its causes are not known and many types are relatively rare. Limiting exposure to environmental toxins and leading healthy lifestyles may help prevent blood cancers in those of average risk. The relative overall five-year survival rate of leukemia between 1996 and 2003 was nearly 50 percent, a survival rate that has more than tripled in patients diagnosed with leukemia since 1947. Relative survival rates vary by age of diagnosis, race, gender, and type of leukemia. Of all types of leukemia, those with CLL had the highest relative survival rate during this period, with 75.8 percent surviving. Hodgkin disease is considered one of the most curable cancers, with many patients cured after their initial treatment. The five-year survival rate has increased dramatically since the 1960’s, reaching 86 percent of patients of all races who were diagnosed with the disease between 1996 and 2003. Similarly, due to advances in treatment of non-Hodgkin lymphoma, the mortality rate has declined considerably since the 1980’s. Susan H. Peterman, M.P.H. u
For Further Information Adler, Elizabeth M. Living with Lymphoma: A Patient’s Guide. Baltimore: Johns Hopkins University Press, 2005. Hoffman, Barbara, ed. A Cancer Survivor’s Almanac: Charting Your Journey. Minneapolis: National Coalition for Cancer Survivorship, 1996. Mauch, Peter M., et al., eds. Hodgkin’s Disease. Philadelphia: Lippincott Williams & Wilkins, 1999. Wiernik, Peter Harris, ed. Neoplastic Diseases of the Blood. 4th ed. New York: Cambridge University Press, 2003. 157
Bone cancers u
Other Resources
American Cancer Society http://www.cancer.org International Myeloma Foundation http://www.myeloma.org The Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Memorial Sloan-Kettering Cancer Center http://www.mskcc.org National Cancer Institute http://www.cancer.gov See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Aleukemia; Amyloidosis; Anemia; Aplastic anemia; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Burkitt lymphoma; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Cutaneous T-cell lymphoma (CTCL); Disseminated intravascular coagulation (DIC); Down syndrome and leukemia; Eosinophilic leukemia; Fanconi anemia; 5Q minus syndrome; Hairy cell leukemia; Hemolytic anemia; Hodgkin disease; Human T-cell leukemia virus (HTLV); Hypercalcemia; Leukemias; Leukopenia; Leukoplakia; Lymphocytosis; Lymphomas; Multiple myeloma; Myelodysplastic syndromes; Myelofibrosis; Myeloma; Myeloproliferative disorders; Myelosuppression; Neutropenia; Pheresis; Polycythemia vera; Richter syndrome; Sézary syndrome; Stem cell transplantation; Superior vena cava syndrome; Thrombocytopenia; Thymomas; Thymus cancer; Transfusion therapy; Umbilical cord blood transplantation; Waldenström macroglobulinemia (WM).
u Bone cancers Category: Diseases, symptoms, and conditions Also known as: Osteosarcoma, osteogenic sarcoma, bone tumor Related conditions: Li-Fraumeni syndrome, Gardner syndrome, retinoblastoma, leukemia, human immunodeficiency virus (HIV) infection Definition: Bone cancers are malignant, unregulated proliferation of neoplasia (new tissue growth) in bone cells. The most common type of bone cancer is osteosarcoma, a highly malignant tumor composed of cells derived from growing connective tissue cells of bone. Osteochondromas are the most common cancerous primary bone tu158
Salem Health: Cancer mors, with giant cell tumors developing in the thighbone near the knee. Ewing sarcoma is the second most common form of childhood bone cancer and is found mostly in the extremities. Chondrosarcomas are cancerous bone tumors that appear in the cartilage of bone in middle age. Other rare sarcomas are parosteal osteosarcomas involving both the bone and membranous covering, fibrosarcomas originating in the ends of bones in the arm or leg and then spreading to soft tissue, and chordomas that develop on the skull or spinal cord. Multiple myeloma is a hematologic cancer that frequently causes bone tumors. Risk factors: The exact cause of osteosarcoma is not known, but inherited or acquired deoxyribonucleic acid (DNA) mutations are the suggested causes. Risk factors include the presence of a benign bone disease; previous treatment with radiation for another cancer, especially at a young age; teenage growth spurts; and disproportionate tallness with age. Certain rare, inherited cancers are also risk factors, such as Gardner syndrome, Li-Fraumeni syndrome (a rare family predisposition to multiple types of cancers caused by a mutation in a cancer-suppressing gene), and retinoblastoma (a malignant tumor of the retina that usually occurs in children younger than five years old). Studies suggest that occupational exposure to wood preservatives and certain herbicides increases the risk of developing soft-tissue sarcomas. Suggested risk factors for myeloma bone disease include age (it rarely occurs under the age of forty), family history, smoking, exposure to petroleum and other chemicals, and exposure to high amounts of radiation. Atomic radiation from nuclear explosions and high-dose exposure to ionizing radiation are known to be risk factors for bone cancer but on a small scale. Virus infections make relatively minor contributions to human bone cancer, except the human immunodeficiency virus (HIV), which causes sarcoma. Etiology and the disease process: Bone cancers are among the class of mesenchymal cancers that originate from the mesenchyme (bone and other tissues derived from embryonic mesoderm). Abnormal or partially differentiated cells develop in the bone marrow and can enter the general circulation and ultimately cause leukemia. (Leukemia can also result from blocked hemopoietic cell differentiation that causes abnormal cells to accumulate in bone marrow.) Initial mutation in a gene linked to DNA repair will cause other mutations to arise and spread more rapidly. Bone cancers usually develop rapidly and metastasize through the lymph channels of the body. Metastatic tumors frequently involve the axial more than the appendicular skeleton.
Salem Health: Cancer
Bone cancers
Malignant primary bone tumors originate in hard bone, in the soft tissue of blood vessels and nerves, or in tissues containing muscles, fat, or fiber. Osteosarcomas can grow quickly along the edge or end of a fast-growing long bone of the arms or legs, sometimes affecting the pelvis, shoulder, and skull. Osteosarcoma may metastasize into nearby tissues of the foot, tendons, and muscles, or spread through the bloodstream to other organs or bones in the body. Ewing sarcoma originates from immature nerve tissue in the bone marrow of the leg, hips, ribs, and arms, but it is mostly found in the extremities, rapidly infiltrating the lungs and metastasizing to other bones, kidneys, heart, adrenal glands, and other soft tissues. Chondrosarcomas usually originate in cartilage in ribs, legs, or hip bones. These grow slowly and take years to spread to other parts of the body. Incidence: In the United States, about 2,400 cases of cancers of bones and joints are reported annually. The American Cancer Society in 2004 reported incidence rates in the United States to be approximately 1 in 113,333 people, or 2,400 people. In 2005, 2,570 new cases An MRI scan of the spine of a seventy-two-year-old patient reveals myeloma of bone and joint cancer were reported, along that has caused one of the vertebrae (sixth from bottom) to collapse. (Zephyr/ Photo Researchers, Inc.) with 1,210 deaths. Osteosarcoma and Ewing sarcoma occur mostly in children, adolescents, and young Genetic association crops up with bone cancer but adults, accounting for 10 to 15 percent of all childhood scarcely accounts for more than 10 percent of cancers. bone cancers but constituting only 1 percent of all cancers. Most other types of bone cancers are usually found only in Symptoms: Pain is the most common symptom of bone adults. cancer, associated with weakened bones and fractures. Osteosarcoma occurs slightly more often in male than Symptoms may include swelling around the affected site, female children and youths, usually between the ages of increased pain with activity or lifting, limping, and deten and twenty, and represents one-fifth of all bone tumors. creased movement of the affected limb. The soft bone tisApproximately 900 new cases of osteosarcoma are resues grow very large and push aside normal tissue. The iniported each year in the United States. tial symptom is usually a painless lump or swelling, which Ewing sarcoma occurs in 0.6 in one million people in later becomes sore and painful as it presses against nearby the United States, more often in male than female children nerves and tissues. and youths between the ages of ten and twenty, and acSymptoms of Ewing sarcoma include pain, swelling counts for 16 percent of bone cancers. and redness around the site of the tumor, typical small Chronic leukemia, resulting from bone marrow cancer, round blue cells, fatigue, fever, paralysis and incontinence is the most common form of leukemia and is twice as com(if the tumor is in the spinal region), numbness, tingling, mon in men as in women. It is ten times more common in weight loss, and decreased appetite. adults than in children but accounts for 75 percent of childThe symptoms for myeloma bone disease are pain, conhood leukemias, with a five-year survival rate of 80 perstipation, nausea, vomiting, fractures in bones, weakness cent. 159
Bone cancers
Salem Health: Cancer
or numbness in legs, weight loss, weakness, fatigue, repeated infections, and problems with urination. Screening and diagnosis: In addition to a complete medical history and physical examination, diagnostic procedures for bone cancers such as osteosarcoma and Ewing sarcoma may include multiple imaging studies, such as X rays, of the tumor and sites of possible metastasis. Osteosarcomas are classified according to subtypes and grades determined by X rays and histological analysis: • Low grade: intraosseous low grade, parosteal • Intermediate grade: periosteal • High grade: conventional, telangiectatic, central, small cell, high-grade surface A radionuclide bone scan is used to determine the cause of pain or inflammation to rule out any infection or fractures. Magnetic resonance imaging (MRI) is done to rule out any associated abnormalities of the spinal cord and nerves. A computed tomography (CT) scan provides more detailed images than general X rays. A complete blood count (CBC) measures the size, number, and maturity of different blood cells in a specific volume of blood, and urine and blood tests (including blood chemistries) are also used for diagnosis. A biopsy is performed on a tissue specimen to determine if cancer or other abnormal cells are present and to determine other courses of action. Myeloma bone disease is additionally diagnosed with aspiration (an examination of a small amount of bone marrow fluid). Cell sorting devices can identify the number of proliferation cells or ploidy status of the nuclear DNA. Chemical proteins
Age at Death for Cancer of the Bones and Joints, 2001-2005 Age Group
Deaths (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
14.8 14.3 7.1 9.5 11.5 13.7 18.3 10.7
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age at death from 2001 to 2005 was fiftyeight, with an age-adjusted death rate of 0.4 per 100,000 men and women.
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(serving as antigens) detected by specific antibodies provide information on the state of cancer cells. Polymerase chain reaction (PCR) kits, which amplify and detect altered DNA base sequences in minute samples of cells, provide additional tumor markers. They make it possible to diagnose cancer types that are difficult to categorize by conventional pathology. Screening of serum sample glycoprotein antigens in the general circulation reveals undetected cancer, and monitors established cancer. Treatment and therapy: Treatment of bone tumors depends on the type of tumor. Treatment is more likely to succeed if fewer cancer cells exist at the beginning of treatment. If the cancer has metastasized, chemotherapy or radiotherapy is used. Chemotherapy is used as a primary therapy or as an addition to other types of treatment and is the main method for treating advanced bone cancer. Typical drugs used are ifosfamide, cisplatin, methotrexate, and doxorubicin, plus some natural products. Drugs are more effective when used in combination. Treatment of osteosarcoma and Ewing sarcoma may include surgery (biopsy, bone/skin grafts, reconstructions, resections, limb salvage procedures), amputation, prosthesis fitting and training, rehabilitation including physical and occupational therapy, psychosocial adapting, supportive care (for the side effects of treatment), antibiotics (to prevent and treat infections), and continued follow-up care (to determine response to treatment, detect recurrent disease, and manage the side effects of treatment). Treatment of osteosarcoma depends on the subtype and grade of the tumor. Low-grade tumors are surgically removed and usually not treated with chemotherapy. Intermediate-grade tumors are treated with both surgery and chemotherapy. High-grade tumors consist of immature cells, which require aggressive chemotherapy. Most osteosarcomas do not respond to radiation therapy. Treatment of myeloma bone disease includes radiation therapy and medications (to control pain), chemotherapy, fracture treatment, bone marrow transplantation, and alpha interferon for immunotherapy. The most common treatment for soft-tissue sarcomas is surgical removal of the tumor, followed by radiation, chemotherapy, or both. Photodynamic therapy involves laser activation of sensitive compounds that generate free radicals. Dietary adjustments, massage, reflexology, acupuncture, and relaxation techniques can relieve pain, anxiety, tension, and depression. Regular exercise provides physical strength and also reduces mental and emotional stress. Prognosis, prevention, and outcomes: Prognosis for bone cancers involves predictions of the rate of growth, the
Salem Health: Cancer likelihood of the cancer to metastasize, the most effective drug or treatment procedure, and the patient’s needs. Prognosis for osteogenic, Ewing, and other sarcomas greatly depends on the extent of the disease; the size and location of the tumor; presence or absence of metastasis; the tumor’s response to therapy; the patient’s age, overall health, and tolerance of specific medications, procedures, and therapies; and continuous follow-up care for the side effects of radiation and chemotherapy as well as secondary malignancies that could occur. Prompt medical attention and aggressive therapy are important for the best prognosis. Five-year event-free survival is expected for 85 percent of patients whose lowgrade osteosarcoma tumors are surgically removed without chemotherapy and for 75 percent of patients with highgrade tumors requiring aggressive chemotherapy. About 50 percent of patients without metastatic Ewing sarcoma may have long-term disease-free survival. The five-year survival rate for sarcomas is about 90 percent if the cancer is discovered before spreading and less than 30 percent for sarcomas that have already metastasized at the time of diagnosis. Since sarcomas arise from chemical reactions within cells, chemoprevention (with minimal side effects) would presumably curb cancer. New legal requirements for carcinogen testing minimize the hazards associated with industrial products; carcinogens cause less than 1 percent of cancers in developed countries. Nevertheless, cancer is still the second highest cause of death in the Western world, suggesting the need for more research and effective controls. Lifestyle modifications for bone cancer prevention include diet management, control of food additive use, tobacco avoidance, regulation of reproductive factors such as contraception, reduction of alcohol consumption, screening for early detection of cancer, and appropriate use and disposal of industrial products. Samuel V. A. Kisseadoo, Ph.D. u
For Further Information Beers, Mark H., ed. The Merck Manual of Medical Information. 2d ed. Whitehouse Station, N. J.: Merck Publishing, 2003. King, Roger J. B., and Mike W. Robins. Cancer Biology. 3d ed. New York: Pearson/Prentice Hall, 2006. O’Neill, Catherine E., ed. New Developments in Bone Cancer Research. New York: Nova Biomedical Books, 2006. Pappo, A. S., ed. Pediatric Bone and Soft Tissue Sarcomas. New York: Springer, 2005. Singh, Gurmit, and Shafaat A. Rabbani, eds. Bone Metastasis. Totowa, N.J.: Humana, 2005.
Bone marrow aspiration and biopsy u
Other Resources
American Cancer Society http://www.cancer.org Free Health Encyclopedia Bone Cancers http://www.faqs.org/health/topics/75/Bonecancers.html Spectrum Health http://www.spectrum-health.org See also Amputation; Bone scan; Childhood cancers; Ewing sarcoma; Fibrosarcomas, soft-tissue; Giant cell tumors (GCTs); Laryngeal cancer; Li-Fraumeni syndrome (LFS); Limb salvage; Metastasis; Nasal cavity and paranasal sinus cancers; Nuclear medicine scan; Orthopedic surgery; Paget disease of bone; Rothmund-Thomson syndrome; Sarcomas, soft-tissue; Simian virus 40; Spinal axis tumors; Uterine cancer; Veterinary oncology; Young adult cancers.
u Bone marrow aspiration and
biopsy Category: Procedures Definition: Bone marrow aspiration involves the removal of a bone marrow sample for laboratory examination. The bone marrow is where all blood cells are created. It is the job of the bone marrow to replace dead and dying red blood cells, white blood cells, and platelets. At times, cancer or other disease may cause this bone marrow production to stop or decrease. Sites for bone marrow aspiration and biopsy are typically the pelvic bone (ilium) or the sternum, larger bones that provide the best samples. A bone marrow biopsy can be performed by a hematologist, medical oncologist, internist, pathologist, or specially trained technologist. The patient can have a bone marrow biopsy at the bedside, in interventional radiology, and even in the operating room. Cancers diagnosed: Leukemia, multiple myeloma, or polycythemia vera, cancers referred to as hematological malignancies; metastatic cancer Why performed: A bone marrow biopsy is done to evaluate the functioning of the bone marrow and to determine the presence or absence of cancer. Patient preparation: The patient will have the procedure explained and provide consent. A numbing medication is 161
Bone marrow aspiration and biopsy injected at the site; it may burn or sting a bit when first used. Once the numbing medication is injected, patients usually feel considerable pressure at the site but not necessarily pain during the procedure. When the biopsy is done in the hip, patients occasionally complain of a quick shooting pain down the leg, but it usually stops once the sample has been taken. A patient with a low platelet count may receive a platelet transfusion immediately before the procedure. Steps of the procedure: The patient will be positioned for the procedure and needs to remain still until its completion. A patient who is having the pelvic bone biopsied will be placed on one side with pillows or blankets used to maintain positioning. A patient who is having the sternum biopsied will lie flat in the bed or on the table. The patient may be given medication for pain and relaxation. The site is scrubbed and cleaned, and then the patient is given medication to numb the site. A small cut is made into the skin. The procedure is done with a device that consists of a large
Salem Health: Cancer hollow needle with an inner attachment (cannula) that allows for the bone to be accessed. The needle is used to make a hole into the bone. Once it is inside the bone, the middle of the needle is removed, and the large hollow needle is then resting in the center of the bone. A large syringe is used to extract a sample of the marrow (aspirate). The section of bone taken when the inner cannula was removed from the needle is also kept for pathology testing. The patient may have this procedure done on both hip bones or at multiple sites in order to establish staging of disease. The samples are placed on slides or in a liquid to preserve them until testing can be completed. After the procedure: Pressure may need to be applied to prevent bleeding. The patient may be asked to lie on that hip to provide extra pressure immediately after the biopsy for ten to fifteen minutes. The cut is typically small enough that a bandage and a little pressure is all that is needed. Some patients may not be able to stop bleeding after the biopsy, usually because their platelet counts are too low. These patients may require a stitch or two at the bone marrow site to stop the bleeding. Patients may remain sore at the site for two to three days after the procedure. If this procedure was performed on an outpatient, then the patient will not be able to drive home and will need a family member or friend to help. Risks: The risks from performing a bone marrow aspiration and biopsy are minimal. As with any invasive procedure, there is a risk for infection. There is also a risk for bleeding and bruising with this procedure. If the sample is taken from the sternum (breast bone), then there is a risk of injury to the heart, lungs, and major blood vessels.
A young patient is undergoing bone marrow aspiration. (National Cancer Institute)
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Results: Findings from the bone marrow aspiration and biopsy show what types of cells are in the bone marrow. The hematologist or pathologist will examine the samples with a microscope to determine what types of cells are present. The physicians are able to determine if these cells are normal, misshapen, or cancerous, as well as the stage of the cancer that may be present. Bone marrow biopsies are also done to evaluate therapy. This is typically seen in leukemia patients. They will have a bone marrow biopsy completed prior to therapy and then a biopsy done at or around day fourteen to determine if the chemotherapy has destroyed the cells in the bone marrow. Katrina Green, R.N., B.S.N., O.C.N.
Salem Health: Cancer u For Further Information Carrier, Ewa, and Gracy Ledinham. One Hundred Questions and Answers About Bone Marrow and Stem Cell Transplantation. Sudbury, Mass.: Jones and Bartlett, 2003. Klag, Michael J., et al., eds. Johns Hopkins Family Health Book. New York: HarperCollins, 1999. Weisbrot, Deborah M., and Alan B. Ettinger. The Essential Patient Handbook: Getting the Health Care You Need—from Doctors Who Know. New York: Demos Medical, 2004.
See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Aplastic anemia; Blood cancers; Childhood cancers; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Eosinophilic leukemia; Fanconi anemia; 5Q minus syndrome; Flow cytometry; Hairy cell leukemia; Hematologic oncology; Hemolytic anemia; Histiocytosis X; Hodgkin disease; Immunocytochemistry and immunohistochemistry; Medulloblastomas; Multiple myeloma; Myelofibrosis; Myeloma; Myeloproliferative disorders; Neuroblastomas; NonHodgkin lymphoma; Polycythemia vera; Retinoblastomas; Rhabdomyosarcomas; Stem cell transplantation; Thrombocytopenia; Veterinary oncology; Waldenström macroglobulinemia (WM).
u Bone marrow transplantation
(BMT) Category: Procedures Also known as: Peripheral blood stem cell transplantation (PBSCT) Definition: Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are procedures used in cancer therapy to provide stem cells to a patient to replace those lost to disease, chemotherapy, and radiation. Stem cells may be obtained from patients themselves, a related or unrelated donor, or umbilical cord blood taken after the birth of a baby. Autologous transplants use the patient’s own stem cells. Allogeneic transplants use stem cells from a related person; the donor is most often a parent or sibling, but an unrelated but matched donor or umbilical cord blood may be used. A syngeneic transplant is done with stem cells from an identical twin. Cancers treated: Leukemia, lymphoma, multiple myeloma, aplastic anemia, and neuroblastoma; additional
Bone marrow transplantation (BMT) cancers eligible for transplant are being evaluated in clinical trials Why performed: Cancer patients are often treated by high doses of chemotherapy and radiation to rid the body of cancer cells. Chemotherapy and radiation therapy target rapidly dividing cells in the body. Because cancer cells and stem cells divide rapidly, they both may be killed by the therapy. BMT and PBSCT are used to rescue patients after high-dose chemotherapy and radiation by replacing destroyed stem cells with healthy stem cells. Transplanted stem cells allow the bone marrow to begin producing blood cells needed by the body. Additionally, white blood cells from the donor will identify any remaining cancer cells in the patient’s body and attack them as foreign, thus providing additional cancer cell kill. This graft-versustumor (GVT) effect—in this case, stem cells versus cancer cells—is important in some kinds of leukemia treated with allogeneic transplants and enhances the effectiveness of the transplant. To understand bone marrow transplantation, it is important to understand the role of stem cells. Stem cells are found in the bone marrow and can develop into different types of cells in the body, such as blood cells. Blood cells originally begin as immature cells, called hematopoietic stem cells, which are constantly and rapidly dividing. Stem cells used in transplantation are not embryonic stem cells, which are used in cloning experimentation. Mature stem cells are available to the body in the bone marrow, but some stem cells circulate in the bloodstream and are called peripheral blood stem cells. The role of stem cells in the body is to fight infection (stem cells that evolve into white blood cells), carry oxygen (stem cells that evolve into red blood cells), and prevent bleeding (stem cells that evolve into platelets). Patient preparation: The first step in the transplant procedure is determining the type of transplant that will be used by determining if the patient has a potential donor. Doctors try to minimize side effects by using stem cells that match as closely as possible the patient’s own stem cells. There are different proteins on the cell surface, called human leukocyte antigens (HLAs), which are identified with a blood test. The success of the transplant depends on how close a match can be made between the donor stem cells and the patient’s stem cells. Close relatives are the most likely sources of matching stem cells, but less than one-third of patients will have a matched sibling. Finding an unrelated, matched donor is possible in about one-half of cases, and the chance of a match increases if the donor and patient are of the same ethnic and racial 163
Bone marrow transplantation (BMT)
Salem Health: Cancer
Inner spongy layer Hard outer layer
Marrow Bone marrow transplantation is used to treat several types of lymphoma.
background. If a potential donor is identified, then blood work will be used to determine the level of the match. A donor registry may also be used to identify donors who have offered to provide stem cells for transplantation if they match a patient in need. If no donor match can be found, then the patient’s own stem cells may be used in an autologous transplant. Stem cells are obtained from the patient and then treated to remove any cancer cells. Extra stem cells are removed from the patient, as some healthy cells may be damaged when the cancer cells are removed. Once the type of transplant is determined, the stem cells are obtained or harvested. The liquid center of the bone is the source for stem cells used in BMT. The donor is given anesthesia to make the harvest procedure pain-free. General anesthesia or regional anesthesia, which numbs the area below the waist, is used. Large needles are inserted into the hip (pelvic) bone or, rarely, the breastbone (sternum), and marrow is drawn out. The harvest procedure takes approximately one hour. The bone marrow is then treated to remove blood and bone fragments, frozen with a preservative if not to be used immediately, and stored until it is time to administer the stem cells to the patient. Stem cells that are frozen (cryopreserved) can be stored for many years. If the doctor determines that a peripheral blood stem cell transplant is the best choice for the patient, then stem cells are harvested from the bloodstream rather than from the bone marrow. Autologous transplants often use peripheral blood stem cells (PBSCs). Apheresis is used to re164
move PBSCs with a machine that removes the stem cells and then returns the remainder of the blood, minus the stem cells, to the donor. Medicine that stimulates the growth of stem cells in the body may be given to the donor for several days before the harvest. Apheresis may take up to six hours. The cells are processed and frozen for future use. Umbilical cord blood may also be a source of stem cells for transplantation. The mother requests that cells be harvested when the birth occurs. Cord blood banks may store the cells for potential use by the family at a later date or may be given to a public cord blood bank for use by any matching patient. Blood is taken from the umbilical cord and placenta and then frozen for storage. Since only a small amount of blood may be available, cord blood transplants are usually most effective in children or small adults. Steps of the procedure: The patient usually receives high-dose chemotherapy (anticancer drugs) and radiation to rid the body of as many cancer cells as possible. Depending on the hospital program, the patient may be admitted to the hospital or may undergo the preoperative regimen as an outpatient. Once the regimen before the transplant is complete, the patient is ready to have the procedure. The stem cells are thawed and given through an intravenous line, as in a blood transfusion. The infusion of the stem cells may take from one to five hours. After the procedure: Once the infusion of the stem cells is complete, the wait begins for the cells to graft (or take)
Salem Health: Cancer and produce new blood cells for the patients. During this time, the patient may be in a room with special air filters and strict infection control guidelines. Because the patient has very few stem cells until the graft occurs, the body is unable to fight infection or control bleeding. The wait for engraftment ranges from two to six weeks. High fevers, chills, shortness of breath, coughing, low blood pressure, and weakness may occur. With allogeneic transplants, the most significant complication that occurs is graft-versushost disease. Once discharge from the hospital occurs, the patient may face a variety of problems. Fatigue, physical problems lingering after the transplant, and psychological problems may occur. Frequent visits to the physician to follow progress after the transplantation and to manage symptoms are expected. The recovery period may be a year in length. Risks: There is minimal risk involved with donating bone marrow or undergoing apheresis. If the match between donor and patient is not complete, then graft rejection may occur in rare instances. The most significant risk with an allogeneic transplant is graft-versus-host disease. Patients may be unable to have children after a transplant, and this topic should be discussed with the physician prior to the transplant. Results: Survival rates after transplantation vary by disease, type of transplant, and the age of the patient. In related donor patient transplants, survival rates are 55 to 70 percent and 25 to 50 percent if the donor is unrelated. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Jenks Kettmann, J. D., and E. M. Altmaier. “Social Support and Depression Among Bone Marrow Transplant Patients.” Journal of Health Psychology 13 (2008): 39-46. Nadir, Y., and B. Brenner. “Hemorrhagic and Thrombotic Complications in Bone Marrow Transplant Recipients.” Thrombosis Research 120, suppl. 2 (2007): 92-98. u
Other Resources
American Cancer Society http://www.acs.org National Cancer Institute Bone Marrow Transplantation http://www.cancer.gov National Marrow Donor Program http://www.marrow.org
Bone pain See also Blood cancers; Graft-versus-host disease (GVHD); Immunocytochemistry and immunohistochemistry; Leukemias; Lymphomas; Organ transplantation and cancer; Pheresis; Stem cell transplantation; Umbilical cord blood transplantation.
u Bone pain Category: Diseases, symptoms, and conditions Also known as: Skeletal pain Related conditions: Bone metastasis, fracture Definition: Bone pain is an uncomfortable response to disease, infection, inflammation, or trauma to bone. Risk factors: Those at greatest risk for bone pain not caused by fracture or other trauma are those with bone disease, including bone cancers. Etiology and the disease process: Bone pain in cancer may be caused by tumors in or near bones or conditions that cause damage within the bone, such as multiple myeloma. Cancer that spreads, or metastasizes, to bone from another part of the body can result in bone pain. Medications given to stimulate the production of blood cells in the bone marrow may cause temporary bone pain. Incidence: Bone pain is experienced in more than half the cases of bone metastasis. There is a higher incidence in patients with advanced disease, particularly in those with breast and prostate cancers. Symptoms: Symptoms include limited mobility, swelling in the area of pain, fatigue, and lack of appetite. Loss of height is associated with bone compression in the vertebrae. Burning or tingling sensations may indicate nerve involvement. Fracture, a late sign of advanced disease, is another source of pain. Screening and diagnosis: Bone lesions are detected on X rays, positron emission tomography (PET) and computed tomography (CT) scans, and magnetic resonance imaging (MRI). A biopsy is necessary to determine if cancer has spread to the bone. The level of pain is assessed using a variety of scales. A commonly used scale uses a zero to ten rating, where zero correlates with no pain and ten with the worst possible pain. Other evaluations are employed to describe the type and quality of pain. Treatment and therapy: Chemotherapy and radiation alleviate or diminish pain by reducing tumor size. Bone pain is managed with medications, including nonsteroidal anti165
Bone scan inflammatory drugs (NSAIDs), steroids, muscle relaxants, opioids, antidepressants, and antianxiety drugs. Nonpharmaceutical interventions used alone or in conjunction with medication can be effective. Examples include physical therapy, exercise, acupuncture, aromatherapy, biofeedback, breathing exercises, hypnosis, massage, and nerve stimulation. Surgery may be necessary to stabilize weakened bones with rods or special cements. Prognosis, prevention, and outcomes: Prognosis depends on the ability to treat the underlying cause of the pain. An increase in bone pain may indicate disease progression that can lead to serious injury, including fracture, loss of bladder and bowel control, and paralysis. Chronic bone pain can be effectively managed to maximize functionality and quality of life in cases in which it cannot be completely eradicated. Linda August Vrooman, R.N., B.S.N., O.C.N. See also Acute lymphocytic leukemia (ALL); Amputation; Blood cancers; Bone cancers; Bone scan; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Limb salvage; Multiple myeloma; Myelofibrosis; Myeloma; Neuroblastomas; Neuroectodermal tumors; Orthopedic surgery; Paget disease of bone; Pain management medications; Radiopharmaceuticals; Waldenström macroglobulinemia (WM); Young adult cancers.
u Bone scan Category: Procedures Also known as: Bone scintigraphy Definition: A bone scan is a procedure that can detect abnormalities in the skeleton. A radioactive substance (known as a tracer) is injected into the body and taken up by the bone. The tracer emits radiation in the form of gamma rays, which can be detected by a special scanning camera. More tracer will accumulate in areas of the bone that are actively rebuilding or breaking down (such as that in the presence of cancer) compared to the inactive areas. Cancers diagnosed: Cancers that have spread to the bone (metastatic cancers), primarily breast, prostate, and lung cancers, and kidney and thyroid cancers to a lesser degree Why performed: Cancer cells can spread from their primary location to the bone in a multistep process known as metastasis. Metastatic bone disease can result in bone pain and an overall decrease in the quality of life. Tumor cells residing in the bone can also cause bone destruction (known as resorption) as a result of both direct effects of 166
Salem Health: Cancer the tumor and the activation of osteoclasts (a type of bone cell responsible for resorption). This process may result in weakened bones and a greater risk of bone fractures. Furthermore, calcium may be released from the bone as it breaks down, and elevated levels of calcium in the blood can cause loss of appetite, nausea, and exhaustion and can affect the heart and kidneys. A bone scan is one method to detect if cancer has spread to the bone and to identify where the cancer is located. Bone scans can also be used to determine the stage of disease, as well as to examine how much bone damage is present. Additionally, bone scans may be performed to monitor the response to treatment, as some cases of bone cancers are treated with drugs such as bisphosphonates in order to reduce bone resorption. Patient preparation: Very little prior preparation is required, and patients do not need to fast. At the time of the scan, patients must remove all metal objects (such as jewelry, zippers, and metal buttons), as they may interfere with the scan. In some cases, the clothes should be removed and the patients will wear a hospital gown. Steps of the procedure: A bone scan will usually be performed in a hospital. The two stages of this procedure are the tracer injection and the scan. A radioactive tracer will be injected into a vein in the patient’s arm. Patients will then wait one to four hours to allow the tracer to be incorporated into the bone tissue. Drinking several glasses of water (at least four) will help to eliminate excess tracer through the urine. Patients will be instructed to empty the bladder before the scan begins. For the scan, patients must lie still on a table while the scanning camera moves overhead and scans the body. The camera will detect the gamma rays emitted by the tracer that has concentrated in the bone. Sometimes the scans will be conducted when patients are in different positions in order to view the bones from various angles. On average, the bone scan lasts about thirty to sixty minutes. After the procedure: Care should be taken when sitting up at the completion of the scan, as dizziness or lightheadedness may result from the extended period of lying down. Patients will be instructed to drink plenty of fluids for at least forty-eight hours after the bone scan to help eliminate the remaining radioactive tracer. Patients who are breastfeeding should also discard their breast milk for the first two days after the procedure. Risks: Common risks include redness, soreness, or swelling at the injection site. In rare cases, patients have allergic reactions to the tracer.
Salem Health: Cancer Results: If the radioactive tracer is distributed equally throughout the bones, then the result will be considered normal. An abnormal result will occur when the tracer concentrates in distinct sites of the bone, resulting in “hot spots.” Hot spots indicate that there is a lot of activity in the bone, both building and resorption, which may be a sign of tumor cells within the bone. Hot spots, however, may also be caused by a fracture or bone infection. Therefore, if hot spots are detected, the doctor will often suggest blood tests, biopsies, or other imaging tests in order to confirm the presence of cancer. Elizabeth A. Manning, Ph.D. u For Further Information Coleman, R. E. “Clinical Features of Metastatic Bone Disease and Risk of Skeletal Morbidity.” Clinical Cancer Research 12, no. 20, pt. 2 (2006): 6243s-6249s. Even-Sapir, E. “Imaging of Malignant Bone Involvement by Morphologic, Scintigraphic, and Hybrid Modalities.” Journal of Nuclear Medicine 46, no. 8 (2005): 1356-1367. Hamaoka, T., et al. “Bone Imaging in Metastatic Breast Cancer.” Journal of Clinical Oncology 22, no. 14 (2004): 2942-2953. Rosenthal, D. I. “Radiologic Diagnosis of Bone Metastases.” Cancer 80, suppl. 8 (1997): 1595-1607. Yoneda, T., and T. Hiraga. “Crosstalk Between Cancer Cells and Bone Microenvironment in Bone Metastasis.” Biochem Biophys Res Commun 328, no. 3 (2005): 679-687. u
Other Resources
American Cancer Society How Is Bone Cancer Diagnosed? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_3X_How_is_bone_cancer_diagnosed_2 .asp?sitearea= What Is Bone Metastasis? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_Is_bone_metastasis_66.asp Mayo Clinic Bone Scan: Using Nuclear Medicine to Find Bone Abnormalities http://www.mayoclinic.com/health/bone-scan/ CA00020 See also Alveolar soft-part sarcomas; Beckwith-Wiedemann syndrome (BWS); Bone cancers; Childhood cancers; Ewing sarcoma; Exenteration; Gallium scan; Glomus tumors; Imaging tests; Lacrimal gland tumors; Mantle cell
Boron neutron capture therapy (BNCT) lymphoma (MCL); Medulloblastomas; Myeloma; Nuclear medicine scan; Paget disease of bone; Pineoblastomas; Pneumonectomy; Radionuclide scan; Rhabdomyosarcomas; Richter syndrome; Spinal axis tumors.
u Boron neutron capture
therapy (BNCT) Category: Procedures Definition: Boron neutron capture therapy (BNCT) is a form of radiation therapy that brings together a stable isotope of boron (boron 10) and a beam of low-energy neutrons to target and destroy tumor cells while leaving adjacent tissue undamaged. Cancers treated: Glioblastoma multiforme (GBM); perhaps other brain tumors and skin melanomas Why performed: Treatments for high-grade gliomas are supportive but not curative. Patients with GBM die within three months when left untreated. Standard approaches using surgical resection, radiation therapy, and chemotherapy increase the median survival time to twelve months, with few patients surviving beyond five years. This is the case because tumor cells infiltrate into surrounding brain tissue and are not readily available to the surgeon, and because glioma cells tend to resist radiation and chemotherapy. Moreover, older patients respond poorly to all current therapies, and there has been no significant new approach to GBM treatment since the early 1980’s. Researchers hope that BNCT will offer some improvement. Patient preparation: Patient preparation is standard for radiation therapy. The size and location of the patient’s tumor are determined using imaging studies such as magnetic resonance imaging (MRI) or computed tomography (CT) scans. Prior to neutron targeting, the patient’s skin is marked to position the head correctly. Steps of the procedure: The patient first receives an intravenous injection of boron 10 that has been chemically tagged to bind with the tumor cells. Neutrons created in a nuclear reactor and modified for BNCT treatment are beamed into the targeted tissue. Neutron activity slows during the ensuing collisions, resulting in a transformation into low-energy thermal neutrons. The boron atoms are then able to capture the thermal neutrons, resulting in boron disintegration into energetic lithium 7 and alpha particles. These cancer-destroying particles react in a very small area, thus confining the ensuing tissue destruction to the tumor. 167
Bowen disease After the procedure: There are no special procedures following BNCT. Risks: The risks are minimal because the path length of the boron elements produced during the procedure is small, limiting the destructive properties to the size of a single cell and leaving nontargeted tissue unharmed. Results: Although work on boron neutron capture therapy continues to hold promise, in general it has proved no more successful than standard therapies and so is not now a routine approach to treatment. Richard S. Spira, D.V.M. See also Radiation oncology; Radiation therapies.
u Bowen disease Category: Diseases, symptoms, and conditions Also known as: Bowen’s disease, squamous cell carcinoma in situ Related conditions: Squamous cell carcinoma (SCC), Bowenoid papulosis, erythroplasia of Queyrat Definition: Bowen disease refers to a type of skin cancer considered squamous cell in situ, named after John Bowen, who documented it in 1912. It may arise anywhere on the skin or the mucous membranes. Bowen disease of the glans penis is called erythroplasia of Queyrat. Unlike other premalignant cancers, Bowen disease possesses a low potential for progression to invasive SCC (less than 5 percent) and an even lower potential for metastasis. Another characteristic feature of Bowen disease is its greater propensity to spread over skin than to invade deeper skin layers. Although its malignant potential is low, extensive skin damage can result from delays in treatment. Risk factors: Repeated exposure to the sun and exposure to the human papillomavirus (HPV), particularly HPV 16, and to arsenic have been implicated as risk factors for Bowen disease. However, more often than not, no risk factor can account for disease development. Etiology and the disease process: Bowen disease originates from the overproliferation of squamous cells, the flat superficial cells that make up the upper layer of the skin (epidermis). The entire epidermal layer is involved in Bowen disease. Triggers of this overproliferation include ultraviolet light from chronic sun exposure and exposure to HPV 16. Both can damage or alter cellular deoxyribo168
Salem Health: Cancer nucleic acid (DNA) and the cellular controls regulating cell division. The TP53 gene is particularly susceptible to ultraviolet light damage and has been implicated as one of many possible mechanisms of cancer proliferation apart from Bowen disease. Arsenic has been hypothesized to enhance the carcinogenic properties of ultraviolet irradiation, as it has a propensity to accumulate in the skin as well as the lungs, bladder, kidney and liver. Incidence: The incidence of Bowen disease has been estimated to range from 14 to 142 cases per 100,000. There is also a predilection for whites as well as older adults. Symptoms: Bowen disease manifests in an insidious manner and often mimics other diseases before being diagnosed. It often appears as a reddish, nonpigmented, raised, and scaly lesion that gradually enlarges. The lesion is easily identifiable as it is well demarcated from surrounding normal skin. The most common sites are the head, neck, and extremities, although any part of the skin or mucous membrane may be affected. As the lesion enlarges, it thickens and starts to exhibit crusting, fissures, or ulcers. These lesions are usually solitary unless malignancy is present. Nonetheless, a full skin examination is warranted. Screening and diagnosis: Bowen disease can easily be mistaken for other skin cancers such as invasive SCC and basal cell carcinoma. Therefore, a punch or shave biopsy of the lesion is essential to initiate appropriate treatment irrespective of location. The sample must include the full thickness of the epidermis and, as much as possible, hair structures in deeper layers. Staging of Bowen disease as a squamous cell carcinoma is not applicable unless invasion of the underlying dermis is seen during microscopic examination. Apart from routine skin examinations as part of a regular physical examination, there are no formal screening tests for Bowen disease. Treatment and therapy: Medical and surgical treatments are available, although the latter are preferred. Medical treatment consists of topical treatment with either 5fluorouracil (5-FU) or imiquimod 5 percent cream. 5-FU is used on the lesion after keratolytic therapy (controlled chemical breakdown) or cryotherapy (freezing). Iontophoresis can also be used to deliver the drug by inducing a drug “gradient” within the lesion. In women, 5-FU must not be taken during pregnancy. Radiotherapy using X rays or grenz rays is reserved for patients who cannot undergo surgery or those with multiple lesions. Lesions may also be treated with photodynamic therapy, in which a chemical agent increases photosensitivity only within tumor cells. This microenvironment is then exposed to a specific
Salem Health: Cancer
Bowen disease
Bowen disease may arise anywhere on the skin. Here it is in the groin. (Custom Medical Stock Photo)
wavelength of light, which causes local toxin and oxygen radical release and immune system activation, leading to tumor cell death. There are many surgical options including excision of both the lesion and a small margin (4 millimeters) of normal tissue, Mohs micrographic surgery, curettage and electrodesiccation, cryotherapy, and carbon dioxide laser ablation. Simple excision is preferred for small lesions in nonproblematic areas where deformities can be easily corrected. Mohs micrographic surgery, which is a very precise procedure also used in removing other skin cancers, is more suited to removing larger or recurring lesions and in areas where skin conservation is required for cosmetic reasons or functional preservation (for example, the face or joints). Curettage and electrodesiccation, cryotherapy, and carbon dioxide laser ablation are also effective treatments but do not provide pathologic specimens to confirm tumor eradication, particularly with deeper-lying lesions. Prognosis, prevention, and outcomes: The overall prognosis of patients after treatment is excellent. Recurrence
is often associated with inadequate removal of the lesion or malignant transformation and spread. Some of the sequelae of treatment include skin deformity, scarring, infection, and underlying damage to blood vessels and nerves. Prevention is aimed at decreasing unnecessary ultraviolet light exposure. This includes patient education regarding sun exposure and measures such as wearing protective clothing and sunscreen with an SPF of at least 15 and avoiding exposure to the sun between 10 a.m. and 4 p.m. Aldo C. Dumlao, M.D. u
For Further Information Fossel, Michael B. Cells, Aging, and Human Disease. Oxford, England: Oxford University Press, 2004. Gupta, Renu. Skin-Care. Delhi, India: Diamond Pocket Books, 2000. McCally, Michael. Life Support: The Environment and Human Health. Cambridge, Mass.: MIT Press, 2003. 169
Brachytherapy u
Other Resources
American Cancer Society Treating Bowen Disease http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Treatment_of_bowens_disease_51.asp American Osteopathic College of Dermatology Bowen’s Disease http://www.aocd.org/skin/dermatologic_diseases/ bowens_disease.html See also Complementary and alternative therapies; Penile cancer; Premalignancies; Skin cancers; Vulvar cancer.
u Brachytherapy Category: Procedures Also known as: Sealed source radiotherapy, endocurietherapy Definition: Brachytherapy is a form of radiation treatment in which the radioactive source consists of small pellets or seeds, ribbons, or wire, each about the size of a grain of rice, that are placed into or next to the area being treated. Brachytherapy is from a Greek word meaning “short,” so literally brachytherapy means “short distance treatment.” It is unlike radiation from an external source, such as a machine, in which the radioactive beam is directed at the tumor from outside the body. There are three types of brachytherapy delivery. Intracavity treatment involves radioactive implants that are placed inside a body cavity, such as the uterus. In interstitial treatment, radiation implants are placed directly in the tumor. They are often permanent and used in prostate cancer treatment. In unsealed internal radiation therapy, radioactive materials are injected into a vein or body cavity. Brachytherapy can be either permanent or temporary. Permanent brachytherapy, or low dose rate (LDR) brachytherapy, is often called seed implantation and involves placing small radioactive seeds at or near the tumor and leaving them there permanently. This is typically used in the treatment of prostate cancer. The radioactivity of the seeds decreases over time, and the seeds left inside the patient cause no discomfort or harm. Temporary brachytherapy, or high dose rate (HDR) brachytherapy, involves radioactive seeds that are left in the body only for a specific amount of time and then are removed. Treatments may consist of several visits to the physician to have the seeds placed and removed. This method is used in the treatment of most of the other cancers. 170
Salem Health: Cancer Radiation works by killing cancer cells when they are trying to multiply. The deoxyribonucleic acid (DNA) of cancer cells is more sensitive to radiation than that of normal cells, so the normal cells are able to repair themselves and the cancer cells die. Cancers treated: Brachytherapy is used for many types of cancer in the body, including prostate, cervical, head and neck, ovarian, breast, lung, gallbladder, uterine, and vaginal cancers, as well as anal/rectal tumors and sarcomas. It can also be used to treat noncancerous conditions such as benign tumors and coronary artery disease. Additionally, brachytherapy can be used in conjunction with other cancer treatments, including chemotherapy and external beam radiation. It can be used as both a curative and a palliative form of treatment. Why performed: Brachytherapy has been in use since the early twentieth century, and it has been proven to be safe and effective. It allows a higher dose of radioactivity to be used with decreased risk of damage to healthy tissue, quicker healing times, and decreased risk of infection. In breast brachytherapy, for example, the therapy is quicker than external beam radiation, and it only treats a portion of the breast. Brachytherapy often can be performed in five days as opposed to five to seven weeks. The patient has a better cosmetic result and healthy tissue is preserved. Patient preparation: Before the treatment begins, patients meet with the physician and receive instructions on how to care for themselves after the treatment. The physician will determine what tests should be done prior to brachytherapy, which may include blood tests, electrocardiograms (ECG or EKG), and X rays. The actual prepping of the patient depends on where the seeds are being placed. Typically, a radiation oncologist, a radiation physicist, a dosimetrist, and a radiation therapist are involved in planning the treatment. The radiation oncologist determines the type of treatment needed and is responsible for the overall treatment plan, including the area to be treated and the dose to be delivered. The physicist calculates the dose to be prescribed. The dosimetrist assists in dose calculation and helps in delivering the prescribed dose. The radiation therapist operates the equipment and delivers the dose. Through special computer programs, the dose, duration, and delivery method of the treatment are determined. Without this specific calculation, the cancer cells might receive too little radiation and the normal tissue could receive too much. Steps of the procedure: The steps of the procedure also vary depending on where the seeds are being placed in the body. The seeds are generally inserted into the site of the
Salem Health: Cancer tumor through a needle or catheter. Sometimes a device to hold the seeds is placed near the tumor. Often, X rays, ultrasound, computed tomography (CT) scans, or even surgery is used to help position and verify placement of the radioactive material or device. Some doses are delivered to the patient on an outpatient basis, in which radiation is delivered to the tumor in a short amount of time and then the delivery device is removed and the patient goes home. The patient may return at intervals for more treatment. Alternatively, a patient may spend a couple of nights in the hospital so that the delivery device can remain in place and the radioactivity can be delivered at a continuous rate. These patients are placed in private rooms, usually with limited or no visitors allowed. The hospital staff will continue to take care of the patient, but they limit the amount of time that they spend with the patient in order to keep their radiation exposure low. A patient may have an intravenous line inserted in order to receive medications. Sedatives or anesthesia may also be used to place the delivery device, again depending on the location of the treatment. After the procedure: Patients typically can go home after the LDR procedure. The physician will give the patient detailed instructions for self-care at home, which may include limiting contact with pregnant women or children for a limited amount of time so as not to expose them to the radioactivity. The patient may have some pain, swelling, or bleeding at the site of the procedure. Educational materials may be very helpful to the patient and family after the procedure. Side effects and precautions can be outlined. Generally, the patient is to avoid heavy lifting or strenuous physical activity for a few days after the procedure. Sometimes the radiation precautions include instructing the patient to sleep alone for a period of time, to avoid sexual relations for a period of time, and to use tweezers, not bare hands, to pick up any seed that may become dislodged. Instructions on what to do with a dislodged seed are also given. HDR patients are usually in the hospital for forty-eight to seventy-two hours and then are discharged once the radiation device is removed. They also receive detailed instructions on how to protect family members from exposure and to watch for side effects such as pain and bleeding. Risks: Like the preparation of the patient and the steps of the procedure, the risks from brachytherapy also vary depending on the area treated. Although relatively safe, brachytherapy is not totally without risks. Patients with permanent brachytherapy seeds continue to give off small amounts of radiation for several weeks. With this type of
Brachytherapy treatment, there is a risk that the seeds will move out of place. Patients are often told to strain their urine at home in case in seeds do migrate. Patients are given special instructions from their doctor about protecting family members from exposure. Brachytherapy for prostate cancer can cause sexual dysfunction such as impotence and bowel problems such as diarrhea, although these are not very common. Urinary irritation is a more common side effect because the urine stream becomes obstructed by swelling in the prostate after therapy. A urinary catheter or Foley catheter is placed to allow urine to flow. The prostate usually returns to normal size and the blockage disappears after several weeks, and the catheter can then be removed. Patients may continue to have some urinary burning for a few weeks, but this also resolves. Results: The physician may order scans or X rays after brachytherapy in order to determine if the treatment was successful. The effectiveness of brachytherapy varies depending on the location of the treatment and the type of cancer that was treated. It has proven to be effective in many types of cancer, especially cervical and prostate cancer. In early prostate cancer, brachytherapy offers ten-year survival rates comparable to surgical removal of the prostate, according to several studies. In general, patients have fewer side effects and a quicker recovery time with this therapy as compared to external beam radiation or surgery. There is also less risk of infection than with surgery. As a result, patients typically have a better quality of life with this procedure, which is easier to tolerate. Michelle Kasprzak, R.N., B.S.N., O.C.N. u
For Further Information Merrick, G. S., et al. “Long Term Rectal Function After Permanent Prostate Brachytherapy.” Cancer Journal 13, no. 2 (March/April, 2007): 95-104. Mitchell, I. “Patient Education at a Distance.” Radiology 13, no. 1 (February, 2007): 30-34. Nag, Subir, ed. Principles and Practices of Brachytherapy. Malden, Mass.: Blackwell, 1997.
u
Other Resources
American Brachytherapy Society (ABS) http://www.americanbrachytherapy.org American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov 171
BRAF gene See also Afterloading radiation therapy; Anal cancer; Carcinomas; Cervical cancer; Endometrial cancer; Iridium seeds; Mayo Clinic Cancer Center; Neurologic oncology; Radiation oncology; Radiation therapies; Rhabdomyosarcomas; Veterinary oncology.
u BRAF gene Category: Cancer biology Also known as: BRAF1, RAFB1, v-raf murine sarcoma viral oncogene homolog B1 Definition: BRAF is an internal part of a cellular signaling pathway. This signaling pathway results in cell growth when the correct chemical message is sent. The mutated form of the BRAF gene has a single base (letter) of deoxyribonucleic acid (DNA) changed; this changes the activity of the BRAF protein. This mutant BRAF protein is broken and is continuously on, sending growth signals even when there are no chemical messages and causing runaway growth of cells. The result is like a broken light switch that will not turn off. Etiology and symptoms of associated cancers: The BRAF protein is central to causing many types of cancer, including melanoma, colon cancer, ovarian cancer, thyroid cancer, and gliomas. Knowledge of the BRAF gene, which was first described as a proto-oncogene in 2002, is useful in diagnosing cancer and deciding what type of treatment to use. The advanced state of knowledge in modern biology and medicine makes it likely that drugs that attack cancers with BRAF mutations will be quickly developed. Tumors are called benign (not harmful) or malignant (harmful). Benign tumors can acquire mutations that change them into malignant cancers. Experts believe that cancer requires multiple steps to form. Many normal functions of cells need to be damaged to create a malignant cancer. Cellular functions typically damaged are cell growth (unregulated cell growth), telomere maintenance (cell aging), apoptosis (cell death), angiogenesis (the ability to grow blood vessels), and metastasis (the ability of cells to detach from one part of the body and migrate to another). BRAF mutations primarily affect the first of these functions, cell growth. When BRAF is mutated in a cell, the cell receives a continuous signal to grow and divide. This signal from BRAF also has a smaller effect of reducing the probability of cells dying by apoptosis, an effect promoting metastasis, and effects promoting angiogenesis. BRAF mutations are often found in benign growths. 172
Salem Health: Cancer Mutations of other genes are needed to destroy the remaining cell functions and make a growth malignant. For example, the destruction of the TP53 gene (also known as p53) will help the cancer overcome cell aging (which normally slows down the overgrowing cells) and apoptosis (which normally kills off some of the overgrowing cells). For comparison, TP53 mutations are rarely found in benign growths and are almost always found as secondary changes in cancers. Because BRAF mutations are found in benign and malignant growths, many people believe BRAF is an early change that eventually leads to malignant cancers. Cancers that seem to begin with BRAF mutations also seem to end up being among the most malignant. Even though BRAF is associated with the worst types of malignancies, the silver lining is that since BRAF mutations happen early, while the tumors are still benign, the BRAF mutation can serve as an early warning. BRAF mutation is not found in all cancer but only in cancers of certain tissues. Most of these tissues are what doctors call adenoid tissues. Specifically, BRAF mutation has been found in melanoma (skin), glioma (nerve), thyroid, ovarian, and colon cancer. Researchers have shown that 80 percent of the benign nevi (moles) studied carried the BRAF mutation and that 66 percent of malignant melanomas studied carried the BRAF mutation. In benign gliomas, BRAF mutation is rarely observed, but in malignant gliomas, the BRAF mutation was almost always observed. Testing and treatment: Standard tests of DNA can be done on blood or tumor tissue samples to detect the BRAF mutation. While these tests are very reliable, the knowledge of the BRAF gene mutation and the tests for it are new and are not yet widely available. BRAF mutation tests will help doctors determine the exact type of cancer, how dangerous it is, and what types of treatment to use. One drug in testing is BAY 43-9006. This drug seems to reverse the effect of BRAF mutation and stop the growth of cells. It also seems to kill the cancer cells by restoring normal cell death (apoptosis). Although only laboratory experiments have been done, some researchers expect that actual tests in people with cancers will show that the drug will not only stop the growth of the cancers but may kill the cancers entirely. History: The discovery of the BRAF mutation is a direct result of the Human Genome Project. In the 1990’s the Human Genome Project sequenced the human genome and described the complete set of about 30,000 human genes, the instructions for the body. In the 2000’s the Cancer Ge-
Salem Health: Cancer
Brain and central nervous system cancers
nome Project started examining all 30,000 genes in cancers to find broken genes. One result was the discovery of the BRAF gene mutation in 2002. Christopher Pung, B.S., C.L.Sp. (CG)
tumors of the cerebellum, and central neuroblastomas, which affect the brain cortex. The naming system for pediatric brain tumors is still evolving and remains controversial.
u
Risk factors: Chemicals such as vinyl chlorides, aromatic hydrocarbons, and N-nitroso compounds in cigarettes; ionizing radiation; electromagnetic fields; and viral infections have been suggested as possible environmental risk factors. Some brain cancers appear to be more common in people working with radiation and chemicals, such as employees of nuclear plants and oil refineries. However, none of these environmental factors have been conclusively shown to cause brain cancer. Genetic risk factors include inherited diseases such as tuberous sclerosis and von Hippel-Lindau disease.
For Further Information Begley, Sharon. “Science Journal: Nature’s Quirks Limit DNA-Based Drug Possibilities.” Pittsburg PostGazette, November 11, 2005. Davies, H., et al. “Mutations of the BRAF Gene in Human Cancer.” Nature 417 (2002): 949-954. Shaw, Gina. “BRAF Mutations Predict Tumor Response.” Drug Discovery and Development 8 (2005): 8. u
Other Resources
Atlas of Genetics and Cytogenetics in Oncology and Haematology BRAF http://atlasgeneticsoncology.org/Genes/ BRAFID828.html The Human Genome Melanoma and the BRAF Gene http://genome.wellcome.ac.uk/doc_WTD020812.html See also Genetics of cancer.
u Brain and central nervous
system cancers Category: Diseases, symptoms, and conditions Also known as: Brain tumors, central nervous system (CNS) tumors, gliomas, glioblastomas, astrocytomas, meningiomas, neuromas Related conditions: Seizures, psychiatric symptoms (including abnormal personality and behavioral characteristics), loss of memory and cognition Definition: Brain and central nervous system cancers are masses of abnormal cells (malignant tumors) in the brain and central nervous system that grow rapidly and can invade surrounding normal tissue. Brain tumors are named for both the type of cell from which they arose and their location in the brain. For example, schwannomas are named after the Schwann cells, astrocytomas after astrocytes, oligodendrogliomas after oligodendrocytes, meningiomas after the meninges or brain membranes, and pinealoblastomas after the pineal gland. Exceptions are medulloblastomas, which are undifferentiated neuroectodermal
Etiology and the disease process: The causes of brain and central nervous system cancers are still unproven. Environmental, genetic, medical, and lifestyle factors may all play a role in causing these cancers. Brain tumors can be primary or secondary. Primary tumors originate in the brain and are rarer than secondary brain tumors, accounting for around one-fourth of all brain tumors. Once they occur, primary brain tumors rarely metastasize to other tissues beyond the spinal cord. Examples of primary brain tumors are schwannomas, astrocytomas, medulloblastomas, meningiomas, and oligodendrogliomas. Secondary or metastatic tumors originate elsewhere in the body and migrate or metastasize to the brain. The types of cancer most likely to metastasize to the brain are breast cancer, lung cancer, melanoma, and colon cancer. Nasopharyngeal cancer can also metastasize to the brain via the cranial nerve or through openings in the bone at the base of the skull called foramina. Incidence: The annual incidence of primary invasive central nervous system tumors in the United States is 6.6 per 100,000 people, with an estimated 4.7 deaths per 100,000 people annually. Approximately 20,500 new cases of brain and central nervous system cancers occurred in the United States in 2007, as well as an estimated 12,740 deaths from these cancers. Brain tumors account for 85 to 90 percent of all primary central nervous system tumors. Primary brain tumors have a higher incidence in whites than in blacks and are more common in men than in women, with three out of five sufferers being men. Brain tumors usually arise in early or middle adult life and are most common in people older than sixty-five. However, brain cancer can occur at any age. Primary brain tumors are rarer than secondary brain tumors, with a ratio of 1 primary brain tumor to every 3 sec173
Brain and central nervous system cancers
Salem Health: Cancer
ondary brain tumors. Some experts put this ratio at closer to 1:10, attributing the increased detection of secondary tumors to more sensitive imaging methods. The most common primary brain tumors are astrocytomas, glioblastomas, meningiomas, and other mesenchymal tumors, which make up around 65 percent of all primary brain tumors. The most common primary spinal tumors are schwannomas, meningiomas, and ependymomas, accounting for 79 percent of primary spinal tumors. Secondary or metastatic brain tumors occur in 20 to 40 percent of brain cancer patients. About 80 percent of secondary tumors occur in the cerebral hemispheres, 15 percent in the cerebellum, and 5 percent in the brain stem. Multiple metastases to the brain are more common than solitary metastases, occurring in more than 70 percent of cases.
(including blurred vision, double vision, or loss of peripheral vision), loss of memory and cognition, personality or behavioral changes, abnormal breathing rates, dizziness, nausea or vomiting, loss of hearing, and hormonal disorders. In one study of brain tumors and seizures, seizures were observed in more than 38 percent of patients with primary brain tumors and in 20 percent of patients with cerebral metastases. Oligodendrogliomas are more likely than other types of central nervous system tumors to be associated with seizures. Screening and diagnosis: The first step of brain tumor screening involves a neurological exam to test vision, hearing, balance, coordination, and reflexes. If the neurological exam results warrant further testing, the doctor may order brain imaging scans, such as computed tomography (CT) and magnetic resonance imaging (MRI) scans, which produce pictures of the brain in which tumors can be distinguished by means of dyes or magnetic fields. Com-
Symptoms: Symptoms of brain tumors include persistent headaches that become more intense and frequent, seizures, problems walking and speaking, vision problems
Incidence of Brain and Central Nervous System Cancer per 100,000 People, by Gender 10 Men
9
Women
8.3 8 7 6
5.9
5
6.0
4.7
4.9 3.9
4
3.5
3.5 3.0
3
2.2 2 1 0 White
Hispanic
Black
Asian/Pacific Islander
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
174
Salem Health: Cancer puted tomography is better at detecting bone calcification and skull lesions. Magnetic resonance imaging is better for detecting soft-tissue and spinal cord tumors. Other tests include an angiogram, in which a dye is injected into the blood to highlight the blood vessels in and around the brain, X-ray scans of the head and skull to reveal changes to skull bones and calcium deposits associated with brain tumors, and positron emission tomography (PET), which identifies areas of abnormal brain metabolism. The discovery of genetic mutations (changes in specific genes) that are linked to different types of cancers has opened the door to future genetic screening for at-risk individuals. A genetic screen involves taking a blood sample and analyzing the deoxyribonucleic acid (DNA) in the sample for genetic mutations that are known to cause a specific type of cancer. When a tumor is detected on a brain scan, a biopsy is usually performed to make a diagnosis. A biopsy involves taking a sample of the tumor; this can be done in a separate procedure or during surgery to remove the tumor. The tumor can be biopsied by open craniotomy, in which the cranium or skull is opened to expose the brain, allowing a sample of the tumor to be surgically removed. Hard-toreach tumors can be sampled by means of a needle biopsy. A small hole, known as the “burr” hole, is drilled in the cranium, and tumor cells are extracted with a narrow-bore needle. The tumor sample is frozen and cut into very thin slices, which are then examined under a microscope. This allows the medical team to confirm the presence of a tumor and determine the specific type of tumor. Additional tests may also be performed to help pinpoint the tumor type. There is no standard method for staging brain tumors. Along with the tumor grade, the type of cell from which the tumor originated and the location in the central nervous system are used for classifying the tumor. Grade I tumors grow slowly and rarely spread to other tissues. The following types of brain tumors are classified as Grade I: pilocytic astrocytomas, Grade I meningiomas, and Grade I ependymomas. Grade II tumors typically grow slowly but may spread to other tissues. Grade II tumors include diffuse astrocytomas, Grade II meningiomas, oligodendrogliomas, Grade II ependymomas, oligoastrocytomas (made up of a mixture of oligodendrogliomal and astrocytomal cells), pinealcytomas, and craniopharyngiomas. Grade III tumors contain fast-growing cells that often spread to other tissues. Grade III tumors include anaplastic astrocytomas, anaplastic oligodendrogliomas, anaplastic ependymomas, anaplastic oligoastrocytomas, and pinealoblastomas. Grade IV tumors grow rapidly, spread aggressively, and contain cells that appear very different from normal cells.
Brain and central nervous system cancers Grade IV tumors include gliobastomas and medulloblastomas, which usually occur in children and adults aged twenty-one to forty. Treatment and therapy: The most common treatment for brain and central nervous system cancers involves surgery to remove as much of the tumor as possible without disrupting neurological function. Surgery usually does not result in the removal of all tumor tissue. In addition, some tumors are located deep in the brain and cannot be reached without considerable damage to the surrounding tissue. These tumors are sometimes diagnosed without conducting a biopsy and treated by nonsurgical means. Radiation treatment and chemotherapy can be used to remove cancer cells remaining after surgery and to treat deep-seated tumors that are not amenable to surgical removal. Radiation therapy is effective for a wider range of brain and spinal cord tumors than chemotherapy. Radiation can enhance the cure rate and prolong disease-free survival. A common type of radiation treatment is external beam radiation therapy (EBRT). Chemotherapy has been shown to prolong disease-free survival in patients with gliomas, medulloblastomas, and some germ-cell tumors. Chemotherapy includes the use of dexamethasone, mannitol, furosemide, and nitrosourea. Anticonvulsants are also used to treat cancer patients with seizures. The majority of brain tumors are accompanied by multiple metastases. These can be treated with a combination of surgery or radiosurgery and whole-brain radiation therapy (WBRT). Radiosurgery is useful for lesions that have a diameter smaller than 3 centimeters. Corticosteroids and anticonvulsants can also be used as needed. Chemotherapy is not as widely used for metastatic brain tumors but may be effective for brain metastases from chemosensitive primary tumors. New therapies that are currently being tested include the use of tyrosine kinase receptor inhibitors, farnesyl transferase inhibitors, viral-based gene therapy, and oncolytic viruses. Patients with tumors that do not respond well to the commonly used treatments can look into clinical trials using combinations of novel therapies with EBRT. Surgery to remove brain tumors can sometimes result in the damage of normal brain tissue. This can cause partial paralysis, changes in sensation, muscle weakness, and defects in thinking and language function. These patients may be referred for physical and speech therapy to regain muscle and language functions, respectively. Follow-up visits are an important part of patient care and usually occur every three to four months for the first two to three years after treatment, then once or twice a year after that. The doctor will discuss treatment side effects, review 175
Brain scan medical history, and conduct various tests to determine if the cancer has recurred or metastasized to other parts of the body. Prognosis, prevention, and outcomes: A cancer patient’s prognosis depends on age (whether younger or older than sixty), the number and location of tumors in the brain and spinal cord, the rate of tumor growth and metastasis, and the tumor’s response to treatment. The prognosis is better for brain metastases from breast cancer and worse for brain metastases from colon cancer. When doctors discuss survival rates, they are referring to the percentage of people with a specific type and stage of cancer who survive for a predetermined period of time after their diagnosis. A common statistic is the five-year survival rate. Doctors may talk about the percentage of people who are alive, the percentage who are symptom-free, or the percentage who are disease-free five years after diagnosis. These numbers are averages for large groups of people and do not predict the specific outcome for an individual patient. Because the causes of brain and central nervous system cancers are not well established, prevention strategies are still evolving. As with other cancers, quitting smoking, maintaining a healthy diet, and exercising probably have beneficial and preventive effects. A novel therapy that has been approved in Switzerland under the brand name DCVax-Brain involves vaccination with dendritic cells that recognize molecules on an individual patient’s tumor cells. When examining outcomes for brain cancer survivors, it is important to also consider their quality of life. A survivor’s quality of life has been directly linked to cognitive impairment, especially defects in speech and language. Ing-Wei Khor, Ph.D. u
For Further Information Connelly, J. M., and M. G. Malkin. “Environmental Risk Factors for Brain Tumors.” Current Neurology and Neuroscience Reports 7 (2007): 208-214. Hutter, A., et al. “Brain Neoplasms: Epidemiology, Diagnosis, and Prospects for Cost-Effective Imaging.” Neuroimaging Clinics of North America 13 (2003): 237-250. Ricci, P. E. “Imaging of Adult Brain Tumors.” Neuroimaging Clinics of North America 9 (1999): 651-669. Wen, P. Y., P. M. Black, and J. S. Loeffler. “Treatment of Metastatic Cancer.” In Cancer: Principles and Practice of Oncology, edited by V. T. DeVita, Jr., S. Hellman, and S. A. Rosenberg. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001. 176
Salem Health: Cancer u
Other Resources
Cedars-Sinai Brain Tumors http://www.csmc.edu/5192.html MayoClinic.com Brain Tumor http://mayoclinic.com/health/brain-tumor/DS00281 National Cancer Institute Brain Tumor http://www.cancer.gov/cancertopics/types/brain Revolution Health Brain Cancer http://www.revolutionhealth.com/conditions/cancer/ brain-cancer/ WebMD http://www.webmd.com See also Acoustic neuromas; Astrocytomas; Ataxia telangiectasia (AT); Carcinomatous meningitis; Cell phones; Cognitive effects of cancer and chemotherapy; Craniotomy; Gliomas; Leptomeningeal carcinomas; Meningeal carcinomatosis; Meningiomas; Neuroblastomas; Neuroectodermal tumors; Neuroendocrine tumors; Neurofibromatosis type 1 (NF1); Neurologic oncology; Oligodendrogliomas; Orbit tumors; Pheochromocytomas; Primary central nervous system lymphomas; Schwannoma tumors; Spinal axis tumors; Spinal cord compression; Turcot syndrome; Von Hippel-Lindau (VHL) disease; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Brain scan Category: Procedures Definition: Computed tomography (CT) scan and magnetic resonance imaging (MRI) are two widely used methods of scanning the brain to distinguish normal tissue from abnormal tissue (tumors or masses). The CT scanner uses X rays and a type of ionizing radiation (dye), to acquire images of bone and tissue. MRI uses nonionizing radio frequency signals to acquire its images and is best suited for noncalcified (soft) tissue. Both CT and MRI scanners generate multiple two-dimensional cross-sections, or “slices,” of tissue and produce three-dimensional reconstructions. For purposes of tumor detection and identification, MRI is generally superior. However, CT usually is more widely available, faster, and much less expensive,
Salem Health: Cancer
Brain scan
This series of MRI images, from left to right, show a brain tumor shrinking after radiation therapy, but with development of metastatic brain disease (far right). The scans were taken at the beginning of treatment and at six and fifteen months. (Custom Medical Stock Photo)
and it may be less likely to require the person to be sedated or anesthetized. If cancer is suspected, then the CT scan will provide X-ray images of the brain or other internal organs to detect masses or tumors. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. Acomputer combines the images by “stacking” them on top of each other to offer an exact three-dimensional rendering. MRI is a procedure using a magnet and radio waves to send a series of detailed images of the brain to a computer. A computer then produces cross-sectional or threedimensional images for evaluation. A substance called gadolinium may be injected into the patient through a vein. The gadolinium collects around the cancer cells so that they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
sensation throughout the body and a metal taste in the mouth. Only the head will be covered by the scanner, and those who experience claustrophobia generally do not have problems with a brain scan. After the procedure: Patients are not restricted after this procedure and may eat and drive as normal.
Why performed: Brain scans are ordered by physicians to offer the clearest information available about the brain. The method of scanning depends on the patient’s history and examination and the choice by the physician for diagnostic testing.
Risks: The MRI examination poses almost no risk to the average patient; however, if sedation is necessary, a nurse or technologist will monitor vital signs to avoid excessive sedation. The magnetic field is not harmful to the patient, but metal devices nearby can create malfunction in the MRI. If dye is injected, then there is a rare risk of mild allergic reaction. The CT scan poses a slight risk of cancer as a result of the exposure to radiation. Studies have shown this risk is equivalent to the amount of radiation to which an average person is exposed in three years from other, unavoidable sources. There is a risk to an unborn fetus; therefore CT scanning is not recommended for pregnant women. Nursing mothers must wait twenty-four hours after the dye is injected to return to nursing. There is always a slight chance of cancer from radiation exposure, but the benefit of an accurate diagnosis far outweighs the risk.
Patient preparation: If the brain scan involves injecting or ingesting a dye, then the patient may be asked to avoid eating or drinking four hours before the exam. All jewelry must be removed prior to the brain scan.
Results: The brain scan will be read by a neuroradiologist, and the results will be shared with the physician to discuss with the patient. Robert J. Amato, D.O.
Cancers diagnosed: Brain tumor, metastasized cancer
Steps of the procedure: The patient will be asked to lay down, placing the head in a stabilizer, and remain very still. If contrast (dye) is required, then it will be injected through the intravenous (IV) line that was placed by a radiology nurse or technologist prior to the exam. During the injection, it is normal for patients to experience a warm
u
For Further Information Buthiau, Didier, and David Khayat. CT and MRI in Oncology. New York: Springer-Verlag, 1998. Lee, Howard S., et al. Cranial and Spinal MRI and CT. 4th ed. New York: McGraw-Hill Professional, 1999. 177
BRCA1 and BRCA2 genes Wolbarst, Anthony Brinton. Looking Within: How X-Ray, CT, MRI, Ultrasound, and Other Medical Images Are Created, and How They Help Physicians Save Lives. Berkeley: University of California Press, 1999. See also Astrocytomas; Brain and central nervous system cancers; Computed tomography (CT) scan.
u BRCA1 and BRCA2 genes Category: Cancer biology Also known as: Breast cancer susceptibility genes; breast cancer 1, early onset; breast cancer 2, early onset Definition: BRCA stands for breast cancer susceptibility. BRCA1, the first breast cancer susceptibility gene, was identified and cloned in 1994. A second breast cancer susceptibility gene, BRCA2, was discovered soon after. Identification of BRCA1 and BRCA2 as breast cancer susceptibility genes has had a profound impact on understanding the disease. The immediate clinical use of their discovery for both diagnosis and accurate assessment of increased risk through screening has been one of the foremost success stories in the fight against cancer. Familial disease: Less than 5 percent of breast cancers are hereditary, but more than 90 percent of hereditary breast cancers are caused by mutations in either BRCA1 or BRCA2. Each year approximately 200,000 women in the United States are diagnosed with breast cancer, and about 5 to 10 percent of these women have an inherited mutant BRCA1 or BRCA2 gene. The mutations can be inherited from either the maternal or the paternal side of the family. Mutations in BRCA1 and BRCA2 increase a woman’s lifetime risk of not only breast cancer but also ovarian, colon, and Fallopian tube cancers. Women with an inherited alteration in one of these genes have an increased risk of developing these cancers before the menopause. Altered BRCA2 poses a greater risk in men than altered BRCA1. Men with altered BRCA2 are at a higher risk of breast cancer and prostate cancer. Alterations in the BRCA2 gene have also been associated with increased risks of lymphoma, melanoma, and cancers of the pancreas, gallbladder, bile duct, and stomach in both men and women. Risks and incidence: Estimates of lifetime risks suggest that approximately 12.9 percent of women in the general population will develop breast cancer, as compared with estimates of 78 percent of women with an altered BRCA1 or BRCA2 gene. The ovarian cancer risk is 49.4 percent in carriers versus 1.7 percent in the general population. 178
Salem Health: Cancer Among men, the breast cancer risk is 5.8 percent for carriers versus 0.01 percent in the general population. In carriers, risks for colon, pancreatic, and stomach cancers are also elevated twofold, threefold, and fourfold, respectively, with no increase in prostate cancer risk. Additionally, in BRCA1 mutation carriers, the lifetime risk of developing cancer of the breast can be as high as 85 percent and that of developing ovarian cancer as much as 42 to 63 percent. In BRCA2 carriers, the lifetime risk of developing breast cancer is as high as 86 percent and that of developing ovarian cancer about 27 percent. The likelihood that breast or ovarian cancer is linked with BRCA1 or BRCA2 mutations is highest in families with a history of multiple cases of breast and ovarian cancer, particularly involving a mother, sister, or daughter; diagnosis of breast cancer before the age of thirty-five; presence of male breast cancer in the family; two or more primary cancers such as breast and ovarian cancers or bilateral breast cancer (separate cancers in each breast) in an individual; other multiple cancers in the family, especially prostate cancer; and an Ashkenazi (central and eastern European Jewish) background. It is important to note that not every woman with this sort of background will carry a defective BRCA1 or BRCA2, and not every cancer that occurs in such families will be due to a BRCA1 or BRCA2 defect. Additionally not all women who carry a BRCA1 or BRCA2 mutation will develop breast or ovarian cancer. Mutations in BRCA1 account for breast or ovarian cancers in 45 percent of families with a history of breast cancer and up to 90 percent in families with a history of both breast and ovarian cancers. BRCA2 mutations account for breast cancer in about 35 percent of families with a history of breast cancer. Studies suggest that women who develop breast cancer before the age of fifty have a one in four chance of carrying a BRCA1 or BRCA2 mutation if they have any relative who also develops the disease before the age of fifty. There is a 50 percent chance that mutant carriers will transmit the mutated gene to their offspring. BRCA1-related breast cancer appears to be more aggressive than other types of breast cancer and has a poorer prognosis, and most BRCA1-related ovarian cancers are of the invasive type. Some characteristics of hereditary breast cancer, such as how it occurs at an earlier age, more often affects both breasts, and is associated with other cancers, make it clinically distinct from sporadic cancer. BRCA1 and BRCA2 were identified by linkage analysis of families with multiple cases of early-onset breast and ovarian cancer. BRCA1 is 5,592 kilobases long with 24 exons, and BRCA2 is twice as long with 10,254 kilobases and 27 exons. More than one hundred different alterations scattered throughout BRCA1 and BRCA2 have been iden-
Salem Health: Cancer tified. These alterations tend to be distinct, and in general, most families have a unique alteration. Mutations anywhere along either gene are associated with an increased risk of breast cancer. Some evidence suggests that mutations in the 5′ end of BRCA1 and mutations in exon 11 of BRCA2 might be associated with ovarian cancer. Alterations in certain regions of the BRCA2 gene are known to predispose individuals to a greater risk of ovarian cancer in women and prostrate cancer in men, as compared with alterations in other parts of the gene. This suggests differences in patterns of cancer between individuals with a BRCA1 mutation versus a BRCA2 mutation. Of the more than one hundred alterations identified in each gene (BRCA1 and BRCA2), three alterations have been identified in Ashkenazi Jewish families with a history of breast cancer. These alterations are 185deIAG and 5382insC (BRCA1) and 6174deIT (BRCA2). The estimated frequencies of the three alterations in the general Ashkenazi population are 1.0 percent, 0.1 percent, and 1.4 percent, respectively. Cellular function: BRCA1 and BRCA2 are tumorsuppressor genes, and the BRCA proteins are involved in a multitude of key cellular processes. Research has demonstrated the involvement of BRCA1 and BRCA2 proteins in complexes that activate repair of double-strand breaks and initiate homologous recombination, suggesting a key role of BRCA proteins in maintaining genome stability and integrity. In response to deoxyribonucleic acid (DNA) damage, BRCA1 is engaged in the transcriptional regulation of several genes such as P21 (CDKN1A) and GADD45, which activate cell-cycle check-point induced replication arrest to allow for repair. It is unclear why a defect in BRCA predisposes predominantly to cancer of the breast and ovary, even though the known functions of BRCA proteins are essential to all cell types. Whether estrogen, a known promoter of sporadic breast cancer, affects the risk of BRCA1- and BRCA2-related breast cancers is not clear. Given that factors that contribute to enhanced exposure to estrogen, such as early onset of menarche and late menopause, correlate with a higher incidence of breast cancer and that premenopausal oophorectomy (the surgical removal of the ovaries) exerts a preventive effect, an association is suggested between BRCA1 and BRCA2 and estrogen receptor alpha (ERα). Prevention: The best opportunity to reduce mortality is through early detection. Preventive mastectomy and preventive oophorectomy to reduce the risk of breast cancer and ovarian cancer respectively are possible options. Although oophorectomies are usually performed to reduce ovarian cancer risk, having an oophorectomy before meno-
BRCA1 and BRCA2 genes pause also reduces the risk of breast cancer. Removal of ovaries is associated with a decrease in the production of the hormones estrogen and progesterone, which play a major role in breast cancer progression. For a premenopausal woman with a BRCA mutation, oophorectomy reduces the risk of breast cancer by about 50 percent, and it reduces the risk of ovarian cancer by 80 percent, irrespective of the menopausal status. However, it is important to note that prophylactic surgery reduces but does not eliminate the risk of cancer and carries additional risks related to surgery. Behaviors that can reduce breast cancer risk include regular exercising, decreased alcohol consumption, early childbirth, and breast-feeding for more than twelve months—although effects of these on BRCA mutation carriers are yet unknown. Even though tamoxifen is known to reduce the risk of invasive breast cancer by 49 percent in patients with an increased risk of developing the disease, limited data are available regarding the use of tamoxifen for chemoprevention in women with BRCA1 and BRCA2 alterations. Existing data suggest that use of tamoxifen reduces the risk of breast cancer in BRCA carriers and is recommended for chemoprevention. Banalata Sen, Ph.D. u
For Further Information Bishop, D. T. “BRCA1 and BRCA2 and Breast Cancer Incidence: A Review.” Annals of Oncology 10, suppl. 6 (1999): S113-S119. Venkitaraman, A. R. “Cancer Susceptibility and the Functions of BRCA1 and BRCA2: AReview.” Cell 108, no. 2 (2002): 171-182.
u
Other Resources
Genetics Home Reference http://ghr.nlm.nih.gov HUGO Gene Nomenclature Committee Symbol Report: BRCA1 http://www.genenames.org/data/ hgnc_data.php?hgnc_id=1100 National Cancer Institute Genetics of Breast and Ovarian Cancer http://www.cancer.gov/cancertopics/pdq/genetics/breastand-ovarian National Human Genome Research Institute http://www.genome.gov See also Ashkenazi Jews and cancer; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; 179
Breakthrough pain Carcinomatosis; Clinical breast exam (CBE); Ductal carcinoma in situ (DCIS); Estrogen-receptor-sensitive breast cancer; Family history and risk assessment; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Hormonal therapies; Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Molecular oncology; Mutagenesis and cancer; Oophorectomy; Ovarian cancers; Ovarian epithelial cancer; Pancreatic cancers; Risks for cancer; Salpingectomy and salpingo-oophorectomy; Tumor markers.
u Breakthrough pain Category: Diseases, symptoms, and conditions Also known as: Episodic or incident pain Related conditions: Breakthrough pain may be related to tumor progression or nerve compression as a result of cancer. It may also be a result of a treatment, including surgery, or a variety of painful disorders, such as arthritis. Definition: Breakthrough pain is a transient and intermittent flare of severe pain that “breaks through” analgesic medications. Risk factors: Anyone undergoing treatment for trauma, illness, and other painful conditions is at risk for breakthrough pain. Cancer patients—particularly those with advanced disease—are at high risk for breakthrough pain. Etiology and the disease process: Breakthrough pain generally is the result of whatever is causing a patient’s baseline persistent pain. Incidence: Approximately one-half to two-thirds of cancer patients and up to 86 percent of people taking painreducing medication for chronic pain experience breakthrough pain. The frequency of breakthrough pain varies among individuals; most patients with cancer-related pain have several episodes daily. Often, breakthrough pain flares up just before the patient is to take the next dose of pain medication; this is termed end-of-dose failure. Symptoms: The severity, duration, and cause of breakthrough cancer pain vary among patients. Typically, breakthrough pain happens fast. The average duration is approximately thirty minutes, but it may last from seconds to hours. Breakthrough pain is often unpredictable; it may occur spontaneously or it may be triggered by an activity, such as coughing or moving. It may manifest as an intensified or all-over dull sensation, or it may be a localized sharp pain. 180
Salem Health: Cancer Screening and diagnosis: There is no independently validated measurement available for the evaluation of breakthrough pain. Treatment and therapy: Breakthrough pain medications are generally short-acting and work rapidly to control sudden flares of pain. Breakthrough pain medications may be administered in several ways: orally, by injection, intravenously, under the tongue (sublingually), rectally, or transmucosally. Traditionally, opioid derivatives, such as morphine, administered intravenously, have been one of the fastest ways to alleviate breakthrough pain. A patientcontrolled analgesia device (PCA) allows for convenient intravenous administration of pain medication. One drug that specifically treats breakthrough pain is oral transmucosal fentanyl citrate. Fentanyl citrate dissolves rapidly (within five to ten minutes) via the mucous membranes. Cognitive techniques (including relaxation training, hypnosis, imagery, and distraction) and touch and music therapy may also help relieve breakthrough pain. Prognosis, prevention, and outcomes: Breakthrough pain medications are often called rescue medicines and are taken only at the time of an episode. It is important to take rescue medications at the earliest signs of breakthrough pain, as it is harder to control pain when it is allowed to build up. Anita Nagypál, Ph.D. See also Antinausea medications; Brief Pain Inventory (BPI); Pain management medications.
u Breast cancer in children and
adolescents Category: Diseases, symptoms, and conditions Also known as: Phyllodes tumors Related conditions: Adenocarcinoma Definition: Breast cancer is a malignant tumor that originates from breast cells. Most breast masses in children and adolescents are benign rather than cancerous in nature. One study noted fewer than fifty documented cases of breast cancer in girls between the ages of three and nineteen. Of these cases, juvenile secretory carcinoma was the most common and responsible for more than 80 percent of cases. The second most common form of breast cancer was intraductal carcinoma. Breast tumors called phyllodes tumors, although usually seen in women around forty-five years old, may occur
Salem Health: Cancer
Breast cancer in children and adolescents
Average Incidence of Breast Cancer, 1975-2000 Age Group 15-19 20-24 25-29
Incidence (per million people) 1.3 12.1 81.1
Source: Data from A. Bleyer, M. O’Leary, R. Barr, and L. A. G. Ries, eds., Cancer Epidemiology in Older Adolescents and Young Adults Fifteen to Twenty-Nine Years of Age, Including SEER Incidence and Survival: 1975-2000, NIH Pub. No. 06-5767 (Bethesda, Md.: National Cancer Institute, 2006)
in adolescents and have been reported in girls as young as ten years. These tumors may be benign, intermediate, or malignant. Another form of breast cancer in adolescents is primary breast carcinoma, which has been reported in girls between the ages of three and nineteen. However, in adolescents, most malignant breast masses are metastases from other cancers, such as Hodgkin disease, nonHodgkin lymphoma, primary hepatocellular carcinoma, neuroblastoma, and rhabdomyosarcoma. Risk factors: Risk factors for breast cancer in adolescents include having received chest-wall radiation and having a family history of breast cancer. If a child or adolescent receives radiation therapy to treat cancer of the chest area, the person’s risk for developing breast cancer later in life is significantly higher. The younger radiation was initiated, the higher the risk. This is especially the case when radiation is given to girls whose breasts are developing. Etiology and the disease process: Breast masses in children before and during puberty usually are breast buds. The development of breast buds in children is usually the first sign of puberty. The development of breast buds in children who are too young for puberty may indicate premature thelarche, or precocious puberty. Biopsy is warranted for cystic lesions that do not resolve with aspiration and for suspicious solid lesions. Some cancers start in glandular tissue that basically produces and secretes a substance. The ducts and lobules of the breast are glandular tissue, and the cancers starting in these areas are sometimes called adenocarcinomas. Incidence: Breast cancer in children and adolescents is rare. Generally, the lifetime probability of developing breast cancer is 1 in 6 overall, and 1 in 8 for invasive breast cancer. Globally, and in terms of all ages, breast cancer in-
cidence rates are highest in North America and northern Europe, and lowest in Asia and Africa. Symptoms: The most common finding with breast cancer in adolescents is a hard irregular mass and usually one that does not cause symptoms. As the cancer grows, symptoms may include a change of shape, size, and feel of the breast. Another symptom is bloody, yellow, or green, puslike drainage from the nipple. Advanced symptoms include bone or breast pain, swelling of the arm on the same side of the body as the breast with cancer, and weight loss. If metastasis occurs, other symptoms can include difficulty breathing, skin rash that is generalized, limb swelling, and back pain. Screening and diagnosis: Because a mass may not produce symptoms in the initial stages, all adolescents, especially girls with a family history of breast cancer or other malignancies, should have their breasts clinically examined regularly and should conduct monthly self-examination. Ultrasonography is the preferred imaging modality for breast masses in adolescents because of the increased density of the adolescent breast. Also the large amount of fibroglandular tissue makes mammography difficult to interpret. The accuracy of ultrasonography in differentiating solid from cystic lesions is 96 to 100 percent. Research suggests that an evaluation is warranted if no breast development occurs by the age of thirteen. The stage of breast cancer is based on tumor size; involvement of the skin, chest wall, or local lymph nodes; and whether the cancer has spread to other organs (metastasis). Stage I and Stage II are referred to as early stage or localized breast cancer. In Stage I the tumor size is less than 2 centimeters (cm) with no lymph node involvement. Stage II can exhibit lymph node involvement, but the nodes are small. The primary tumor size is larger than 2 cm but not larger than 5 cm. A tumor that is larger than 5 cm must be node-negative to be considered early stage. Stage III breast cancers are referred to as locally advanced breast cancer. In this stage, the tumors are large and greater than 5 cm across. There can be extensive axillary nodal involvement or nodal involvement of the soft tissues above or below the collarbone. A tumor is also designated Stage III if it extends to underlying muscles of the chest wall or the overlying skin. In Stage III, the breast may be undergoing the inflammatory process and appear red and swollen. Stage IV breast cancer, also known as metastatic breast cancer, consists of tumors that have spread to areas such as the brain, bones, skin, and even other organs. There may be any number of affected lymph nodes, and the primary tumor may be any size. 181
Breast cancer in men Treatment and therapy: The subsequent management of the adolescent with a breast mass depends on the type of mass. Surgical resection (excisional biopsy) may be necessary for cystic lesions that do not resolve with aspiration, when aspiration is not productive or not feasible, and for suspicious solid lesions. Although uncommon, more advanced forms of breast cancer have the potential to be treated similarly to the condition found in adults. Prognosis, prevention, and outcomes: The five-year survival rate refers to the number of patients who live at least five years after their cancer is found. According to the American Cancer Society (ACS), the five-year survival rates for persons with breast cancer that is appropriately treated are 100 percent for Stage I, 81 to 92 percent for Stage II, 54 to 67 percent for Stage III, and 20 percent for Stage IV. Jeffrey P. Larson, P.T., B.S., A.T.C. u For Further Information American Joint Committee on Cancer. AJCC Cancer Staging Manual. 5th ed. Philadelphia: Lippincott-Raven, 1997. Barry, Joanne. “Reaching Out to Educate.” Canadian Nurse 103, no. 8 (October, 2007): 34-35. Mandrell, B. N. “Secondary Breast Cancer in a Woman Treated for Hodgkin Lymphoma as a Child.” Oncology 21 (October, 2007): 27-29. Twombly, R. “Childhood Cancer Survivor Study Doubles to Examine Late Effects of New Treatments.” Journal of the National Cancer Institute 99, no. 21 (November 7, 2007): 1574-1576. u
Other Resources
National Cancer Institute Breast Cancer http://www.cancer.gov/cancertopics/types/breast UpToDate Overview of Breast Masses in Children and Adolescents http://patients.uptodate.com/topic.asp?file=adol_med/ 11491 See also Adenocarcinomas; Breast cancers; Breast selfexamination (BSE); Calcifications of the breast; Childhood cancers; Clinical breast exam (CBE); Cutaneous breast cancer; Phyllodes tumors; Young adult cancers.
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u Breast cancer in men Category: Diseases, symptoms, and conditions Also known as: Infiltrating or invasive ductal carcinoma, ductal carcinoma in situ, inflammatory breast cancer, Paget disease of the nipple Related conditions: Gynecomastia, fibroadenomas, papillomas Definition: Breast cancer occurs in men when malignant (cancerous) cells develop in the breast tissue of the male breast. The cancer can then spread into other tissues. Risk factors: Advanced age is a risk factor for men, just as it is for women. The median age of diagnosis for male breast cancer is sixty-eight. Men who have a close female relative with breast cancer are at risk and may be evaluated for the presence of a mutation in the BRCA2 gene. This mutation is responsible for 15 percent of breast cancers in men, and men with the mutation have a 6 percent lifetime risk for breast cancer. Other risks include radiation exposure (which may be occupational but is more often a result of treatment of other cancers) and liver disease, such as cirrhosis, which causes an increase in estrogen and a decrease in androgen hormones. Obesity and cigarette smoking may also play a role as risk factors. Many male breast cancers are estrogen-receptor-positive, which means that estrogen will increase the risk of development or accelerated growth of the cancer. Estrogen is given to some men to slow the growth of prostate cancer and is used by some men who are undergoing gender transformation. One risk specific to men for the development of breast cancer is Klinefelter syndrome, a genetic mutation involving at least one extra X chromosome, a condition that affects 1 in 850 men. These men have higher levels of estrogen and lower levels of androgens and therefore are at particular increased risk. Etiology and the disease process: There are a number of risk factors for male breast cancer, but none of the known causes can be eliminated. Most male breast cancers are invasive, infiltrating ductal carcinomas and are far more treatable in early localized stages. Therefore, efforts should be concentrated on early identification and treatment by increasing awareness of risk factors, heightening surveillance of those with nonmodifiable risks, and attempting to change those risks that can be modified. Incidence: Both men and women have breast tissue, and breast cancer occurs in men but is much rarer in men than in women, comprising only 1 percent of all cancers in men.
Salem Health: Cancer
Breast cancer in men
Stage at Diagnosis and Five-Year Relative Survival Rates for Invasive Male Breast Cancer, 1988-2001 Stage
Survival Rate (%) a
Localized Regionalb Distantc Unstaged
96.9 78.1 23.0 64.2
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
The American Cancer Society states that in the United States in 2005 more than 1,500 cases of male breast cancer were diagnosed and almost 500 deaths occurred. Symptoms: Symptoms of breast cancer in men include breast lumps as well as nipple and skin changes. The cancer is most often diagnosed when a man goes to his doctor after finding a mass below the nipple in one breast. Nipple changes can include redness or patchy scaling of the skin, nipple retraction (pulling inward), and nipple discharge. Skin changes may include puckering and dimpling as well as redness and scaling; however, chest hair may obscure subtle skin changes, and men are not accustomed to examining their breasts in a way that would help them find early lumps. Even when men find early symptoms, they may be misinformed about male breast cancer or embarrassed and delay seeking medical care. Screening and diagnosis: Providing information that male breast cancer does occur and describing early symptoms may be the best screening tools to offer. Screening for male breast cancer is not common among primary care providers, but if a lump is detected or brought to the provider’s attention by the patient, the first step is a mammography done with spot compression or magnification and possibly ultrasound, followed by a biopsy. A biopsy is the only definitive way to diagnose breast cancer. Staging assesses the size, location, lymph node involvement, and degree of metastasis of the cancer, ranging from Stage 0, which is the earliest stage, to Stage IV, which is the most advanced.
Treatment and therapy: Treatment usually involves surgery to remove the breast tissue and often lymph nodes and some of the chest muscles as well. Sentinel lymph node biopsy can be used to attempt to avoid more radical removal of lymph nodes. Radiation therapy and chemotherapy may be employed. If the cancer is determined to be estrogen-receptorpositive, the antiestrogen drug tamoxifen can be used to slow the growth and reproduction of cells that require estrogen. Another drug used in treatment is megace, an antiandrogen drug that blocks the effects of androgen in the breast. Prognosis, prevention, and outcomes: Prognosis is similar for male and female breast cancer when cancers of the same stage are compared; however, male breast cancer often is not discovered as early as is female breast cancer. Early detection is especially important because men have less breast tissue than women, and therefore their cancers can more easily reach and invade the chest muscles. Age at diagnosis and general health influence outcomes. With advanced medical care, five-year survival rates now vary from close to 100 percent for cancers caught in Stage 0 to 25 percent for cancers that have progressed to Stage IV. Prevention efforts center on screening for risk factors that may heighten surveillance for disease and on patient education about early self-detection of changes in the male breast. Outcome also depends on prevention of recurrence, and increased screening as well as adjuvant chemotherapy may improve long term outcomes. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP) u
For Further Information Berek, J. S., and N. F. Hacker. Practical Gynecologic Oncology. Philadelphia: Lippincott Williams & Wilkins, 2005. DeVita, V. T., S. Hellman, and S. A. Rosenberg. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Estala, E. M. “Proposed Screening Recommendations for Male Breast Cancer.” The Nurse Practitioner 31, no. 2 (2006): 62-63.
u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Male Breast Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ malebreast/ 183
Breast cancer in pregnant women See also Breast cancers; Breast self-examination (BSE); Clinical breast exam (CBE); Cutaneous breast cancer; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas.
u Breast cancer in pregnant
women Category: Diseases, symptoms, and conditions Also known as: Gestational breast cancer, lactational breast cancer, postpartum breast cancer
Salem Health: Cancer forty-four; of these women, only 10 percent will be pregnant at the time of diagnosis. Based on several analyses, the actual incidence of breast cancer during pregnancy has been estimated to fall between 1/3000 and 1/10,000 of all pregnant women. Breast cancer during pregnancy is second only to cervical cancer as the most common malignancy occurring during pregnancy. Of concern is that the incidence will most likely increase as women delay childbearing. In fact, women who have their first term pregnancy after the age of thirty have a twofold to threefold increased risk of breast cancer compared with women who have their first term pregnancy before the age of twenty.
Related conditions: Lactating adenoma, fibroadenoma, cystic disease, lobular hyperplasia, milk retention cyst (galactocele), abscess, lipoma, hamartoma, leukemia, lymphoma, sarcoma, neuroma, tuberculosis
Symptoms: Most often, women with breast cancer during pregnancy complain of a painless mass in the breast or a nipple discharge; a bloody nipple discharge is particularly concerning.
Definition: Gestational breast cancer is defined as breast cancer that occurs during pregnancy or up to one year thereafter.
Screening and diagnosis: All pregnant women should undergo a complete physical examination at the time they register for prenatal care, including a thorough breast examination. All new breast masses or nipple discharges should be evaluated promptly and not delayed until the pregnancy has been completed. The mean age at diagnosis of breast cancer during pregnancy is thirty-two to thirtyfour years. In most cases, the disease is advanced at the time of diagnosis. In general, the number of positive lymph nodes is greater, the tumors are larger, the steroid hormone status is more often negative, the number of cells synthesizing deoxyribonucleic acid (DNA) is greater, the number of mutations involving BRCA1 and BRCA2 is greater, and the tumor suppressor p53 is more often downregulated. Although the usefulness of mammography has been questioned in women less than thirty-five years of age because of higher breast density, mammography during pregnancy (in which breast density is increased) has been shown to be 90 percent sensitive in detecting malignancies. The irradiation exposure to the fetus is negligible and should not be a deterrent. Ultrasound, which carries no fetal irradiation risk, has been shown to be 100 percent sensitive in detecting a malignancy when the breast mass is palpable. The diagnosis rests, however, with pathologic confirmation, which can be obtained with a fine needle biopsy, a core needle biopsy, or an excisional biopsy. Staging is performed to determine if metastasis has occurred.
Risk factors: It is generally believed that breast cancer is years in the making; thus, pregnancy itself can be an aggravating risk factor for breast cancer because the physiologic changes that occur in the breast during pregnancy may mask an occult or nonpalpable mass. Further, there is often denial on the part of the physician or patient that breast cancer can occur during pregnancy, further aggravating the underlying risk. Moreover, the elevated levels of estrogen (hundredfold increase) and progesterone (thousandfold increase) during pregnancy may also stimulate cancer growth. Other traditional risk factors for breast cancer include a history of benign breast disease, menarche (onset of menstrual activity) before the age of twelve, drinking three or more alcohol-containing drinks daily, increased bone density, a sedentary lifestyle, nulliparity (no previous live births), first birth after the age of thirty, a firstdegree relative (mother or sister) with breast cancer, upper socioeconomic status, a history of endometrial or ovarian cancer, chest irradiation, increased breast density, a history of breast cancer, dietary fat intake (especially saturated fat), and obesity. Etiology and the disease process: Like all cancers, breast cancer arises when an oncogene (cancer-causing gene) is activated or the tumor-suppressor gene controlling the oncogene is silenced. Regardless of the precipitating risk factor, breast cancer appears to reflect the cumulative exposure to estrogen and progesterone. Incidence: Of all women diagnosed with breast cancer, only 12.7 percent will be between the ages of twenty and 184
Treatment and therapy: The management of breast cancer during pregnancy has the same goal as in patients who are not pregnant. Termination of pregnancy is not indicated. Surgery is generally delayed until the second trimester, and for nonmetastatic diseases, a modified radical
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Breast cancers
mastectomy is considered the standard conservative procedure. Similarly, even though all chemotherapeutic agents are category D (teratogenic), they have accumulated a favorable safety profile when used in the second and third trimesters. Fetal malformations range from 19 percent in the first trimester to 1.3 percent in the second and third trimesters based on nearly 100 pregnant women treated with 5-fluorouracil, doxorubicin, and cyclophosphamide (a standard chemotherapeutic regimen).
u Breast cancers
Prognosis, prevention, and outcomes: Women who are diagnosed with breast cancer during pregnancy are often diagnosed at a later stage, because breast changes during pregnancy, including increased breast size and changes in breast texture, make small, early-stage tumors harder to detect and diagnose. Roughly half of new cases are found in a late stage (III or IV), as compared with just over a quarter of cases that are diagnosed at Stage I and another quarter or so at Stage II. The five-year survival rate for women with negative lymph nodes is 82 percent; however, lymph node metastasis occurs in 65 percent of women with breast cancer during pregnancy. The overall survival for breast cancer during pregnancy is 70 percent. D. Scott Cunningham, M.D., Ph.D.
Definition: Breast cancer is the occurrence of a malignant tumor in the breast tissue. The most commonly diagnosed breast tumors are ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). When discovered early, these tumors are easily treated. However, if gone undetected, the tumors can eventually metastasize, meaning that some of the cancer cells detach from the tumor and spread throughout the body, acting as “seeds” to trigger the further development of malignancy in distant body parts. Once metastatic breast cancer (MBC) forms, the cancer becomes much more difficult to treat.
u For Further Information Barnes, D. M., and L. A. Newman. “Pregnancy-Associated Breast Cancer: A Literature Review.” Surgical Clinics of North America 87 (2007): 417-430. Leslie, K. K., and C. A. Lange. “Breast Cancer and Pregnancy.” Obstetrics & Gynecology Clinics of North America 32 (2005): 547-558. u
Other Resources
National Breast Cancer Foundation http://www.nationalbreastcancer.org/about-breastcancer/ National Cancer Institute http://www.cancer.gov Susan G. Komen for the Cure http://cms.komen.org/komen/AboutBreastCancer/ index.htm See also Adenocarcinomas; Breast cancers; Breast selfexamination (BSE); Calcifications of the breast; Childbirth and cancer; Clinical breast exam (CBE); Cutaneous breast cancer; Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Ductogram; Estrogen-receptorsensitive breast cancer; Pregnancy and cancer.
Category: Diseases, symptoms, and conditions Also known as: Metastatic breast cancer (MBC), ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) Related conditions: Intraductal papillomas, noncancerous adenomas (growths) of the breast tissue, cysts
Risk factors: Some risk factors have been established as very important for determining patients who would benefit from more careful preventative care and observation. However, the presence of one or more risk factors does not necessarily mean that the patient will actually develop a breast tumor. Conversely, up to 70 percent of women who develop breast cancer did not have any known risk factors before diagnosis. Women who previously had a breast tumor in one breast have a significantly increased risk of developing cancer in the other breast. The cancer in the second breast is considered unrelated and not a recurrence of the cancer in the first breast. Several factors are considered to moderately increase the risk of breast cancer in some women. As women age, they develop an increasing risk of developing breast cancer. For example, women between the ages of forty and forty-nine have a 1 in 68 risk of developing breast cancer; this risk nearly doubles to 1 in 37 for women between the ages of fifty and fifty-nine. Nearly half of women diagnosed with breast cancer are over sixty-five and postmenopausal. Mutations in two key genes, BRCA1 and BRCA2, have also been associated with an increased risk of developing breast cancer. These genes are considered tumor suppressors, and mutations can lead to their dysfunction. These mutations seem to be inherited, and having a direct family relative with breast cancer also increases the risk of developing breast cancer. This is most true for first-degree relatives, such as a mother, sister, or daughter. One first-degree relative with breast cancer can nearly double the risk for an individual to develop breast 185
Breast cancers cancer; two first-degree relatives with breast cancer causes the individual to be up to five times as likely to develop breast cancer. Other factors have been shown to only slightly increase the risk of developing breast cancer. These include obesity and increased alcohol intake. Further, women who began to menstruate early (prior to age twelve), who enter into menopause late (after age fifty-five), or who never have children have a small increase in the chance of developing breast cancer. This is thought to be due to the increased exposure these women have to estrogen, a hormone that can increase breast cancer development. Etiology and the disease process: One of the most commonly accepted models of breast cancer formation stems from the development of genetic aberrations in breast cells. Activated mutations in oncogenes, genes responsible for the growth and proliferation of cells, and inhibitory mutations in tumor-suppressor genes that negatively regulate cell growth play an instrumental role in cellular trans-
Salem Health: Cancer formation. Cell transformation is the process by which a normal cell changes into a tumorigenic cell, capable of growing into a malignant mass. A breast tumor begins when one or more tumorigenic cells form within the epithelial layer, the internal tissue lining of the breast. As the tumor grows, it spreads past the epithelium, invading into the deeper tissues of the breast. If left untreated, the breast tumor will eventually metastasize, as the tumor cells break away from the primary tumor and are dispersed throughout the body via the circulatory system. Breast cancers are primarily differentiated as hormonereceptor-positive or -negative. These receptors are the estrogen receptor (ER), progesterone receptor (PR), or both. The distinctions among these tumors are critical, as they are a major determinant in choosing the proper therapy. Both hormone receptors have a similar action: After either hormone binds to its respective receptor inside the cell, it subsequently transports into the nucleus, where it plays a major role in regulating gene expression. Incidence: Breast cancer is one of the most frequently diagnosed cancers in women in the United States, with an estimated more than 175,000 new cases per year. Breast cancer development seems to be affected by race, with a higher incidence occurring in white and African American women compared with Hispanic, American Indian, and Asian American women. Breast cancer is second only to lung cancer in inducing cancer-related deaths in women, but it is the primary cause of cancer-related mortality in younger women, ages twenty to fifty-nine. Since the early 1990’s, the incidence of breast cancer-related deaths has steadily decreased, a reduction most dramatically seen in younger white and African American women. The cause of this reduction is attributed to both improved anticancer therapy and earlier diagnostic abilities. The risk of a woman developing breast cancer at some point in her lifetime is nearly 1 in 8, or 13 percent. Although breast cancer most often occurs in women, it can rarely occur in men. Symptoms: Early breast cancer is usually free of symptoms. The first sign of breast cancer is most often a persistent lump in the breast. As the tumor develops, the individual may begin to experience other symptoms, including swelling of the armpit or breast and thickening of the breast tissue. Patients may also notice slight pain or tenderness in the breast. Changes in how the nipple looks is also frequently observed with breast cancer.
A mammogram showing a breast tumor. (©Visuals Unlimited/ Corbis)
186
Screening and diagnosis: Aclinical breast exam is a common method to detect lumps or abnormal changes in the breast tissue. If a lump is detected, the clinician will assess the characteristics of the lump. Lumps that are soft,
Salem Health: Cancer smooth, and round and move about easily are more likely to be benign, compared to hard, nonsymmetrical lumps that are tightly attached to the breast tissue, which are more likely to be cancerous. It is also recommended that women perform monthly breast self-examinations at home to detect changes between checkups. Subtle changes that may not register as a lump by touch can often be detected by mammograms, X-ray images taken of the breast. Further, many clinicians use mammograms to provide a more detailed look at lumps identified during an examination. Ultrasound and magnetic resonance imaging (MRI) can be used to directly image breast abnormalities. If a clinician feels that a certain breast abnormality warrants further investigation, a biopsy is performed to remove tissue that a pathologist can use to determine if any cancer is present. At the time of first diagnosis, most patients are diagnosed either with early, localized breast cancer or regional breast cancer. Only a small minority of patients receive a primary diagnosis of metastatic breast cancer (MBC). Recurrent breast cancer is a malignancy that has returned after previously being treated to the point of not being detected. Recurrence may occur locally in or near the breast or in distant parts of the body, such as the bone, liver, or lungs. Once a diagnosis is made, the stage of the breast cancer is determined. This is necessary for the physician to determine the extent of the disease and to prescribe the appropriate treatment. Stage 0 is described as in situ carcinoma. In situ carcinoma is noninvasive, meaning the cancer cells have not begun to spread beyond the epithelium, or tissue surface. The most common breast cancer of this stage is ductal carcinoma in situ (DCIS), in which cancerous cells develop within the milk ducts. Stage I is the earliest form of invasive breast cancer. At this point, the tumor is smaller than 2 centimeters (cm) in diameter and is confined to the breast. In Stage II, the tumor is either between 2 and 5 cm and has spread to the lymph nodes under the arm or is larger than 5 cm but has not spread outside the breast. Stage III is characterized by larger tumors that may have spread to lymph nodes and areas beyond the underarm, such as behind the breastbone or near the collarbone. Stage IV is the most advanced stage. At this point, the cancer is classified as distant metastatic cancer. Treatment and therapy: The main goals of breast cancer therapy are to eradicate the tumor and prevent its recurrence. Treatments can be categorized as either local or systemic, and the use of either or both is determined by the extent and stage of disease. Local therapies include surgery and radiation therapy. Surgery can be either minimal, such as a lumpectomy in which only the lump is removed, or
Breast cancers
Stage at Diagnosis and Five-Year Relative Survival Rates for Women with Breast Cancer, 1996-2004 Women Diagnosed (%)
Stage a
Localized Regionalb Distantc Unstaged
61 31 6 2
Survival Rate (%) 98.0 83.5 26.7 56.9
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
more drastic, such as a mastectomy in which the majority of the breast is removed. If the breast cancer has spread to local lymph nodes, these also may be removed at the time of surgery. Surgery is often used in conjunction with other therapies, including radiation therapy and systemic drug therapy. Once the breast cancer has metastasized and become MBC, surgery is not a viable therapeutic option. For MBC, systemic therapy is generally the standard treatment and consists of three main categories: chemotherapy, endocrine therapy, and biological therapy. The most effective chemotherapeutic agents for breast cancer are taxanes and anthracyclines, although other drug classes can be used. Despite the benefit these drugs can offer in lengthening patient survival, the accompanying toxic side effects can dramatically decrease the patient’s quality of life. Endocrine therapy is the standard of care for hormone-receptor-positive breast cancer. The most common type of endocrine therapy is the selective estrogen receptor modulator (SERM) tamoxifen, which can reduce the proliferative effect that estrogens have in the breast tumor cells. Although tamoxifen is generally tolerated better than chemotherapies, there is a high risk for developing resistance, after which the drug loses its benefit. The newest addition to the breast cancer therapy arsenal is targeted biological therapy. The prototypical example of this in breast cancer is trastuzumab, an antibody that recognizes and inhibits the human epidermal growth factor receptor (HER2) present on the surface of the breast cancer cell. HER2 is an effective breast cancer target because it is often overactivated in breast cancer, increasing the proliferative signaling downstream of its activation. 187
Breast implants Prognosis, prevention, and outcomes: The improvement of screening and diagnostic techniques has been instrumental in increasing the discovery of breast cancer early in development, when it is most easily treated. Additionally, the development of novel drugs and therapies has caused a significant increase in extending survival of breast cancer patients. Clinicians measure disease outcome by measuring survival rates; a disease-free survival of at least five years is generally considered to be a cure. Currently, the five-year survival rate for patients diagnosed with local breast cancer that has not spread beyond the breast is 98 percent. This survival rate is lowered to 83.5 percent in patients with regional metastasis. Patients with Stage IV metastatic breast cancer have a five-year survival rate of only 26.7 percent. Much effort has gone into determining methods of preventing breast cancer. Because many breast tumors depend on estrogen for growth and survival, decreasing unnecessary estrogen exposure may help prevent breast cancer. Some women with an especially high risk of breast cancer may elect to have an oophorectomy, surgery to remove both ovaries, the primary source of estrogen in premenopausal women. Additionally, regular exercise may reduce the amount of estrogen naturally produced by the body, decreasing the amount of estrogen to which the breast is exposed. An extreme preventative measure in women with a high risk for developing breast cancer is prophylactic mastectomy, a surgical procedure to remove the breast before any signs of cancer. Lisa M. Cockrell, B.S. u For Further Information Bowcock, Anne M, ed. Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics. Totowa, N.J.: Humana Press, 1999. Craig, Jordan V., and Barrington J. A. Furr, eds. Hormone Therapy in Breast and Prostate Cancer. Totowa, N.J.: Humana Press, 1999. Grobstein, Ruth H. The Breast Cancer Book: What You Need to Know to Make Informed Decisions. New Haven, Conn.: Yale University Press, 2005. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: B. C. Decker, 2006. Manni, Andrea, ed. Endocrinology of Breast Cancer. Totowa, N.J.: Humana Press, 1999. u
Other Resources
American Cancer Society http://www.cancer.org National Breast Cancer Foundation http://www.nationalbreastcancer.org 188
Salem Health: Cancer National Cancer Institute Breast Cancer http://www.cancer.gov/cancertopics/types/breast Susan G. Komen for the Cure http://www.komen.org See also Accelerated partial breast irradiation (APBI); Adenocarcinomas; Aging and cancer; Antiestrogens; Antiperspirants and breast cancer; Birth control pills and cancer; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast implants; Breast reconstruction; Breast ultrasound; Calcifications of the breast; Childbirth and cancer; Clinical breast exam (CBE); Cutaneous breast cancer; Diethylstilbestrol (DES); Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Ductogram; Estrogen-receptorsensitive breast cancer; Fertility drugs and cancer; Fibroadenomas; Fibrocystic breast changes; Genetic counseling; Genetic testing; Hormone receptor tests; Hormone replacement therapy (HRT); Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Lumpectomy; Lumps; Lymphadenectomy; Lymphangiography; Lymphangiosarcomas; Lymphedema; Mammography; Mastectomy; Medullary carcinoma of the breast; Metastasis; Microcalcifications; Needle localization; Obesity-associated cancers; Phyllodes tumors; Pregnancy and cancer; Premalignancies; Progesterone receptor assay; Tubular carcinomas; Wire localization.
u Breast implants Category: Procedures Also known as: Autologous breast implants, saline breast implants, saline-filled breast implants, silicone breast implants, silicone-filled breast implants Definition: Breast implants are used to reconstruct the natural appearance of one or both breasts following mastectomy for breast cancer. Breast implants may be composed of the patient’s own tissue taken from elsewhere on the body (autologous breast implants) or made of artificial substances (saline or silicone breast implants). Cancers treated: Breast cancer Why performed: Breast reconstruction is a choice for women following mastectomy. Mastectomy involves surgically removing one or both breasts for the treatment of breast cancer. Breast implants are used to replace breasts that have been removed, to create a symmetrical appear-
Salem Health: Cancer
Breast implants
Reconstructed breast Chest wall after mastectomy
Implant
Reconstruction of a breast following a total mastectomy. (©Visuals Unlimited/Corbis)
ance if only one breast was removed, or to replace the one breast that was removed and enhance the appearance of the remaining breast to improve symmetry. Breast implants are an option to wearing breast prosthetics (removable breast forms). Patient preparation: Breast implants come in a variety of shapes, sizes, and compositions. The plastic surgeon guides the patient in the selection process. Tissue expanders may or may not be used to stretch the skin in preparation for breast implant placement. In some cases, the tissue expander may be filled with saline and remain in the body, serving as the breast implant. There are two basic types of artificial implants, saline breast implants and silicone breast implants. Saline breast implants have a silicone outer shell and are filled with saline, a saltwater solution. Saline implants may be prefilled by the manufacturer or filled at the time of surgery and adjusted after surgery. Silicone breast implants have a silicone outer shell and are filled with silicone, a natural substance. Silicone breast implants may be prefilled with silicone by the manufacturer and nonadjustable, prefilled with silicone and allow
for saline insertion at the time of surgery, or prefilled with silicone and allow for saline insertion at the time of surgery and postsurgical adjustments. Saline implants were approved for use in the United States by the Food and Drug Administration (FDA) in 2000. Silicone implants were approved by the FDA in 2006. Both types of implants are not meant to last a lifetime, may need to be replaced, and have a risk of rupture. Saline implants are advantageous in that ruptures are readily identified because the breast size decreases and the saline solution is absorbed by the body. The size of saline implants can be adjusted easily. Some people believe, however, that saline implants do not look or feel as natural as silicone implants. Silicone implants have a texture similar to natural breast tissue. While silicone breast implants may look and feel more natural than saline implants, ruptures may not be as easily noticed with silicone breast implants. Following a rupture, the silicone remains near the implant and is not absorbed by the body. Autologous implants are made of tissue or a tissue flap that is taken from the patient, commonly the abdomen and buttocks. The tissue may contain fat, muscles, blood ves189
Breast reconstruction sels, and nerves. Autologous implants are a more specialized procedure involving microsurgery and take longer to heal, but they do not have the risk of rupture and do not need to be replaced over time. Some people believe that autologous implants produce the most natural results. Steps of the procedure: Breast implants may be inserted at the time of the mastectomy or at a later time in another surgery. Patients receiving radiation therapy following mastectomy may need to delay breast reconstruction. Breast implant procedures do not delay chemotherapy. Breast reconstruction surgery is performed with general anesthesia. Nipple reconstruction may take place following a breast implant procedure. After the procedure: Patients may spend one to six days in the hospital, depending on the procedure. Patients wear bandages and support garments while healing. Activities may be temporarily restricted, but most activities can be resumed in six to eight weeks. Artificial implants typically need to be replaced in time. Breast implants should not affect breastfeeding. Special mammography procedures may be needed, however. Breast implants only rarely obscure the detection of new cancer formation. Risks: The risks of artificial breast implants include rupture, leakage, rippling, infection, and capsular contraction (in which scar tissue surrounding the implants shrinks or hardens). Other risks include the general risks associated with surgery and anesthesia. Results: The optimal result is symmetrical, naturalappearing breasts. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Poeppl, N., et al. “Does the Surface Structure of Implants Have an Impact on the Formation of a Capsular Contracture?” Aesthetic Plastic Surgery 31, no. 2 (March/April, 2007): 133-139. “Silicone Gel-Filled Breast Implants Approved.” FDA Consumer 41, no. 1 (January/February, 2007). Stevens, W. G., et al. “A Comparison of Five Hundred Prefilled Textured Saline Breast Implants Versus Five Hundred Standard Textured Saline Breast Implants: Is There a Difference in Deflation Rates?” Plastic and Reconstruction Surgery 117, no. 7 (June, 2006): 21752181. Vázquez, G., and A. Pellón. “Polyurethane-Coated Silicone Gel Breast Implants Used for Eighteen Years.” Aesthetic Plastic Surgery 31, no. 4 (July/August, 2007): 330-336. 190
Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org American Society of Plastic Surgeons http://www.plasticsurgery.org Breast Implant Safety.org http://www.breastimplantsafety.org See also Breast cancers; Breast reconstruction; Mastectomy; Self-image and body image; Sexuality and cancer.
u Breast reconstruction Category: Procedures Also known as: Breast implants; deep inferior epigastric perforator (DIEP) flap; free flap; gluteal flap; latissimus dorsi flap; pedicle flap; saline breast implants; silicone breast implants; transverse rectus abdominis muscle (TRAM) flap Definition: Breast reconstruction is a complex procedure performed by a plastic surgeon that restores the appearance of a breast after mastectomy to treat breast cancer. Cancers treated: Breast cancer Why performed: Breast reconstruction is performed to reconstruct the size and shape of the breast in a patient who has had a mastectomy. Most women who have had a mastectomy can have breast reconstruction, which may be done either at the time of mastectomy or at a later date. Breast reconstruction may improve the self-esteem and body image of a woman who has had a mastectomy. Patient preparation: A patient facing a mastectomy who is interested in breast reconstruction probably will be advised to consult with a plastic surgeon experienced in breast reconstruction prior to the mastectomy. Ideally, the breast surgeon and the plastic surgeon work together to develop the best surgical and breast reconstruction strategy for each patient, even if the reconstructive surgery will be done later. Two or more operations probably will be needed to achieve a satisfactory result. A patient will be given specific instructions prior to surgery. Since smoking can decrease a patient’s blood circulation, which is critical to the survival of transplanted tissue, a patient who is a smoker will be given instructions and tips to quit smoking prior to reconstruction procedures that involve the use of transplanted tissue. Steps of the procedure: There are two basic types of breast reconstruction, implant procedures and tissue flap
Salem Health: Cancer procedures. A combination of these procedures may also be used. Either type of procedure may be begun either at the same time as the mastectomy (immediate reconstruction) or at a later time (delayed reconstruction). Saline-filled implants are the most common type of implant used and consist of external silicone shells filled with sterile saline. The use of silicone gel-filled implants has decreased because of concerns of possible health risks if silicone leaks from the implant, although recent research has not found any health dangers associated with their use. Sometimes a one-stage procedure is possible, where the implant is placed behind the pectoral muscle in the chest in the first surgery. For most patients, a two-stage procedure is used in which a tissue expander, like a balloon, is implanted beneath the skin and chest muscle. Over a period of several months, the surgeon injects a saline solution at regular intervals to fill the expander and stretch the chest pocket. At the appropriate time, the expander is removed in a second operation and the permanent implant is put into place. Tissue flap procedures involve autologous tissue reconstruction and are the more surgically complex option
Breast reconstruction for breast reconstruction. Tissue from the abdomen or back (more commonly), or buttocks or thighs (less commonly), is used. Two types of methods, pedicle flap and free flap, are in use. In a pedicle flap procedure, some of the blood vessels feeding the tissue to be transferred are cut and some are kept intact. The tissue is tunneled beneath the skin to the chest area, where a new breast mound or pocket for an implant is created. In a free flap procedure, the flap of skin, fat, blood vessels, and muscle tissue is disconnected from its blood supply completely and removed from its original location, and intricate microsurgical techniques are used to reattach the tissue flap to new blood vessels near the chest. This procedure typically takes longer to complete than a pedicle flap procedure. Four main tissue flap procedures are performed: the TRAM (transverse rectus abdominis muscle) flap, the DIEP (deep inferior epigastric perforator) flap, the latissimus dorsi flap, and the gluteal flap. The TRAM flap procedure uses tissue and muscle from the lower abdominal wall, which may be transferred as a free flap or a pedicle flap. This procedure also results in a tightening of the lower abdomen, or a “tummy tuck.” Vari-
A transverse rectus abdominis muscle (TRAM) flap breast reconstruction. (Custom Medical Stock Photo)
191
Breast reconstruction ations on this procedure use different amounts of abdominal muscle. The use of less muscle for reconstruction may help the patient retain abdominal strength after surgery. The newer DIEP flap procedure uses skin, fat, and minimal abdominal muscle tissue, and it uses a free flap approach. Patients generally retain more abdominal strength with this type of breast reconstruction. The latissimus dorsi flap procedure transfers skin, fat, muscle, and blood vessels from the upper back as a pedicle flap, tunneling the tissue under the skin to the front of the chest. The amount of skin and other tissue used in this procedure is generally less than in a TRAM flap surgery, making it useful for reconstructing small and medium-sized breasts or for creating a pocket for a breast implant. The gluteal flap is a free flap procedure that uses skin, fat, blood vessels, and gluteal muscle tissue from the buttocks to create the breast shape. This procedure is an option for women who cannot use the abdominal site due to thinness or incisions, or for patient preference. Nipple and areola reconstruction is optional and, if done, is performed as a last step after the patient has healed from the first surgeries. The nipple is reconstructed using tissue from the breast itself or from another part of the patient’s body such as the inner thigh. The areola may be created by tattooing the skin to make it match the natural nipple and areola. Saving the nipple from the breast with cancer that is removed (called nipple saving or nipple banking) is sometimes done but is risky because the nipple tissue might contain cancer cells. After the procedure: A patient will likely feel tired and sore for a week or two after implant reconstruction, and longer, perhaps months, after tissue flap reconstruction. The patient will probably be discharged from the hospital with a surgical drain in place to allow excess fluids to drain from the surgical site. Stitches will be in place after the surgery, but they will most likely be absorbable sutures that will not have to be removed. Scars will fade over time but never go away entirely. It takes about six to eight weeks for the patient to return to normal, depending on the type of procedure performed. A patient will be advised to take it easy during this period and avoid overhead lifting and strenuous physical activity. Risks: Some risks of breast reconstructive surgery are bleeding, fluid collection, swelling and pain, excessive scar tissue, infection, the death of all or part of the flap, problems at the donor site, fatigue, changes in the affected arm, and the need for additional surgeries to correct problems. If an infection develops after the implant surgery, then the implant may need to be removed until the infection 192
Salem Health: Cancer clears. If an infection develops after flap surgery, then surgical cleaning of the wound may be necessary. Sometimes local complications occur with breast implants. The most common of these is capsular contracture, which can occur if the scar or capsule around the implant begins to tighten and squeeze down on the soft implant, making the breast feel hard. More surgery may be needed to remove the scar tissue, or the implant may need to be removed or replaced. Rarely, rupture of the implant may occur. Implants may not last a lifetime, so additional surgeries may be needed to replace them. Breast reconstruction has no known effect on the recurrence of breast cancer, and neither implant nor flap procedures decrease the likelihood of detection of a recurrence of breast cancer. Results: Breast reconstruction after a mastectomy can improve a woman’s appearance and self-confidence. Although the surgeon will try to create a breast shape that matches the other breast closely, a perfect match is not possible, and a reconstructed breast does not have natural sensations. In some cases, surgery on the other breast is performed to improve the match. Jill Ferguson, Ph.D. u
For Further Information Ahmed, S., et al. “Breast Reconstruction.” British Medical Journal 330 (2005): 943-948. Edlick, R. F., et al. “Advances in Breast Reconstruction After Mastectomy.” Journal of Long-Term Effects of Medical Implants 15 (2005): 197-207. Farhadi, J., et al. “Reconstruction of the Nipple-Areola Complex: An Update.” Journal of Plastic, Reconstructive & Aesthetic Surgery 59 (2006): 40-53. Fentiman, I. S., and H. Hamed. “Breast Reconstruction.” International Journal of Clinical Practice 60 (2006): 471-474. Piasecki, J. H., and K. A. Gutowski. “Breast Reconstruction.” Clinical Obstetics and Gynecology 49 (2006): 401-413. Serletti, J. M. “Breast Reconstruction with the TRAM Flap: Pedicled and Free.” Journal of Surgical Oncology 94 (2006): 532-537. Spear, S. L., and A. N. Mesbahi. “Implant-Based Reconstruction.” Clinics in Plastic Surgery 34 (2007): 63-73. u
Other Resources
American Cancer Society Breast Reconstruction After Mastectomy http://www.cancer.org/docroot/CRI/content/ CRI_2_6X_Breast_Reconstruction_After_ Mastectomy_5.asp
Salem Health: Cancer
Breast self-examination (BSE)
American Society of Plastic Surgeons Breast Reconstruction http://www.plasticsurgery.org/patients_consumers/ procedures/BreastReconstruction.cfm Breastcancer.org Reconstruction http://www.breastcancer.org/bey_tre_recon_idx.html Mayo Clinic Breast Reconstruction After Mastectomy http://www.mayoclinic.com/health/breastreconstruction/WO00083 See also Breast cancers; Breast implants; Mastectomy; Self-image and body image; Sexuality and cancer.
u Breast self-examination (BSE) Category: Procedures Definition: The National Breast Cancer Foundation recommends that all women age twenty and older conduct a breast self-examination (BSE) on a monthly basis, in addition to undergoing a clinical breast examination periodically, depending on age and state of health. Cancers diagnosed: Breast cancer Why performed: Breast self-examinations are performed by women on their own breasts to detect unusual swellings, lumps, thickenings, or other conditions that may suggest the possibility of a breast disorder, including breast cancer. It is believed that, if performed every month at the same time (in relation to the menstrual cycle), this examination will educate a woman about how her breasts feel normally and will alert her to any sudden changes, thereby facilitating early detection of a precancerous or cancerous mass. Patient preparation: It is recommended that the examination take place in the shower (where water smooths the skin and makes it easier to detect changes) or lying prone. Steps of the procedure: Using the left hand to examine the right breast (and vice versa), the woman should, with fingers flat, move gently over every part of the breast in a systematic fashion (vertically up to down or circularly from well beyond the exterial margins inward), starting well above the top margin of the breast and beyond each right and left margin as well. The examination should be conducted three times using light, medium, and heavy
A woman performs a breast self-examination. (PhotoDisc)
pressure. Women must also visually inspect their breasts in a mirror, raising arms overhead and looking at the breasts from all sides. Muscles should be both flexed and relaxed. Women should be particularly alert to any swellings, dimpling of the skin, “orange-peel” (peau d’orange) appearance, discoloration, changes in or discharges from the nipple, lumps no matter how small, or other unfamiliar signs. After the procedure: If a woman detects a change in how her breasts or nipples feel, then she should promptly schedule an appointment with her physician for follow-up tests. Risks: There are no risks in performing the examination, and generally such examinations cause no pain. Results: Women who perform a self-exam become familiar with their own breasts and are able to report abnormalities much earlier than is possible if they wait for an annual clinical examination or mammogram. Early detection of 193
Breast ultrasound precancerous or cancerous tissue greatly increases not only early treatment but also survival rates. Christina J. Moose, M.A. See also Breast cancer in pregnant women; Breast cancers; Calcifications of the breast; Clinical breast exam (CBE); Mammography; Nipple discharge; Palpation; Screening for cancer.
u Breast ultrasound Category: Procedures Also known as: Sonography, ultrasonography Definition: Breast ultrasound is the use of high-frequency sound waves to produce an image of the breast tissue. The sound waves used are in the range of 20,000 to 10,000,000 cycles per second and are inaudible to the human ear. They are bounced off of the breast tissue and are able to distinguish between solid tumors and fluid-filled cysts. The density and elasticity of tissues affect the velocity of the sound waves traveling through them. Tissues that are denser and less elastic slow the sound waves and appear as shaded areas on the screen image. Tissues that are less dense and more elastic do not interfere with the sound waves and appear as clear areas. The interpretation of the sound wave data is performed by a computer. An advantage of breast ultrasound is that it does not use radiation. Cancers diagnosed: Breast cancer Why performed: There are several reasons that breast ultrasounds are performed. After a questionable mammogram, a breast ultrasound may be used to further examine the breast tissue. Some breast conditions may look like a possible cancer on a mammogram but can be identified as benign on ultrasound. For example, breast cysts and some fibroadenomas appear as clear areas on a breast ultrasound, whereas a breast cancer would not. In women under the age of thirty-five, breast ultrasound may be the procedure of choice for screening for breast cancer because younger women have denser breast tissue, which makes it difficult to assess for abnormalities on mammography. Breast ultrasound may also be used to guide a needle biopsy, or needle localization. Ultrasound has proved effective at examining the breasts of women with breast implants. It is often able to illustrate whether the implant has ruptured or not. Mammography does not show fluid leaking from the implant. Patient preparation: No preparation of the patient is required. 194
Salem Health: Cancer Steps of the procedure: For a breast ultrasound, the patient puts on a hospital gown, which is open in the front, and then lies supine on a table. A pillow is placed under the shoulder of the breast to be scanned. The area to be scanned is uncovered. The patient’s arm is placed up over the head, resting on the examination table. The radiology technician or physician uses a transducer (an instrument to transmit and receive sound waves) to scan the breast tissue. A transducer looks like a small cell phone. A gel is used between the transducer and the patient to enhance the transmission of the sound waves for the scan. The transducer is moved slowly and lightly over the breast tissue. Usually, the breast lesion is viewed in several planes, so that its features can be defined. This is accomplished by changing the angle of the transducer in relation to the breast tissue. The images of the breast are printed for further examination. After the procedure: No additional patient care is required, so the patient can go home. Risks: There are no known risks of breast ultrasound for the patient. It appears that sound waves are safe for use on human beings. For the physician, however, there is the risk of making an incorrect diagnosis about the presence of breast cancer. Breast ultrasounds do not differentiate microcalcifications (mineral deposits) in the breast tissue. Microcalcifications that are clustered can be a first sign of a developing breast cancer. The accuracy of breast ultrasounds can vary with the skill of the technician. Once the ultrasound images have been printed, there is no way to determine the angle of the transducer, or to manipulate the images, as can be done with mammograms. Also, breast ultrasound is not as accurate at assessing the whole breast. It is most effective at assessing a small area of breast tissue. Results: The images of the breast ultrasound demonstrate the different breast tissues, with the ducts appearing darker than the adipose (fatty) tissue between the ducts. The breast ultrasound is most accurate at identifying breast cysts, which are fluid-filled. If on ultrasound an area of the breast appears particularly dense and opaque, then a breast cancer could be present. Breast ultrasound does not differentiate between benign tumors and malignant (cancerous) tumors or growths. As a result, a breast biopsy is required to identify the type of lesion. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Love, Susan M., and Karen Lindsay. Dr. Susan Love’s Breast Book. Rev. 4th ed. Cambridge, Mass.: Da Capo Press, 2005.
Salem Health: Cancer
Breslow’s staging
Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006.
progress, or stage, of the cancer and whether the cancer has spread. The stage helps oncologists choose the best treatment and determine the best prospects for recovery.
u
Patient preparation: No special preparation is needed for a skin biopsy.
Other Resources
American Cancer Society Mammograms and Other Breast Imaging Procedures http://www.cancer.org/docroot/CRI/content/ CRI_2_6X_Mammography_and_Other_Breast_ imaging_Procedures_5.asp Health A to Z Breast Ultrasound http://www.healthatoz/atoz/ency/ breast_ultrasound.jsp Imaginis Breast Cancer Diagnosis http://www.imaginis.com/breasthealth/ ultrasound_images.asp Yale Medical Group Breast Imaging at Yale http://www.yalemedicalgroup.org/news/dxrad/ ymg_breastimaging.html See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Calcifications of the breast; Clinical breast exam (CBE); Imaging tests; Mammography; Microcalcifications; Needle biopsies; Premalignancies; Screening for cancer; Ultrasound tests.
u Breslow’s staging Category: Procedures Also known as: Breslow thickness, Breslow measurement, Breslow’s depth of invasiveness Definition: Breslow’s staging is a test to measure, in millimeters (mm), the vertical thickness (how far a tumor reaches into the skin) of a malignant melanoma tumor. The test was developed by Alexander Breslow (1928-1980), an American pathologist, in the 1970’s. Cancers diagnosed: Melanoma, the most deadly form of skin cancer Why performed: Once melanoma is confirmed by a skin biopsy, Breslow’s staging helps oncologists establish the
Steps of the procedure: A skin biopsy is usually done in the doctor’s office. A local anesthetic is injected into the area with a small needle. A sample of skin tissue is then removed for examination. After the procedure: The patient feels no pain and may go home. The skin sample is examined in a laboratory. If melanoma is confirmed, then the sample is subjected to Breslow’s staging to help determine prognosis and treatment. Risks: Small skin biopsies are generally safe and carry only a small risk of bleeding or infection. Sometimes a biopsy may leave a scar. Results: Early diagnosis is the most effective way of improving the cure rate for patients with melanoma. When laboratory tests confirm melanoma, Breslow’s staging classifies the progress of the cancer according to one of five stages. In the first stage, malignant melanoma cells are found only in the outer layer of skin and have not yet invaded the deeper layers or spread. Most patients with melanoma only in the outer layer of skin can be cured with surgery. The Breslow thickness of a melanoma tumor predicts the approximate five-year survival rate after the tumor is surgically removed.
• • • •
Smaller than 1 mm: 95-100 percent 1.0-2.0 mm: 80-96 percent 2.1-4.0 mm: 60-75 percent More than 4.0 mm: 50 percent
In the last stage, the melanoma could be any thickness but has spread to other parts of the body, most likely to the nearest lymph nodes. The majority of patients with melanoma that has spread to nearby lymph nodes cannot be cured with current treatments. The average survival of patients with melanoma that has spread to the lymph nodes is only 7.5 months. Only 5 to 10 percent of patients survive beyond five years. Wendell Anderson, B.A. See also Melanomas. 195
Brief Pain Inventory (BPI)
u Brief Pain Inventory (BPI)
Salem Health: Cancer See also Breakthrough pain; Pain management medications.
Category: Procedures Definition: The Brief Pain Inventory (BPI) is a questionnaire used to measure pain in cancer patients and other patients suffering from chronic pain. The BPI provides information on the intensity of pain (known as the sensory dimension) and the impact of pain on a patient’s daily routine (known as the reactive dimension). The BPI was developed in 1989 by Charles Cleeland, M.D., while with the Pain Research group at the University of Wisconsin. Cancers diagnosed or treated: All cancers that cause chronic or severe sporadic pain Why performed: The BPI is administered to determine cancer patients’ level of pain. Once the level of pain is determined, oncologists work to manage the painful symptoms of cancer and to make patients more comfortable. Pain management is especially important for terminal patients. Cancer pain appears when a tumor presses against organs, nerves, or bone. Treatments for cancer—such as chemotherapy, radiation therapy, and especially surgery— also can cause pain. The Veterans Administration and the Joint Commission on Accreditation of Health Care Organizations consider pain the fifth vital sign and require physicians to ask patients about their pain. Patient preparation: Taking the BPI requires no patient preparation. Steps of the procedure: The questionnaire for the BPI is usually filled out by the patient. In some cases, a doctor, nurse, or social worker helps by interviewing the patient and recording the answers. Filling out the short version of the BPI takes about five minutes, while the long version takes about ten minutes. After the procedure: After the patient completes the BPI, it is scored on a scale of 0-10 for both the severity and the impact dimensions of the pain. Risks: There are no inherent risks involved with the BPI. Its validity has been tested many times, and it has been translated into twenty-five languages. The only possible problem involved with the BPI is a patient’s inability or reluctance to report pain accurately. Results: The results of an individual patient’s BPI can be tabulated in a few minutes. The results help oncologists, nurses, and other caregivers develop a pain management plan for the cancer patient. Wendell Anderson, B.A. 196
u Brompton cocktail Category: Chemotherapy and other drugs Also known as: Brompton’s mixture, hospice mix Definition: Brompton cocktail is a palliative elixir containing morphine, cocaine, ethanol, and other ingredients to lessen or prevent the pain and distress associated with terminal illness, especially advanced cancer. It is no longer part of standard care. Cancers treated: Previously used for advanced, painful tumors in patients near death Delivery routes: Oral as a liquid How this substance works: Elixirs of morphine and cocaine were first described in 1896 as treatments for the pain associated with advanced cancer by the English surgeon Herbert Snow. A specific mixture was published under the auspices of the Royal Brompton Hospital in London in 1952; the ingredients included morphine hydrochloride, cocaine hydrochloride, alcohol, and chloroform water. Several different formulations calling for heroin (diacetylmorphine), cannabis, antiemetics, distilled spirits, and sedatives have been promoted over the years. Flavoring syrup is sometimes added. It was widely used in the early 1970’s, mostly in hospice care. Two of its main proponents were Cicely Saunders, founder of the modern hospice movement, and Elisabeth Kübler-Ross, a psychiatrist and authority on end-of-life care. The active ingredients are intended to provide a welcome combination of analgesia, disinhibition, and stimulation. Cough suppression was an important effect in patients with lung or airway malignancies (or end-stage tuberculosis). The mixture was promoted as more cost effective at treating intractable cancer pain than parenteral narcotics. Several significant liabilities have contributed to the disappearance of the Brompton cocktail from modern oncology practice. In 1979, controlled trials showed that oral morphine alone gave pain relief equivalent to the cocktail, that oral morphine and oral heroin were equally effective, and that oral cocaine had no effect on patients’ alertness or sociability. One study concluded that “the Brompton Cocktail is no more than a traditional British way of administering oral morphine to cancer patients in pain.” The potential for diversion and abuse was illustrated by a case report in which an individual obtained the mixture illicitly
Salem Health: Cancer and injected it in lieu of heroin. Each of the cocktail’s active ingredients has addictive and tolerization potential, making discontinuation difficult. Even though terminal cancer patients often require multiple drugs for symptom management, the convenience of an “all-in-one” mixture of drugs such as the Brompton cocktail is outweighed by the benefits obtained by monitoring and adjusting analgesics, antineoplastics, antiemetics, and psychoactive drugs individually. Side effects: The side effects include sedation, confusion, constipation, decreased breathing, tolerization, and addiction. John B. Welsh, M.D., Ph.D. See also Do-not-resuscitate (DNR) order; End-of-life care; Home health services; Hospice care; Pain management medications; Palliative treatment.
u Bronchial adenomas Category: Diseases, symptoms, and conditions Also known as: Bronchial gland tumors, mucous gland adenomas, bronchial carcinoid tumors, cylindromas Related conditions: Carcinoid syndrome Definition: A bronchial adenoma is a slow-growing tumor in the windpipe (trachea) or in the large air passages (bronchi) leading from the windpipe to the lungs. Risk factors: The cause and risk factors for bronchial adenomas are not known. Etiology and the disease process: A bronchial adenoma can be one of several types of tumors that begin in the mucous glands; the main types of tumors are carcinoids and adenoid cystic carcinoma (also called cylindroma). The tumors are usually small and slow growing and therefore may not be diagnosed for years. Symptoms of bronchial adenoma may be confused with those of bronchial asthma or chronic bronchitis. Incidence: Approximately 1 to 3 percent of pulmonary (relating to the lungs) tumors are bronchial adenomas. Bronchial adenomas can be found in individuals of all ages but usually are found in people between the ages of thirty and fifty; the incidence is equal for men and women. Symptoms: Some of the symptoms of bronchial adenomas are difficulty breathing, hoarseness, a persistent cough, coughing up blood (hemoptysis), wheezing sounds, or pneumonia that recurs or is slow to end.
Bronchoalveolar lung cancer Screening and diagnosis: A chest X ray, computed tomography (CT) scan, or magnetic resonance imaging (MRI) can be used to detect a tumor. Often physicians will use a bronchoscopy, a procedure in which a thin, flexible tube with a very small camera is used to look at the trachea and bronchi and to take a sample of cells (biopsy) for testing. This test can distinguish a bronchial adenoma from other types of tissue growths. Sometimes it may be necessary to insert a needle through the chest wall, between the ribs, to take the biopsy for determination of the type of tumor. Treatment and therapy: Treatment of bronchial adenoma is by surgical removal of the tumor. Surgery may be bronchoscopic surgery (during a bronchoscopy) if the tumor is small or open-lung surgery. There is a small chance of recurrence of a bronchial adenoma and a very small chance of metastases. Laser ablation (removal) of a bronchial adenoma may be done through a bronchoscope, especially for tumors that have recurred. Prognosis, prevention, and outcomes: Following removal of the tumor there is an excellent long-term prognosis for individuals with a bronchial adenoma. Vicki Miskovsky, B.S., R.D See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Bronchoalveolar lung cancer; Bronchography; Bronchoscopy; 1,4-Butanediol dimethanesulfonate; Carcinoid tumors and carcinoid syndrome; Coughing; Laryngeal cancer; Lung cancers; Pneumonia.
u Bronchoalveolar lung cancer Category: Diseases, symptoms, and conditions Also known as: Non-small-cell lung cancer (NSCLC), bronchioloalveolar lung cancer, lung adenocarcinoma Related conditions: Pleural effusion, pneumonia Definition: Bronchoalveolar lung cancer is a type of NSCLC that arises in the alveoli (air sacs of the lung). It can begin as either a single site or multiple sites, or spread rapidly as a pneumonic form. Bronchoalveolar lung cancer is less likely than other types of NSCLC to spread beyond the lungs. Risk factors: The most common cause of lung cancer is smoking cigarettes. Another major cause is exposure to secondhand smoke. Other risk factors include exposure to radon gas or asbestos, environmental pollution, tuberculosis, lung disease, and an inherited predisposition to lung cancer. 197
Bronchoalveolar lung cancer Etiology and the disease process: With bronchoalveolar lung cancer, cells in the alveoli begin to grow wildly. As they grow, they progress along the alveolar walls. Multiple sites may develop and then converge to consolidate some areas of the lungs. An obstructed area of the lung may become pneumonic. Incidence: NSCLCs account for about 75 percent of all lung cancers. Bronchoalveolar lung cancer makes up about 2 to 3 percent of this group. Although 10 percent of patients with lung cancer in the United States are nonsmokers, 25 to 30 percent of patients with bronchoalveolar lung cancer are nonsmokers. It is more common in women. Symptoms: The symptoms of bronchoalveolar cancer are coughing, shortness of breath, wheezing, chest pain, large amounts of watery sputum, and hemoptysis (coughing up blood). On physical examination, the lungs are dull to percussion (tapping on the chest wall), and breath sounds may be weak or absent on auscultation (listening with a stethoscope). If the tumor is pressing on a nerve, it can cause shoulder pain or hoarseness. Screening and diagnosis: Currently, there is no accurate, inexpensive screening test for bronchoalveolar lung cancer. Researchers are working to develop such a test by looking at a marker in the blood and also at breath analysis. To diagnose lung cancer, pulmonary function tests and a chest X ray may be performed. Chest X rays can demonstrate most lung cancers, except the very small. More sensitive tests are computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans. To differentiate between the types of lung cancer, a biopsy of the tumor must be performed. Bronchoscopy, thoracoscopy, or mediastinoscopy may be performed to examine pulmonary secretions and the lymph nodes of the lung. If the cancer exists on the periphery of the lung, it may be necessary to perform a needle biopsy through the chest wall. If none of these procedures is effective in determining the type of lung cancer, a surgical procedure called a thoracotomy (opening the chest) can be performed. The actual diagnosis of bronchoalveolar lung cancer is made by the pathologist, who examines the tumor cells under a microscope. The pathologist identifies the type of lung cancer and stages the cancer. All NSCLCs are staged in the same way, using a combination of numeric tumor grading and the TNM (tumor/lymph node/metastasis) stages. The stages are as follows: • Stage IA, T1 N0 M0: The tumor is less than 3 centimeters (cm) and there is no lymph node involvement or metastases. 198
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•
Stage IB, T2 N0 M0: The tumor is greater than 3 cm, but it has not spread beyond the lung. • Stage IIA, T1 N1 M0: The tumor is less than 3 cm, and there is spread to local lymph nodes. • Stage IIB, T2 N1 M0, or T3 N0 M0: Either the tumor is greater than 3 cm, or it has spread into the outside of the lungs, the chest cavity, or the pericardium (sac around the heart). • Stage IIIA, T 1-3 N2 M0, or T3 N1 M0: Either the cancer has spread to distant lymph nodes but has not metastasized, or the cancer has spread into adjacent tissues and muscles and has spread to local lymph nodes. • Stage IIIB, T4 N3 M0: Either the cancer has spread to nearby organs or it has spread to distant lymph nodes but has not metastasized. • Stage IV, M1: The cancer has metastasized to distant organs. Treatment and therapy: Treatment of lung cancer can include surgery, chemotherapy, and radiation. To remove a bronchoalveolar tumor, the surgeon can perform a wedge resection, a lobectomy, or a pneumonectomy. Chemotherapy for lung cancers is effective only 35 percent of the time. The most commonly used drugs are combinations of cisplatin (Platinol), carboplatin (Paraplatin), vinorelbine (Navelbine), vincristine (Oncovin), vinblastine (Velban), paclitaxel (Taxol), docetaxel (Taxotere), and gemcitabine (Gemzar). Newer chemotherapy drugs that interfere with cell growth and reproduction as well as angiogenesis (formation of new blood vessels) are being used. They are gefitinib (Iressa), erlotinib (Tarceva), and bevacizumab (Avastin). Radiation therapy for bronchoalveolar lung cancer is not effective as a cure, so it is reserved for treatment when surgery is not possible. Prognosis, prevention, and outcomes: Patients with lower stage cancers survive longer than those with highstage cancers. Research has shown that patients who have never smoked respond better to treatments for bronchoalveolar cancer. The best way to avoid lung cancer is by not smoking and by avoiding exposure to secondhand smoke. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Houlihan, Nancy G. Lung Cancer. Pittsburgh: Oncology Nursing Society, 2004. Hunt, Ian, Martin Muers, and Tom Treasure. ABC of Lung Cancer. Malden, Mass.: Blackwell, 2008. Roth, Jack A., James D. Cox, and Waun Ki Hong, eds. Lung Cancer. 3d ed. Malden, Mass.: Blackwell, 2008.
Salem Health: Cancer u
Other Resources
LungCancer.org http://www.lungcancer.org/ MayoClinic.com Lung Cancer http://www.mayoclinic.com/health/lung-cancer/ DS00038 National Cancer Institute Lung Cancer http://www.cancer.gov/cancertopics/types/lung See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Bronchial adenomas; Bronchography; Bronchoscopy; 1,4-Butanediol dimethanesulfonate; Carcinoid tumors and carcinoid syndrome; Coughing; Laryngeal cancer; Lung cancers; Pneumonia.
u Bronchography Category: Procedures Also known as: Bronchogram, laryngography Definition: Bronchography is a radiographic evaluation that examines the interior passageways of the larynx, trachea, and bronchi. Bronchography is used somewhat infrequently because of technological advances with computed tomography (CT) scans and bronchoscopy. Cancers diagnosed: Lung cancers Why performed: Bronchography is performed to examine structural or functional abnormalities of the lower respiratory tract. Abnormalities that are commonly investigated with bronchography include bronchiectisis, hemoptysis, chronic bronchitis, chronic pneumonia, and tumors. Patient preparation: The patient is asked to not eat or drink for several hours before the procedure. The patient may also be asked to perform thorough mouth hygiene before the procedure. Steps of the procedure: The patient is asked to remove all clothing, jewelry, and dentures; to dress in a gown; and to empty the bladder. Vital signs (such as blood pressure and respiratory rate) are taken. The patient is positioned on a table that can tilt in various directions. The patient may also be given a sedative. Next, numbing medication is injected into the back of the patient’s throat to prevent gagging. Finally, the physician passes the bronchoscope down the back of the throat into the trachea and bronchi. Contrast dye is released from the bronchoscope as it advances.
Bronchoscopy The dye forms a coating on the lining of the interiors of the bronchi, trachea, and larynx. The physician then takes several X rays from different positions, after which the bronchoscope is removed. After the procedure: The patient is moved to a recovery room and has vital signs monitored for several hours postprocedure. The patient will not be allowed to eat or drink until the gag reflex has returned. The patient may be asked to gently cough up any remaining contrast dye. Normal diet may be resumed after the procedure. The throat may feel sore after bronchography. A follow-up chest X ray is often performed twenty-four to forty-eight hours after the bronchography to verify the removal of the contrast dye from the airways. Risks: Risks of the procedure include infection or pneumonia and airway obstruction from the contrast dye in patients with emphysema or chronic obstructive pulmonary disease (COPD). Results: The contrast dye allows the physician to assess the likely presence or absence of respiratory system abnormalities, such as tumors, in the larynx, trachea, or bronchi. If abnormalities are detected, then the physician will either perform a confirmatory diagnostic procedure or devise a treatment plan based on the specific test results. Jeremy W. Dugosh, Ph.D. See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Bronchial adenomas; Bronchoalveolar lung cancer; Bronchoscopy; 1,4-Butanediol dimethanesulfonate; Carcinoid tumors and carcinoid syndrome; Coughing; Laryngeal cancer; Lung cancers; Pneumonia.
u Bronchoscopy Category: Procedures Also known as: Fiber-optic bronchoscopy Definition: Bronchoscopy uses a bronchoscope to allow a doctor to see, examine, and biopsy tissues in the respiratory tract and lungs. The procedure is used to check for cancer cells. A bronchoscope is a thin tube equipped with fiber optics or a miniature camera that produces images of the internal airways and lungs. Cancers diagnosed: Respiratory tract cancer, lung cancer Why performed: Bronchoscopy is a diagnostic procedure used to view the inside of the airways and lungs. Suspicious tissues are biopsied and examined in a laboratory in order to detect the presence of cancer cells. 199
Burkitt lymphoma
Salem Health: Cancer gen levels, and heart activity. Oxygen is delivered through a nasal cannula. The bronchoscope is inserted through the nose or mouth. The airways and lungs are inspected. A bronchoalveolar lavage may be performed, which involves inserting sterile fluid to remove mucus or cells for examination. A tissue biopsy is taken by clipping a sample of abnormal tissue. At the end of the procedure, the fluid and bronchoscope are removed. After the procedure: Patients may receive a chest X ray following the procedure to ensure that the lungs were not punctured. Patients should not eat or drink until the anesthesia wears off in order to prevent choking. Patients may be hoarse, experience fever, or cough up small amounts of blood. Risks: Bronchoscopy is considered a safe procedure. The primary risks are infection and bleeding. There is a slight risk of lung perforation, heart attack, irregular heartbeat, and low blood oxygen. Results: A healthy respiratory tract and lungs are free of swelling and abnormal growths. Suspicious growths are biopsied to determine whether cancer is present. Mary Car-Blanchard, O.T.D., B.S.O.T.
A physician uses a bronchoscope. (National Cancer Institute)
Patient preparation: Patients should stop taking aspirin or blood-thinning medication a week before the procedure. Brochoscopy uses local or general anesthesia. Patients receiving general anesthesia should not eat or drink after midnight prior to the day of the procedure. Bronchoscopy is usually an outpatient procedure, and patients should arrange to have someone else drive them home. Patients wear an examination gown, which is removed from the waist up during the procedure, and receive a sedative before the bronchoscopy begins. Steps of the procedure: Patients receive general or local anesthesia, depending on whether a rigid or a flexible bronchoscope is used. Local anesthesia is injected or sprayed into the throat. Patients receive medication to eliminate secretions and to prevent coughing or gagging. Monitors are placed to measure blood pressure, blood oxy200
See also Bronchial adenomas; Bronchoalveolar lung cancer; Bronchography; Carcinoid tumors and carcinoid syndrome; Computed tomography (CT) scan; Coughing; Endoscopy; Gastrointestinal cancers; Hemoptysis; Lambert-Eaton myasthenic syndrome (LEMS); Lung cancers; Mesothelioma; Otolaryngology; Pneumonia; Sputum cytology.
u Burkitt lymphoma Category: Diseases, symptoms, and conditions Also known as: B-cell lymphoma, small noncleaved cell lymphoma Related conditions: Non-Hodgkin lymphoma Definition: Burkitt lymphoma, first described by Denis Parsons Burkitt in 1956, is a type of non-Hodgkin lymphoma that develops from B lymphocytes, the cells that produce antibodies and fight infections. Risk factors: Most people who develop Burkitt lymphoma have no identifiable risk factors, but age, sex, ex-
Salem Health: Cancer
Burkitt lymphoma
posure to chemicals that damage deoxyribonucleic acid (DNA), infections such as the Epstein-Barr virus (EBV), and a weakened immune system may be factors leading to its development. Etiology and the disease process: In North America most cases of Burkitt lymphoma are sporadic and caused by a chromosomal rearrangement. Of these rearrangements, 90 percent involve a chromosomal exchange called a translocation between chromosomes 8 and 14. This translocation moves the MYC gene from its normal position on chromosome 8 to the vicinity of the gene producing immunoglobulin G (IgG) on chromosome 14. In 10 percent of Burkitt lymphoma cases, MYC has been translocated to the vicinity of antibody-producing genes on either chromosome 2 or chromosome 22. In its new chromosomal location, MYC is overactive and results in uncontrolled cell growth. The MYC gene encodes for a transcription factor that activates other genes. One gene that is activated is HMG-I/Y, whose product transforms normal B lymphocytes into rapidly growing tumor cells. Burkitt lymphoma is endemic in equatorial Africa and is associated with not only chromosomal translocations but also the Epstein-Barr virus (EBV), which also causes infectious mononucleosis and other cancers. About 30 percent of Burkitt lymphoma patients in the United States harbor EBV. In children the disease usually begins in the abdomen, develops rapidly, and metastasizes quickly. Abdominal swelling, fluid retention, and vomiting often occur. In adults the disease often begins with a painless enlargement of a lymph gland or abdominal swelling. Depending on the location of the affected lymph node, a variety of conditions may develop. Occasionally, Burkitt lymphoma affects the blood and may result in anemia, increased bleeding, and susceptibility to infections. The B cells may invade other tissues, causing a variety of symptoms. Because the cancer is one of the most rapidly growing human tumors, most cases are in either Stage III or Stage IV at the time of diagnosis. Incidence: Burkitt lymphoma is common in central Africa, where it accounts for as much as 50 percent of cancer deaths in children. The disease is relatively rare in the United States, but when it does occur, the average age at diagnosis is seven years, and the disease accounts for about 3 percent of the total cancer deaths in people under twenty years old. The disease is also three times as likely to occur in boys as in
girls and is more common in white children than children of other races. It is 1,000 times more likely to occur in acquired immunodeficiency syndrome (AIDS) patients. Symptoms: Although most cases in the United States develop in the abdomen, the first symptom is usually a painless swelling of an axillary, neck, or groin lymph node. The affected lymph node or nodes will grow rapidly and may form lumps. Depending on where the disease develops, other symptoms may occur. In Africa, where Burkitt lymphoma is endemic, the disease often affects the face and jaw, causing extensive swelling. Screening and diagnosis: Diagnosis is by biopsy of the affected tissue followed by histological examination. Spinal fluid analysis, blood cell and platelet counts, X rays, computed tomography (CT) scans, gallium scans, and positron emission tomography (PET) scans also can be
A child with a large facial tumor caused by Burkitt lymphoma. (Centers for Disease Control and Prevention)
201
1,3-Butadiene
Salem Health: Cancer
Relative Survival Rates for Burkitt Lymphoma, 1988-2001 Years
Survival Rate (%)
1 2 3 5 8 10
53.5 47.8 47.4 45.4 45.1 45.1
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
therapy, bone marrow transplants, and monoclonal antibodies also have been used to treat the disease. Prognosis, prevention, and outcomes: If the disease is relatively localized and has not spread, aggressive chemotherapy can cure up to 80 percent of the cases. If the central nervous system or the bone marrow has become involved, the effectiveness of treatment is significantly less. Charles L. Vigue, Ph.D. u
For Further Information Magrath, Ian, ed. The Non-Hodgkin’s Lymphomas. New York: Oxford University Press, 1997. Mauch, Peter, et al., eds. Non-Hodgkin’s Lymphomas. Philadelphia: Lippincott Williams & Wilkins, 2004.
u
used to diagnose the disease. The St. Jude’s Children’s Research Hospital system is commonly used to stage the disease in children. • Stage I: Lymphoma is localized to a single site. • Stage II: Lymphomas involve more than one site but are localized to one side of the body. • Stage III: Lymphomas involve multiple sites on both sides of the body but do not involve bone marrow or the nervous system. • Stage IV: Lymphomas involve the bone marrow or the nervous system. The Ann Arbor system is used for adults with the disease. • Stage I: Lymphoma is limited to one lymph node either above or below the diaphragm or is limited to one organ. • Stage II: Lymphomas are either in two or more lymph nodes on the same side of the diaphragm or are limited to one organ and the lymph nodes near that organ. • Stage III: Lymphomas have spread to lymph nodes on both sides of the diaphragm and may involve an organ. • Stage IV: Lymphomas have metastasized throughout one or more organs and may involve lymph nodes. Treatment and therapy: In children, Burkitt lymphoma is usually treated by aggressive and intense chemotherapy that may last for several months. The most common chemotherapeutic agent used is cyclophosphamide (Cytoxan), usually in combination with another chemotherapeutic agent. If large tumors are involved, radiation therapy may be indicated. In some cases surgery may be required to remove affected tissues. In adults Burkitt lymphoma is treated with chemotherapy involving a combination of chemotherapeutic agents. Radiation therapy is often used in combination with chemotherapy. Stem cell 202
Other Resources
Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org/hm_lls Lymphoma Information Network Burkitt’s Lymphoma/Leukemia http://www.lymphomainfo.net/nhl/types/burkitts.html National Cancer Institute Non-Hodgkin Lymphoma http://www.cancer.gov/cancertopics/types/nonhodgkins-lymphoma See also Childhood cancers; Epstein-Barr virus; Genetics of cancer; Hepatitis C virus (HCV); Hodgkin disease; Infectious cancers; Lymphomas; Molecular oncology; MYC oncogene; Non-Hodgkin lymphoma; Oncogenic viruses; Proto-oncogenes and carcinogenesis; Viral oncology; Virus-related cancers; Young adult cancers.
u 1,3-Butadiene Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Vinylethylene, bivinyl, buta-1,3-diene, α,γ-butadiene Related cancers: Leukemia, lymphosarcoma, reticulosarcoma, hematopoietic cancers Definition: 1,3-Butadiene is a hydrocarbon molecule made up of four atoms of carbon and six atoms of hydrogen. The first and last pairs of carbon atoms are held together by two chemical bonds or four electrons. The two and three carbons share a single pair of electrons. This atomic arrangement makes 1,3-butadiene highly flammable and extremely reactive.
Salem Health: Cancer Exposure routes: Inhalation, ingestion, dermal contact, exhaust from motor vehicles and cigarette smoke Where found: Industries involved in the synthesis of rubber-like materials, resins, and polymers At risk: Workers who deal with synthetic rubber, organic chemicals, and resins Etiology and symptoms of associated cancers: In all species studied, including humans, 1,3-butadiene has been shown to be oxidized to rings that involve two of the carbon atoms and one atom of oxygen. Such epoxides are chemically similar to the known carcinogen ethylene oxide. Tumor production in both rodents and humans involves reaction with deoxyribonucleic acid (DNA), producing genetic alterations in tumor-suppressor genes. History: The shortage of natural rubber in World War II caused an intense search for synthetic latex. It was determined that 1,3-butadiene reacts readily with other similar hydrocarbons to produce a wide variety of polymeric substances. An example is copolymerization with styrene, a molecule involving the carcinogen benzene. Uncertainty in early studies of 1,3-butadiene carcinogenicity resulted when conditions also involved benzene. More than 75 percent of 2 million metric tons of 1,3-butadiene produced in a typical year are consumed by the rubber industry; the compound is also involved in nylon synthesis. Studies of workers in synthetic rubber plants beginning in 1943 gave conflicting evidence concerning the carcinogenicity of 1,3-butadiene. Later animal studies with rats and mice exhibited a strong pattern of incremental risk for a variety of cancers. More carefully controlled studies of production workers in the early 1990’s documented 1,3butadiene’s carcinogenic nature. Extensive federal regulation of 1,3-butadiene exists. The U.S. Department of Transportation (DOT) lists the chemical as hazardous and requires special marking, labeling, and transporting precautions. The U.S. Environmental Protection Agency (EPA), acting under the Clean Air Act (1970), lists 1,3-butadiene as one of thirty-three hazardous air pollutants that present the greatest threat to public health and requires that as little as ten pounds of the substance must be reported. The Occupational Safety and Health Administration (OSHA) has set the permissible exposure limit at one part per million. K. Thomas Finley, Ph.D. See also Air pollution; Carcinogens, known; Carcinogens, reasonably anticipated.
1,4-Butanediol dimethanesulfonate
u 1,4-Butanediol
dimethanesulfonate Category: Carcinogens and suspected carcinogens; chemotherapy and other drugs RoC status: Known human carcinogen since 1985 Also known as: Myleran, busulfan Related cancers: In patients receiving busulfan for chronic myeloid leukemia (CML), cytological anomalies and cancers were observed at a variety of sites, including breast cancer, female genital cancers, and leukemia. Cancer patients given busulfan for bronchial cancer developed leukemia that was not dose related. Definition: Busulfan is a sulfonurea alkylating agent that contains reactive alkyl groups that readily combine with other molecules via cross-linking of deoxyribonucleic acid (DNA) strands in the nuclei of rapidly dividing cells, thereby destroying them. A prescription drug employed in chemotherapy of leukemias, especially CML, busulfan does not selectively harm cancer cells but kills normal cells as well, and it is considered to be mitogenic, carcinogenic, and leukemogenic. Locally it may cause blistering of the skin and damage to the eyes and respiratory tract. Systemic toxic effects include nausea and vomiting, reduction in both leukocytes and erythrocytes, and hemorrhage. Exposure routes: Intravenous (IV), oral/ingestion of tablets Where found: People may be exposed via chemotherapy (oral or IV) for treatment of various types of leukemia, especially CML, and before bone marrow transplants (used to treat CML), in combination with cyclophosphamide used as a conditioning regimen. At risk: There is a potential for occupational exposure in employees who formulate and package busulfan tablets, and for health care professionals who administer IV busulfan to patients. Etiology and symptoms of associated cancers: Busulfan may cause cellular dysplasias and cytologic abnormalities. Busulfan, which is both leukemogenic and carcinogenic, has been shown to cause cancer of the breast and female reproductive organs as well as leukemias in humans, though evidence is limited in animal studies. Related symptoms and signs vary by cancer. For leukemia, they in203
1,4-Butanediol dimethanesulfonate clude weakness, fever, bleeding gums, petechiae, swollen glands, and enlarged spleen or liver; for breast cancer, a new lump or mass in the breast; and, for endometrial cancer, postmenopausal, or irregular vaginal bleeding. History: Introduced in 1950, busulfan raised the median survival time for CML to approximately 3.5 to 4.5 years. However, because busulfan proved more efficient at destroying normal stem cells than CML cells, it has been largely supplanted by more specific and less toxic agents. Malignant tumors and acute leukemias have been reported in patients who were treated with busulfan; the World
204
Salem Health: Cancer Health Organization (WHO) found a cause-and-effect relationship between busulfan and secondary malignancies. The International Agency for Research on Cancer found four cases of acute leukemia among 243 patients treated with busulfan as adjuvant chemotherapy following surgical removal of bronchogenic carcinoma, suggesting that busulfan is leukemogenic. Cynthia Racer, M.A., M.P.H. See also Carcinogens, known; Carcinogens, reasonably anticipated; Chronic myeloid leukemia (CML).
Salem Health: Cancer
u CA 15-3 test Category: Procedures Also known as: Carbohydrate antigen 15-3, cancer antigen 15-3 Definition: CA 15-3 is a transmembrane glycoprotein (carbohydrate-containing protein) found in several tissue types. It is classified as a MUC1 member of the mucin family of proteins. This class of glycoproteins is thought to play a role in reducing cell-to-cell interaction and inhibition of tumor cell cytolysis. The core protein component is identical; the carbohydrate concentration (degree of glycosylation) is the component differentiating between tissue types. Serum/plasma levels are determined by immunoassay. Cancers diagnosed: CA 15-3 is not an organ-specific marker and has been found at elevated levels in ovarian, prostatic, and lung cancer. Additionally, increased CA 15-3 levels can be found concomitant with benign conditions such as breast or ovarian disease, endometriosis, pelvic inflammatory disease, hepatitis, pregnancy, and lactation. Why performed: Because CA 15-3 is not sensitive or specific enough to be used as a screening test, its primarily utility is as a tumor marker for monitoring response to therapy and recurrence in breast cancer patients. At least 70 percent of advanced breast cancer cases have tumors that shed CA 15-3. Blood levels typically are proportional to the tumor burden (mass), with higher levels of CA 15-3 indicative of the presence of a larger tumor. Patient preparation: No special patient preparation is required for accurate CA 15-3 analysis. Steps of the procedure: A blood sample is collected, typically by venipuncture. The collected serum (or plasma) is tested by immunoassay, which involves capturing the CA 15-3 present in the sample by means of monoclonal antiCA 15-3 antibodies. A second, detection (labeled) antibody is then introduced, which subsequently binds to the CA 15-3/anti-CA 15-3 complex. The addition of a substrate results in a detectable signal, the level of which is directly proportional to the amount of the CA 15-3 present in the sample. After the procedure: Pressure should be applied to the venipucture site in order to avoid the development of hematoma (a mass of clotted blood resulting from bleeding under the skin).
CA 19-9 test Risks: The risks of venipuncture are slight but include excessive bleeding, fainting, hematoma, and infection (always a slight risk any time the skin is broken). Results: Although each laboratory establishes reference intervals based on the local, normal population, a basic interpretive guideline would place normal at 0-31 units per milliliter (U/mL) and elevated at more than 31 U/mL. Pam Conboy, B.S. See also CA 19-9 test; CA 27-29 test; CA 125 test; Tumor markers.
u CA 19-9 test Category: Procedures Also known as: Carbohydrate antigen 19-9, cancer antigen 19-9 Definition: CA 19-9 is a glycolipid (carbohydratecontaining fat) characterized glycoprotein (carbohydratecontaining protein, or mucin). It is similar to the type A blood group protein, with additional sialic acid residues. CA 19-9 is found in normal fetal cells as well as in the pancreas, salivary ducts, gastric and colonic epithelium, pancreatic and gastric fluid, saliva, and meconium (first stool of a newborn). It is normally removed from circulation by the biliary system. Serum/plasma levels are determined by immunoassay. Cancers diagnosed or treated: CA 19-9 is elevated in patients with gastrointestinal tract carcinoma, including cancer of the pancreas, stomach, colon, and ovaries. Abnormally high values may also be detected in benign conditions such as acute pancreatitis, cirrhosis, cholecystitis, biliary obstruction, gastric ulcer, pulmonary disease, and chronic hepatitis C and in patients who smoke. Why performed: Because CA 19-9 is not sensitive or specific enough to be used as a screening test, its primarily utility is as a tumor marker for monitoring response to therapy and recurrence in pancreatic cancer patients. Levels are typically proportional to the tumor burden (mass), with higher levels of CA 19-9 indicative of the presence of a larger tumor. Very elevated levels, defined as more than 1,000 kilounits per liter (kU/L), are highly specific for pancreatic cancer and indicate very advanced disease. Patient preparation: No special patient preparation is required for accurate CA 19-9 analysis. 205
CA 27-29 test Steps of the procedure: A blood sample is collected, typically by venipuncture. The collected serum (or plasma) is tested by immunoassay, which involves capturing CA 19-9 present in the sample by means of monoclonal anti-CA19-9 antibodies. A second, detection (radiolabeled) antibody is then introduced, which subsequently binds to the CA 19-9/ anti-CA 19-9 complex. The addition of a substrate results in a detectable signal, the level of which is directly proportional to the amount of the CA19-9 present in the sample. After the procedure: Pressure should be applied to the venipucture site in order to avoid the development of a hematoma. Risks: The risks of venipuncture are slight but include excessive bleeding, fainting, hematoma, and infection (always a slight risk any time the skin is broken). Results: Although each laboratory establishes reference intervals based on the local, normal population, a basic interpretive guideline places normal at 0-40 kilounits per milliliter (kU/mL) and elevated at more than 40 kU/mL. Pam Conboy, B.S. See also Bile duct cancer; CA 15-3 test; CA 27-29 test; CA 125 test; Pancreatic cancers; Tumor markers.
u CA 27-29 test Category: Procedures Also known as: Carbohydrate antigen 27-29, cancer antigen 27-29 Definition: Similar to CA 15-3, CA 27-29 is a transmembrane glycoprotein (carbohydrate-containing protein, or mucin) found in several tissue types. This class of glycoproteins is thought to play a role in reducing cell-to-cell interaction and the inhibition of tumor cell cytolysis. The core protein component is identical; the carbohydrate concentration (degree of glycosylation) is the component differentiating between tissue types. Serum/plasma levels are determined by immunoassay. Cancers diagnosed: CA 27-29 is not an organ-specific marker and has been found at elevated levels in breast, ovarian, colon, stomach, kidney, lung, pancreas, uterus, and liver cancers. Additionally, increased CA 27-29 levels can be found concomitant with benign conditions such as first trimester pregnancy, endometriosis, ovarian cysts, and breast, kidney, and liver disease. Why performed: Because CA 27-29 is not sensitive or specific enough to be used as a screening test, its primary 206
Salem Health: Cancer utility is as a tumor marker for monitoring response to therapy and recurrence in previously treated Stage II and Stage III breast cancer patients. Blood levels are typically proportional to the tumor burden (mass), with higher levels of CA 15-3 indicative of the presence of a larger tumor. Physicians will typically order either CA 27-29 levels or CA 15-3 levels but not both, as they are considered essentially equivalent in diagnostic value. Patient preparation: No special patient preparation is required for accurate CA 27-29 analysis. Steps of the procedure: A blood sample is collected, typically by venipuncture. The collected serum (or plasma) is tested by immunoassay, which involves capturing CA 2729 present in the sample by means of monoclonal anti-CA 27-29 antibodies. A second, detection (labeled) antibody is then introduced, which subsequently binds to the CA 2729/anti-CA 27-29 complex. The addition of a substrate results in a detectable signal, the level of which is directly proportional to the amount of the CA 27-29 present in the sample. After the procedure: Pressure should be applied to the venipuncture site in order to avoid the development of a hematoma. Risks: The risks of venipuncture are slight but include excessive bleeding, fainting, hematoma, and infection (always a slight risk any time the skin is broken). Results: Although each laboratory establishes reference intervals based on the local, normal population, a basic interpretive guideline for CA 27-29 places normal at 0-32 units per milliliter (U/mL) and elevated at more than 32 U/mL. Pam Conboy, B.S. See also CA 15-3 test; CA 19-9 test; CA 125 test; Tumor markers.
u CA 125 test Category: Procedures Also known as: Cancer antigen 125, CA125, CA-125, CA125-II Definition: CA 125 is a mucinous glycoprotein that may be elevated in some cancer cells, particularly those associated with ovarian cancer. Cancers diagnosed: Ovarian cancer, uterine cancer, breast cancer, lung cancer
Salem Health: Cancer
Cachexia
Why performed: CA 125 serves as a biomarker or tumor marker to determine the presence of cancer. It is generated on the surface of cells and released into the bloodstream. Concentrations of CA 125 often are elevated in ovarian cancer patients.
u Cachexia
Patient preparation: No special preparation is necessary.
Related conditions: Anorexia
Steps of the procedure: To determine the level of CA 125 in a patient, blood is drawn from a vein, typically from the inside of an elbow or sometimes from the back of a hand. The site of extraction is first cleaned with an antiseptic. An elastic band is often applied around the upper arm to apply pressure and cause the vein to engorge with blood. After a needle is inserted into the selected vein, blood is collected in a syringe or an airtight vial. Once the blood is collected, the needle is removed and the puncture site is bandaged to stop any subsequent bleeding.
Definition: Cachexia is a complex syndrome in which changes in the way the body uses food—particularly fat and carbohydrates—lead to loss of muscle and fat. Anorexia (loss of appetite) is sometimes, but not always, associated with cachexia.
After the procedure: There may be throbbing or bruising around the extraction site. Risks: The risks involved in collecting blood to ascertain CA 125 levels include the possibility of excessive bleeding, fainting or light-headedness, blood accumulating under the skin (hematoma), and infection around the puncture site. There is always the possibility of multiple punctures being necessary to find a vein that will yield blood. Results: A CA 125 level greater than 35 units per milliliter (U/mL) of blood is considered to be elevated. In many cases, elevated levels are not an indication of cancer but instead can be attributed to other conditions, such as endometriosis and benign ovarian cysts. The lack of specificity is a key problem when using CA 125 as a cancer marker. In 79 percent of women tested with known ovarian cancers, CA 125 levels were elevated, while the other 21 percent showed no elevated CA 125 concentrations. The CA 125 test for ovarian cancer is most reliable in women who have gone through menopause. Tracking CA 125 levels periodically over time to determine the rate at which levels fluctuate is much more definitive than a single CA 125 test. Elevated CA 125 levels, particularly in postmenopausal women, indicate the need for further screening that may include ultrasonic imaging, computed tomography (CT) scans, and surgery. Alvin K. Benson, Ph.D. See also CA 15-3 test; CA 19-9 test; CA 27-29 test; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Ovarian cancers; Ovarian cysts; Ovarian epithelial cancer; Proteomics and cancer research; Tumor markers; Uterine cancer.
Category: Diseases, symptoms, and conditions Also known as: Wasting syndrome, anorexia-cachexia syndrome
Risk factors: Certain cancers such as lung cancer or any cancer of the digestive tract—particularly of the esophagus, stomach, and pancreas—are more likely to be accompanied by cachexia. It is also common in advanced cancer, although infrequently it occurs in early cancers, sometimes even before diagnosis. Cachexia can also occur with acquired immunodeficiency syndrome (AIDS). Etiology and the disease process: In cancer-related cachexia, it is thought that the tumor releases chemicals that change food metabolism. Patients with cachexia tend to have poor appetites. Even with nutritional supplementation, the wasting cannot be reversed while the cancer remains. Incidence: When diagnosed, about 80 percent of patients with cancers in the upper gastrointestinal tract and 60 percent of patients with cancers of the lung have already lost considerable weight. More than 80 percent of patients who die from any cancer or from AIDS have cachexia. Patients with any solid tumor except breast cancer are generally more prone to cachexia, and it is also more common and more pronounced as the disease progresses in children and in the elderly. Symptoms: Cachexia is one of the most overwhelming symptoms of cancer, demolishing quality of life with numbing fatigue, loss of appetite or changes to taste, and severe weight loss of 10 percent or more of body weight. Screening and diagnosis: When a person experiences unexplained weight or appetite loss or fatigue, medical practitioners without more specific clues might perform such general screens as a complete blood count and a chest X ray. When the source of the problem is suspected, tests are more specific. With a known cancer, cachexia diagnosis is based on clinical history, substantial weight loss, and physical examination. The concentration of plasma albumin in blood will usually be low. Extensive diagnostics are not normally required. 207
Cadmium and cadmium compounds Treatment and therapy: The best course of action for cachexia is treatment of the underlying disease. After successful treatment, patients regain lost muscle and fat mass. Prognosis, prevention, and outcomes: Prognosis is very poor with cachexia in advanced disease. When cachexia occurs in the early stages of cancer, the cancer that causes it is often responsive to treatment, and successful treatment removes the source of changes to metabolism. Jackie Dial, Ph.D. See also Antinausea medications; Appetite loss; Nutrition and cancer treatment.
u Cadmium and cadmium
compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Cadmium chloride, cadmium sulfate, cadmium nitrate, cadmium oxide, cadmium sulfide, cadmium carbonate, greenockite, capsebon, cadmopur yellow Definition: Cadmium is a natural metal, usually occurring in combination with other elements rather than in its pure state. It is most frequently found in zinc deposits as cadmium sulfide. Commercial use of cadmium began at the end of the nineteenth century and became widespread by the middle of the twentieth century. The noncorrosive properties of cadmium led to its use in batteries, electroplating, and coating of other metals, such as steel. Workers are at risk for occupational exposure to cadmium through inhalation, but cadmium also may be released into the environment through these industrial processes. Additionally, cadmium is released into the environment from other sources, including forest fires, volcanos, weathering of rocks, and combustion of fossil fuels such as coal. Both industrial and natural releases of cadmium into the atmosphere put the general public at risk for exposure through contaminated water, air, and soil. Plants can absorb cadmium from contaminated soil, so the major exposure to cadmium in the general public is through the food supply. Tobacco plants are among those that absorb cadmium, so tobacco smoking is another source of exposure in the general public. Related cancers: Lung cancer, possibly prostate and kidney cancer Exposure routes: Inhalation and ingestion 208
Salem Health: Cancer Where found: Food (particularly grain cereal products, potatoes, and other vegetables), cigarette smoke, zinc and lead ores, electroplating and -coating, alloys, pigments (paint, glass, ceramics, porcelain, textiles, plastics, paper, and fireworks), stabilizers in plastics, nickel-cadmium batteries, smoke detectors, radiation detectors, and various electronics and laboratory equipment At risk: Workers who refine and smelt zinc and lead ores, workers in industries using thermal processes (iron production or welding cadmium-coated steel), and tobacco smokers Etiology and symptoms of associated cancers: Cadmium exposure can be acute or chronic. Acute toxicity through ingestion of cadmium may cause only short-term illness, but acute toxicity through inhalation can lead to severe damage to the lungs and even death. Chronic exposure to cadmium can cause damage to the lungs, kidneys, and sometimes bones. Studies have shown that inhalation of cadmium in the workplace is associated with lung cancer. Laboratory studies using cultured cells have shown that cadmium damages the dexoyribonucleic acid (DNA) of the cells and affects the cells’ ability to repair DNAdamage. These factors are likely to be the mechanism through which cadmium contributes to the formation of cancer in humans. Lung cancer can affect one lung or both. Lung cancer detection often occurs when the disease has progressed to late stages because symptoms may take years to appear. When symptoms do appear, they often are mistaken for other less serious conditions. Common signs and symptoms of lung cancer are persistent cough (not related to smoking); persistent pain in the chest, shoulder, or back; coughing up mucus or blood; recurrent respiratory infections; shortness of breath; fatigue; unexplained weight loss; and loss of appetite. Many of these symptoms may be attributed initially to other causes before lung cancer is eventually diagnosed. Lung cancer is the only cancer that has been confirmed to be associated with cadmium exposure. Studies from the 1960’s and later have had conflicting results regarding a connection between cadmium and prostate cancer. A number of studies have shown increases in the occurrence of prostate cancer in workers exposed to cadmium in nickel-cadmium battery plants and other industrial sites, but conflicting studies have indicated no increases or increases that were too small to be statistically significant. Cadmium has also been implicated in kidney cancer, with early studies showing a correlation between exposure and increases in kidney cancer. However, further studies have not confirmed this association.
Salem Health: Cancer History: Industrial use of cadmium became widespread in the middle of the twentieth century, and the toxic effects due to occupational exposure began to be recognized by the early 1950’s. Studies that examined workers who had been exposed to high levels of cadmium were used to examine the toxic effects, and by the 1960’s researchers were investigating cadmium’s potential carcinogenicity. Experimental animal studies also were conducted to research the toxicity and carcinogenicity of cadmium. Regarding the role cadmium played in the development of lung cancer, initial studies were inconclusive or conflicting. Confounding factors, such as workers who were also tobacco smokers or were exposed to additional heavy metals, contributed to the confusing results. Because of its toxic effects, many federal, state, and local agencies, including the Environmental Protection Agency (EPA), began to regulate cadmium in a variety of ways, including stipulation of allowable amounts in air and water. In 1992 the Occupational Safety and Health Administration (OSHA) ruled on permissible exposure limits (PELs) for workers exposed to airborne cadmium in the workplace. By 2000 sufficient studies reported that cadmium contributed to the development of lung cancer for it to be designated as a known human carcinogen by the U.S Department of Health and Human Services. Michelle L. Herdman, Ph.D. u For Further Information Klaassen, Curtis D., ed. Casarett and Doull’s Toxicology: The Basic Science of Poisons. New York: McGrawHill, 2001. Silvera, S. A. N., and T. E. Rohan. “Trace Elements and Cancer Risk: A Review of the Epidemiologic Evidence.” Cancer Causes Control 18 (2007): 7-27. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Waisberg, M., P. Joseph, B. Hale, and D. Beyersmann. “Molecular and Cellular Mechanisms of Cadmium Carcinogenesis.” Toxicology 192 (2003): 95-117. u
Other Resources
Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov U.S. Department of Labor Occupational Safety and Health Administration http://www.osha.gov
Caffeine U.S Environmental Protection Agency http://www.epa.gov See also Chewing tobacco; Coke oven emissions; Free radicals; Kidney cancer; Nickel compounds and metallic nickel; Soots; Urinary system cancers.
u Caffeine Category: Lifestyle and prevention; carcinogens and suspected carcinogens ATC code: N06BC01 Also known as: Trimethylxanthine, coffeine, theine, mateine, guaranine, methyltheobromine Definition: Sometimes considered the most widely used drug in the world, caffeine is an alkaloid stimulant found naturally in coffee, tea, cocoa, and many carbonated drinks. Caffeine is a secondary metabolite substance that plants manufacture as a pesticide against insects and other invertebrates. Humans use the naturally bitter caffeine as a stimulant. Coffee, tea, and cocoa have become extraordinarily popular in most cultures of the world. In the United States, for example, it is estimated that 80 percent of adults drink either coffee or tea and over 70 percent of adults and children consume soft drinks that contain caffeine. Different studies support different arguments that caffeine has a positive or negative correlation with cancer. Related cancers: Skin cancer, breast cancer, colon cancer, rectal cancer, bladder cancer, kidney cancer, ovarian cancer, pancreatic cancer Delivery routes: Caffeine is most often ingested as a stimulant in coffee, tea, cocoa, chocolate, soft drinks, and “energy drinks.” Caffeine tablets are also taken orally as a stimulant. Caffeine is also an ingredient in certain nonprescription drugs designed to address colds, flu, headache, and pain, as well as preparations that function as stimulants to allow users to stay awake. How this drug works: Caffeine acts as a stimulant because it inhibits neurotransmitters that normally act as depressants. Specifically, caffeine occupies the neuron’s receptor sites for adenosine, which is a neuron inhibitor. Instead of being blocked and inhibited, the neuron remains active, thereby increasing neuron activity. Despite numerous studies, the relationships between caffeine intake and cancer risk remain inconclusive at best and contradictory at worst. Some studies show an inverse relationship between caffeine intake and cancer risk, while 209
Caffeine other studies suggest that caffeine increases the risk of certain cancers. Links between caffeine and cancer risk are based on the suggestion that caffeine and some of its metabolites can cause changes in cell reproduction that might enhance growth and proliferation, thereby increasing the growth and spread of cancerous cells that develop. Alternatively, other studies have suggested that caffeine and a related molecule called theophylline can block production of an enzyme that is crucial for cell growth, thereby inhibiting tumor proliferation. Studies at Rutgers University demonstrated that hairless mice treated with caffeine showed much greater resistance to skin tumors than untreated mice, but the experiment has yet to be conducted on human volunteers. Possibly the greatest concern is about a possible relationship between caffeine consumption and breast cancer incidence, with some studies suggesting that a combination of caffeine and methylxanthines showed positive correlation to breast cancer and other diseases of the mammary glands. For example, caffeine and methylxanthines (also found in coffee and tea) are associated with increased severity of fibrocystic breast disease, which may lead to the development of breast cancer, but this finding is contradicted by other studies, leading the American Cancer Institute to announce that there is no evidence between breast cancer and caffeine intake at any level. Although numerous studies have suggested a causal re-
Salem Health: Cancer lationship between coffee intake and pancreatic cancer, none so far has provided conclusive support. The relationship between caffeine and cancer is complex and remains unproven; both the International Agency for Research on Cancer and the American Cancer Society have concluded that there is no evidence that caffeine is carcinogenic. This verdict is echoed by the World Health Organization (WHO) and the Food and Drug Administration (FDA).
Side effects: In the short term caffeine increases attention span and simultaneously decreases the feeling of tiredness and weariness. Caffeine intake in children may cause hyperactive behavior. Caffeine can offset some of the effects of alcohol, but performance and coordination remain unaffected. Caffeine also increases plasma levels of fatty acids, cortisol, and epinephrine. Negative effects of excessive caffeine consumption vary with age, diet, and exercise levels. Generally, higher caffeine intake may elevate blood levels of sugars and fats, increase blood pressure, irritate the lining of the stomach, and cause heartburn, irregular heartbeat, irritability, nervousness, anxiety, depression, insomnia, and the disruption of sleeping habits. Excessive caffeine intake has also been linked to stroke and heart attack. The relationship between caffeine intake and heart problems is of great concern. Recent studies by the Adventist Health Study group reported finding a 50 percent increase in risk of serious heart disease, including heart palpitations and cardiac arrhythmias, both of which can lead to heart attacks. Other studies, however, have failed to demonstrate any relationship between coronary heart disease, stroke, and caffeine intake. Some researchers have also suggested a relationship between caffeine doses and the severity and duration of premenopausal syndrome (PMS) in females among heavy consumers of coffee, tea, and other fluids containing caffeine. Other studies have linked higher-thannormal caffeine consumption with lowered rates of conception, birth defects, retarded fetal growth, reduced birth weight, spontaneous abortion, premature delivery, and stillbirth. There is some evidence that caffeine intake by males prior to mating may result in significant fetal growth retardation, but this too remains problematic A cup of cappuccino contains the alkaloid stimulant known as caffeine. (©Draganr/ and awaits further study. While none of Dreamstime.com)
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Salem Health: Cancer these claims is absolute, women are advised not to consume caffeine while pregnant or planning on becoming pregnant, since blood levels of caffeine can be transferred through the placenta and can be metabolized by a developing fetus. Finally, high caffeine intake reduces the absorption of dietary iron by 40 to 60 percent and reduces calcium intake while simultaneously increasing the rate of calcium loss, all of which may lead to serious calcium imbalance in blood and body fluid levels. Dwight G. Smith, Ph.D. u For Further Information Gilbert, S. G. A Small Dose of Toxicology: The Health Effects of Common Chemicals. Boca Raton, Fla.: CRC Press, 2004. Porta, M., et al. “Coffee Drinking: The Rationale for Treating It as a Potential Effect Modifier of Carcinogenic Exposures.” European Journal of Epidemiology 18, no. 4 (2003): 289-298. Rowley, R., M. Zorch, and D. B. Leeper. “Effect of Caffeine on Radiation-Induced Mitotic Delay: Delayed Expression of G2 Arrest.” Radiation Research 97, no. 1 (January, 1984): 178-185. Waldren, C. A., and I. Rasko. “Caffeine Enhancement of X-Ray Killing in Cultured Human and Rodent Cells.” Radiation Research 73, no. 1 (January, 1978): 95-110.
See also Benign prostatic hyperplasia (BPH); Clinical breast exam (CBE); Diarrhea; Esophagitis; Fatigue; Fibrocystic breast changes; Gastric polyps; Gastrointestinal complications of cancer treatment; Green tea; Hot flashes; Nutrition and cancer prevention; Side effects.
u Calcifications of the breast Category: Diseases, symptoms, and conditions Also known as: Microcalcifications, macrocalcifications Related conditions: Hyperplasia, precancer of the duct, fibroadenoma Definition: Calcifications are calcium deposits in breast tissue, not detectable by touch but visible on mammograms as white spots. Macrocalcifications are large deposits, not indicative of cancer. Microcalcifications appear as tiny white specks on mammograms. Scattered throughout a mammogram, they are usually not cause for concern. They may indicate possible precancer when they appear in irregular patterns or are concentrated in one area of the breast.
Calcifications of the breast Risk factors: Macrocalcifications and 80 percent of microcalcifications are harmless. Women in their childbearing years are prone to microcalcifications. Etiology and the disease process: Macrocalcifications are related to changes in the breast due to inflammation, injury, or aging. Microcalcifications may appear in areas of rapidly dividing cells and therefore can indicate precancer. Incidence: Macrocalcifications occur in about half of women over age fifty and in about 1 in 10 women under the age of fifty. Microcalcifications are usually evident in women only during their childbearing years. Symptoms: No symptoms are associated with calcifications of either kind. Screening and diagnosis: Calcifications are visible only on radiologic images. Macrocalcifications are harmless and require no further attention. Doctors may order special magnified mammographic views of microcalcifications in clusters or in odd patterns. Generally a biopsy is not needed at the first appearance of suspect patterns. Doctors typically have the patient repeat the mammogram three to six months later. If the repeat mammogram does not exhibit any obvious changes in the pattern or number of microcalcifications, a regular schedule of mammograms is adequate to monitor further changes. If microcalcifications appear particularly suspect on first appearance or if changes are noted in the repeat mammogram, a core needle biopsy or a surgical biopsy can be done to rule out precancer. Treatment and therapy: If a patient has microcalcifications removed for biopsy that prove to be precancerous, she should be followed closely with regular mammograms to identify any future occurrences. Prognosis, prevention, and outcomes: Macrocalcifications and the majority of microcalcifications (80 percent) have no relation to cancer. If a precancerous area is identified in microcalcifications, it can be removed completely many years before it has a chance to develop into actual cancer, and the patient’s prognosis is excellent. Any other suspect microcalcifications should be removed fully and analyzed. Patients should be closely followed for the occurrence of new microcalcifications. After menopause, microcalcifications generally no longer occur. Charlotte Crowder, M.P.H., ELS See also Breast ultrasound; Ductogram; Fibroadenomas; Hormone replacement therapy (HRT); Lobular carcinoma in situ (LCIS); Microcalcifications; Tubular carcinomas; Wire localization. 211
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u Calcium Category: Lifestyle and prevention Also known as: Calcium carbonate, calcium citrate, calcium phosphate Definition: Calcium is the most abundant mineral in the body. About 1 percent of calcium is found circulating in the blood, while the remaining 99 percent is stored in bones and teeth. Calcium must be obtained from the diet. It is found primarily in dairy products and is sold as a dietary supplement. Cancers treated or prevented: Colorectal cancer, breast cancer Delivery routes: Oral tablet How this substance works: Circulating levels of calcium help control metabolic events such as muscle contraction and nerve impulse transmission. In healthy people, the amount of calcium in the blood is kept within narrow limits by hormonal regulation. Calcium also helps to build strong bones and delay bone loss caused by aging (osteoporosis). The United States Office of Internal Medicine has established a maximum safe intake level for calcium of 2,500 milligrams per day for persons over one year of age. Animal studies and several human observational and research studies have found that increased intake of calcium is protective against the development of colorectal cancer. The reason for this protective effect is not understood, and not all studies have found calcium to be protective against colorectal cancer. In 2007, the Women’s Health Initiative study of more than 36,000 women aged fifty to seventy-nine found no effect of calcium on the development of colorectal cancer. More research must be done on the relationship between cancer and calcium in different age and gender groups before drawing any firm conclusions. Animal studies have also suggested that calcium may protect against breast cancer. In 2007, a peer-reviewed study of 10,500 premenopausal women found that when the intakes of calcium and vitamin D were simultaneously increased for an extended period, the risk of developing breast cancer was reduced by almost one-third. This effect was not seen in postmenopausal women. Clinical trials examining the relationship between cancer and calcium are under way; information is available at http://www .clinicaltrials.gov. Side effects: Complicating the situation with calcium is evidence that increasing calcium intake in men in amounts ranging from 600 to 2,000 milligrams or more per day may 212
Salem Health: Cancer increase the risk of developing prostate cancer. This is not, however, a consistent finding, and more rigorous studies need to be done. Many tumors that invade bone release stored calcium and cause the blood level of calcium to increase independent of dietary intake. This condition, called hypercalcemia, is the most common life-threatening metabolic disorder associated with cancer. Martiscia Davidson, A.M. See also Bone scan; Breast cancers; Caffeine; Calcifications of the breast; Cartilage supplements; Chemoprevention; Colon polyps; Colorectal cancer; Ductogram; Fiber; Gastrointestinal cancers; Hypercalcemia; Kidney cancer; Microcalcifications; Nutrition and cancer prevention; Polyps.
u Cancell Category: Complementary and alternative therapies; chemotherapy and other drugs Also known as: Entelev, Sheridan’s Formula, Jim’s Juice, Canctron, JS-114, JS-101, 126-F Definition: Cancell (previously known as Entelev) is a controversial and unapproved therapy developed in the late 1930’s. Cancell is a combination of chemicals that is thought to kill cancer cells by affecting their cellular respiration and/or electrical voltage. No clinical trials using Cancell have been published in peer-reviewed journals, and in 1989, the U.S. Food and Drug Administration (FDA) declared it illegal for manufacturers to sell and/or transport Cancell across state lines. Cancers treated or prevented: The manufacturers claim that Cancell can treat all types of cancer; however, it is not approved by the FDA. Delivery routes: Cancell is in liquid form and has been taken by mouth, inserted into the rectum, or applied to the skin (on the wrist or ball of the foot). How this substance works: Cancell (then known as Entelev) was first envisioned in the late 1930’s by the biochemist James V. Sheridan. In 1984, Edward J. Sopcak began making Cancell. Sheridan believed that Cancell affects cellular respiration, a chemical process that uses oxygen and provides energy to a cell. He further speculated that cells which do not require oxygen for respiration are “primitive” and that these primitive cells may be recognized, attacked, and killed by the body’s immune system or through other processes. Accordingly, Sheridan be-
Salem Health: Cancer lieved that Cancell could change cancer cells to a primitive state. Similarly, Sopcak thought that Cancell affected the vibrational frequency and energy of cancer cells, which may disrupt cancer proteins and change cancer cells to primitive cells. In either theory, the hypothesis is that Cancell makes cancer cells become primitive, which would allow the body to get rid of them. Cancell contains various ingredients, including the chemicals inositol, nitric acid, sodium sulfite, potassium hydroxide, sulfuric acid, and catechol. Laboratory studies conducted by the National Cancer Institute (NCI) found that Cancell could not be taken safely by humans at doses high enough to kill cancer cells. Therefore, the NCI concluded that Cancell did not show sufficient anticancer activity to merit continuing the studies. Furthermore, no studies of Cancell (in either animals or humans) have been published in peer-reviewed scientific journals. Side effects: The main side effects of Cancell include tiredness during the first few weeks of treatment, as well as nausea and diarrhea. Elizabeth A. Manning, Ph.D. See also Essiac; Laetrile; Mistletoe; PC-SPES; Sun’s soup.
u Cancer biology Category: Cancer biology Definition: The transformation of a normal cell into a cancerous one is a complicated process consisting of multiple steps and many changes to the cell and its normal control mechanisms. The fact that most human cancers develop later in life reflects the time required for these changes to occur. These changes include the activation of oncogenes, the inactivation of tumor-suppressor genes, and acquisition of a cell’s ability to become immortal, to invade new tissues at distant locations, and to induce the formation of new blood vessels. Characteristics of human cancers: Mutations that are present in the germ cells (egg and sperm) can be passed to the next generation. Mutations that occur in any other cells of the body, called somatic mutations, may affect the cell or tissue in which they occur, but they will not be passed to the next generation. Both germ-line and somatic mutations can cause cancer; it is estimated that approximately 10 percent of cancers are caused by germ-line, or inherited, mutations. Tumors can be either benign (those that remain localized and noninvasive), malignant (those that invade the
Cancer biology basement membrane and underlying tissue), or metastatic (those that shed cells that seed tumors in other locations of the body). Progressive degrees of abnormality are observed in benign, malignant, and metastatic tumors, suggesting that cancer develops in a stepwise process. Cancers can arise in almost all tissue types in the body, although approximately 80 percent of human cancers arise from epithelial cells—those cells that cover internal and external surfaces of the body, including the linings of internal organs and glands. The incidence of many types of cancer varies worldwide, and epidemiologic studies show that environment is the largest factor in variations in cancer incidence from country to country. Indeed, a number of environment and lifestyle elements, tobacco smoking being the most obvious, are known to be strongly correlated with the incidence of certain types of cancer. In 1975, it was shown that many chemicals that are capable of causing mutations in deoxyribonucleic acid (DNA) are also capable of causing cancer in laboratory animals. Later research showed, however, that not all chemicals that cause cancer also cause mutations. Therefore, other mechanisms besides DNA mutation must be involved in at least some cancers. Gene expression and signaling pathways: For the cells of an organism’s various tissues (lung and bone, for example) to display complex, tissue-specific characteristics, large groups of genes must be coordinately expressed while other genes must be repressed. Specialized proteins known as transcription factors are responsible for achieving this coordinated expression. Transcription factors bind to specific DNA sequences in the control region of each gene. The transcription of most genes is controlled by the binding of several distinct transcription factors in the gene’s control region. A single transcription factor can affect the expression of multiple genes that contain its binding sequence in their control regions. In cancer cells, a defective transcription factor may affect the expression of multiple genes, the end result of which is to create a cancer cell from a normal cell. Normal cells within tissues and within an organism communicate with each other in a regulated fashion through a multitude of chemical signals and pathways. Disruption of these normal signaling pathways is an important component of the formation of cancer. In normal cells, signals are transmitted through the various pathways in a number of ways: by a change in the level of activity of signaling molecules by noncovalent modifications, changes in the concentration of a signaling molecule inside a cell, or the direction of signaling molecules to particular locations within the cell. 213
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Salem Health: Cancer surface to which growth factors bind; signal transducers, proteins that make up the signaling pathways between the growth factor receptor and the cell nucleus; and transcription factors.
Tumor-suppressor genes: The class of tumorsuppressor genes includes a large number of genes whose protein products are involved in a multitude of normal cellular functions that in some way regulate a cell’s division and reduce the chance that the cell will become cancerous. Tumor-suppressor genes in cancer cells are often inactivated through mutation or other mechanisms. An inherited increased risk of developing a specific type of cancer in some families is often the result of the presence of a defective tumor-suppressor gene. It is the loss of function of tumor-suppressor genes that can lead to cancer, in contrast to oncogenes, which have gained functions or lost the ability to be controlled in their mutant form. The protein product of a particularly important tumor-suppressor gene, called TP53, causes cessation of cell division and even programmed cell death (apoptosis) in normal cells if the process of cell division malfunctions. In this way the cell’s well-being is monitored, protecting the organism from the effects of runaway division of wayward cells by activating the apoptotic pathway in such Colon cancer under the microscope. (©Micro Discovery/Corbis) cells. Apoptosis is an orderly process in which the DNA of a cell is degraded and the cell itself fragmented into smaller pieces that are taken up by Oncogenes: Normal cells contain a class of genes innearby white blood cells whose job is to clean up such devolved in the regulation of growth and division called bris. Loss of the ability to undergo apoptosis allows cancer proto-oncogenes. A proto-oncogene can mutate into a vercells to survive a variety of environmental stresses and sigsion that is permanently activated and causes uncontrolled naling imbalances. The TP53 gene in the DNA of cancer cell division, one of the hallmarks of a cancer cell. The cells often carries mutations that cause it to malfunction; transformation of a proto-oncogene into an oncogene may more than 90 percent of small-cell lung cancers and more involve a change to the structure of the protein itself or an than 50 percent of breast and colon cancers have been increase in its expression. Achange involving the structure shown to be associated with mutant forms of TP53. of the protein itself may require only very small changes; Normal cells throughout the body grow and divide to in some cases a single base pair mutation is sufficient. A generate two daughter cells in a highly organized and conchange involving an increase in expression often occurs trolled series of events called the cell cycle. A subclass of through increasing the number of copies of the gene in the tumor-suppressor genes controls cell-cycle events in norDNA. There are several ways that amplification of a gene mal cells. Control mechanisms at various steps of the cell can occur: by enhanced replication of a chromosome segcycle function to ensure that a preceding step is completed ment that carries its DNAor by the breaking away of such a before the next step can begin. These control mechanisms are inactivated in many types of cancer cells, allowing chromosome segment to form a small chromosome-like them to divide in an unregulated fashion. A particularly particle that is capable of replicating independently. important tumor-suppressor gene in this class is the retinoScientists have identified more than one hundred oncoblastoma (RB1) gene. The protein product for which the genes. They include growth factors, proteins that signal a RB1 gene codes, pRb, is affected in most if not all types of cell to divide; growth factor receptors, proteins on the cell 214
Salem Health: Cancer human cancer cells. Loss of normal regulation of the signaling pathway of which pRb is a component leads to unrestrained cell proliferation. Cell immortalization: The ability of a cell to divide indefinitely, called cell immortalization, appears to be a characteristic of all cancer cells. This ability has been shown to be related to the structures of the ends of chromosomes, called telomeres, which are composed of several thousand repeats of a six-base-pair sequence element. Every time a cell duplicates its DNA, the telomeres are shortened by fifty to one hundred base pairs, with the result that normal cellular DNA has the capacity for a finite number of replications. The ability to indefinitely maintain telomere length has been observed in virtually all types of cancer cells, the majority of which accomplish this by increasing the expression of the enzyme, telomerase, which is responsible for synthesizing telomeres. Angiogenesis: All cells depend on the availability of oxygen and nutrients for their growth and survival. Virtually all cells in a tissue must be located close to a capillary blood vessel that can deliver nutrients and take away metabolic waste products. For a cancer cell to progress to a macroscopic tumor, it must acquire the ability to induce the formation of new blood vessels, a process called angiogenesis. In normal cells, various negative and positive signaling pathways control the angiogenic process. Cancer cells appear to induce angiogenesis in a number of steps that change the balance of angiogenesis inducers and inhibitors during tumor development. Metastasis: Most types of human cancer will at some point undergo metastasis, the process whereby new tumors are seeded at distant sites from the primary tumor. Metastases are responsible for approximately 90 percent of all cancer deaths. Metastasis involves tumor cells leaving the primary tumor, invading adjacent tissues, and from there traveling to sites where they are able to settle and start the growth of new tumors. The primary route of metastasis is through the circulatory system, although metastatic cancer cells may also spread through lymph ducts to lymph nodes. Sometimes cancer cells traveling through the circulation form small obstructions that lodge in the arterioles and capillaries of various tissues. Complex interactions between the metastasizing cell and the microenvironment of the host tissue in which it lands govern the process of invasion into the tissue and colonization to form a metastasis in a process that is not well understood. Cancer cells that metastasize do not appear to have undergone major changes in their DNA compared with other cells in the original tumor. However, cancer cells that pos-
Cancer biology sess metastatic potential have alterations in several classes of proteins involved in the attachment of cells to their surroundings in a tissue, which render them less able to form such attachments. Cancer cells with metastatic potential may also have an increased ability to degrade proteins in their immediate environment. Metastasizing cells from various types of cancers tend to spread preferentially to some organs; for instance, prostate and breast cancers have a strong tendency to metastasize to the bone marrow, and colon cancer has a strong tendency to metastasize to the liver. The reason for this phenomenon is not well understood. Genomic instability: It has been estimated that multiple genetic changes, perhaps five to seven, are needed for the development of a full-fledged human cancer. A normal cell has numerous control and repair mechanisms that ensure the fidelity of DNA replication and, therefore, that the occurrence of mutations is rare. Malfunctioning of components of these control and repair mechanisms, such as TP53, leads to the observed chromosomal instability and variability of cancer cells. Genetic instability is pervasive in human cancer cells, which commonly exhibit various types of aberrantly structured chromosomes: the loss of entire chromosomes, the presence of extra copies of chromosomes, or the fusion of part of one chromosome with part of another. These chromosomal abnormalities disrupt normal DNA sequence and arrangement and probably help explain how precancerous cells acquire the necessary mutations to render them cancerous. Jill Ferguson, Ph.D. u
For Further Information Hanahan, D., and R. A. Weinberg. “The Hallmarks of Cancer.” Cell 100 (2000): 57-70. Karp, Gerald. Cell and Molecular Biology. 4th ed. New York: John Wiley, 2004. Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, 2007.
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Other Resources
Emory University CancerQuest: Important Tumor Suppressors http://www.cancerquest.org/index.cfm?page=52 Inside Cancer http://www.insidecancer.org National Cancer Institute Cancer Topics http://www.cancer.gov/cancertopics 215
Cancer care team See also Angiogenesis; BRAF gene; BRCA1 and BRCA2 genes; Carcinogens, known; Carcinogens, reasonably anticipated; Cyclin-dependent kinase inhibitor-2A (CDKN2A); Cytokines; Epidemiology of cancer; Estrogen receptor downregulator (ERD); Genetics of cancer; Human chorionic gonadotropin (HCG); Immune response to cancer; Mitochondrial DNA mutations; MLH1 gene; MSH genes; Mutagenesis and cancer; MYC oncogene; Oncogenes; Placental alkaline phosphatase (PALP); PMS genes; Proteomics and cancer research; RB1 gene; RhoGD12 gene; SCLC1 gene; TP53 protein; Tumor necrosis factor (TNF); Tumor-suppressor genes.
u Cancer care team Category: Medical specialties Definition: The cancer care team consists of all the allied health professionals who are involved in a patient’s cancer diagnosis, treatment, and recovery or end-of-life planning. The team can include others who are not health professionals but are nonetheless an important part of the team. These can include spiritual leaders, social workers, and volunteers who provide assistance with transportation or housekeeping, as well as any other people who provide support or care for the individual with cancer. Subspecialties: There is a nearly infinite number of subspecialists who make up the cancer care team. The most important member of the cancer care team is the patient, because this person has the ultimate say in what services and treatment are received. A family member or friend who provides day-to-day care throughout the duration of the cancer treatment and afterward may have no medical training but is nonetheless an integral part of the cancer care team. In addition, the team contains those medical professionals attempting to treat the cancer, such as medical or surgical oncologists, and those whose main function is to help the patient live more fully or more comfortably, such as physical and occupational therapists, psychological counselors, and nutritionists. Also in the team are those whose primary function is to provide emotional support or generalized help for the patient and family, such as social workers, clergy members, and volunteers who provide transportation, help with meals, or simply companionship. Cancers treated: All types of cancer are treated by a cancer care team. The type of cancer the individual has and the planned treatment affect which professionals will be members of the team. The outcome of the cancer treatment 216
Salem Health: Cancer can also determine which professionals are part of the cancer care team. An individual diagnosed with a cancer that is in an early stage and is likely to go into remission probably will be involved with team members to help with the recovery process, such as occupational and physical therapists. An individual diagnosed with a cancer with a high mortality rate that has already spread significantly is likely to have a cancer care team that includes individuals trained in palliative care and end-of-life planning, such as hospice workers and financial planners. Training and certification: The training and certification required to be a member of the cancer care team depends on the role of the team member. A surgical oncologist requires an undergraduate degree, a medical degree, a long surgical residency, and additional surgical oncological training. Depending on the level of care nurses are allowed to provide, they may require various levels of training, including a master’s or doctoral degree. Psychological counselors or therapists usually are required to complete a master’s or doctoral level program. Assistants who are specialists in running certain types of machinery or equipment or assisting other health care professionals may have an associate degree or have completed a special certificate program. Some members of the cancer care team who assist with functions such as changing linens or retrieving necessary items may have received all of their training on the job. Services and procedures performed: The cancer care team sees the patient through the entirety of the cancer care process, from diagnosis and treatment to recovery or endof-life planning. The first member of the cancer care team that an individual usually sees is a general practice physician, gynecologist, dermatologist, or other doctor who determines that cancer is possibly present. At that point the member of the cancer care team who is seen next depends on the type of cancer suspected. A person might next see a radiological technologist who will take X rays or other images and submit them to the radiologist for reading. The person might instead see a technician who takes a biopsy sample of the lump if it is breast cancer that is suspected. If a biopsy or other sample is done, then the next member of the cancer care team may be the pathologist, who will do laboratory tests to determine whether cancer is present and, if so, which type of cells it contains. Once a diagnosis of cancer has been made, then the cancer care team expands dramatically. Often the team includes a case manager, who will coordinate all aspects of a patient’s care. The case manager may work with the patient’s primary physician, the primary oncologist, nurses,
Salem Health: Cancer pharmacists, and other professionals who are providing care to the patient. This way, one person knows everything that is going on and can help ensure that nothing is being missed or done unnecessarily. The case manager may even help with scheduling appointments and may be able to recommend people such as social workers to assist the patient. The team may also contain a social worker who is specially trained in helping cancer patients. The social worker can provide information about services available to the cancer patient and help with government paperwork and other issues that are often present during cancer care. The actual medical treatment for the cancer may be provided by a large number of oncologists with different specialties. Each of these oncologists works with a staff of medical professionals to help provide care. All these people are important members of the cancer care team, including any assistants or technicians who may help the patient get ready for procedures or teach them about proper selfcare for afterward. Although many members of the cancer care team are focused on trying to cure the cancer, other members of the
Cancer care team team are primarily interested in helping the patient maintain as good a standard of living and degree of independence as possible throughout the treatment and afterward. Physical and occupational therapists can help patients regain lost skills or mobility and help patients plan for the challenges of treatment, such as by teaching them energy conservation techniques to use while receiving chemotherapy treatments. A nutritionist can ensure that the patient gets all the required vitamins and nutrients during treatment and can help the patient work through issues such as weight loss or gain. If the cancer treatment is not successful, professionals can help patients and their families and friends with palliative care and end-of-life planning. These are important members of the cancer care team, even though trying to cure the cancer is not their goal. If the patient chooses hospice care, doctors and nurses who are specially trained in providing end-of-life care and comfort will become important members of the team. Financial planners, lawyers, and others can help the family ensure that all the cancer patient’s wishes will be carried out. Special bereavement
Many different health care professionals are part of the cancer care team. (Digital Stock)
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Cancer clusters counselors can also be part of the team to help the family make the most of the time that is left. Related specialties and subspecialties: There are many related specialties and subspecialties that provide support for the cancer care team. These include technicians who operate or service necessary machinery and equipment, technicians, schedulers and office staff, record keepers, and insurance liaisons. Helen Davidson, B.A. u For Further Information Corner, Jessica, and Christopher Bailey, eds. Cancer Nursing: Care in Context. Malden, Mass.: Blackwell, 2008. Hamilton, William, and Tim J. Peters. Cancer Diagnosis in Primary Care. New York: Churchill Livingstone/ Elsevier, 2007. Lyons, Lyman. Diagnosis and Treatment of Cancer. New York: Chelsea House, 2007. Nakamura, Robert M., et al., eds. Cancer Diagnostics: Current and Future Trends. Totowa, N.J.: Humana Press, 2004. u
Organizations and Professional Societies
American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 Society of Surgical Oncology http://www.surgonc.org 85 West Algonquin Road, Suite 550 Arlington Heights, IL 60005 u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Cancer education; Caregivers and caregiving; Case management; Counseling for cancer patients and survivors; End-of-life care; Genetic counseling; Home health services; Hospice care; Living with cancer; Longdistance caregiving; Medical oncology; Oncology; Oncology clinical nurse specialist; Oncology social worker; Primary care physician; Psycho-oncology; Psychosocial aspects of cancer; Radiation oncology; Relationships; Second opinions; Support groups; Surgical oncology. 218
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u Cancer clusters Category: Social and personal issues Definition: A cancer cluster is a significantly higher than expected number of cases of cancer in a certain group, area, or time period. Identifying a possible cancer cluster: Cancer is a very common disease. The United States Centers for Disease Control and Prevention (CDC) estimate that about one in every three Americans will develop cancer at some point during his or her lifetime. With a disease as common as cancer, it is not unusual for two friends, coworkers, or neighbors to be diagnosed with the same kind of cancer or to be diagnosed at similar times. However, sometimes it may seem like more than just a normal coincidence. Sometimes it may seem as if many people in the same workplace, neighborhood, or family are being diagnosed with cancer. In these cases, a cancer cluster may exist. Many suspected cancer clusters are reported each year. According to the American Cancer Society, as of 2006 more than one thousand reports of suspected cancer clusters were being made to state health agencies every year. The vast majority of these suspected cancer clusters turn out not to be true cancer clusters after careful investigation and statistical analysis. For many of the clusters that are believed to be true cancer clusters, an underlying cancer agent is never satisfactorily identified. However, in some cases, a cancer cluster is identified and an environmental or other agent is found to be responsible. This is one way that substances can be identified as causing an increased risk of cancer. Just having a group of people who all seem to have been diagnosed with cancer at a similar time or who have a similar type of cancer is not enough to indicate that a true cancer cluster exists. A group of cancer cases is more likely to be a cancer cluster if one or more of certain factors exist. It is more likely to be a true cancer cluster if there is only one primary diagnosis of cancer involved and the cancer is an uncommon one. According to the American Cancer Society, it is estimated that more than 170,000 new cases of breast cancer were diagnosed in the United States in 2007. Therefore, if ten women in the same moderately sized town were diagnosed with breast cancer, it would be unlikely to indicate a cancer cluster, but if the same number of women were diagnosed with an extremely rare form of cancer, a cancer cluster might be more likely. If a very large number of cases of a common form of cancer occur, this may be a possible indication of a cancer cluster. Additionally, if cancer occurs in a particular group of people in whom it is not usually seen, such as breast can-
Salem Health: Cancer cer in men, or a type of cancer that usually develops in adults is diagnosed in children, it may be a sign of a possible cancer cluster. If a set of people who share a welldefined characteristic, such as all working in the same factory over the same period of time, are involved in the suspected cluster, it is generally more likely to be a true cancer cluster than if the suspected cancer cluster involves people who do not share a very specific common trait. Investigating a suspected cancer cluster: When a cancer cluster is suspected, it is usually reported to a state board of health or to a state cancer registry. Cancer registries collect information about cancer occurrences and cancer-related mortality statistics. Anyone can report a suspected cancer cluster; it does not have to be reported by a government employee or by a doctor or other health professional. Once a suspected cancer cluster has been reported, the state health department or other agency will collect information about the people in the suspected cluster. This will include information about the age and ethnic background of the people involved, the type or types of cancers, the places in which the individuals have lived and worked, the time period during which the cancers occurred, specific medical information about the cancers, and any other available information. The health agency will also try to gather information about what possible causes for the cancers exist, such as if there are any known or suspected carcinogens in the places in which the affected people work or live. They may also collect information about any other possible causes of the cancer, such as a history of smoking. After analyzing all the gathered information, experts at the health agency will decide if there is reason to suspect that a true cancer cluster exists. According to the American Cancer Society, four out of five of all reported possible cancer clusters are determined not to be true clusters based on preliminary information. This is because often what may seem like a large number of cases of cancer is still within reasonable expectations given the population and other variables. One of the ways that experts can determine whether it is possible that the group of cancers constitute a true cancer cluster is by doing statistical analysis to determine if the number of cancers is statistically significant. A group of cancers is statistically significant if it is more than the number of cancers that are expected to occur in the group by chance. In most cases, 5 percent is considered the benchmark to determine if something is statistically significant. This means that out of one hundred towns of the same size and population, for example, the number of cancers seen in the town in question would occur in five or fewer of the towns by chance alone. If it is determined that there may be a true cancer clus-
Cancer clusters ter, the state health agency, scientists, medical professionals, and sometimes federal agencies such as the CDC will begin to investigate in more depth. This may involve getting detailed medical records and histories, interviewing people in the area in question, and testing possible sources of carcinogens. It is usually a very time-consuming, manpower-draining, and money-intensive investigation. Once all the evidence has been gathered, experts try to determine if there is a true cancer cluster and what caused the cluster. Unfortunately, in many cases, it is never possible to determine a definite cause. This is because the factors that cause cancer are complex and interactive, and cancer may not be diagnosed for ten or more years after exposure to the believed carcinogen. Historic cancer clusters: Several well-known cancer clusters have been documented in the United States since the 1960’s. In some cases these clusters were linked to environmental toxins, such as toxic waste spills, and in other cases they have been linked to workplace-related exposures. Some cancer clusters have even helped identify substances that are carcinogenic that were not formerly known to be harmful. Possibly the most famous cancer cluster is the cluster in Hinkley, California, which was the basis for the film Erin Brockovich (2000). The cause believed to be at the root of the town’s problems was chromium-6 that had been dumped into unlined ponds by the Pacific Gas and Electric plant near the town. The chromuim-6 was believed to have leached out of the ponds and into the ground and drinking water of the residents of Hinkley. Another well-known cancer cluster was in Toms River, New Jersey. In Toms River, 118 children were found to have cancer between 1979 and 1995, far more than could be reasonably attributed to chance for that population. Investigations found that 4,500 barrels of toxic waste had been dumped at a landfill and much of the toxic waste had leached into the Toms River water supply. In the 1960’s, a very high number of cases of mesothelioma were found and were determined to have been caused by prolonged exposure to asbestos. At the time, asbestos was used frequently in consumer products and in shipbuilding. The discovery of the cancer cluster and the subsequent discovery of its cause led to a drastic change in the way asbestos is handled, its removal from schools and other public places, and the development of safe handling practices and alternative technologies. Without someone noticing and reporting the high incidence of mesothelioma, many more people might have been harmed by asbestos exposure. Helen Davidson, B.A. 219
Cancer education u For Further Information Carcinogens. Davenport, Iowa: Mangan Communications, 2007. Carney, Jan K. Public Health in Action: Practicing in the Real World. Sudbury, Mass.: Jones and Bartlett, 2006. Duffy, Jim. “Cancer Clusters.” Ecologist 37, no. 5 (June, 2007): 9-18. Greenberg, Michael R. Environmental Policy Analysis and Practice. New Brunswick, N.J.: Rutgers University Press, 2007. u
Other Resources
Centers for Disease Control and Prevention Cancer Clusters http://www.cdc.gov/nceh/clusters National Cancer Institute Cancer Clusters http://www.cancer.gov/cancertopics/factsheet/risk/ clusters See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Ethnicity and cancer; Geography and cancer; Latinos/Hispanics and cancer; Mesothelioma; Native North Americans and cancer; Occupational exposures and cancer; Poverty and cancer; Statistics of cancer.
u Cancer education Category: Medical specialties Also known as: Health education, patient education, cancer study and teaching Definition: Cancer education involves the creation and distribution of information to teach health professionals by assisting their study and advancement of oncology procedures and enhancing their teaching of patients, the public, and peers. Cancer educators emphasize prevention, detection, and treatment methods to control cancers. Subspecialties: An interdisciplinary effort, cancer education encompasses diverse specialties, including oncology, nursing, pediatrics, dentistry, pharmacy, dietetics, genetic counseling, physical therapy, occupational therapy, psychology, physician assistance, and social work. Cancers treated: Cancer education addresses all known cancers, focusing on commonly occurring cancers, particularly breast, prostate, and colon cancers, which medical professionals frequently diagnose in patients. Interna220
Salem Health: Cancer tionally, medical, dental, and nursing schools educate students regarding cancers they will probably encounter in their residencies and practices. Graduate medical students obtain advanced cancer education according to specialties they pursue in their training and research. Training and certification: Cancer educators often receive basic training for educational procedures as part of health-related degrees they earn. The American Association for Cancer Education (AACE) offers workshops and clinics at its annual conferences, during which participants can acquire skills and learn developments in cancer education research and practices to earn credits and certificates acknowledging they participated in those educational experiences. The American Cancer Society (ACS) and Oncology Nursing Society present continuing education opportunities for cancer educators to complete specific training to learn methods and strategies for more effective cancer education services for patients and their caregivers. Services and procedures performed: Cancer education experts instruct medical professionals while they attend school and throughout their careers concerning methods to diagnose cancers in patients and to determine which treatments to recommend. Governments, academic institutions, and such groups as the American Cancer Society fund research to enhance educational opportunities for physicians and health professionals to provide suitable, up-to-date medical care for cancer patients. Professional and licensing organizations such as the American College of Surgeons offer resources in their educational departments. The American Association for Cancer Education and European Association for Cancer Education reinforce their members’ educational and teaching skills in medical and dental colleges, hospitals, and other forums by offering information in such specific areas of cancer education as oral oncology and palliative care and by encouraging continued training in cancer education. Those professional organizations collaboratively publish The Journal of Cancer Education, which contains news and articles evaluating cancer education techniques, communication, and research. Representatives of the American Association for Cancer Education survey cancer education taught at U.S. medical and dental schools to evaluate the curricula offered and offer insights regarding what cancer education should address in schools. Health professionals supply information to assist people in acquiring knowledge to prevent or mitigate cancer through informed decisions, early detection of symptoms, and the choice of effective treatments. Cancer educators inform both children and adults in their communities re-
Salem Health: Cancer garding cancer issues. Educators present cancer prevention information at schools and workplaces, advising healthy nutrition and behaviors to minimize risks associated with cancer. Cancer educators convey information concerning genetic testing for potentially inherited cancer vulnerabilities. Medical personnel realize cancer education counters misinformation and enables better medical care, helping adjust perceptions concerning cancer by explaining that many cancers are treatable, not terminal. Cancer educators create and distribute accessible information, assessing literacy and cultural factors to achieve effective communication. Educators evaluate attitudes regarding cancer in individual patients and their caregivers to determine the specific educational materials, ranging from pamphlets to videotapes and Internet resources, most likely to assist them. Cancer educators assist comprehension of information to ease physical and emotional aspects of cancer by explaining tests, procedures, medications, and side effects. Many hospitals and cancer centers maintain cancer education information in health libraries and learning centers with education personnel designated to administer those resources. Cancer groups, hospitals, and drug manufacturers publish educational material to assist cancer educators to learn about new treatments and pharmaceuticals. The American Cancer Society has pursued education through media, a Facts About Cancer pamphlet, lists of seven basic cancer symptoms, and educational guides devoted to specific cancers. The National Cancer Institute (NCI) contributes to cancer education by helping both health provider educators and people seeking cancer information. The institute published the Trainer’s Guide for Cancer Education (2005) and established a Cancer Information Service and an Office of Cancer Communications. The NCI Patient Education Branch created the Cancer Patient Education Network. The Wellness Community also provides cancer education resources. Elizabeth D. Schafer, Ph.D.
Candidiasis don. Patient Education in Health and Illness. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Saca-Hazboun, Hanan. “Empowering Patients with Knowledge: An Update on Trends in Patient Education.” ONS Connect 22, no. 5 (May, 2007): 8-12. Varricchio, Claudette, et al., eds. A Cancer Source Book for Nurses. 8th ed. Sudbury, Mass.: Jones and Bartlett, 2004. Wilkes, Gail M., and Terri B. Ades. Patient Education Guide to Oncology Drugs. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2004. u
Organizations and Professional Societies
American Association for Cancer Education http://www.aaceonline.com 620 Walnut Street 330 WARF Building Madison, WI 53726 European Association for Cancer Education http://www.eaceonline.com Academie Gezondheidzorg Saxion Hogescholen Postbus 70.000 7500 KB Enschede The Netherlands u
Other Resources
Cancer Patient Education Network http://www.cancerpatienteducation.org The Wellness Community http://www.thewellnesscommunity.org See also Cancer care team; Caregivers and caregiving; Case management; Clinical trials; Counseling for cancer patients and survivors; Family history and risk assessment; Genetic counseling; Primary care physician; Psychosocial aspects of cancer; Second opinions; Support groups.
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For Further Information Labus, James B., and Alison A. Lauber. Patient Education and Preventative Medicine. Philadelphia: W. B. Saunders, 2001. National Cancer Institute. Trainer’s Guide for Cancer Education. Bethesda, Md.: National Institutes of Health, National Cancer Institute, 2005. Osborne, Helen. Health Literacy from A to Z: Practical Ways to Communicate Your Health Message. Sudbury, Mass.: Jones and Bartlett, 2005. Rankin, Sally H., Karen Duffy Stallings, and Fran Lon-
u Candidiasis Category: Diseases, symptoms, and conditions Also known as: Thrush, yeast infection, fungal infection Related conditions: Fever, infections, and sepsis in cancer treatment Definition: Candida species are fungi that are found as part of the normal flora in humans and are also major hu221
Candidiasis
Salem Health: Cancer
pases) can alter protective mucous membranes, allowing penetration into the tissues beneath. The cell wall of Candida species is made up of beta-glucans, mannoproteins, and chitins (carbohydrates). Different growth conditions can result in changes in cell-wall components that drastically alter the morphology. Outside the body and on mucosal surfaces, Candida species exist as yeasts (round or oval, single-celled organisms). When tissues are invaded, the amount of cell-wall chitin is increased, and mycelia (long filaments) are formed rather than yeasts. This phenomenon is called dimorphism and may make the organism more challenging for the immune system. Formation of finger-like projections from yeast cells (pseudohyphae) seems to be imporCandidiasis in the mouth. (Custom Medical Stock Photo) tant in penetration into host cells. These and other candida virulence factors are man pathogens. The diseases caused by Candida species important contributors to disease causation, but it is the are termed candidiasis. impaired immune system of the host that usually tips the balance. Risk factors: Candida colonization increases after antibiotic (antibacterial) therapy, and the broader the spectrum Incidence: Autopsies of leukemia patients reveal dissemiof antibacterial therapy, the greater the growth. Cancer nated candidiasis involving major organs in 20 to 33 persurgery, particularly if it involves the gastrointestinal (incent of cases. Bloodstream invasion has been documented cluding oral) or female genital tract, can allow candida in more than 10 percent of patients with leukemia and present in the normal flora of these areas to enter into the about 1 percent of patients with lymphoma. The incidence previously protected underlying tissues. Cancer chemois lower in patients with solid tumors and in children. therapy can impair the immune system by decreasing the Symptoms: Symptoms can be quite varied, as many difproduction of white blood cells by the bone marrow. When ferent areas of the body and organs can be infected. Oral corticosteroids are used as part of the cancer chemotherdiscomfort and swallowing pain and difficulty may acapy, both neutrophil and lymphocyte function is impaired. company oral and esophageal candidiasis. Abdominal Radiation can damage mucous membranes and, in some pain can occur with stomach and intestinal ulcerations cases, the bone marrow as well. Vascular catheters used to caused by candida in cancer patients. Vaginal discharge administer cancer chemotherapy and other drugs are freand itching is often associated with candida vaginitis. quently ports of entry for candida. Urinary and gastroinEndophthalmitis can cause blurred vision. Infected petestinal catheters can also assist invading organisms. ripheral and central intravascular catheters may have minLeukemias, lymphomas, and bone marrow metastases can imal symptoms heralding the underlying suppurative result in diminished numbers of the normally functioning thrombophlebitis. However, the most common symptom neutrophils and lymphocytes essential to fight invading or sign of candidiasis, especially disseminated, is fever. organisms. Etiology and the disease process: Candida species are commensal organisms and are found as part of the normal human flora because of their ability to adhere to and persist on mucosal surfaces. It is only when this natural balance is upset that these opportunistic pathogens cause disease. Candidal organisms possess a number of virulence factors. Production of hydrolytic enzymes (proteinases and li222
Screening and diagnosis: The diagnosis of candidiasis may be presumptively made by physical examination of the cancer patient. Examination of the skin and oral cavity for plaques, ulcers, and erythema may be revealing. Candida endophthalmitis, resulting from bloodstream infection, is strongly suspected when characteristic cottonwool lesions are observed on ophthalmoscopic examina-
Salem Health: Cancer
Carcinoembryonic antigen antibody (CEA) test
tion of the retina. A new heart murmur may be the result of candida endocarditis associated with vascular catheter infection. Rales and decreased breath sounds may be present during candida pneumonia. Intraluminal urine seen in indwelling urinary catheters is frequently cloudy with white fluffy debris when urinary candida infection occurs. Intravascular catheter sites may reveal erythema, induration, or purulent drainage, but these signs can be subtle or absent in the neutropenic patient. Endoscopic examination can be helpful with gastrointestinal candidiasis, particularly esophagitis. Computed tomography (CT) and magnetic resonance imaging (MRI) scans of the abdomen can demonstrate abscesses. Blood tests for candida antigens, beta-glucan, and polymerase chain reaction (PCR) may provide a specific diagnosis. Microscopic examination of urine and tissue biopsies is also helpful. Culture of blood, urine, tissue biopsies, and the like provides specific diagnostic information, and the cultured Candida can be speciated and tested for susceptibility to antifungal agents.
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Treatment and therapy: The relatively nontoxic azole and echinocandin antifungals are most often used to treat candidiasis. Amphotericin B has long been standard therapy for invasive candidiasis, but the comparatively high toxicities have limited its use to refractory or resistant cases. If candida has been cultured, then fungal susceptibilities can be used to guide therapy. It is important to begin therapy as early as possible to achieve the best outcome, and this mandates that therapy be commenced in high-risk cancer patients before the availability of diagnostic studies if candidiasis is suspected. Adjunctive measures are also important. Vascular, gastrointestinal, or urinary catheters should be removed if possible. Immune function must be optimized. Colony-stimulating factors can increase neutrophil numbers in the neutropenic cancer patient.
See also Antifungal therapies; Fever; Gastrointestinal complications of cancer treatment; Taste alteration.
Prognosis, prevention, and outcomes: Disseminated candidiasis with candidemia in cancer patients has a crude mortality rate of 70 to 75 percent with an excess mortality rate of about 40 percent. Without treatment survival rates are less than 5 percent. Prevention is best accomplished by reducing the risk factors for infection. Removing catheters promptly, treating neutropenia, and using antibacterials only when absolutely necessary are all beneficial. Antifungal prophylaxis has been shown to reduce the incidence of candidiasis in cancer patients with neutropenia and also in patients for whom treatment has included bone marrow or solid organ transplantation. H. Bradford Hawley, M.D.
For Further Information Bodey, Gerald P., ed. Candidiasis. 2d ed. New York: Raven Press, 1993. Ostrosky-Zeichner, Luis, et al. “Deeply Invasive Candidiasis.” Infectious Disease Clinics of North America 16 (2002): 821-835. Pappas, Peter G., et al. “Guidelines for Treatment of Candidiasis.” Clinical Infectious Diseases 38 (2004): 161189.
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Other Resources
Centers for Disease Control and Prevention Candidiasis http://www.cdc.gov/nczved/dfbmd/disease_listing/ candidiasis_gi.html Mycology Online Candidiasis http://www.mycology.adelaide.edu.au/Mycoses/ Cutaneous/Candidiasis/
u Carcinoembryonic antigen
antibody (CEA) test Category: Procedures Also known as: Carcinoembryonic antigen antibody test Definition: Carcinoembryonic antigen antibody (CEA) tests are used primarily to monitor cancer patients to determine whether their disease is recurring and, if so, its stage and extent. CEAis a tumor marker, because anti-CEAantibodies bind to epitopes on carcinoembryonic antigens, allowing CEA quantification in body fluids (primarily serum) and CEA detection on cells or tissue sections by immunostaining. Cancers diagnosed: Primarily colorectal and gastrointestinal cancers, as well as cancers of the rectum, lung, breast, liver, pancreas, stomach, and ovaries Why performed: Anti-CEA antibodies are primarily used in the diagnosis of colorectal cancer; they are not recommended for cancer screening, but preoperative determination may assist in staging and surgical treatment planning. After treatment, anti-CEA antibodies may detect recurrence earlier than other techniques. Anti-CEA antibodies are also informative in lung, liver, breast, ovarian, stomach, and pancreatic cancers as they provide prognostic in223
Carcinogens, known formation. Anti-CEA antibodies can also be evaluated in urine (bladder cancer), bronchial lavage fluid (lung cancer), or cerebrospinal fluid (brain tumors) to improve diagnostic accuracy. Patient preparation: No preparation on the part of the patient is necessary. Steps of the procedure: The procedure involves a simple blood test and so consists only of the drawing of a blood sample from the patient. When anti-CEA antibodies are used for quantitative determination of CEA in body fluids, a typical solid-phase immunoassay protocol is used. This involves addition of the standards and samples to wells or beads with an adsorbed monoclonal anti-CEA antibody to “catch” and immobilize CEA by high-affinity binding to one of CEA’s epitopes. After incubation and washing steps, a second, enzyme-conjugated monoclonal antiCEA antibody against a different CEA epitope is added. CEA present in the specimen is “sandwiched” between the two different antibodies and serves to bind the enzyme to the well or bead. After washing, colorigenic substrate is added. The rate of color development indicates the activity of the antibody-conjugated enzyme, which is used to infer the CEA concentration in the sample by comparison with known standards. When anti-CEA antibodies are used to semiquantitatively visualize CEA in immunostaining procedures, the cells or tissues are typically fixed and embedded in paraffin, then sectioned onto glass slides for staining and conventional microscopy. Polyclonal anti-CEA antibodies may be chosen for immunostaining to improve sensitivity. After the procedure: No special care is needed other than to keep the area of the needlestick clean until it is healed, in order to avoid infection. Risks: No physical risks or side effects accompany a CEA test, although caution must be used in interpreting results. The CEA test itself poses no risk to the patient. Test results must not be interpreted in isolation to avoid overtreatment or undertreatment. Results: Standard levels have not been established for CEA tests and vary depending on the patient’s age and condition as well as testing methods. Anti-CEA-based assays of CEAin body fluids are difficult to interpret in isolation; serial measurements usually are inspected for recognizable patterns that indicate response to therapy, lack of response to therapy, or recurrence of disease. Because of heterogeneity among anti-CEA antibodies, the same reagents and methods should be used during longitudinal monitoring. In immunostaining procedures, many anti224
Salem Health: Cancer CEA antibodies recognize antigens shared by members of the CEA family of glycoproteins, resulting in extensive background staining. In particular, cells from the liver and gallbladder often react with anti-CEA antibodies because they contain biliary glycoprotein. Each test report should include a reference range and be interpreted by the consulting physician. In general, patients with early-stage, small tumors may have low, even normal, CEA levels; later-stage and metastatic disease may yield initially high CEA levels. A subsequent lower CEA level usually indicates reduced tumor activity, whereas a CEA level that rises over time may indicate tumor recurrence. John B. Welsh, M.D., Ph.D. See also Bile duct cancer; Colorectal cancer; Malignant tumors; Pathology; Placental alkaline phosphatase (PALP); Tumor markers.
u Carcinogens, known Category: Carcinogens and suspected carcinogens Definition: A carcinogen is any substance that causes cancer. A “known” human carcinogen is a chemical compound identified by the National Toxicology Program of the U.S. Department of Health and Human Services as displaying “sufficient evidence of carcinogenicity in humans [to indicate] a causal relationship between exposure to the agent, substance, or mixture and human cancer.” Chemicals and cancer: Certain chemicals are capable of causing cells in an organ of the body to grow uncontrollably. As early as a century ago, scientists knew of malignant growths produced by exposure to particular chemicals. The National Toxicology Program (NTP) produces a biennial Report on Carcinogens (RoC), which deals with carcinogenic compounds in humans, potential human exposure to these substances, and federal regulations of exposure limits to the chemicals. The introduction to the report defines a known carcinogen as a chemical for which there is sufficient evidence indicating a causal relationship between exposure and human cancer. Definitive data on carcinogenicity is difficult to obtain, because there often is a need for multiple exposures to the substance and a long induction period before a tumor appears. Genetics, lifestyle, and ethnic factors are also important in the development of certain tumors. The National Toxicology Program employs a variety of approaches but considers two-year studies in rodents to be its primary method of determining what substances are carcinogens.
Salem Health: Cancer
Carcinogens, known
Development of cancer: Cancers seem to develop in stages showing substantial overlap and not progressing uniformly. Much research on the initiation stage has been devoted to the study of changes in deoxyribonucleic acid (DNA). Many carcinogenic chemicals have been shown to cause mutations. Bonding to a strand of DNA produces a mutation that might be replicated before it can be repaired. Such an error might be passed along to future generations. Most such mutations do not affect the cell, but if a protein associated with growth is involved, it might create the potential for future rapid cell growth. It is also believed that reactions between potential carcinogens and DNA do not occur in a random process but rather in the production of genes. The way in which the promotion stage of cancer development proceeds is still obscure, but the nature of promoting substances provides clues. These compounds are believed to stimulate the production of multiple benign tumors. Their effect is reversible; with their withdrawal,
the tumor disappears. They are, however, not able to produce the cancer by themselves. At some point in the progression stage, another genetic change occurs that results in a selective growth advantage for the mutant cell. There are several ways in which such an event might take place: additional exposures to the original carcinogen, spontaneous mutation from replication enzymes, or changes in the genes caused by initiating mutations. The result is an irreversible change in the cell. The malignant conversion stage produces a distinct growth advantage for the affected cell. There is evidence from rodent studies that genetics is an important factor in these late-stage changes as well as in the early development of the cancer. Experiments reveal protein synthesis, amplification of gene creation, and further DNA reactions at this stage in the tumor cell. Testing for carcinogens: In testing to determine whether a substance is a carcinogen, scientists use animal testing
Known Human Carcinogens
• • • • • • • • • • • • • • • • • • • • • • • •
Aflatoxins Alcoholic beverage consumption 4-Aminobiphenyl Arsenic compounds, inorganic Asbestos Azathioprine Benzene Benzidine and dyes metabolized to benzidine Beryllium and beryllium compounds 1,3-Butadiene 1,4-Butanediol dimethylsulfonate (Myleran) Cadmium and cadmium compounds Chlorambucil 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU) bis(Chloromethyl) ether and technical-grade chloromethyl methyl ether Chromium hexavalent compounds Coal tars and coal tar pitches Coke oven emissions Cyclophosphamide Cyclosporin A Diethylstilbestrol Erionite Estrogens, steroidal Ethylene oxide
• • • • • • • • • • • • • • • • • • • • •
Hepatitis B virus Hepatitis C virus Human papillomaviruses: some genital-mucosal types Ionizing radiation: X radiation and gamma radiation, neutrons, radon, thorium dioxide Melphalan Methoxsalen with ultraviolet A therapy (PUVA) Mineral oils (untreated and mildly treated) Mustard gas 2-Naphthylamine Nickel compounds and metallic nickel Phenacetin and analgesic mixtures containing phenacetin Silica, crystalline (respirable size) Soots Strong inorganic acid mists containing sulfuric acid Tamoxifen 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Thiotepa Tobacco-related exposures: environmental tobacco smoke, smokeless tobacco, tobacco smoking Ultraviolet radiation-related exposures: solar radiation, exposure to sunlamps or sunbeds, broad-spectrum ultraviolet (UV) radiation, ultraviolet A, B, and C radiation Vinyl chloride Wood dust
Source: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Report on Carcinogens. 11th ed. (Research Triangle Park, N.C.: Author, 2005)
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Carcinogens, known
Salem Health: Cancer Extensive studies conducted by the National Toxicology Program and the International Agency for Research in Cancer (IARC) show that only one-third of suspected chemicals are actually carcinogenic. Approximately 96 percent of human cancer results from naturally occurring carcinogens. Intense study of such carcinogenic compounds shows that 95 percent involve only three types of chemicals: • Alkylating agents: Transfer small fragments (CH3) to DNA • Arylkylating agents: Transfer aromatic rings (C6H5) to DNA • Arylhydroxylamines: Transfer amines, containing NH2, to DNA. A common aspect of these materials is their ability to produce structures that have a deficiency of electrons. Such structures react rapidly with the electron-rich oxygen, sulfur, and nitrogen atoms of nucleic acids. K. Thomas Finley, Ph.D. u
Many carcinogens are alkylating agents, arylkylating agents, or arylhydroxylamines. (Pascal Goetgheluck/Photo Researchers, Inc.)
and also test for mutagens, relying on the fact that nearly all carcinogenic molecules also produce mutations. However, there are significant problems involved. A direct effort along this line involves seeking a lethal mutation involving the X chromosome, which determines the sex of the offspring. The realization that intermediate products from detoxification may be the cause of the initiation phase of cancer development has led to the development of tests involving bacteria and enzymes. These procedures greatly reduced cost (one-thousandth as much as mice) and time (two days compared with at least a year). It has become possible to test all new compounds for mutations and to conduct animal tests only on those showing positive results. All these approaches are actively being used by the National Toxicology Program. Achieving a balance: Although carcinogenic chemicals are of concern, it is important to recognize the actual risk. 226
For Further Information Perantoni, Alan O. “Carcinogenesis.” In The Biological Basis of Cancer, edited by Robert G. McKinnell et al. New York: Cambridge University Press, 1998. Ruddon, Raymond W. “Causes of Cancer.” In Cancer Biology. 4th ed. New York: Oxford University Press, 2007. Tomatis, Lorenzo, and James Huff. “Evolution of Research in Cancer Etiology.” In The Molecular Basis of Human Cancer, edited by William B. Coleman and Gregory T. Tsongalis. Totowa, N.J.: Humana Press, 2002. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Yuspa, Stuart H., and Peter G. Shields. “Etiology of Cancer: Chemical Factors.” In Cancer: Principles and Practice of Oncology, edited by Vincent T. DeVita, Jr., et al. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001.
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Other Resources
American Cancer Society Known and Probable Carcinogens http://www.cancer.org/docroot/PED/content/ PED_1_3x_Known_and_Probable_Carcinogens.asp International Agency for Research on Cancer http://www.iarc.fr
Salem Health: Cancer National Toxicology Program http://ntp-server.niehs.nih.gov/index.cfm See also Acrylamides; Aflatoxins; Agent Orange; Air pollution; Alcohol, alcoholism, and cancer; 4-Aminobiphenyl; Arsenic compounds; Asbestos; Azathioprine; Bacteria as causes of cancer; Benzene; Benzidine and dyes metabolized to benzidine; Beryllium and beryllium compounds; Birth control pills and cancer; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; Bisphenol A (BPA); 1,3-Butadiene; 1,4-Butanediol dimethanesulfonate; Cadmium and cadmium compounds; Caffeine; Carcinogens, reasonably anticipated; Cell phones; Chewing tobacco; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Chromium hexavalent compounds; Cigarettes and cigars; Coal tars and coal tar pitches; Coke oven emissions; Cyclophosphamide; Cyclosporin A; Di(2-ethylhexyl) phthalate (DEHP); Diethanolamine (DEA); Diethylstilbestrol (DES); Dioxins; Electromagnetic radiation; Epstein-Barr virus; Erionite; Ethylene oxide; Fertility drugs and cancer; Formaldehyde; Free radicals; Hair dye; Helicobacter pylori; Hepatitis B virus (HBV); Hepatitis C virus (HCV); HER2/neu protein; Herpes simplex virus; Herpes zoster virus; HIV/AIDSrelated cancers; Hormone replacement therapy (HRT); Human growth factors and tumor growth; Human papillomavirus (HPV); Human T-cell leukemia virus (HTLV); Ionizing radiation; Melphalan; Mineral oils; Mustard gas; 2-Naphthylamine; Nickel compounds and metallic nickel; Oncogenes; Oncogenic viruses; Organochlorines (OCs); Pesticides and the food chain; Phenacetin; Plasticizers; Polycyclic aromatic hydrocarbons; Radon; Report on Carcinogens (RoC); Silica, crystalline; Simian virus 40; Soots; Sunlamps; Thiotepa; Ultraviolet radiation and related exposures; Vinyl chloride; Wood dust.
u Carcinogens, reasonably
anticipated Category: Carcinogens and suspected carcinogens Definition: Chemical compounds similar chemically to those that have shown carcinogenicity are labeled “reasonably anticipated carcinogens” by the National Toxicology Program of the U.S. Department of Health and Human Services. Describing cancer: Cancer has been studied intensely for a long time, yet its causes remain elusive and uncertain.
Carcinogens, reasonably anticipated There is much evidence that when certain chemical compounds are introduced to the human body, the probability of a tumor forming is increased. Scientists have used several methods to gather evidence about the carcinogenicity of a chemical before allowing general use. A central difficulty with methods of studying cancer is that a specific chemical, introduced by a particular route, does not always produce a tumor. Therefore carcinogenicity is defined in terms of the increased risk of producing a tumor. Because the primary interest of such studies is tumors produced in human beings, there is a species problem. It is very difficult to show that susceptibility to increased rates of tumor production in test animals predicts a similar outcome in humans. The National Toxicology Program (NTP) uses animal testing in its basic studies. Research conducted with bacteria also shows great promise. Such complications have resulted in the creation of a rather limited list of carcinogenic chemicals. It pays to take a conservative position in the field of public health, so there is a much longer list of suspected carcinogens. The National Toxicology Program issues a biennial Report on Carcinogens (RoC) in which compounds may be labeled “reasonably anticipated carcinogens” if they meet the following criteria: • There are limited studies in humans. • Sufficient animal studies exist. • Astructural relationship to a known carcinogen exists. Carcinogens and suspected carcinogens: Reports concerning chemicals linked to cancer make the public suspicious of all chemicals. Studies have shown that only onefourth to one-third of suspected molecules are actually cancer causing. More than 95 percent of carcinogenic chemicals belong to three general types of compounds. Chemists who work with organic compounds have always appreciated this relationship. A powerful tool in managing such compounds has been the structure-activity relationship. A given set of atoms, arranged in a particular pattern, will often lead to very similar chemical behavior. The chief cancer-causing molecules predominantly display one of the following chemical structural types: polycyclic aromatic hydrocarbons, aromatic amines, or alkylating agents. Polycyclic aromatic hydrocarbons: As their name suggests, polycylic aromatic hydrocarbons are composed only of atoms of the elements carbon and hydrogen, and the carbon atoms are linked together in a ring or cycle. The simplest chemical in this class is the known carcinogen benzene, which has a single ring of six carbon atoms. Mol227
Carcinogens, reasonably anticipated
Salem Health: Cancer
ecules of four or more benzene rings that are fused together by sharing two carbon atoms are quite common. Aromatic amines: As with the hydrocarbons, aromatic amines generally have the six-carbon atom ring, but they also have a nitrogen atom attached to that ring. The most common example is 2-naphthylamine. This compound has two benzene rings attached to each other and an ammonia-like nitrogen atom containing two hydrogen atoms attached to the second carbon atom. Alkylating agents: Although the first two categories of carcinogenic compounds are characterized by their struc-
ture, alkylating agents share a common chemical function. An alkyl group is a fragment of a molecule that is of high energy and therefore reacts rapidly. One of the most common is the methyl group composed of a single carbon atom and three hydrogen atoms. A methylating agent would be a molecule that can transfer such a reactive fragment during a chemical reaction. There are many compounds that can perform this function, but one of the most active subgroups is that of the nitrosamines, for example, Nnitrosodimethylamine. Like the aromatic amines, there is a nitrogen atom, but in place of the two hydrogen atoms, there are two methyl groups. The aromatic ring is replaced by a second nitrogen atom connected to an oxygen atom.
Reasonably Anticipated Human Carcinogens
• • • • • • • • • • • • • • • • • • • • • • • • • • • 228
Acetaldehyde 2-Acetylaminofluorene Acrylamide Acrylonitrile Adriamycin (doxorubicin hydrochloride) 2-Aminoanthraquinone o-Aminoazotoluene 1-Amino-2,4-dibromoanthraquinone 1-Amino-2-methylanthraquinone 2-Amino-3,4-dimethylimidazo [4,5-f]quinoline (MelQ) 2-Amino-3,8-dimethylimidazo [4,5-f]quinolaxine (MelQx) 2-Amino-3-methylimidazo [4,5-f]quinoline (IQ) 2-Amino-1-methyl6phenylimidazo[4,5-b]pyridine (PhlP) Amitrole o-Anisidine hydrochloride Azacitidine Benzotrichloride Bromodichloromethane 2,2-bis(Bromomethyl)-1,3propanediol (technical grade) Butylated hydroxyanisole (BHA) Carbon tetrachloride Ceramic fibers (respirable size) Chloramphenicol Chlorendic acid Chlorinated paraffins (C12, 60 percent chlorine) 1-(2-Chloroethyl)-3-cyclohexyl-1nitrosourea bis(Chloroethyl) nitrosourea
• • • • • • • • • • • • • • • • • • • • • • • • • •
Chloroform 3-Chloro-2-methylpropene 4-Chloro-o-phenylenediamine Chloroprene p-Chloro-o-toluidine and p-Chloroo-toluidine hydrochloride Chlorozotocin C.I. basic red 9 monohydrochloride Cisplatin Cobalt sulfate p-Cresidine Cupferron Dacarbazine Danthron (1,8-dihydroxyanthraquinone) 2,4-Diaminoanisole sulfate 2,4-Diaminotoluene Diazoaminobenzene 1,2-Dibromo-3-chloropropane 1,2-Dibromoethane (ethylene dibromide) 2,3-Dibromo-1-propanol tris(2,3-Dibromopropyl) phosphate 1,4-Dichlorobenzene 3,3′-Dichlorobenzidine and 3,3′-dichlorobenzidine dihydrochloride Dichlorodiphenyltrichloroethane (DDT) 1,2-Dichloroethane (ethylene dichloride) Dichloromethane (methylene chloride) 1,3-Dichloropropene (technical grade)
• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Diepoxybutane Diesel exhaust particulates Diethyl sulfate Diglycidyl resorcinol ether 3,3′-Dimethoxybenzidine and dyes metabolized to 3,3′-dimethoxybenzidine 4-Dimethylaminoazobenzene 3,3′-Dimethylbenzidine and dyes metabolized to 3,3′dimethylbenzidine Dimethylcarbamoyl chloride 1,1-Dimethylhydrazine Dimethyl sulfate Dimethylvinyl chloride 1,4-Dioxane Disperse blue 1 Epichlorohydrin Ethylene thiourea di(2-Ethylhexyl) phthalate Ethyl methanesulfonate Formaldehyde (gas) Furan Glass wool (respirable size) Glycidol Heterocyclic amines Hexachlorobenzene Hexachloroethane Hexamethylphosphoramide Hydrazine and hydrazine sulfate Hydrazobenzene Iron dextran complex Isoprene Kepone (chlordecone) Lead and lead compounds
Salem Health: Cancer
Carcinogens, reasonably anticipated
A summary of suspected carcinogens: Some common examples of probable carcinogens would include: • Dimethyl sulfate, which, like N-nitrosodimethylamine, has two methyl groups available to be transferred. The new compound has a sulfur atom and four oxygen atoms in place of the nitrogen and oxygen atoms of the carcinogen. • Benzo[a]pyrene has five benzene rings, all sharing two or more carbon atoms. • 2-Toluidine resembles 2-naphthylamine but has the second benzene ring replaced by a single methyl group. Bear in mind that while these compounds are suspected of being carcinogenic and proper safeguards are needed when they are used, there are many examples showing that
compounds with similar structure have very different, or no, carcinogenic properties. K. Thomas Finley, Ph.D. u
For Further Information Perantoni, Alan O. “Carcinogenesis.” In The Biological Basis of Cancer, edited by Robert G. McKinnell et al. New York: Cambridge University Press, 1998. Ruddon, Raymond W. “Causes of Cancer.” In Cancer Biology. 4th ed. New York: Oxford University Press, 2007. Tomatis, Lorenzo, and James Huff. “Evolution of Research in Cancer Etiology.” In The Molecular Basis of
Reasonably Anticipated Human Carcinogens (continued)
• • • • • • • • • • • • • • • • • • • • • • • • •
Lindane and other hexachlorocyclohexane isomers 2-Methylaziridine (propylenimine) 4,4′-Methylenebis(2-chloroaniline) 4,4′-Methylenebis (N,N-dimethyl)benzenamine 4,4′-Methylenedianiline and its dihydrochloride salt Methyleugenol Methyl methanesulfonate N-Methyl-N′-nitro-Nnitrosoguanidine Metronidazole Michler’s ketone (4,4′(dimethylamino)benzophenone) Mirex Naphthalene Nitrilotriacetic acid o-Nitroanisole Nitroarenes (1,6-dinitropyrene; 1,8-dinitropyrene; 6-nitrochrysene; 1-nitropyrene; 4-nitropyrene) Nitrobenzene Nitrofen (2,4-dichlorophenylp-nitrophenyl ether) Nitrogen mustard hydrochloride Nitromethane 2-Nitropropane N-Nitrosodi-n-butylamine N-Nitrosodiethanolamine N-Nitrosodiethylamine N-Nitrosodimethylamine N-Nitrosodi-n-propylamine
• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
N-Nitroso-N-ethylurea 4-(N-Nitrosomethylamino)-1(3-pyridyl)-1-butanone N-Nitroso-N-methylurea N-Nitrosomethylvinylamine N-Nitrosomorpholine N-Nitrosonornicotine N-Nitrosopiperidine N-Nitrosopyrrolidine N-Nitrososarcosine Norethisterone Ochratoxin A 4,4′-Oxydianiline Oxymetholone Phenazopyridine hydrochloride Phenolphthalein Phenoxybenzamine hydrochloride Phenytoin Polybrominated biphenyls (PBBs) Polychlorinated biphenyls (PCBs) Polycyclic Aromatic Hydrocarbons Benz[a]anthracene Benzo[b]fluoranthene Benzo[j]fluoranthene Benzo[k]fluoranthene Benzo[a]pyrene Dibenz[a,h]acridine Dibenz[a,j]acridine Dibenz[a,h]anthracene 7H-Dibenzo[c,g]carbazole Dibenzo[a,e]pyrene Dibenzo[a,h]pyrene Dibenzo[a,i]pyrene
• • • • • • • • • • • • • • • • • • • • • • • • • • • • • • •
Dibenzo[a,l]pyrene Indeno[1,2,3-cd]pyrene 5-Methylchrysene Procarbazine hydrochloride Progesterone 1,3-Propane sultone β-Propiolactone Propylene oxide Propylthiouracil Reserpine Safrole Selenium sulfide Streptozotocin Styrene-7,8-oxide Sulfallate Tetrachloroethylene (perchloroethylene) Tetrafluoroethylene Tetranitromethane Thioacetamide 4,4′-Thiodianiline Thiourea Toluene diisocyanate o-Toluidine and o-toluidine hydrochloride Toxaphene Trichloroethylene 2,4,6-Trichlorophenol 1,2,3-Trichloropropane Urethane Vinyl bromide 4-Vinyl-1-cyclohexene diepoxide Vinyl fluoride
Source: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Report on Carcinogens. 11th ed. (Research Triangle Park, N.C.: Author, 2005)
229
Carcinoid tumors and carcinoid syndrome Human Cancer, edited by William B. Coleman and Gregory T. Tsongalis. Totowa, N.J.: Humana Press, 2002. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Yuspa, Stuart H., and Peter G. Shields. “Etiology of Cancer: Chemical Factors.” In Cancer: Principles and Practice of Oncology, edited by Vincent T. DeVita, Jr., et al. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001. u
Other Resources
American Cancer Society Known and Probable Carcinogens http://www.cancer.org/docroot/PED/content/ PED_1_3x_Known_and_Probable_Carcinogens.asp International Agency for Research on Cancer http://www.iarc.fr National Toxicology Program http://ntp-server.niehs.nih.gov See also Acrylamides; Aflatoxins; Agent Orange; Air pollution; Alcohol, alcoholism, and cancer; 4-Aminobiphenyl; Arsenic compounds; Asbestos; Azathioprine; Bacteria as causes of cancer; Benzene; Benzidine and dyes metabolized to benzidine; Beryllium and beryllium compounds; Birth control pills and cancer; Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether; Bisphenol A (BPA); 1,3-Butadiene; 1,4-Butanediol dimethanesulfonate; Cadmium and cadmium compounds; Caffeine; Carcinogens, known; Cell phones; Chewing tobacco; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Chromium hexavalent compounds; Cigarettes and cigars; Coal tars and coal tar pitches; Coke oven emissions; Cyclophosphamide; Cyclosporin A; Di(2-ethylhexyl) phthalate (DEHP); Diethanolamine (DEA); Diethylstilbestrol (DES); Dioxins; Electromagnetic radiation; Epstein-Barr virus; Erionite; Ethylene oxide; Fertility drugs and cancer; Formaldehyde; Free radicals; Hair dye; Helicobacter pylori; Hepatitis B virus (HBV); Hepatitis C virus (HCV); HER2/neu protein; Herpes simplex virus; Herpes zoster virus; HIV/AIDSrelated cancers; Hormone replacement therapy (HRT); Human growth factors and tumor growth; Human papillomavirus (HPV); Human T-cell leukemia virus (HTLV); Ionizing radiation; Melphalan; Mineral oils; Mustard gas; 2-Naphthylamine; Nickel compounds and metallic nickel; Oncogenes; Oncogenic viruses; Organochlorines (OCs); 230
Salem Health: Cancer Pesticides and the food chain; Phenacetin; Plasticizers; Polycyclic aromatic hydrocarbons; Radon; Report on Carcinogens (RoC); Silica, crystalline; Simian virus 40; Soots; Sunlamps; Thiotepa; Ultraviolet radiation and related exposures; Vinyl chloride; Wood dust.
u Carcinoid tumors and
carcinoid syndrome Category: Diseases, symptoms, and conditions Also known as: Gastrointestinal tract tumors, adenocarcinoid tumors Related conditions: Colon cancer, small bowel lymphoma Definition: A carcinoid tumor arises from hormoneproducing cells that line the small intestine, appendix, bronchi, colon, pancreas, ovaries, testes, bile ducts, gallbladder, stomach, and liver. Carcinoid syndrome is a group of symptoms caused by the release of hormones from a carcinoid tumor. Risk factors: No risk factors for carcinoid syndrome or carcinoid tumors have been identified, although they are thought to be related to a genetic mutation that is either inherited or spontaneous. Etiology and the disease process: Carcinoid tumors are slow-growing tumors that develop from enterochromaffin cells. These cells secrete hormones such as serotonin, histamine, prostaglandins, polypeptides, and tachykinins. Some 65 percent of carcinoid tumors occur in the gastrointestinal tract, and 25 percent are found in the lungs. The remaining 10 percent arise from other organs, or the primary site is unknown. Benign carcinoid tumors are small and have a low rate of recurrence. Malignant carcinoid tumors tend to be larger than 2 centimeters (cm) and are more likely to metastasize (spread to other organs). They also can invade adjacent tissue. The hormones secreted by gastrointestinal carcinoid tumors are broken down in the liver, so patients with these types of tumors do not experience carcinoid syndrome. However, if there are liver metastases, carcinoid syndrome can develop. Carcinoid tumors of the lungs, ovaries, and testes are more likely to cause carcinoid syndrome. Incidence: Research suggests a rate of from 1.5 to 8 cases per 100,000 people. Carcinoid syndrome is rare.
Salem Health: Cancer Symptoms: Large gastrointestinal tumors may cause abdominal pain, abdominal mass, bleeding, nausea and vomiting, obstruction, and diarrhea. Carcinoid tumors of the lungs cause coughing, chest pain, wheezing, blood-tinged sputum, and pneumonia. Lung carcinoid tumors cause the carcinoid syndrome about 20 percent of the time. The most common symptom of the carcinoid syndrome is facial flushing that can last from hours to days. Other common symptoms are diarrhea, abdominal pain, wheezing, valvular heart disease, sweating, rapid heart rate, weight gain, weakness, secondary diabetes, and increased body and facial hair. These symptoms are caused by the high levels of hormones released by the tumor. Screening and diagnosis: There is no routine screening for carcinoid tumors. Larger carcinoid tumors can be diagnosed by computed tomography (CT) scans or magnetic resonance imaging (MRI). If the CT scan shows abnormal lymph nodes or a liver tumor, a needle biopsy can be performed. Carcinoid tumors can also be found by somatostatin (a hormone) receptor scintography, a nuclear imaging scan. This scan uses indium 111 octreotide as a radioactive dye. Octreotide has an affinity for hormone-producing cells. This test is quite accurate, but it can miss very small tumors and tumors that do not have somatostatin receptors. Two other nuclear imaging procedures are used. They are positron emission tomography (PET) and metaiodobenzylguanidine (MIBG) scans. The PET scan picks up areas of the body with higher than normal metabolism. Like octreotide, MIBG is attracted to carcinoid tumors. The only way to verify that a tumor is a carcinoid tumor is to biopsy it. Biopsy may be done by endoscopy, bronchoscopy, or needle biopsy. Diagnosis of carcinoid syndrome can be done by performing a twenty-four hour urine test for 5-hydroxyindolacetic acid (5-HIAA). The normal rate of urinary excretion of 5-HIAA is 8 milligrams (mg). Persons with carcinoid syndrome can excrete between 100 and 2,000 mg of 5-HIAA. The staging for carcinoid tumors is based on the primary site. Treatment and therapy: If a carcinoid tumor is less than 2 centimeters (cm) in size, it can be removed by surgery. If the carcinoid tumor is larger than 2 cm, there are multiple tumors, or there are metastases, a cure is less likely. Surgery may be performed to ease the symptoms from the tumor or the carcinoid syndrome.
Carcinoid tumors and carcinoid syndrome Sometimes the goal of surgery is debulking (decreasing the size of the tumor). This is done to decrease symptoms of carcinoid syndrome or in preparation for chemotherapy or radiation therapy. Debulking can be performed by surgical resection, cryoablation (freezing), radiofrequency ablation (radiation), or hepatic artery embolization (blocking the blood supply to the liver). Chemotherapy may be used to treat carcinoid tumors. The chemotherapeutic drugs most frequently used are 5fluorouracil (Adrucil), cyclophosphamide (Cytoxan), streptozocin (Zanosar), and doxorubicin (Adriamycin). Interferon, an immune system stimulator, may be used with chemotherapy. Chemotherapy is effective in about 30 percent of cases, and its effects are short term. External radiation therapy can be administered to decrease tumor size and to decrease the symptoms that the patient is experiencing. Radiation is not effective against liver metastases. Medications can be used to treat carcinoid syndrome. Octreotide has been effective in reducing the size of some carcinoid tumors. Imodium, lomotil, ondansetran (Zofran), and cyproheptadine (Periactin) may eliminate the diarrhea. Tamoxifen (nolvadex), phenothiazides, gastric histamine receptor antagonists, phentolamine alpha blockers, and corticosteroids may decrease the flushing. Patients with carcinoid syndrome must take a niacin supplement and ingest adequate protein. Carcinoid tumors use nicotinic acid (a niacin breakdown product) and tryptophan to create serotonin and can deplete the body’s stores of niacin. Prognosis, prevention, and outcomes: With appropriate treatment, a person with carcinoid cancer or carcinoid syndrome can live for ten to fifteen years with a fairly good quality of life. There is no way to prevent carcinoid tumors. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Babovic-Vuksanovic, Dusica, et al. “Familiar Occurrence of Carcinoid Tumors and Association with Other Malignant Neoplasms.” Cancer Epidemiology Biomarkers and Prevention 8 (August, 1999): 715-719. Wilander, Erik, Monalill Lundqvist, and Kjell Öberg. Gastrointestinal Carcinoid Tumors. New York: Fischer, 1989. Zuetenhorst, Johanna M., and Babs G. Taal. “Metastatic Carcinoid Tumors: A Clinical Review.” The Oncologist 10, no. 2 (February, 2005): 123-131. 231
Carcinoma of unknown primary origin (CUP) u
Other Resources
American Cancer Society Detail Guide: Gastrointestinal Carcinoid Tumors http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=14 Medicinenet Carcinoid Syndrome (Carcinoid Tumor) http://www.medicinenet.com/carcinoid_syndrome/ article.htm See also Achlorhydria; Antidiarrheal agents; Appendix cancer; Barium swallow; Bronchial adenomas; Duodenal carcinomas; Endocrine cancers; Gastric polyps; Gastrointestinal oncology; Grading of tumors; 5-Hydroxyindoleacetic acid (5HIAA) test; Imaging tests; Interferon; Neuroendocrine tumors; Nuclear medicine scan; Small intestine cancer; Stomach cancers; Surgical biopsies; Thymomas; Thymus cancer.
u Carcinoma of unknown
primary origin (CUP) Category: Diseases, symptoms, and conditions Related conditions: Skin cancer, lung cancer, prostate cancer, breast cancer, lung cancer, recurrent carcinoma Definition: Carcinoma of unknown primary origin (CUP) is an abnormal growth of cells, resulting in malignant (metastasized) cancer with no known origin. Carcinoma represents the most common cancers, including the common forms of skin, breast, prostate, lung, and colon cancer. Risk factors: Malignant transformation can be caused by exposure to toxic carcinogens such as such as radiation, tobacco smoke, and certain chemicals. Some viruses have been linked to cancer: Epstein-Barr virus and lymphoma, human papillomavirus and cervical cancer, hepatitis B virus and liver cancer, and Kaposi sarcoma-associated virus and Kaposi sarcoma. Additionally, many carcinomas are the result of a random genetic mutation, resulting in abnormally formed cells that can be cancerous. There are strong hereditary factors involved in carcinoma, so that having a family history of cancer can mean being predisposed to developing cancer. Etiology and the disease process: The origin of carcinoma is in the cells of the epithelium, which lines both the outside (skin) and the inside cavities and lumen of tissues and organs. In normal tissue, cells multiply to form new 232
Salem Health: Cancer cells, and the old or damaged cells self-destruct by apoptosis, or cell suicide. However, when cells undergo malignant transformation (genetic mutations that lead to cancer), they divide and grow at a rapid rate, and tumors form and grow. Tumors can grow quickly if the cells are dividing at a high rate, while slow-growing tumors result from slowly dividing cells. As more and more of these dividing cells accumulate, the normal tissue becomes diseased. The cancer can spread to other regions of the body. Incidence: Over 80 percent of all diagnosed cancers are a result of carcinoma. Of those, 2 to 4 percent are carcinomas of unknown origin, in that they have metastasized from an unknown location. Symptoms: Symptoms of carcinoma of unknown primary origin include local symptoms, metastasis symptoms, and systemic systems. Local symptoms include unusual bumps, nodes, cysts, or swelling; bleeding (usually found internally or in urine tests); and pain from compression of the tissues surrounding the area of a tumor growth. Metastasis symptoms include enlarged lymph nodes, neurological symptoms, an enlarged liver, and occasionally coughing or broken bones. Systemic symptoms refer to symptoms that affect the entire body, such as weight loss, excessive sweating, hormonal changes, or lack of iron in the bloodstream. Screening and diagnosis: Cancer is usually classified according to the tissue from which the cancerous cells originate, as well as the normal cell type they most resemble. Sometimes, however, although cancerous cells are present, their origin is unknown. Depending on symptoms present, a patient may undergo several tests including blood, urine, stool tests, and X rays. If carcinoma is suspected, the physician will usually order a biopsy to examine a small piece of the cancerous tissue under a microscope. Cancer is determined to be carcinoma of unknown primary origin when there is no evidence to determine the origin of the cancerous cells. By examining the pattern of spreading for the cancer, the physician may derive more information about where it originated. In cancers that appear above the diaphragm, lung cancer is usually the cause. Research has shown that over half of patients with carcinoma of unknown primary origin have cancer that originated in the lung or pancreas. According to the National Cancer Institute, physicians classify carcinoma of unknown primary origin into one of the following categories: • Poorly differentiated carcinomas: The cancer cells look very different from normal cells. • Metastatic melanoma to a single nodal site: Cancer of
Salem Health: Cancer the cells that color the skin (melanocytes) has spread to lymph nodes in only one part of the body. • Cancer in the cervical lymph nodes: Cancer is in the small, bean-shaped organs that make and store infectionfighting cells (lymph nodes) in the neck area. • Isolated axillary metastasis: Cancer has spread only to lymph nodes in the area of the armpits. • Inguinal node metastasis: Cancer has spread to lymph nodes in the groin area. • Multiple involvement: Cancer has spread to several different areas of the body. Treatment and therapy: Treatment of carcinoma of unknown primary origin depends on the suspected origin of the cancer, the microscopic analysis of the cancer cells, and other factors. Surgery is a common treatment for carcinoma of unknown primary origin; the cancer and a small portion of the healthy tissue surrounding it are removed. Various surgical procedures are used, depending on the location of the cancer. Radiation therapy is often used before surgery to shrink tumors or after surgery to kill remaining cancer cells; it can also be used as a therapy without surgery. Chemotherapy is a systemic treatment that uses drugs to kill cancerous cells. Once the drugs enter the body and travel through the bloodstream, they kill cancerous cells throughout the body. Drugs can be administered orally or by injection into the veins or muscles. Occasionally chemotherapy is administered after surgery has removed all cancer cells as a preventive measure to ensure that new cancer cells do not develop (adjuvant therapy). Hormone therapy has shown success in halting the production of hormones that assist in the growth of cancerous cells. Synthetic hormones or other drugs block the body’s natural hormones, or hormone-producing glands are removed by surgery. If carcinoma of unknown primary origin has been categorized, the treatment is more specific. If the cancer is classified as poorly differentiated cells or discovered within the abdomen, the most common treatment is chemotherapy. If the cancer is found in the neck area, treatment may include removal of the lymph nodes and tonsils, radiation therapy, or neck surgery. A lymph node dissection may be performed if the cancer has spread to the lymph nodes. When cancer is found in lymph nodes near the armpit, surgery is performed to remove the nodes and often the breast tissue, along with radiation and chemotherapy. If the cancer is found in the lymph nodes near the groin area, surgery is performed to remove the lymph nodes and some groin tissue. If the cancer is found in several areas of the body,
Carcinomas usually a systemic therapy such as chemotherapy or hormone therapy will be used to deliver treatment to the entire body. Prognosis, prevention, and outcomes: The prognosis for patients with carcinoma of unknown primary origin is poor. The average survival is approximately three to five months; 25 percent of patients survive one year, and only 10 percent of patients survive five years. Studies have shown that cancer found in the lymph nodes has a longer survival rate. Colonoscopies, mammograms, and prostate cancer screenings can lead to early detection and possibly longer survival times. Robert J. Amato, D.O. u
For Further Information Fizazi, Karim, ed. Carcinoma of an Unknown Primary Site. New York: Taylor & Francis, 2006. Icon Health. The Official Patient’s Sourcebook on Carcinoma of Unknown Primary: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2002.
u
Other Resources
American Cancer Society Detailed Guide: Cancer of Unknown Primary http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?rnav=cridg&dt=58 National Cancer Institute Cancer of Unknown Primary http://www.nci.nih.gov/cancertopics/types/ unknownprimary/ See also Breast cancers; Carcinogens, known; Carcinogens, reasonably anticipated; Carcinomas; Carcinosarcomas; Lung cancers; Metastasis; Prostate cancer; Skin cancers; Survival rates.
u Carcinomas Category: Diseases, symptoms, and conditions Also known as: Epithelial cell cancer Related conditions: Dysplasia, metaplasia Definition: Carcinoma refers to any type of cancer that arises from epithelial cells. Carcinomas are distinguished from cancers of connective tissue (sarcomas), from cancers of blood-forming cells (leukemias and lymphomas), and from germ-cell tumors (teratomas). Carcinomas aris233
Carcinomas ing from stratified squamous epithelium are termed squamous cell carcinomas; those arising from glandular epithelium are termed adenocarcinomas. Risk factors: Risk factors fall into two categories: environmental and hereditary. Environmental risk factors include exposure to carcinogenic chemicals or ionizing radiation, or infection with oncogenic viruses. Thousands of carcinogenic chemicals are known, and many are subject to strict regulations regarding exposure. Exposure to ionizing radiation, the most important source of which is the ultraviolet portion of sunlight, is another risk factor. Other important risk factors are inborn genetic variations that predispose individuals to particular cancers and immune system dysfunction.
Salem Health: Cancer gen (PSA) is used to screen men at risk for prostate cancer; those with high levels are then candidates for diagnostic biopsy. Diagnosis of carcinoma is usually done by pathologists based on microscopic examination of biopsied tissue. Features of carcinoma include cellular traits such as abnormally large nuclei, loss of multicellular organization, and disruption of the basement membrane. Staging of carcinoma is based on searches for malignant cells in adjacent structures and lymph nodes. Carcinoma staging uses the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) system that describes the tumor itself, lymph node involvement, and metastatic lesions; however, other staging systems are also used, such as Dukes’ classification of colon cancer.
Symptoms: Symptoms of early carcinoma vary widely according to the epithelial cells affected and their growth pattern. Advanced or terminal carcinoma symptoms include cachexia, pain, fatigue, and depression.
Treatment and therapy: Treatment options for carcinoma include surgery, chemotherapy, radiotherapy, immunotherapy, monoclonal antibody therapy, and other, less common approaches. Treatment plans are made based on the disease grade and stage and the functional status of the patient. Surgical therapy (mechanical removal of the tumor) reliably reduces the tumor burden and offers complete resection as the best outcome. Examples include surgical removal of the breast (mastectomy) or prostate (prostatectomy). Chemotherapy (systemic administration of anticarcinoma drugs) can damage tumor cells anywhere in the body, usually by interfering with deoxyribonucleic acid (DNA) replication. Many chemotherapy regimens harm healthy tissue as a dose-limiting toxicity. Radiotherapy is the use of high-energy electromagnetic radiation (X rays or gamma rays) to damage or kill cancer cells; radiation can be delivered from the outside or by implantation of radioactive pellets (brachytherapy). Immunotherapy refers to attempts to attack carcinoma cells with the patient’s own immune cells. Monoclonal antibody therapy depends on knowledge of signal transduction pathways and uses antibodies to block or disrupt the malignant cells’ growth. An example includes the use of monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) such as trastuzumab to interfere with signals generated by the HER2 receptor in breast cancer.
Screening and diagnosis: Carcinoma screening consists of careful inspection of epithelial cells at risk as well as blood tests for circulating tumor markers. Inspection for skin cancer may be as straightforward as looking for suspicious changes on the skin, whereas screening for cervical cancer involves scraping or brushing cells from the uterine cervix followed by staining and microscopic examination (a Pap smear). Blood tests can also be used to screen for carcinoma based on shedding of tumor-specific molecules into the circulation. A blood test for prostate-specific anti-
Prognosis, prevention, and outcomes: Although some types of carcinoma are quite deadly, many forms are indolent and manageable. Prognosis depends mostly on the type of carcinoma, the histologic grade, and the anatomic stage. Prevention efforts can reduce the incidence of carcinomas within populations and take the form of avoidance of or reduction of exposure to carcinogens. Examples include smoking-cessation campaigns to prevent some cases of lung cancer and promotion of sunscreen use to prevent some cases of melanoma. Individuals may further reduce
Etiology and the disease process: Epithelial cells are more prone to malignant transformation than other types of cells because they are routinely exposed to the outside environment. Therefore, carcinoma is far more prevalent than sarcoma, leukemia, or other forms of cancer. The etiology of carcinoma hinges on cellular alterations that confer several key traits on the cell: unregulated growth, stimulation of new blood vessel formation, tissue invasion, and metastatic potential. Infection by oncogenic viruses causes carcinoma by introduction of foreign genes into the cell; these oncogenic genes (oncogenes) can confer the attributes of malignancy to the infected cells. Gene disruption can cause carcinoma via abnormal activation of oncogenes or, alternatively, by abnormal inactivation of tumor-suppressor genes. Incidence: Carcinoma is by far the most prevalent form of cancer, accounting for more than 90 percent of new cancer cases and cancer deaths. In 2005, there were approximately 1.2 million new cases and 500,000 deaths from carcinoma in the United States.
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Salem Health: Cancer their risk of cancer by losing weight and being physically active. Outcomes continue to improve because of the integration of treatments and supportive care. John B. Welsh, M.D., Ph.D. u For Further Information Hanahan D., and R. A. Weinberg. “The Hallmarks of Cancer.” Cell 100 (2000): 57-70. Kufe, D. W., et al., eds. Holland Frei Cancer Medicine. 7th ed. Hamilton, Ont.: BC Decker, 2006. Ruddon, R. W. Cancer Biology. 4th ed. New York: Oxford University Press, 2007. Schottenfeld, D., and J. F. Fraumeni, Jr., eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, 2006. Weinberg, R. A. The Biology of Cancer. New York: Garland Science, 2007. u
Other Resources
American Cancer Society http://www. cancer.org National Cancer Institute http://www.cancer.gov See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Adrenocortical cancer; Appendix cancer; Ascites; Basal cell carcinomas; Bile duct cancer; Birt-Hogg-Dubé syndrome (BHDS); Bladder cancer; Bowen disease; Breast cancer in men; Breast cancers; Bronchoalveolar lung cancer; Carcinoma of unknown primary origin (CUP); Carcinomatosis; Carcinomatous meningitis; Carcinosarcomas; Cervical cancer; Chordomas; Choriocarcinomas; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Duodenal carcinomas; Endocrine cancers; Epidermoid cancers of mucous membranes; Ethnicity and cancer; Fallopian tube cancer; Gallbladder cancer; Granulosa cell tumors; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary mixed polyposis syndrome; Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Invasive ductal carcinomas; Invasive lobular carcinomas; Leptomeningeal carcinomas; Liver cancers; Lobular carcinoma in situ (LCIS); Lung cancers; Medullary carcinoma of the breast; Meningeal carcinomatosis; Merkel cell carcinomas (MCC); Metastatic squamous neck cancer with occult primary; Mucinous carcinomas; Multiple endocrine neoplasia type 2 (MEN 2); Ovarian epithelial cancer; Pancreatic cancers; Parathyroid cancer; Penile cancer; Pituitary tumors; Prostate cancer; SCLC1 gene; Skin cancers; Small intestine cancer; Squamous cell carcinomas;
Carcinomatosis Stomach cancers; Teratocarcinomas; Thymus cancer; Transitional cell carcinomas; Trichilemmal carcinomas; Tubular carcinomas; Urethral cancer; Urinary system cancers; Uterine cancer; Vaginal cancer; Virus-related cancers; Vulvar cancer; Yolk sac carcinomas.
u Carcinomatosis Category: Diseases, symptoms, and conditions Also known as: Carcinosis Related condition: Metastasis Definition: Carcinomatosis is a condition in which a malignant tumor (or carcinoma), originating in the epithelial cells lining the internal and external surfaces or passageways that run through all organs, has spread via the bloodstream or lymphatic system through a process called metastasis. This is in contrast to carcinoma in situ, in which the cancer has not spread to neighboring tissues and involves only the cells where it originated. Although strictly speaking carcinomatosis should be used only for epithelial cancers, or carcinomas, it is sometimes employed to describe other types such as sarcomas—cancers of connective tissues such as bone, cartilage, or fat—that have spread widely throughout the body. Carcinomatosis is also used to describe a cancer in a relatively large region of the body. Risk factors: Cancer risk increases as a function of smoking; consuming a high-fat diet; being overweight or obese; unprotected exposure to the sun’s ultraviolet rays; increasing age; gender (often men have a higher risk); race (which race has an increased risk depends on the cancer); poverty and thus access to health care, screening, and early diagnosis; genetics (sometimes tied to ethnicity or religion); or environment (exposure to pollution, toxins, and ionizing radiation). However, every cancer has distinct risk factors. Etiology and the disease process: Just as every cancer has distinct risk factors, every cancer also has distinct, organ-specific causes. However, what is common among cancers is the out-of-control growth and accumulation of abnormal cancer cells. Carcinogens—substances that cause gene mutation—may be chemical, irradiative, viral, immunological, or hereditary. Incidence: In the United States the incidence of cancer among men is as follows: prostate, 33 percent; lung, 13 percent; colorectal, 10 percent; bladder, 7 percent; nonHodgkin lymphoma, 6 percent; and skin melanoma, 5 percent. Among women the rates were breast, 32 percent; 235
Carcinomatosis lung, 12 percent; colorectal, 11 percent; endometrial, 6 percent; and non-Hodgkin lymphoma, 4 percent. Symptoms: Most cancers develop from a single aberrant cell. This cell then proliferates to generate a clinically detectable tumor, which may be benign or malignant. In some cases, multiple primary tumors may occur; this may or may not be followed by metastasis. The symptoms may evidence the progression from normal cell through premalignant lesions to fully malignant cancers capable of moving to distant sites. Screening and diagnosis: Screening may be general through blood tests, X rays, computed tomography (CT scans), and endoscopy. However, for some cancers, there are specific screening tests. For example, for prostate cancer, screenings include digital rectal examinations to detect irregularities of the prostate gland and blood tests to detect levels of prostate specific antigen (PSA), but prostate biopsies are more definitive. Similarly, colonoscopies (colorectal examinations) help identify precancerous or cancerous polyps or tumors that may also be confirmed by biopsies, and Pap smears test for abnormal cells that might signal the start of cervical cancer. Most types of cancer are categorized in Stages I, II, III, and IV. These stages of cancer are based on the extent of spread and whether the cancer has moved to lymph nodes or other organs. Each stage classification is slightly different for every type of cancer, ranging from the least extensive spread (Stage I) to the most extensive (Stage IV), where the cancer has spread through the bloodstream beyond the primary site; that is, it has metastasized. The condition of carcinomatosis usually refers to cancers in Stage III or IV. Treatment and therapy: Treatment options include surgery, radiation therapy, chemotherapy, and hormone therapy. Radiation therapy uses X rays or other high-energy rays to kill cancer cells or shrink tumors. Radiation may be used alone, or before or after surgery. Chemotherapy uses drugs (singly or in combination) to kill cancer cells. Alternative therapies include dietary formulas, homeopathy, or hypnotherapy. Complementary therapies consist of such procedures as massage or even music, often to reduce the anxiety that often accompanies a cancer diagnosis. Prognosis, prevention, and outcomes: Thanks to the increasing numbers of diagnostic tools and treatment options, the prognosis for specific forms of cancer has improved even though predicting the outcome of any individual treatment is very difficult. As for prevention, avoidance of smoking drastically reduces the incidence of lung cancer, while reducing the 236
Salem Health: Cancer body mass index to below twenty-five cuts down the risk of colon, kidney, pancreatic, esophageal, uterine, and breast cancer. Reducing the intake of processed meats and to a lesser extent red meat diminishes the likelihood of colorectal cancer. Limiting direct exposure to the sun reduces malignant skin melanomas. Modifying not only lifestyle risk factors but also occupational factors such as avoiding the inhalation of asbestos fibers at the workplace also helps cancer prevention. The use of specific drugs may also be preventive, as is testing for such genes as BRCA1 and BRCA2, which cause breast cancer. Various forms of screening such as Pap smears, colonoscopies, and PSA tests have also been found to be effective preventive measures. As for outcomes, mortality rates for the most common forms of cancer among men were as follows: lung cancer, 31 percent; prostate, 10 percent; colorectal, 10 percent; pancreatic, 5 percent; and blood leukemia, 4 percent. Among women, the corresponding figures were lung, 27 percent; breast, 15 percent; colorectal, 10 percent; ovarian, 6 percent; and pancreatic, 6 percent. Peter B. Heller, Ph.D. u
For Further Information Eyre, Harmon J., et al., eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta, Ga.: American Cancer Society, 2002. “Facts About Cancer.” In American Medical Association Family Medical Guide. 4th ed. Hoboken, N.J.: John Wiley, 2004. Kleinsmith, L. J. Principles of Cancer Biology. San Francisco: Pearson Benjamin Cummings, 2006. Tannock, I. F., et al., eds. The Basic Science of Oncology. 4th ed. New York: McGraw Hill, 2005. Turkington, Carol A., and William LiPera, eds. The Encyclopedia of Cancer. New York: Facts on File, 2005.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Appendix cancer; Ascites; Carcinomatous meningitis; Carcinosarcomas; Fallopian tube cancer; Gynecologic cancers; Hyperthermic perfusion; Leptomeningeal carcinomas; Lumbar puncture; Meningeal carcinomatosis.
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u Carcinomatous meningitis Category: Diseases, symptoms, and conditions Also known as: Meningeal carcinomatosis, leptomeningeal carcinomatosis, leptomeningeal metastasis Related conditions: Almost any type of cancer can be associated with this condition, but it is generally seen with melanoma and breast and lung cancers. Definition: Carcinomatous meningitis is the spread or infiltration of tumor cells from a primary central nervous system (CNS) source, such as a brain tumor, or from a distant or secondary source, such as a lung or breast tumor, via the blood to the subarachnoid space, where it spreads via the fluid covering the brain, called the cerebral spinal fluid (CSF), to involve the coverings of the brain, known as the leptomeninges. The leptomeninges are further subdivided into the pia mater and the arachnoid. The space between the two is called the subarachnoid space, and this space acts as the conduit for the spread of tumor cells as it contains the CSF fluid. Risk factors: In adults, primary brain tumors such as oligodendroglioma or secondary tumors, also called metastases, from lung, breast, melanoma, lymphoma, ovarian, or gastric cancer can spread to the brain surfaces. In children, primary brain tumors such as ependymoma, pineal tumors, meduloblastoma, germinoma, or glioblastoma can spread to the leptomeninges. Etiology and the disease process: The leptomeninges are the coverings of the brain. The leptomeninges can be further subdivided into the pia mater, a thin translucent sheet or membrane that adheres to the surfaces of the brain and spinal cord, and the arachnoid, a delicate weblike membrane between the dura and pia mater. The space between the two is called the subarachnoid space and is filled with fluid called cerebral spinal fluid, which nourishes the brain and cushions it. When tumor cells invade the subarachnoid space between the pia mater and the arachnoid, that invasion is called carcinomatous meningitis. Unlike other forms of meningitis, where the invading organism is a bacteria, fungus, or virus, the invaders in carcinomatous meningitis are cancer cells, and therefore it is not an infection. Tumor growth in carcinomatous meningitis is along the CSF and can involve the dura, pia-arachnoid, or rarely the spinal cord itself. In adults, tumor growth usually results from spread of a primary brain tumor (a cancer that starts in the brain) such as oligodendroglioma or of secondary cancers from lymphoma, melanoma, or lung, breast, or
Carcinomatous meningitis gastric tumors. A secondary cancer occurs when cancer cells leave the primary site (usually the breast in carcinomatous meningitis) and spread to another organ or different parts of the body (metastasize). These secondary cancer cells can stay inactive for many years, so even when a cancer appears to have been successfully treated, it can recur. No one knows what triggers the cancer cells to become active again. It is estimated that between 3 and 5 out of every 100 patients with cancer will develop carcinomatous meningitis, and it can occur with any type of cancer but most commonly occurs in breast cancer. Incidence: The incidence of carcinomatous meningitis is increasing because cancer patients are surviving longer. It is seen in about 3 to 5 percent of patients who have cancer. Symptoms: Patients usually complain of nonspecific symptoms such as headache or back pain, or focal neurologic deficits such as weakness in an extremity. Screening and diagnosis: Carcinomatous meningitis can be diagnosed by magnetic resonance imaging (MRI) or myelography together with computed tomography (CT). A cerebral spinal fluid (CSF) or spinal tap (also called a lumbar puncture), whereby a needle is inserted into the spinal fluid within the subarachnoid space and the CSF fluid is sampled, is the usual form of diagnosis, although CSF cytology is negative in 10 percent of cases. On noncontrast CT, there is obliteration of basal cisterns or sulci with hydrocephalus as an indirect sign. Contrast-enhanced MRI is more sensitive than CT and typically shows enhancement of the basilar cisterns or sulci with focal subarachnoid masses less common. It should be noted that up to 30 percent of confirmed cases of meningeal metastases will have a negative MRI. Treatment and therapy: This disease is difficult to cure, and the treatment aim is usually to ameliorate symptoms, usually by chemotherapy injected into the spinal fluid via lumbar puncture (intrathecal methotrexate) or by radiotherapy to the brain. Prognosis, prevention, and outcomes: Some patients respond to treatment; however, the prognosis is generally poor, with death occurring within one month if the disease is untreated. Treatment can extend median survival to three to six months. New treatment options involving new chemotherapy regimens are being tested. Debra B. Kessler, M.D., Ph.D. u
For Further Information Carpenter, Malcolm B. Core Text of Neuroanatomy. 2d ed. Baltimore: Williams & Wilkins, 1981. 237
Carcinosarcomas Grossman, Robert I., and David M. Yousem. Neuroradiology: The Requisites. St. Louis: Mosby-Year Book, 1994. Osborn, Anne G. Diagnostic Neuroradiology. St. Louis: Mosby-Year Book, 1994. Robbins Pathologic Basis of Disease. 5th ed. Philadelphia: W. B. Saunders, 1994. Watanabe, M., R. Tanaka, and N. Takeda. “Correlation of MRI and Clinical Features in Meningeal Carcinomatosis.” Neuroradiology 35 (1993): 512-515. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Acoustic neuromas; Carcinosarcomas; Craniotomy; Infection and sepsis; Leptomeningeal carcinomas; Lumbar puncture; Meningeal carcinomatosis.
u Carcinosarcomas Category: Diseases, symptoms, and conditions Also known as: Mixed epithelial-stromal carcinomas, mixed epithelial-nonepithelial malignant tumors, collision tumors, malignant mixed mullerian tumors, sarcocarcinomas Related conditions: Carcinoma, carcinoma in situ, carcinoma of unknown primary, carcinomatosis, carcinomatous meningitis Definition: Carcinosarcomas are malignant tumors (abnormal masses of tissue that can invade and destroy local tissue and spread to other regions) that are a combination of carcinoma (cancer of epithelial tissue, which is skin or tissue that lines organs) and sarcoma (cancer of connective tissue, such as bone) that occur throughout the body. The stromal (connective tissue) component is usually high grade (contains abnormal cells that will most likely grow and spread quickly). The mesenchymal (the mass of tissue that develops mainly from the mesoderm, the middle layer of the trilaminar germ disc during development) component is classified into two groups: the homologous form composed of cell types that are normally found and the heterologous form composed of cell types that are not normally found.
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Salem Health: Cancer Risk factors: Tamoxifen (a nonsteroidal triphenylethyl compound), widely used as adjuvant therapy in the treatment of breast cancer, has been positively correlated with the development of uterine carcinosarcoma. Radiation and chemical exposure also have been associated with carcinosarcomas. Etiology and the disease process: The cause of carcinosarcomas is poorly defined. For malignant mixed mullerian tumors (carcinoma of the endometrium), based on histological staining preparations, the epithelial and stromal components are presumed to originate from the same cell. Incidence: Incidence depends on the type of carcinosarcoma. Uterine carcinosarcoma is estimated at 33.4 and 17.0 per million in black and white women respectively. Symptoms: Carcinosarcomas can occur anywhere in the body. They often produce no signs and symptoms in their early stages. They may grow and produce a lump or swell. A tumor may cause pain if it impinges on nerves or muscles. The tumor may cause blockage, bleeding, or other pathological features depending on the location. Screening and diagnosis: Carcinosarcomas, like many cancers, are staged according to their size and location, their spread to lymph nodes, their spread to other regions in the body, and their grade. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound are frequently used for diagnosis. Biopsies are conducted to determine the malignancy and the grade (aggressiveness) of the tumor. Treatment and therapy: Treatment options for carcinosarcomas, as with other cancers, depends on size, type, location, and stage. Prognosis, prevention, and outcomes: Prognosis and outcome are determined primarily by depth of invasion and stage. Rena C. Tabata, M.Sc. See also Carcinoma of unknown primary origin (CUP); Carcinomatosis; Carcinomatous meningitis; Meningeal carcinomatosis; Metastatic squamous neck cancer with occult primary; Uterine cancer.
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u Cardiomyopathy in cancer
patients Category: Diseases, symptoms, and conditions Also known as: Doxorubicin-induced cardiomyopathy, secondary cardiomyopathy, bleomycin-induced cardiomyopathy, radiation-induced cardiomyopathy Related conditions: Breast cancer, esophageal cancer, lymphoma, metastases from primary cancers Definition: Cardiomyopathy is a disease in which the heart muscle is abnormally enlarged, thickened, or stiffened, decreasing its ability to pump blood. According to the World Health Organization, cardiomyopathies can be divided into three types: dilated, restrictive, and hypertrophic, both primary (or idiopathic) and secondary. Cardiomyopathy in cancer patients involves the secondary type of cardiomyopathy, due to a specific cause, usually chemotherapeutic agents such as doxorubicin as well as radiation, which is often employed for lymphoma or cancer of the breast or esophagus. In addition, metastases to the heart muscle from a cancer found elsewhere in the body can result in a restrictive form of cardiomyopathy. Risk factors: Risk factors for cardiomyopathy in cancer patients include radiation and chemotherapy. Etiology and the disease process: Both doxorubicin and bleomycin cause a dilated type of cardiomyopathy in which both the left and right ventricles are enlarged. The drugs most frequently associated with cardiotoxicity are doxorubicin (Adriamycin) and daunorubicin, which are anthracyclines. The total dose of anthracyclines a person receives determines the probability of developing chronic cardiomyopathy. Other chemotherapeutic drugs that can cause dilated cardiomyopathy include mitoxantrone, interferon, aldesleukin, trastuzumab (a monoclonal antibody), bleomycin, cyclophosphamide, 5-fluorouracil, vincristine, vinblastine, busulfan, mitomycin C, cisplatin, amsacrine, paclitaxel, and docetaxel. In dilated cardiomyopathy due to chemotherapeutic agents, the left ventricle typically demonstrates global hypokinesis, whereas the right ventricle has a less severe abnormality of contractility. Because of the ventricular dilatation, both mitral and tricuspid regurgitation are common, and patients with this condition also exhibit reduced ejection fractions. Decreased cardiac output, decreased stroke volume, and decreased systolic function are seen as well. Mural thrombi may also be present due to akinesis of the cardiac apex. Radiation to the chest can cause a restrictive form of
Cardiomyopathy in cancer patients cardiomyopathy. In this condition the normal heart muscle is replaced by abnormal tissue. This abnormal tissue restricts the diastolic relaxation of the heart muscle so that the heart has normal ventricular size and contractility but aberrant diastolic relaxation leading to elevation of end diastolic pressures of the ventricles. Incidence: The incidence of congestive heart failure secondary to cardiomyopathy from epirubicin is 0.7 percent. Doxorubicin is more cardiotoxic than epirubicin, and the incidence of congestive heart failure ranges from 3 to 4 percent. Symptoms: In restrictive cardiomyopathy, the signs and symptoms are related to congestive failure and arrhythmias. In dilated cardiomyopathy due to chemotherapeutic agents, occasionally these agents will cause an acute cardiotoxic effect, with symptoms such as abnormal heart rhythms and electrocardiogram changes. Screening and diagnosis: Chest X ray demonstrates the paradox of a huge heart with clear lungs in dilated cardiomyopathy. In the restrictive form of cardiomyopathy, the chest X ray often shows a normal-size heart with pulmonary congestion. Because the resultant abnormal physiology of restrictive cardiomyopathy is similar to that of constrictive pericarditis, distinction between these two entities is difficult. Magnetic resonance imaging (MRI), like computed tomography (CT), demonstrates a pericardial thickness greater than 4 millimeters in all patients with constrictive pericarditis, but this is rarely seen in restrictive cardiomyopathy. In restrictive cardiomyopathy, the electrocardiogram shows low voltage in the late stages, and echocardiography shows decreased diastolic function with normal to
Some Common Symptoms of Cardiomyopathy
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Tiredness Weakness Abnormal heart rhythm (rapid or pounding) Heart murmur Swelling of legs, ankles, and feet Bloating of the abdomen Shortness of breath while at rest or after exercise Dizziness, fainting, or light-headedness during exercise
Source: National Heart, Lung, and Blood Institute
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Cardiopulmonary resuscitation (CPR)
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decreased ejection fractions. In dilated cardiomyopathy, echocardiography always demonstrates a decreased ejection fraction because of an enlarged left ventricle with global hypokinesis. Systolic function is normal in restrictive cardiomyopathy, whereas it is always decreased in dilated cardiomyopathy. The reverse is true with diastolic function, where it is normal in dilated cardiomyopathy but decreased in restrictive cardiomyopathy. Gated myocardial scintigraphy shows decreased left ventricular ejection fraction, shortened ventricular ejection time, and decreased rate of ejection in dilated cardiomyopathy. Because marked focal wall abnormalities are usually absent in dilated cardiomyopathy, this may help distinguish it from endstage coronary artery disease, which can manifest with focal-wall motion abnormalities.
u
Treatment and therapy: Nuclear medicine techniques have become important in monitoring left and right ventricular function in patients receiving chemotherapeutic agents that are cardiotoxic, including anthracyclines such as doxorubicin and daunorubicin. Gated myocardial scintigraphy is reproducible, allowing for serial assessment of ejection fractions and the selection of patients who may best tolerate the medication. Gated myocardial scintigraphy is especially important in monitoring patients to determine the onset of cardiac toxicity. Many clinicians allow the ejection fraction to fall to 0.45 in patients receiving doxorubicin before discontinuing therapy. Newer forms of anthracyclines called liposome encapsulates have been shown to be less toxic to the heart and still effective against cancer.
Category: Procedures Also known as: Basic life support
Prognosis, prevention, and outcomes: Lifestyle changes can reduce symptoms of heart failure from cardiomyopathy. Reducing salt and fluid intake and avoiding alcohol are beneficial as well as a judicious exercise plan to increase stamina without overtaxing a failing heart. Some patients whose cardiomyopathy progresses despite medication may be candidates for cardiac transplant. Debra B. Kessler, M.D., Ph.D. u
For Further Information Brandenberg, R. O., et al. “Report of the WHO/ISFC Task Force on Definition and Classification of Cardiomyopathies.” Circulation 64 (1981): 437A. Brant, William E., and Clyde A. Helms. Fundamentals of Diagnostic Radiology. Baltimore: Williams and Wilkins, 1994. Mettler, Fred A., and Milton J. Guiberteau. Essentials of Nuclear Medicine Imaging. 3d ed. Philadelphia: W. B. Saunders, 1991. 240
Other Resources
American Heart Association Cardiomyopathy http://www.americanheart.org/ presenter.jhtml?identifier=4468 The Cardiomyopathy Association http://www.cardiomyopathy.org/ See also Nuclear medicine scan; Radionuclide scan.
u Cardiopulmonary
resuscitation (CPR) Definition: Cardiopulmonary resuscitation (CPR) is an emergency procedure performed by health care providers and laypeople that maintains breathing and circulation after a person’s heartbeat and breathing cease. Cancers treated: Can be used to support those with cancer with an advance directive declaring a desire for life support Why performed: CPR is performed to maintain breathing and circulation and to prevent brain death when a person suffers cardiopulmonary arrest. Patient preparation: Before beginning CPR, the patient is placed on a flat firm surface in a face-up position. If the patient is found face down, then the patient must be logrolled into a face-up position. Steps of the procedure: The health care provider makes sure that the patient is unresponsive by tapping the patient on the shoulder and asking, “Are you all right?” The health care provider activates the emergency system, calls for a defibrillator, and begins CPR. The patient’s airway is opened using the head tilt-chin lift maneuver unless a head or neck injury is suspected. To perform this maneuver, the health care provider places one hand on the patient’s forehead and applies pressure firm enough to tilt the patient’s head back. Next, the health care provider places the fingertips of the other hand under the bony portion of the patient’s lower jaw near the chin and then lifts the chin. If a head or neck injury is suspected, then a jaw-thrust maneuver is performed. To perform this maneuver, the health care provider gets into position at the patient’s head, rests the thumbs (pointing toward the patient’s feet) on the patient’s lower jaw near the corners of
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Cardiopulmonary resuscitation (CPR)
A man receives CPR. (Digital Stock)
the mouth, and opens the airway by lifting the lower jaw with the fingertips. While keeping the airway open, the health care provider looks, listens, and feels for breathing. If no breathing is detected within ten seconds, then the health care provider gives two breaths (each over one second). Each breath should deliver enough volume to make the patient’s chest rise. If the patient has no response, then the health care provider checks to see whether the patient has a pulse. If a pulse is present, then the health care provider continues delivering eight to ten breaths per minute. If no pulse is detected, then the health care provider kneels (or stands, if the patient is in a bed) next to the patient’s chest and begins compressions. Chest compressions are begun by placing the heel of one hand on the sternum in the middle of the chest and then placing the heel of the second hand on top of the first. The sternum is depressed 1.5 to 2.0 inches (for an adult), and compressions are delivered at a ratio of thirty compressions to two breaths. Approximately one hundred compressions are delivered each minute. Cycles of thirty compressions and two breaths are delivered continuously until an automated external defibrillator (AED) or stan-
dard defibrillator arrives, the patient begins to move, or the advanced cardiac life support team arrives. When a defibrillator arrives, it is attached to the patient, and the patient’s heart rhythm is evaluated. If the heart rhythm is shockable, then the health care providers stand clear of the patient while a shock is delivered. If the patient’s rhythm returns to normal and the patient begins to move, then CPR is stopped. Ir the patient’s condition remains unchanged, then CPR is continued for five cycles immediately after the shock. The heart rhythm is checked again, and another shock is delivered if the rhythm is shockable. If the rhythm is not shockable, then CPR is resumed while advanced cardiac life support is administered. After the procedure: During advanced cardiac life support, an endotracheal tube is inserted through the patient’s nose or mouth and then advanced into the airway. This tube is used to administer oxygen directly into the patient’s lungs. The patient is attached to a portable continuous cardiac monitor, and a large intravenous (IV) catheter is inserted. The IV catheter is used to administer fluids and medications to help establish a normal heart rhythm and maintain blood pressure. 241
Caregivers and caregiving When the patient’s heart rhythm begins to stabilize, the patient is transferred to the intensive care unit (ICU). The respiratory therapist attaches the patient to a mechanical ventilator to assist the patient’s breathing. The ICU nurses attach the patient to a continuous cardiac monitor and an automatic blood pressure cuff so that they can closely monitor the patient’s heart rhythm and vital signs. The nurses also listen to the patient’s heart and lungs. A chest X ray is obtained to make sure that the endotracheal tube is in the proper location. A 12-lead electrocardiogram and blood samples are obtained to help determine the cause of cardiac arrest. When the cause is determined, an individualized treatment plan is developed. The length of stay in the ICU depends upon the patient’s condition and response to treatment. Risks: According to the American Heart Association, CPR can double a patient’s chance of survival if provided immediately after cardiac arrest. CPR is not without risk, however. It can cause sternal and rib fractures, pneumothorax (collection of air in the chest cavity), hemothorax (collection of blood in the chest cavity), injury to the heart and great vessels, organ laceration, or aspiration of stomach contents into the lungs. Results: Positive results of CPR are the return of spontaneous breathing and normal heart rhythm without signs of brain damage. When CPR is ineffective, death commonly results. Collette Bishop Hendler, R.N., M.S. u For Further Information American Heart Association. “2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.” Journal of the American Heart Association 112, no. 24 (December 13, 2005). BLS for Health Care Providers. Dallas: American Heart Association, 2006. Cardiovascular Care Made Incredibly Visual. Philadelphia: Lippincott Williams & Wilkins, 2007. Thygerson, A., et al. First Aid, CPR, and AED. 5th ed. Sudbury, Mass.: American College of Emergency Physicians/Jones & Bartlett, 2006. u
Other Resources
American Heart Association http://www.americanheart.org See also Advance directives; Do-not-resuscitate (DNR) order; End-of-life care; Living will. 242
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u Caregivers and caregiving Category: Social and personal issues Definition: Caregivers are people who are engaged in providing care to an ill person. There are two categories of caregivers, paid professionals and informal caregivers. Professional caregivers—home health aides, companions, and hospice workers—are trained to provide caregiving services. Informal caregivers, usually family and friends of the ill person, typically provide services without charge because of their relationship with the person. Statistics: According to the Family Caregiver Alliance, there are an estimated 44 million people in the United States who are engaged in caregiving for a family member. Three out of five informal caregivers are women. A majority of caregivers are middle-aged, and a quarter of all caregivers provide care for someone over the age of fifty. Half of all caregivers are employed full or part time and provide fewer than eight hours of care per week. The average caregiver spends four to five years in this role. Many informal caregivers provide care for a loved one living in close proximity; however, a number of caregivers fall into the long distance category, spending on average $392 a month on travel and out-of-pocket expenses as part of their caregiving duties. The role of the caregiver: There is no “typical” caregiver in terms of the support the person provides to an ill person. Some caregivers help with grocery shopping and laundry, others take a loved one to doctor visits and help change bandages, while still others provide long-distance support
Tips for Self-Care for Caregivers
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Recognize the signs of stress and learn to manage it. Take breaks from caregiving without feeling guilty. Seek help from others, whether relatives, friends, agencies, or professionals. Recognize your emotions and try to understand what they are telling you. Seek counseling or care if depression strikes you. Pay attention to your own health needs. Get enough sleep and eat a balanced diet. Engage in exercise on a regular basis. Keep the lines of communication flowing among you, the ill person, and the health care team. Identify specific problems and seek solutions.
Source: Family Caregiver Alliance
Salem Health: Cancer
Caregivers and caregiving
to someone by checking in with the individual on a regular basis and lending an ear. According to the American Cancer Society, for caregivers to give appropriate care, they need to take time to listen to the person requiring caregiving and ask what types of help that person may need on an ongoing basis. Open communication is vital. A caregiver may think the patient needs help with something that the person feels capable of handling. To keep conflict and frustration to a minimum, the caregiver and cancer patient must be willing to listen to each other’s needs and concerns. Both parties need to keep focused on their goal: to provide the About 44 million people in the United States are engaged in providing care for a family member. (Digital Stock) most appropriate care and make sure all needs are met. In addition to the important role a can provide services, long-distance caregivers can consult caregiver plays in the life of the patient, the caregiver is a local telephone book or do an Internet search. The type of also a vital part of the health care team. Caregivers can proprofessional caregiver hired will vary depending on a pavide important information on the patient’s health by obtient’s needs. It is also helpful for a long-distance caregiver serving health signs and symptoms while they help the pato make a list of the ill person’s local friends and contact tient. Typically, caregivers look for changes in mental and them to see if they would be willing to check in on the indiemotional function and any noticeable changes in the pavidual on occasion and help with tasks that must be done in tient’s condition. Caregivers should ask the medical properson. It may also be wise to set aside money on a regular viders how to keep records and how to perform any tasks basis to pay for those times when the caregiver may unex(such as bandage changing) that they are being asked to pectedly need to travel to the patient’s side. do. The American Red Cross offers caregiving courses onProfessional caregivers can perform a number of tasks line and in person that may help caregivers feel more comand go by different names, according to the National Assopetent in their new role. ciation for Homecare. For example, a home health aide can Caregivers need to take time to think about what tasks administer medical treatments, while a companion will sit must be done and determine what they realistically can and with the ill person and may help with light housekeeping want to provide for the ill person. They must determine but is not trained to perform medical duties. Regardless of what they will do themselves and what they will delegate the services the professional caregiver is providing, the to other family members or a hired professional, according main caregiver needs to ask questions to determine whom to the National Cancer Institute. No single person can do to hire. The content of these questions concerns how long everything, and a caregiver’s hardest decision may be dethe caregiver has been working in the field, what kind of termining what tasks must be delegated to others. There is training he or she received, and the professional’s fee and no reason that caregivers should feel guilty about not being work availability. In addition, the employer should check able to do everything alone. When caregivers ask friends the caregiver’s references. Payment for professional careor relatives to help they should not be offended if they are giving services is typically through a combination of selfrefused, as people may have other demands on their time pay and public and private entities. and other priorities. However, when people offer to help, caregivers should take them up on their offers. Those providing long-distance support need to deterCare for caregivers: Some challenges caregivers typimine in what ways the cancer patient needs help and then cally talk about include having less time for their personal find professional or informal caregivers to help with those lives and the difficulty of trying to balance their current responsibilities with their caregiving role. Other concerns needs. To find contact information for local agencies that 243
Caregivers and caregiving include financial strains and feeling physically, emotionally, and mentally distressed. It is important for caregivers to take time to take care of themselves. Many caregivers become so focused on helping someone else that they forget to make themselves a priority. Caregivers can temporarily put aside their needs to help someone else, but putting aside these needs for long periods of time is not wise and can be detrimental to their physical and emotional health. Studies show that informal caregivers are at a higher risk for physical, mental, and emotional illness. They have increased risk for cardiovascular disease, can have impaired immune systems, and may have increased blood pressure and insulin levels. In addition, caregivers are prone to depression, anxiety disorders, and feelings of guilt. Emotionally, caregivers can feel a sense of anger at themselves and the patient, be prone to irritability that leads to moodiness, and be unable to concentrate. To combat the potentially harmful effects of caregiving, it is important for caregivers to make time for themselves and maintain a routine that will be beneficial to their own health. For example, they should make time to exercise, eat well, and get enough sleep as well as to connect with friends and families, pursue their own interests, and do nice things for themselves. Caregivers should also find ways to deal with their emotions regarding their role. Many caregivers will face emotions that range from anger, grief, and guilt to anxiety, depression, and loneliness. These feelings are all normal, and having other caregivers with whom to share their experiences or just being able to vent their emotions is important. Caregiver support groups: Many caregivers find it easier to cope with their role by reaching out to others who share their experiences. From in-person support groups held at local community centers and hospitals to online chat rooms, there are a number of ways a caregiver can connect with other caregivers. Caregivers should try out various types of support groups to find the best option. There are also a number of books about caregiving that include stories by other caregivers. There is no reason caregivers should have to cope alone, as there are many opportunities for caregivers to connect with each other. Jennifer M. Hickin, B.S. u
For Further Information Barry, Michael S. The Art of Caregiving: How to Lend Support and Encouragement to Those with Cancer. Colorado Springs, Colo.: Life Journey, 2007. Capossela, Cappy, and Sheila Warnock. Share the Care: 244
Salem Health: Cancer How to Organize a Group to Care for Someone Who Is Seriously Ill. Rev. ed. New York: Simon and Schuster, 2004. Gilbar, Ora, and Hasida Ben-Zur. Cancer and the Family Caregiver: Distress and Coping. Springfield, Ill.: Charles C Thomas, 2002. Hennessey, Maya. If Only I’d Had This Caregiving Book. Bloomington, Ind.: AuthorHouse, 2006. Houts, Peter S., and Julia A. Bucher, eds. Caregiving: A Step by Step Resource for Caring for the Person with Cancer at Home. Rev. ed. Atlanta: American Cancer Society, 2003. Intner, Riki, and Roberta Cole. Caregiving from the Heart: Tales of Inspiration. San Francisco: Elders Academy Press, 2006. Kane, Jeff. How to Heal: A Guide for Caregivers. New York: Allworth Press, 2003. Mintz, Suzanne Gebben. Love, Honor, and Value: A Family Caregiver Speaks Out About the Choices and Challenges of Caregiving. Sterling, Va.: Capital Books, 2002. Perry, Angela, ed. The American Medical Association Guide to Home Caregiving. New York: J. Wiley & Sons, 2001. Rose, Susannah, and Richard Hara. One Hundred Questions and Answers About Caregiving for Family or Friends with Cancer. Sudbury, Mass.: Jones & Bartlett, 2004. u
Other Resources
American Cancer Society Caregiving: How to Care for a Loved One with Cancer—and Yourself http://www.cancer.org/docroot/MLT/content/ MLT_3_1x_Caregiving_—_How_to_Care_for_a_ Loved_One_With_Cancer_And_Yourself.asp CancerCare http://www.cancercare.org Family Caregiver Alliance http://www.caregiver.org National Alliance for Caregiving http://www.caregiving.org National Association for Home Care and Hospice http://www.nahc.org ARCH National Respite Network Respite Locator http://www.respitelocator.org
Salem Health: Cancer See also Advance directives; Aging and cancer; Aids and devices for cancer patients; Cognitive effects of cancer and chemotherapy; Counseling for cancer patients and survivors; Do-not-resuscitate (DNR) order; Elderly and cancer; End-of-life care; Financial issues; Grief and bereavement; Home health services; Hospice care; Informed consent; Karnofsky performance status (KPS); Living with cancer; Long-distance caregiving; Palliative treatment; Personality and cancer; Poverty and cancer; Prayer and cancer support; Psychosocial aspects of cancer; Relationships; Second opinions; Self-image and body image; Sexuality and cancer; Singlehood and cancer; Stress management; Support groups; Survivorship issues; Transitional care; Watchful waiting.
Carotenoids found in the thyroid, adrenal gland, breast, brain, and testes. Symptoms of these tumors can include rash, fever, and joint pain. Screening and diagnosis: Although no standard screening guidelines exist for Carney complex, it is recommended that people suspected of having the disease receive an echocardiogram and blood tests (particularly for prolactin, cortisol, and insulin-like growth factor 1, or IGF-1) once a year, as well as frequent skin, thyroid, and genital exams. If a diagnosis of Carney complex is made, patients should be referred to an oncologist, as there is an increased risk in the development of cancer in patients with Carney complex. Treatment and therapy: Treatment and therapy are based on the symptoms exhibited by the patient.
u Carney complex Category: Diseases, symptoms, and conditions Also known as: Nevi, atrial myxoma, myxoid neurofibroma, and ephelides (NAME) syndrome; lentigine, atrial myxoma, mucocutaneous myxoma, blue nevi (LAMB) syndrome Related conditions: Cushing syndrome, multiple thyroid nodules, benign tumors Definition: Discovered in 1985 by J. Alden Carney, Carney complex is a very rare, inherited genetic condition that can cause a variety of symptoms, ranging from skin pigmentation to tumor growth throughout the body. It primarily involves the endocrine system and, depending on the severity of its symptoms, can lead to cancer or heart failure. Risk factors: Because Carney complex is an inherited condition, risk factors include family members with Carney complex. Genetic testing or screening is advised for patients with family members who have been previously diagnosed with Carney complex. Etiology and the disease process: The genes PRKAR1A and CNC2 have been identified in causing Carney complex. It is thought that additional genes are also involved. Incidence: Carney complex is a rare condition with only 400 cases being documented worldwide. Symptoms: Onset of Carney complex usually begins in a person’s twenties, and symptoms can include spotted pigmentation of the skin on the eyes, lips, mouth, and genitals, as well as heart-related conditions, such as tumors in the chambers of the heart, which, while typically benign, can lead to stroke or heart failure. These tumors can also be
Prognosis, prevention, and outcomes: As Carney complex has been diagnosed in less than 400 people throughout the world, with approximately 50 to 75 percent of those cases due to genetic inheritance, prevention is limited to repetitive screening and genetic testing. The outcome of Carney complex is determined by the severity of the symptoms and the speed of diagnosis. Anna Perez, M.Sc. See also Adrenal gland cancers; Adrenocortical cancer; Cushing syndrome and cancer; Endocrine cancers; Genetic counseling; Genetic testing.
u Carotenoids Category: Lifestyle and prevention Also known as: Carotenes (alpha-carotene, betacarotene) Definition: Carotenoids are chemical substances found in yellow, orange, and red fruits as well as dark green, leafy vegetables. They are rich in antioxidants, and some studies suggest that inclusion of carotenoids in diets sharply reduces the risks of a variety of cancers. Other studies warn that they may actually promote cancer when taken in pill or capsule form, especially in smokers or former smokers. Cancers treated or prevented: May reduce risk of prostate, breast, lung, cervical, colon, stomach, rectal, ovarian, oral, pharyngeal, bladder, and other cancers Delivery routes: Oral in diet, tablet, or capsule How these compounds work: Carotenoids are chemicals produced by plants best known for their reddish and yellowish colors, as in the reds of a tomato or carrot. Carot245
Cartilage supplements enoids reduce the risk and incidence of cancer by acting as antioxidants, binding with and thereby reducing the amount of free radicals in the human body. Free radicals (which act as oxidants) are unstable molecules that lack a sufficient number of electrons. In their quest to become stable, they can wreak havoc on genetic material and proteins, disrupting cell molecules and chemical processes and making cells more susceptible to cancer. Antioxidants eliminate many of these cell-harming free radicals, in theory reducing the predisposition of cells to become cancerous. Studies have also suggested that carotenoids in the diet can inhibit cancer development by stimulating the manufacture of detoxifying enzymes and inhibiting the proliferation of cancer cells by the regulation of communication between cancer cells. The mechanism by which carotenoids may affect or prevent cancerous cells is unknown. Lycopene and betacarotene are the two most widely studied carotenoids, though there are at least six hundred known carotenoids in all. Researchers have shown in the laboratory that small concentrations of alpha- or beta-carotene severely hindered the growth and spread of neuroblastoma cells. The N-myc gene exists in all cells and codes for proteins that stimulate cell growth. Usually, this gene is dormant unless the cell becomes damaged or receives signals to activate cellular growth. Carotenoids inhibit this gene activity, causing a decrease in activation or complete inactivation of this gene in cancerous cells. Most—but not all—studies show an inverse relationship between serum levels of carotenoids and cancer incidence, but others show no affiliation and still others even show that high levels of certain carotenoids such as 3carotene may increase the risk of certain types of cancers. All, however, agree that the antioxidant role of carotenoids reduces the concentration of harmful oxidants, and many more studies are being conducted that may better control for lifestyle differences, age, gender, and genetic predisposition. It remains the consensus among researchers and physicians that regardless of the study outcomes, carotenoids are most likely beneficial and play some role in cancer prevention. Side effects: Although no specific side effects are known, consumption of large amounts of 3-carotene may increase the risk of lung cancer, especially in smokers. As stated in the Wellness Guide to Dietary Supplements (produced by the Berkeley Wellness Letter, available online at http:// www.wellnessletter.com/): Don’t assume that beta carotene or other antioxidants in supplement form are beneficial, or even harmless. Don’t
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Salem Health: Cancer take beta carotene pills, particularly if you’ve ever been a smoker. Beta carotene is plentiful in vegetables and fruits, and is safe and beneficial when consumed from such foods.
Dwight G. Smith, Ph.D. See also Antioxidants; Beta-carotene; Chemoprevention; Fruits; Nutrition and cancer prevention; Stomach cancers.
u Cartilage supplements Category: Complementary and alternative therapies; lifestyle and prevention; chemotherapy and other drugs Also known as: Shark cartilage, bovine cartilage Definition: Cartilage is a type of dense, semi-opaque, elastic connective tissue found in humans and animals that has no blood supply of its own. It consists of cells called chondrocytes in a matrix of collagen, protein, and sugar. Cartilage supplements, often promoted as a treatment for cancer, come from animal sources, particularly the heads and fins of sharks and the windpipes of cattle. Cancers treated or prevented: Lymphoma, breast cancer, colon cancer, lung cancer, prostate cancer, brain cancer Delivery routes: Administered orally via pills, powders, or liquids; also given as enemas, by topical application, or through intravenous and intramuscular injection How this substance works: The use of shark cartilage for cancer treatment is based on the process of angiogenesis, the development of new blood vessels. In the 1970’s, Dr. Judah Folkman noted that most tumors require a supply of nutrients and oxygen carried through blood in order to grow. It was found that shark cartilage has a protein that inhibited angiogenesis in the laboratory. Therefore, it was proposed that it could block the blood supply to tumors and literally “starve” them. William Lane, who holds a Ph.D., investigated this possibility and in 1993 published Sharks Do Not Get Cancer, which established shark cartilage as a leading alternative cancer therapy. Cases of tumors in sharks, however, have been documented. It has also been found that an active ingredient in shark cartilage is too large to be absorbed into the human bloodstream from the digestive tract. Dr. John Prudden in the 1950’s found that bovine cartilage contains complex molecules called mucopolysaccharides, which were thought to stimulate the immune system to fight off cancer and to block cell division and
Salem Health: Cancer growth. Although there has been much continuing research, results on the use of cartilage supplements have been mixed. Extensive clinical studies so far, however, conclude that none of the cartilage supplements offers any significant benefits for cancer patients. Side effects: Cartilage supplements contain high amounts of calcium. Taking them with thiazide diuretics, which raise calcium levels in the blood, may therefore result in dangerous calcium levels. Supplements not from reputable manufacturers may be contaminated. One case of shark cartilage-induced hepatitis has been noted. Large doses may cause nausea. Because cartilage supplements stop or hinder the development of new blood vessels, pregnant or breastfeeding women, children, and patients recovering from surgery or heart attack should not take them. Martha O. Loustaunau, Ph.D. See also Calcium; Complementary and alternative therapies; Integrative oncology; Nutrition and cancer prevention.
u Case management Category: Social and personal issues Also known as: Medical case management, disease management, care management, patient care management, care coordination, care planning Definition: In general terms, case management is a process that brings together the resources of disparate people and agencies to evaluate a person’s health needs and put together, implement, coordinate, and monitor a plan to address them. The process combines, as needed, the resources of patients and their families, health care professionals, social service agencies, community groups, employers, and insurance carriers to meet its goals. Goals of case management: The principal goal of case management is to help patients and their families navigate the complex and fragmented health care system by coordinating efforts among service providers to deliver timely, appropriate, and cost-effective care according to each individual’s needs. Health care has been increasingly moving toward a patient-centered model, in which the values, preferences, cultural traditions, family situations, and lifestyles of patients and their families are taken into consideration. Therefore, case management typically tries to involve patients and their families in prevention plans, treatment options, and financial decisions. It also aims to
Case management reduce health care costs for patients and service providers. By coordinating all the various functions of treating people for serious diseases such as cancer, efficiency is increased and cost is decreased. Case management also tries to improve the standards of care for patients. Many medical and government organizations—along with individual hospitals, clinics, and medical centers (including cancer centers)—have established case management guidelines. These guidelines, based on empirical research and numerous trials and observations, provide a system to help patients across what is known as the continuum of care. Clinical and ethical standards apply in all areas of care, from prevention of disease to end-of-life issues, and to all the components of case management. Case management components: Case management has developed a set of core components: screening and assessment, treatment, community involvement, arranging for nonmedical services, monitoring, and reassessment. These core components, along with sets of subcomponents, come together to create a specific care plan for each patient. For example, the case management components and subcomponents for the care plan of a seventy-five-year-old man with prostate cancer might include the following: • Screening and assessment: examinations by the patient’s primary care provider, referrals to an oncologist or urologist, testing to determine the nature of the disease, establishing a treatment plan based on the stage of the cancer, evaluating the patient’s financial status, creating the cancer care plan • Treatment: aggressive radiation therapy, five days a week for seven weeks at a cancer center • Community involvement: scheduling rides for the patient to and from the cancer center with volunteers from the local chapter of the American Cancer Society, introducing the patient and the patient’s family to a local support group, referring the patient to an oncology social worker • Arranging for nonmedical services: working with Medicare or Medicaid to pay for treatment • Monitoring: periodic checking to see that all components of the cancer care plan are functioning, and adjusting the plan if necessary • Reassessment: scheduled follow-up visits with doctors, the oncology social worker, and Medicare or Medicaid Managing all these components to create the cancer care plan is the job of the medical case manager. The medical case manager: Most medical case managers (MCMs) are registered nurses. The medical case manager may also be a staff member of a hospital or cancer center and is often hired by an employer or insurance carrier. The 247
Castleman disease role of the medical case manager includes, but is not limited to, the following: • Overseeing patients’ cancer care throughout diagnosis, treatment, and follow-up • Assessing patients’ health, nutrition, psychological, and care needs • Assessing patients’ financial needs • Educating patients on different cancer types, treatments and side effects, and possible outcomes to allow them to make informed decisions about their care • Helping patients communicate more effectively with their doctors • Linking patients with the appropriate community resources • Coordinating the efforts of the cancer care team The cancer care team: Each cancer patient’s needs are different. Meeting those needs requires a team of professionals with different expertise. Depending on the patient, the cancer care team may consist of the following individuals, all under the watchful eye of the medical case manager: • Oncology social worker: a professional trained in counseling and providing practical assistance in navigating the health care system • Psychiatrist or psychologist: to help the patient who has trouble coping psychologically with cancer • Nurses: providers of a wide range of help, from implementing the care plan to answering questions for the patient and family • Home health aide: a worker who helps cancer patients at home with daily living tasks • Rehabilitation specialists: physical, occupational, and speech therapists who help patients recover from the physical changes caused by cancer or cancer treatment • Oncology nutritionist: a specialist who advises on diet to help the patient cope with the consequences of cancer and side effects of treatment • Hospice workers: caregivers who focus on the special needs of patients with terminal cancer Wendell Anderson, B.A. u
For Further Information Cohen, E., and T. Cesta. Nursing Case Management: From Concept to Evaluation. 3d ed. St. Louis: Mosby, 2000. Fattoursso, D., and C. Quinn. A Case Manager’s Study Guide. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2004. Mullahy, C. The Case Manager’s Handbook. Sudbury, Mass.: Jones and Bartlett, 2004. 248
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Other Resources
Case Management Society of America http://www.cmsa.org National Cancer Institute http://cancer.gov See also Cancer care team; Cancer education; Caregivers and caregiving; Counseling for cancer patients and survivors; Family history and risk assessment; Genetic counseling; Home health services; Hospice care; Karnofsky performance status (KPS); Living with cancer; Longdistance caregiving; Medical oncology; Oncology; Oncology clinical nurse specialist; Oncology social worker; Pharmacy oncology; Primary care physician; Psychooncology; Radiation oncology; Rehabilitation; Surgical oncology.
u Castleman disease Category: Diseases, symptoms, and conditions Also known as: Angiofollicular lymph node hyperplasia, angiomatous lymphoid, Castleman tumor, giant benign lymphoma, Castleman’s disease Related conditions: Angiocentric immunoproliferative lesion, lymphomatoid papulosis Definition: Castleman disease is a rare disorder of the lymphatic system that causes the growth of benign tumors. Two localized forms often appear in the mediastinum: hyaline-vascular, accounting for almost 90 percent of the cases, and plasma cell. The multicentric type involves several different areas of the body. Risk factors: Human immunodeficiency virus (HIV) infection is the only known risk factor. It is much more common in HIV patients, particularly in those who have developed acquired immunodeficiency syndrome (AIDS). Etiology and the disease process: The etiology of this disease remains unknown. Increased production of interleukin-6 (IL-6) in the lymph nodes may play a role in the development of the disease. Human herpesvirus 8 (HHV-8) also plays a role in the development of the multicentric type. Incidence: Although the number of patients diagnosed annually is unknown, Castleman disease is a very rare condition. Two leading cancer centers in the United States each see about two cases per year. The number of cases has
Salem Health: Cancer been rising over the past twenty years, however, as the incidence of HIV infection has increased. Symptoms: Most patients who have the hyaline-vascular type are asymptomatic. Those who have the plasma cell type may have excessive sweating, fatigue, fever, skin rash, or weight loss. Those who have the multicentric type may have a variety of symptoms depending on the areas affected—a common finding is enlarged liver or spleen. Screening and diagnosis: There is no screening method. Diagnosis is suggested by the appearance of benign lymphatic tumors on imaging studies and the presence of elevated IL-6 levels. Definitive diagnosis can be made only by removal or biopsy of the tumor for histologic examination. Treatment and therapy: Therapy is usually symptomatic. For localized types, the most common treatment is surgical removal of the tumor. Corticosteroids are used to treat specific symptoms associated with plasma cell and multicentric types, and the multicentric type is sometimes treated with chemotherapeutic agents. Prognosis, prevention, and outcomes: Prognosis for the localized types is good following complete surgical removal of the tumor. Prognosis is poor, however, for the multicentric type, with an overall mortality rate of 50 percent and median survival of twenty-six months. Jeremy W. Dugosh, Ph.D. See also Benign tumors; Cutaneous T-cell lymphoma (CTCL); Lymphomas; Mycosis fungoides.
u Cell phones Category: Carcinogens and suspected carcinogens Also known as: Cellular phones Related cancers: Gliomas, astrocytomas Definition: Cell phones are handheld electronic communication devices that send and receive wireless electromagnetic signals. Their ubiquitous use and proximity to the brain during use has prompted concerns over their long-term impact on human health, including their potential association with cancers. Exposure routes: Radiation that is strong enough to penetrate human tissue Where found: Electronic devices such as mobile or cellular phones, microwave ovens, and computer monitors that emit radiofrequency radiation
Cell phones At risk: Possibly people who are exposed to high levels of electromagnetic radiation, such as electric railway workers and those exposed to lower levels of radiation over many years Etiology and symptoms of associated cancers: Of the dozens of epidemiological studies published since the 1990’s on the harmful effects of cell phones, only a few have indicated a possible relationship between cell phone usage and cancer. The overwhelming scientific evidence supports the conclusion that cellular phones do not pose a health risk for the more than one billion users worldwide. The electromagnetic frequency range of cell phones is from about 850 to 1900 megahertz. Regulatory bodies in the United States do not recognize radiofrequency radiation emitted from a cell phone as a carcinogen. At high enough levels, radiofrequency energy can damage biological tissue through the application of heat. This energy is essentially what gets produced in a microwave oven when it cooks food. Since mobile or cellular phones emit very low levels of radiofrequency radiation, it had always been assumed that these small electronic devices do not pose a health risk. However, some scientists have argued that long-term exposure to even low intensities of radiation could promote the development and growth of tumors as well as contribute to other kinds of health problems. Because cell phones are placed right against the head, in close proximity to the radiofrequency waves being sent and received, researchers wondered if they would cause damage. Brain tumors, originating from different types of cells, have received the most attention, particularly tumors that have developed on the same side of the head that the individual most often uses when talking on the phone. Of the 47,000 new cases of brain tumors diagnosed each year in the United States alone, only a small number of cases can be understood in terms of what has caused the cancer to develop. Unfortunately, little is known about potential mechanisms that might cause brain cancers to develop in general. In terms of cell phone radiation as a possible cause of cancer, no hypothesis has been offered that adequately explains how low levels of radiofrequency energy emitted from cell phones could alter biological tissue or bring harm to the user. History: The incidence of brain tumors began rising in the 1990’s, and this increase cannot be fully explained by the improved diagnostic methods used to detect these tumors. One way to study possible external factors that might be responsible for the increase in tumors is to conduct an epidemiological study. Epidemiological studies look at the 249
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frequency of a health problem—such as cancer—in different groups of people. For example, those who have been diagnosed with a brain tumor are compared with a group who share similar characteristics except they do not have a brain tumor. Scientists can then explore how these two groups might differ in terms of frequency, duration, and exposure intensity of radiofrequency radiation from cellular phone usage. One weakness of this type of study is that it is not particularly well suited to determine cause-andeffect relationships. In 2002, Lennart Hardell from University Hospital, Orebro, Sweden, and his colleagues found an increase in malignant brain tumors associated with the use of analog, digital, and cordless phones. He also found that risks for astrocytomas increased over time and that risk of glioma went up for periods greater than ten years. There did not appear to be an increased risk for meningioma over a long period of time. In another study, Hardell came to the conclusion that there is no association between cell phones and salivary gland tumors. Although Hardell and colleagues have published data that support claims that cellular phone use is associated with brain cancer, dozens of other studies have found results to the contrary. Several studies conducted after 2002 have inCell phone radiation has been suggested as a source of brain cancer, cluded much larger numbers of people. Increasing but little scientific evidence supports this theory. (©Popa Sorin/Dreamstime.com) the number of participants can strengthen the research by making it easier for scientists to generalize the results to the overall population. In one of the the Risk for Malignant Brain Tumours.” International largest studies on the use of cell phones and risk for cancer Journal in Radiation Biology 78 (2002): 931-936. ever conducted, more than 420,000 Danish citizens were Schuz, J., et al. “Cellular Telephone Use and Cancer Risk: followed for up to twenty-one years. The researchers Update of a Nationwide Danish Cohort.” Journal of the found no evidence for risk of tumor development from the National Cancer Institute 98 (2006): 1707-1713. use of cell phones either in short-term use or in those who had been using cell phones for more than ten years. Overall, the vast majority of research supports the conu Other Resources clusion that cellular phones do not pose a threat for cancer International Commission for Electromagnetic development. No relationship has been reliably found Safety when variables such as the number of years used, the cuBenevento Resolution mulative hours of phone use, or the number of calls has http://www.icems.eu/benevento_resolution.htm been taken into consideration. Bryan C. Auday, Ph.D. u
For Further Information Connelly, Jennifer M., and Mark Malkin. “Environmental Risk Factors for Brain Tumors.” Current Neurology and Neuroscience Reports 7 (2007): 208-214. Hardell, L., M. Hansson, and M. Carlberg. “Case-Control Study on the Use of Cellular and Cordless Phones and 250
National Cancer Institute Cellular Telephone Use and Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ cellphones See also Electromagnetic radiation; Ultraviolet radiation and related exposures.
Salem Health: Cancer
u Cervical cancer Category: Diseases, symptoms, and conditions Also known as: Cervical squamous cell/ adenocarcinoma, cervical intraepithelial neoplasm (CIN) Related conditions: Squamous intraepithelial lesion (SIL), dysplasia, human papillomavirus (HPV) infection Definition: Cervical cancer is a slow-growing cancer of the female reproductive organs. The two primary types of cervical cancer are squamous cell carcinoma and adenocarcinoma. Classified by microscopic examination, squamous cell carcinoma accounts for 90 percent of diagnosed cases. The majority of the remaining cases are classified as adenocarcinoma, a cancer that develops from the mucus-producing gland cells in the endocervix. Additionally, a very small minority of cervical cancer cases demonstrate characteristics of both types and are therefore classified as adenosquamous or mixed carcinomas. Risk factors: The most significant risk factor for developing cervical cancer is infection with high-risk types of human papillomavirus (HPV). HPV is sexually transmitted, and certain sexual behaviors can increase the risk of infection: sex at an early age, multiple sexual partners (directly or indirectly through a partner who has multiple sexual partners), and sex with an uncircumcised partner. Although use of condoms does not eliminate the potential for HPV infection because any skin-to-skin contact can be sufficient to transmit the virus, condoms nonetheless do provide limited protection. Studies have identified the following additional risk factors: • Obesity/low-fiber diet • Smoking • Concomitant infection with another sexually transmitted disease such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), or chlamydia • Long-term oral contraceptive use • Multiple full-term pregnancies • In utero exposure to diethylstilbestrol (DES, a hormone prescribed from 1940 to 1971 for some pregnant patients considered at high risk for miscarriage) • Family history of cervical cancer Etiology and the disease process: Human papillomavirus (HPV) is a group of more than one hundred distinct viruses, with approximately forty strains capable of infecting the genital tract. Researchers have classified fifteen HPV types as high risk for cancer development, with a nearly two-thirds prevalence of types 16 and 18 in cervical cancer samples. In the vast majority of cases, HPV infec-
Cervical cancer tion is spontaneously cleared by a healthy immune system. In a minority of cases, however, the virus can remain latent for years before eventually converting normal cervical cells to cancerous ones. Because only a small percentage of women infected with HPV progress to cervical cancer, lifestyle and immune system competence are believed to play a vital role in the progression of the disease. Incidence: Cancer of the cervix is second only to breast cancer in prevalence among women worldwide. Nearly 500,000 new cases are diagnosed each year, with a greater than 80 percent occurrence in developing countries. Age-standardized incidence rates fall in the 15 per 100,000 range for most first-world countries. In the United States, more than 11,000 new cases are diagnosed each year, with nearly 4,000 deaths annually. Symptoms: Early cervical cancer does not generally produce any distinguishable signs or symptoms. Abnormalities found in screening tests are the most common and effective method for detecting the presence of precancerous and cancerous cervical cells. As untreated disease progresses, symptoms may include unusual vaginal bleeding (after intercourse, between periods, postmenopausal); watery, bloody, and foul-smelling vaginal discharge; pelvic pain; or pain during intercourse. Screening and diagnosis: Extensive cervical screening programs designed to detect early, precancerous cervical changes are well established in most developed countries. Exfoliative cytology (Pap test) is the primary component of these programs, although molecular HPV deoxyribonucleic acid (DNA) testing is also commonly incorporated. Colposcopy is a second-level diagnostic procedure used as a follow-up to abnormal screening results. Named after the physician who developed the procedure (Papanikolaou), exfoliative cytology, or Pap test, is a screening procedure involving the collection and microscopic evaluation of cervical cells. During a routine pelvic examination, cervical cells are collected by broom, brush, spatula, or other means. These cells are either smeared directly onto a microscope slide (as in the traditional, “dry” Pap smear) or transferred into a liquid medium to concentrate the cells for subsequent transfer onto a slide. This new liquid-based cytology has demonstrated greater test sensitivity because more cells can be analyzed. The HPV DNA test is a molecular analysis of a cervical sample to determine the presence of HPV and its type. This test is used in conjunction with an abnormal Pap test as an additional diagnostic tool. A colposcopy is a pelvic examination in which a light source and binocular microscope are used to enable a di251
Cervical cancer
Salem Health: Cancer
Five-Year Survival Rates for Cervical Cancer, by Stage Stage
Survival Rate (%)
IA IB1 IB2 IIA/B IIIA/B IV
95+ 90 80-85 75-78 47-50 20-30
rect magnified inspection of the patient’s cervix, vagina, and vulva. Application of a weak acetic acid solution also serves to highlight any suspicious abnormalities. Following abnormal screening results, additional tests may be ordered to confirm diagnosis and determine how far the cancer has spread (staging): • Biopsy: Analysis of a small section of tissue collected from the cervix • Proctoscopy: Visual inspection of the rectum for the presence of cancer • Imaging (such as X ray, magnetic resonance imaging, computed tomography, positron emission tomography): Patient/organ appropriate imaging to inspect for cancer spread (metastasis) Cervical cancer is staged based on tumor size, invasive nature, and degree of metastasis (spread to lymph nodes/ organs). Cervical cancer is staged with the International Federation of Gynecology and Obstetrics (FIGO) system: • Stage 0: Carcinoma in situ; superficial cancer is detected in the cervical lining. • Stage I: Cancer has invaded the cervix but has not spread. • Stage IA: Microscopic amounts of cancer cells are present. • Stage IA1: Cancer invasion is less than 3 millimeters (mm) deep and less than 7 mm wide. • Stage IA2: Cancer invasion is between 3 and 5 mm deep and less than 7 mm wide. • Stage IB: Cancer is greater than 5 mm deep and greater than 7 mm wide. • Stage IB1: Cancer is visible but less than 4 centimeters (cm). • Stage IB2: Cancer is visible and greater than 4 cm. • Stage II: Cancer has spread beyond the cervix but is contained within the pelvis. • Stage IIA: Cancer has spread to the upper part of the vagina. 252
•
Stage IIB: Cancer has spread to the parametrial tissue (next to the cervix). • Stage III: Cancer has spread to the lower part of the vagina or the pelvic wall. • Stage IIIA: Cancer has spread to the lower third of the vagina. • Stage IIIB: Cancer has spread to the pelvic wall or blocks urine flow. • Stage IV: Cancer has spread to nearby organs. • Stage IVA: Cancer has spread to the bladder or rectum. • Stage IVB: Cancer has spread to more distant organs. Treatment and therapy: Treatment of cervical cancer largely depends on disease stage. The three treatment options are surgery, radiation, and chemotherapy. Surgical removal is used primarily for nonmetastatic lesions. Cryosurgery uses a metal probe cooled with liquid nitrogen to freeze cancerous cells. Laser surgery uses a laser to burn (vaporize) cancerous cells. In conization, a thin, heated wire (LEEP, or loop electrosurgical excision procedure) or surgical/laser knife (cold knife cone biopsy) removes the affected tissue. Rarely used as a sole treatment, conization aids in diagnosis before additional surgery or alternative treatment. In a hysterectomy, the degree of the removal of uterine tissue (simple vs. radical) depends on the stage and patient circumstances. Radiation employs high-energy X rays to kill cancer cells, either externally (external beam radiation) or internally via a radioactive capsule (brachytherapy). Chemotherapy uses anticancer drugs (such as cisplatin, paclitaxel, topotecan, ifosfamide, or fluorouracil) taken orally or intravenously to treat metastasized cancer. Prognosis, prevention, and outcomes: Early detection through effective screening programs offers a high probability for complete cancer eradication. Continued adherence to annual cervical screening and healthy habits is integral to continued remission. A new vaccine, Gardasil, approved by the Food and Drug Administration offers protection against the most dangerous, high-risk HPV types 16 and 18. It also protects against types 6 and 11, which cause genital warts. For greatest efficacy, the vaccine should be administered before the patient has become sexually active. The Federal Advisory Committee on Immunization Practices (ACIP) recommends vaccination for girls aged eleven and twelve. The committee also recommends that nonvaccinated women from age thirteen to twenty-six receive catchup vaccinations. Although the American Cancer Society (ASC) agrees with the initial vaccination protocol, it recommends catch-up vaccinations for young women aged
Salem Health: Cancer thirteen to eighteen only. ACS recommends that older women discuss the potential benefit of the vaccination with regard to their personal risk factors for previous exposure to HPV. Pam Conboy, B.S. u
For Further Information Devita, Vincent T., Jr., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Saslow, D., et al. “American Cancer Society Guideline for Human Papillomavirus (HPV) Vaccine Use to Prevent Cervical Cancer and Its Precursors.” CA: A Cancer Journal for Clinicians 57 (2007): 7-28. Stewart, Bernard W., and Paul Kleihues, eds. World Cancer Report. Lyon, France: IARC Press, 2003. u
Other Resources
American Cancer Society http://www.cancer.org American College of Obstetricians and Gynecologists http://www.acog.org American Society for Colposcopy and Cervical Pathology http://www.asccp.org Gynecologic Cancer Foundation http://www.thegcf.org International Agency for Research on Cancer http://www.iarc.fr National Cancer Institute http://www.cancer.gov National Cervical Cancer Coalition http://www.nccc-online.org World Health Organization http://www.who.org See also Afterloading radiation therapy; Antiviral therapies; Benign tumors; Biological therapy; Birth control pills and cancer; Carcinomas; Carcinomatosis; Colposcopy; Conization; Diethylstilbestrol (DES); Endometrial cancer; Exenteration; Fertility drugs and cancer; Gynecologic cancers; Human papillomavirus (HPV); Hysterectomy; Hystero-oophorectomy; Infectious cancers; Loop electrosurgical excisional procedure (LEEP); Pap test; Pelvic examination; Pregnancy and cancer; Vaccines, preventive; Vaginal cancer; Virus-related cancers.
Chemoembolization
u Chemoembolization Category: Procedures Also known as: Transcatheter chemoembolization, transarterial chemoembolization (TACE) Definition: Chemoembolization is a method of treating cancer by introducing chemotherapy drugs directly into a tumor using a catheter placed in an artery that supplies blood flow to the tumor. Chemoembolization works by blocking the flow of healthy blood to the tumor, thereby shrinking the tumor. It is among the category of procedures known as minimally invasive treatments because it targets the tumor and spares healthy tissues. Cancers treated: Primary liver cancer (hepatoma); other cancers, such as colon cancer, that have spread (metastasized) to the liver. Individuals who have obstruction in vessels of the liver or have liver diseases such as cirrhosis are not usually eligible for chemoembolization. The use of chemoembolization also depends on the number and size of the tumors. Why performed: Chemoembolization is used primarily for cancer in the liver, whether the cancer is confined to the liver or has spread to the liver from another organ. It is sometimes used in combination with surgery, external radiation therapy, or other cancer treatments. In advanced cancers, chemoembolization is used as a palliative treatment (directed at providing comfort and quality-of-life care) to manage symptoms related to the cancer, such as pain or fluid buildup in organs. Chemoembolization offers advantages over traditional chemotherapy, since high doses of chemotherapy drugs can be given directly into the tumor rather than systemically. Also, since the blood supply to the tumor (which is needed for tumor growth) is blocked, the chemotherapy drugs can remain in direct contact with the tumor for a longer time than with traditional chemotherapy. The treatment can also be given more often, usually with fewer side effects since the drug is limited to distribution directly to the tumor area and is not circulating throughout the body. Chemoembolization is also more cost-effective than some other cancer treatments such as surgery or conventional radiation therapy. Patient preparation: A few days prior to the procedure, the patient has blood work to make ensure good liver and kidney functioning. Blood-clotting tests are also done to make sure the patient’s blood clots properly. The patient is usually seen by an interventional radiologist, a medical doctor who is specially trained in treatment and diagnostic procedures using catheters, probes, and im253
Chemoprevention age X-ray-guidance. The interventional radiologist will perform the chemoembolization procedure. The physician will also need to know if the patient is taking any bloodthinning medications such as aspirin or coumadin, since they can affect the procedure. The patient is usually admitted to the hospital on the day of the procedure. Steps of the procedure: An intravenous (IV) line is started in the patient for medication and to provide fluid to the patient throughout the procedure. Although a medication is given through the IV to help the patient to relax, the patient is essentially awake throughout the procedure. An interventional radiologist performs the procedure under angiography (a special X ray of the arteries and veins) so that the catheter can be placed in the correct vessel that supplies blood to the tumor. A local anesthetic is used to numb the femoral artery area in the groin, where a small incision is made through which the catheter will be inserted. The physician follows the catheter placement via a monitoring screen. Once the interventional radiologist has threaded the catheter through the artery branches supplying the tumor, the chemotherapy drug used to embolize or block the blood supply is injected through the catheter. The patient may feel a momentary pressure or burning sensation. After the procedure: After the chemoembolization, a pressure dressing is applied to the groin, and the patient must lie flat for approximately eight hours. Patients may experience pain in the tumor area or groin, and possibly some nausea and fever as a result of the procedure. Since these symptoms may last for up to a week, patients are given pain medications to control symptoms and antibiotics on discharge from the hospital. Usually a one- to twonight stay in the hospital is required so that the patient can be monitored. Most patients can resume normal activities within one to two weeks. A follow-up computed tomography (CT) scan or magnetic resonance imaging (MRI) is usually ordered by the interventional radiologist one month after chemoembolization in order to assess the continued effectiveness of the treatment on the tumor. Thereafter, a CT scan or MRI is usually done every three months. Risks: As with any invasive procedure, there are potential risks. Risks of the chemoembolization procedure include infection at the catheter insertion site or blood clots occurring in vessels other than the one supplying the tumor. Results: Chemoembolization is considered a treatment for liver cancer but should not be considered curative. Although it may be used to treat liver tumors and cause 254
Salem Health: Cancer shrinkage and symptom control, studies to date have not suggested chemoembolization as a cure or first-line treatment. Jo Gambosi, M.A., B.S.N. u
For Further Information Baert, A. L., C. Bartolozzi, and R. Lencioni. Liver Malignancies: Diagnostic and Interventional Radiology. New York: Springer, 2003. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. VanSonnenberg, Eric, William McMullen, and Luigi Solbiati. Tumor Ablation: Principles and Practice. New York: Springer, 2005. u
Other Resources
National Cancer Institute http://www.cancer.org Society of Interventional Radiology http://www.sirweb.org See also Arterial embolization; Embolization; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Leiomyomas; Liver cancers; Urinary system cancers; Virusrelated cancers.
u Chemoprevention Category: Chemotherapy and other drugs; lifestyle and prevention Definition: Chemoprevention is a pharmacological approach to preventing the development of cancer using one or several natural or laboratory-made substances (such as drugs, vitamins, dietary supplements, or foods) that interfere with carcinogenesis (the transformation of normal living cells into cancer cells). Discussion: Cancer affects people of all ages in the United States. The incidence rates of some forms of cancer have declined over the past few years while those of others have increased. Many financial and human resources have been spent on the diagnosis and treatment of cancer, and much research has been done on its prevention. Most of this research has confirmed that certain lifestyle choices play a significant role in the development of cancer. In fact, an estimated two-thirds of all cancers could be eliminated through healthy lifestyle choices. Changes in diet could eliminate almost one-third of cancers. Exercise and diet
Salem Health: Cancer are primary ways that people can diminish their chances of developing cancer. Prevention research has increasingly focused on chemoprevention for persons at high risk for certain cancers. These studies are designed to evaluate the effectiveness and usefulness of substances that may serve as chemoprevention. Since the 1980’s the National Cancer Institute has identified more than four hundred agents that may have the ability to prevent cancer. The value of these compounds in human subjects is the focus of numerous clinical trials. How chemoprevention works: Research has focused on ways to arrest or even reverse the process of carcinogenesis (the transformation of normal living cells into abnormal or cancer cells). Studies show that certain substances have the ability to stop the formation of cancer tumors by one of two means: preventing mutations (genetic cellular changes) that often lead to cancer or stopping the duplication of damaged cells that can result in malignant tumors. Substances can interact at various points along the process of carcinogenesis: the beginning (initiation), middle (promotion), and end (progression). These substances may inactivate the cancer-causing agent, suppress tumor growth, induce useful enzymes, or act as antioxidants. Chemoprevention is the result of studies directed toward the prevention of cancer rather than its treatment. An optimal chemoprevention agent should be nontoxic, safe for long-term use, easy to administer, inexpensive, and effective. Chemoprevention compounds may be natural dietary products or synthetic compounds. Unlike chemotherapy, which kills normal healthy cells as well as cancer cells in people with active cancer, chemoprevention uses relatively harmless substances that may prevent cancer in people with no known malignancy but who are at increased risk for cancer development. Examples of chemoprevention: Breast cancer is a primary concern for women in the United States, with an average lifetime risk of 12.7 percent, or 1 in 8 women. Chemoprevention may be effective in preventing breast cancer in women who are at high risk or in preventing cancer in the second breast of women who have been diagnosed with breast cancer. Breast cancer prevention studies specifically target women who are cancer free but at high risk. The National Cancer Institute (NCI) funded the Breast Cancer Prevention Trial (BCPT), with recruitment of subjects from 1992 through 1997. This study used the antiestrogen drug tamoxifen and had promising results, with 49 percent fewer diagnoses of invasive and noninvasive cancer in the group that took the drug. However, both temporary and some long-term adverse side effects
Chemoprevention such as endometrial cancer, uterine sarcoma, pulmonary embolism, and deep vein thrombosis occurred. Another study of breast cancer prevention in high-risk women compared outcomes using the chemoprevention drugs tamoxifen and raloxifene. Still other National Cancer Institute clinical trials have begun to investigate the effectiveness of soy protein, soy isoflavones, grape seed extract, and green tea extract in preventing breast cancer. Another possible chemoprevention for breast cancer is indole 3-carbinol from broccoli. With the exception of skin cancer, prostate cancer is the most common cancer and is the second leading cause of cancer-related deaths in American men. The National Cancer Institute has several ongoing clinical trials assessing if certain antiandrogens and antiestrogens can prevent prostate cancer. One clinical trial used a drug called finasteride to reduce dihydrotestosterone (a metabolite of testosterone), associated with prostate cancer; results showed a reduction in the incidence of prostate cancer. However, there were side effects such as decreased libido (sexual drive), increased erectile dysfunction, and gynecomastia (excessive breast development in males). One study used pomegranate juice to slow or halt the increase in prostate specific antigen (PSA); an increase in PSA would indicate the prostate cancer had returned. Another study employed a dietary approach to reduce the intake of fat and increase the intake of fruit and vegetables. Supplementation with vitamin E, selenium, or lycopene and dietary substances such as tea, soy products, and indole-3-carbinol (in broccoli) may be chemoprotective, but these have not been proven effective at reducing the incidence of prostate cancer. Other subjects of clinical trials at the National Cancer Institute have included aspirin, fish oil, and lycopene (found in tomatoes, watermelon, and pink grapefruit). Colorectal cancer is the third most common cancer in the United States and also ranks third in cancer-related deaths. Increased consumption of fruits and vegetables seems to provide some protection against colorectal cancer. The National Cancer Institute has a commitment to develop and validate other possible ways to prevent colon cancer. One study involved the chemoprevention effect of calcium and vitamin D. Another study looked at consuming eicosapentaenoic acid (EPA), a highly purified form of omega-3 fatty acids that naturally occurs in fish. A third study focused on the use of selenium, a naturally occurring micronutrient found in dietary sources such as nuts (especially Brazil nuts), meat, eggs, and fish. Several investigations have begun examining the use of curcumin, part of a common spice used in Indian curries, for its antitumor and anti-inflammatory effects and its possible ability to prevent the intestinal inflammation associated with colon 255
Chemoprevention cancer. Another topic of investigation has been the adding of high-fiber foods or wheat cereal to the diet to prevent colon cancer. Drugs that have begun to be studied regarding chemoprevention of colorectal cancer include aspirin, calcium carbonate, and 1α 25-dihydroxy cholecalciferol (active vitamin D3). Cancer of the cervix (the organ that connects the vagina to the uterus) is a national concern. The National Cancer Institute estimated that in 2007 more than 11,000 cases would be diagnosed in the United States and more than 3,600 women would lose their lives to this cancer. Research has shown that persistent exposure to the human papillomavirus (HPV) is a primary key to cervical cancer development. In early 2007, the Journal of the American Medical Association (JAMA) reported that 26.8 percent of women in the United States between the ages of fourteen and fifty-nine tested positive for HPV. More than one hundred viruses are strains of HPV, and more than thirty of these are transmitted sexually. Some produce genital warts or benign tumors, and some place women at high risk for cervical cancer. In 2006, the United States Food and Drug Administration approved new vaccines that target the strains of HPV most commonly responsible for cervical cancer. One vaccine is effective against two high-risk HPVs that cause about 70 percent of cervical cancers. Vaccines given to young women before they become sexually active serve as chemoprevention for cervical cancer. Women may take the vaccines after they become sexually active, but they provide less protection because infection may already have occurred. As with all drugs, some side effects may occur. Chemoprevention is being viewed as a key to cancer prevention in various other cancers. Researchers have begun testing whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent oral cancers. Some studies show that black raspberry extract may prohibit cancer growth in the mouth, as might Bowman-Birk inhibitor (BBI), a substance found in soybeans. The prevention of liver cancer, which kills 14,000 people annually, may be possible using oltipraz, a compound with properties resembling the antioxidant properties of broccoli, cabbage, and other cruciferous vegetables. Though liver cancer accounts for only about 2 percent of all cancers, the incidence is rising, and chemoprevention could slow this rate. The use of vaccines for the hepatitis B virus may protect against liver cancer. Benefits and risks of chemoprevention: Some 1.4 million people are diagnosed annually with cancer in the United States. The goal of chemoprevention is to reduce the incidence of new cancers, which will improve the qual256
Salem Health: Cancer ity of life for many Americans and keep the workforce in place. In one study, cancer was associated with the highest loss of work days because of illness or impairment. The cost of cancer to the workers themselves and to their employers reinforces the need for measures and interventions such as chemoprevention to reduce the incidence of cancer. Chemoprevention targets only high-risk populations because chemoprevention medications are not seen as useful or applicable for the general public. However, changes in diet and in the choice of foods consumed may affect the incidence of certain cancers. Most authorities do not recommend taking vitamins and supplements but rather endorse eating a well-balanced diet that is low in fat and high in fruits and vegetables. This is commonsense cancer prevention. Successes are not seen quickly but rather may become visible over extended periods of time. In fact, one study, called the Alpha-Tocopherol, Beta-Carotene Lung Cancer Prevention Study, demonstrated an 18 percent increase in lung cancer in the beta-carotene group. Clearly, judicious use of supplements is warranted because negative outcomes as well as positive ones can occur. People who are considering a change in diet should check with their health care providers, as some vitamins and supplements can interact adversely with some prescription medications. Summary: The research involving chemoprevention is encouraging and warrants more study and research dollars. Studies show that simple changes in lifestyle and eating habits can make a sizable impact on the incidence of cancer in the United States. Chemoprevention may some day be able to prevent people at high risk from developing cancer and keep cancer away in those who are in remission. The already burdened health care system could use its limited resources in trying to prevent other chronic diseases. Chemoprevention may not be the answer, but maybe it can be an answer to cancer in the United States. Marylane Wade Koch, M.S.N., R.N. u
For Further Information Loop, Matthew J. Cracking the Cancer Code: The Secret to Transforming Your Health from Inside Out. New York: iUniverse, 2006. Runowicz, Carolyn D., and Sheldon H. Cherry. The Answer to Cancer. Emmaus, Pa.: Rodale Books: 2004. Sheridan, Stacey L., Russell P. Harris, and Steven H. Woolf. “A Suggested Approach from the U.S. Preventive Services Task Force, Shared Decision-Making Workgroup of the U.S. Preventive Services Task
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Chemotherapy
Force, Elsevier Science.” American Journal of Preventive Medicine 26, no. 1S (2003): 56-66. Sporn, Michael B., and Nanjoo Sun. “Prevention of Cancer.” Carcinogenesis 21, no. 3 (2000): 525-530. Varona, Verne. Nature’s Cancer Fighting Foods. New York: Penguin Putnam, 2001. u
Other Resources
Centers for Disease Control and Prevention HPV Vaccine Questions and Answers http://www.cdc.gov/std/HPV/STDFact-HPVvaccine.htm#hpvvac1 National Cancer Institute http://www.cancer.gov See also Antioxidants; Beta-carotene; Bioflavonoids; Calcium; Carotenoids; Cartilage supplements; Coenzyme Q10; Dietary supplements; Fiber; Folic acid; Garlic and allicin; Ginseng, panax; Glutamine; Green tea; Herbs as antioxidants; Indoles; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Omega-3 fatty acids; Phytoestrogens; Prevention; Resveratrol; Saw palmetto; Soy foods; Sun’s soup.
u Chemotherapy Category: Chemotherapy and other drugs Definition: Chemotherapy is the treatment of cancer with medications that have a certain toxic effect on cancer cells. Chemotherapy drugs are used to slow the growth of cancer cells, shrink tumors prior to other treatments such as surgery or radiation, or cure a specific cancer. • First-line or standard chemotherapy: Given to destroy cancerous cells before disease progression or recurrence; first-line chemotherapy has been determined, through research studies and clinical trials, to have the best probability of treating a certain type of cancer • Second-line chemotherapy: Given to destroy cancerous cells when the disease has not responded to firstline chemotherapy or has recurred after first-line chemotherapy • Adjuvant chemotherapy: Given to destroy cancerous cells that may remain after a known cancerous tumor has been surgically removed or after radiation therapy has been given • Consolidation or intensification chemotherapy: Given once a remission is achieved, with the goal of sustaining a remission.
Six drugs commonly used to treat cancer. (National Cancer Institute)
• •
Induction chemotherapy: Given to induce a remission Maintenance chemotherapy: Given in lower doses to help prolong a remission • Palliative chemotherapy: Given to ease the symptoms of cancer and improve a patient’s quality of life Cancers treated: All Subclasses of this group: Alkylating agents, anthracyclines, antimetabolites, corticosteroid hormones, mitotic inhibitors, nitrosoureas, topoisomerase inhibitors; some chemotherapy drugs do not fit into these classifications, including dactinomycin (Cosmegen), hydroxyurea (Droxia), L-asparaginase (Elspar), procarbazine (Matulane), and thalidomide (Thalomid) Delivery routes: Chemotherapy drugs are most commonly administered intravenously (through an IV) or orally (by mouth) as pills, capsules, or liquid. They may also be administered topically (applied to the skin) as creams or lotions or injected directly into a tumor (intratumorally or intralesionally), into the muscle (intramuscularly), or under the skin (subcutaneously). The administration method 257
Chemotherapy is dependent on the drug’s specific action, dose, and potential side effects. In some cases, two or more administration methods may be used at once. Intravenous chemotherapy medications may be infused through a peripheral central catheter (thin, flexible tube) inserted into a vein in the arm or hand; through a central venous catheter, also called a vascular access device; or through a port implanted into a large vein in the neck, chest, or arm. A central venous catheter is used to deliver chemotherapy when several drugs need to be administered at the same time, when continuous infusion chemotherapy is being given, or when long-term therapy is needed. A catheter may also be placed in an artery (intra-arterial), in the cerebrospinal fluid (intrathecal), in the chest (intrapleural), in the abdomen (intraperitoneal), or in the bladder (intravesical) to deliver the medication. A medication infusion pump is sometimes used with a catheter to deliver a preprogrammed dose of medication. Chemotherapy can be administered on an inpatient, outpatient, or at-home basis, depending on the specific drug and the type of cancer, its location, and its aggressiveness. Where chemotherapy is administered may be dependent upon the patient’s insurance requirements, as well as the physician’s and patient’s personal preferences. Chemotherapy drug dosages are based on a patient’s body weight in kilograms or a patient’s body surface area expressed in meters squared, which is calculated using the patient’s height and weight. Chemotherapy is given at regular intervals, or cycles, depending on the type and stage of cancer and how many chemotherapy drugs are being given at the same time. Rest periods between doses allow normal cells to recover from the effects of the medication. It is important for patients to receive the full recommended course of therapy to achieve the maximum therapeutic benefit. In some cases, the physician may adjust the course of treatment based on the incidence of certain side effects. Liposomal therapy is a newer chemotherapy delivery method in which liposomes (microscopic synthetic capsules) are used to deliver chemotherapy drugs. The coating on the liposome capsules allows the medication to remain in the circulation for a longer period of time, so that the drugs selectively target cancer cells and decrease side effects on healthy tissue. Some liposomal medications currently available include doxorubicin liposomal (Doxil) and daunorubicin liposomal (DaunoXome). How these drugs work: In the 1940’s, nitrogen mustard became the first chemotherapy agent used to treat cancer. The use of chemotherapy for cancer treatment was discovered accidentally during World War II when a group of soldiers exposed to sulfur mustard gas, a chemical warfare 258
Salem Health: Cancer agent, were later found to have very low white blood cell counts. Scientists hypothesized that this agent would have a similar effect on cancer. An IV injection of nitrogen mustard was given to several patients with advanced lymphomas and was successful in treating the cancer. More than one hundred types of chemotherapy drugs are now available, with many more being investigated. Chemotherapy is a systemic treatment; the medicines travel through the whole body and are not confined to one specific treatment area. Chemotherapy drugs therefore can reach cancer cells that may have traveled from the main tumor through the blood or lymph systems to other parts of the body. Chemotherapy drugs may be given alone or in combination with other drugs or treatments, such as radiation therapy or surgery. The chemical composition, action, and side effects of chemotherapy drugs vary. Chemotherapy drugs are classified according to how they affect cancer cells’ molecular context, cellular activities or processes, and specific phases of the cell cycle. Targeted cancer therapies block the growth and spread of cancerous cells by interfering with cancer cell development, growth, and division. Some targeted therapies interfere with the proteins that are involved in the process that signals normal cells to turn into cancerous cells. Targeted therapy is available with a few chemotherapy drugs, while many other targeted therapy medications are under investigation. Monoclonal antibodies are synthetic forms of protein that can help guide chemotherapy drugs directly into a tumor. Monoclonal antibodies are used only for certain types of cancer in which antigens and the respective antibodies have been identified, such as some types of breast cancer and lymphomas. Angiogenesis inhibitor drugs may prevent the growth of blood vessels that supply oxygen from surrounding tissue to cancerous cells or tumors, thereby starving the cells of oxygen. The type of chemotherapy prescribed is different for each patient and is based on the type of cancer, the stage of the disease, the patient’s age and overall health, the presence of coexisting medical conditions, and other cancer treatments that may have been given previously. Side effects: Because chemotherapy drugs are systemic, they target cancerous as well as normal tissue and can have toxic side effects, depending on the specific drug, its dosage, the duration of administration, and the patient’s physical condition. One of the most common side effects of chemotherapy is fatigue (tiredness), which may be the result of anemia (a (continued on page 260)
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Chemotherapy
Chemotherapy Drugs by Group Type
Drug Name
Trade Names
Alkylating agents
busulfan injection carboplatin chlorambucil cisplatin cyclophosphamide dacarbazine ifosfamide mechlorethamine (nitrogen mustard) melphalan hydrochloride thiotepa temozolomide
IV Busulfex, Myleran Paraplatin Leukeran Platinol AQ Cytoxan, Neosar DTIC-Dome Ifex, Mitoxana Mustargen Alkeran Thioplex Temodar
Anthracyclines, antitumor antibiotics
bevacizumab bleomycin daunorubicin doxorubicin epirubicin idarubicin mitoxantrone
Avastin Blenoxane Cerubidine Adriamycin, Doxil, Rubex Ellence Idamycin PFS Novantrone
Antimetabolites
5-fluorouracil capecitabine clofarabine injection cytarabine mercaptopurine methotrexate injection thioguanine
Adrucil Xeloda Clolar Cytosar-U Purinethol Rheumatrex Thioguanine Tabloid
Corticosteroid hormones
dexamethasone prednisone methylprednisolone sodium succinate
Decadron, Dexone, Solurex Prednisone Intensol, Sterapred Solu-Medrol
Mitotic inhibitors, plant alkaloids
docetaxel paclitaxel vinblastine vincristine vinorelbine
Taxotere Onxol, Taxol Velban Oncovin, Vincasar Navelbine
Nitrosoureas
carmustine fotemustine lomustine streptozocin
BiCNU Muphoran CeeNU, CCNU Zanosar
Topoisomerase inhibitors
etoposide injection irinotecan paclitaxel teniposide topotecan hydrochloride
Toposar, VePesid injection Camptosar Onxol Vumon Hycamtin
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Chemotherapy
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decrease in oxygen-carrying red blood cells) or the result of the increased energy required to recover from the effects of the chemotherapy drugs. Other factors contributing to fatigue include poor appetite, lack of sleep, and emotional stress. Depressed blood cell counts may increase the patient’s risk of infection and anemia. In addition, reduced platelets can cause easy bruising or bleeding including nosebleeds, bleeding gums, blood in the urine or stool, and unusually heavy menstrual flow. Other common side effects include nausea and vomiting, loss of appetite, diarrhea, and fluid retention. A registered dietitian can provide nutritional therapy to help the patient develop an eating plan that meets dietary requirements but reduces these side effects and helps make treatment more tolerable. In some cases, antinausea or antidiarrheal medications may be prescribed to help prevent these troublesome side effects. It is important for patients to ask their physicians first before taking overthe-counter remedies for these side effects, as they could interfere with the action of the chemotherapy drug. Since many chemotherapy drugs kill fast-growing cancer cells, they may also target fast-growing normal cells in the hair follicles, which can lead to alopecia (hair loss).
Some chemotherapy drugs may cause only hair thinning, while others may cause complete hair loss, including loss of body hair and eyebrows. Hair loss is temporary, and hair will regrow after the cancer treatments are completed. Emotional or mood changes, such as depression or anxiety, may occur. Patients should discuss their concerns about these side effects with their physician; support groups are available to help patients cope, and antidepressant medications can be prescribed when necessary. In some cases, chemotherapy can cause certain side effects that are painful, such as burning or pain in the fingers or toes. Pain medications may be prescribed to reduce pain associated with cancer treatment. Some chemotherapy drugs may lead to infertility (both amenorrhea in women and impaired spermatogenesis in men). In extreme cases, chemotherapy can lead to heart muscle damage (cardiotoxicity), which would mitigate the chemotherapy regimen. There are several lifestyle changes a patient can make to manage certain side effects, such as fatigue and mouth, gum, and throat problems. The National Cancer Institute offers a publication, Chemotherapy and You, that provides several techniques for managing side effects. The time it takes to recover from chemotherapy side ef-
Chemotherapy Drug Groups, Actions, and Cancers Treated Drug Class
Action
Cancers Treated
Alkylating agents
Directly damage the DNA of cancer cells to prevent the cells from reproducing
Chronic leukemias; non-Hodgkin lymphoma; Hodgkin disease; multiple myeloma; lung, breast, ovarian, and other cancers
Anthracyclines, antitumor antibiotics
Act by binding with DNA and preventing RNA synthesis, a key step in the creation of proteins
Breast, colorectal, lung, and other cancers
Antimetabolites
Interfere with the growth of DNA and RNA
Leukemias; breast tumors; ovarian, gastrointestinal, and other cancers
Corticosteroid hormones
Slow the growth of some cancers that depend on hormones
Lymphoma, leukemias, multiple myeloma, and other cancers
Mitotic inhibitors
Prevent cell division by interfering with tubulin, a protein that is the basic building block of the fibers responsible for cell multiplication
Myeloma; lymphoma; leukemia; breast, lung, and other cancers
Nitrosoureas
Interfere with the enzymes in cancer cells that are responsible for copying and repairing DNA
Brain tumors, non-Hodgkin lymphoma, Hodgkin disease, multiple myeloma, malignant melanoma, and other cancers
Topoisomerase inhibitors
Interfere with the action of topoisomerase enzymes, the enzymes that control the manipulation of the structure of DNA
Leukemias; lung, ovarian, gastrointestinal, and other cancers
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Salem Health: Cancer fects varies, depending on the patient’s physical condition and the type of chemotherapy drug, dosage, and how long the medication was taken. Chemotherapy side effects are usually short term and often go away once treatment is finished. Patients should ask their doctor about the risk of side effects, both short term and long term, and the risk of serious side effects. Angela M. Costello, B.S. u For Further Information Chabner, Bruce A., and Dan L. Longo, eds. Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2006. Fischer, David S., et al. The Cancer Chemotherapy Handbook. 6th ed. St. Louis: Mosby, 2003. National Cancer Institute. Chemotherapy and You. NIH Publication No. 07-7156. Bethesda, Md.: National Institutes of Health, U.S. Department of Health and Human Services, 2007. Also available at http://www .cancer.gov. Skeel, Roland T. Handbook of Cancer Chemotherapy. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007.
u
Other Resources
American Cancer Society http://www.cancer.org CancerCare http://www.cancercare.org Chemocare.org http://www.chemocare.org National Cancer Institute http://www.cancer.gov/ See also Alkylating agents in chemotherapy; Androgen drugs; Angiogenesis inhibitors; Antiandrogens; Antiestrogens; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Antiviral therapies; Benzodiazepines; Biological therapy; Chlorambucil; Cyclophosphamide; Cyclosporin A; Cytokines; Drug resistance and multidrug resistance (MDR); Immunotherapy; Interferon; Interleukins; Matrix metalloproteinase inhibitors; Monoclonal antibodies; Plant alkaloids and terpenoids in chemotherapy; Proteasome inhibitors; Topoisomerase inhibitors; Tyrosine kinase inhibitors; Vaccines, therapeutic.
Chewing tobacco
u Chewing tobacco Category: Lifestyle and prevention; carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Smokeless tobacco, chew, snuff, dip, plug tobacco Related cancers: Oral cancers and cancers of the esophagus, larynx, pharynx, stomach, and bladder Definition: Also called smokeless tobacco, these tobacco and tobacco-based products that are not smoked but chewed or otherwise used in the mouth, such as chew, snuff (both oral and inhaled), dip, and plug tobacco, cause or are associated with certain cancers and other disorders of the mouth. Exposure routes: Oral by chewing, sucking, and ingestion Where found: Sold in the form of snuff, chewing tobacco, and plug tobacco At risk: Users of smokeless tobacco Many individuals use tobacco by smoking it in the form of cigarettes or cigars, and in pipes. Other individuals use tobacco by simply chewing it. Some do not even chew it, but use it by keeping it inside their mouth, such as in a cheek or between the teeth and lower lip, and absorb it by sucking on it. The tobacco products release their chemicals, like nicotine, and these are absorbed into the body. Relative to cigarettes, three to four times as much nicotine is absorbed into the body per dose with smokeless tobacco. Additionally, because having these substances in the mouth will generate saliva, individuals who use them may frequently be spitting out the saliva and part of these products or their juices in the process of using them. Such products include chew, snuff, and dip. Chew is a form of shredded tobacco leaves. Snuff is processed tobacco that is fine-grained and smaller particles, similar to prepared spices or tea; it may even be powdery. It is so fine in some cases that users may inhale or sniff it, rather than use it orally. Dip is another term for snuff and refers to how individuals will use the material. For instance, they may dip their finger into a packet or pinch it to get the dose required to place in the mouth. Plug tobacco is similar to chew, but instead of having loose leaves, the tobacco is compressed into a hard plug that is placed in the mouth between the cheek and gums for use. All serve the same function—to dispense nicotine to the user—and all are classified under the general term of chewing tobaccos. 261
Chewing tobacco
Salem Health: Cancer
these products is worldwide. Approximately 90 percent of individuals with mouth cancers are tobacco users. In the United States, approximately 3 percent of adults, 8 percent of high school students, and 3 percent of middle school students are smokeless tobacco users. Many high school and middle school students learn about smokeless tobacco through its use by members of professional sports teams, such as baseball players and hockey players. Recent prevention efforts have focused on sports players who have endured problems related to oral cancers telling their stories and warning students about the risks to dissuade them from starting this habit. Relative to women, men are about two to ten times as likely to use smokeless Gum damage caused by chewing tobacco. (Science Source) tobacco, depending on the age group examined. In the United States, 9 perEtiology and symptoms of associated cancers: Many incent of smokeless tobacco users are American Indians and dividuals wrongly believe that because they are not smokAlaska natives, relative to 4 percent of whites, 2 percent of ing tobacco, they are skirting the normal cancer risks African Americans, 1 percent of Hispanics, and 0.6 perposed by tobacco in cigarettes. However, this is not true. In cent of Asian Americans. Oral cancers usually occur in infact, chewing tobacco also carries health and cancer risks. dividuals aged forty to sixty; however, they may occur at Smokeless tobacco contains at least twenty-eight known any age. Tobacco use combined with alcohol use can dracarcinogens. These cancer-causing agents form in the tomatically increase the risk of cancers related to smokeless bacco while it is growing, being processed, and being aged tobacco. Oral cancers account for only 2 to 4 percent of for use. They include substances such as acetylaldehyde, cancers diagnosed in the United States annually, but they arsenic, benzopyrene, cadmium, formaldehyde, hydrazine, have one of the lowest survival rates. and nitrosamines. Nitrosamines are some of the most danNancy A. Piotrowski, Ph.D. gerous carcinogens in smokeless tobacco. Oral cancers are commonly associated with such tou For Further Information bacco use and are somewhat of a function of the direct or Bellinir, Karen, ed. Tobacco Information for Teens: close contact of the substance with parts of the mouth, Health Tips About the Hazards of Using Cigarettes, such as the bones, cheeks, floor of the mouth, gums, roof Smokeless Tobacco, and Other Nicotine Products. Deof the mouth, and tongue. Further, users sometimes swaltroit: Omnigraphics, 2007. low juices from these products, causing them to travel Icon Health. Smokeless Tobacco: A Medical Dictionary, elsewhere into the body. As a result, smokeless tobacco Bibliography, and Annotated Research Guide to Interuse is associated with cancers of the esophagus, larynx, net References. San Diego, Calif.: Author, 2004. pharynx, stomach, and bladder. Often problems will show MacKay, Judith, and Michael P. Eriksen. The Tobacco Atup first as sores in the mouth that will not heal, difficulty las. Geneva: World Health Organization, 2002. swallowing or chewing, ear pain, voice changes, or sore Snell, Clete. Peddling Poison: The Tobacco Industry and throats that seem to persist. Another sign might be lesions Kids. Westport, Conn.: Praeger, 2005. or areas of discoloration, such as white patches or red sores Winter, John C. Tobacco Use by Native North Americans: on the gums, tongue, or cheeks. Exposed tooth roots may Sacred Smoke, Silent Killer. Norman: University of also begin to have problems. Oklahoma Press, 2000. History: Reports on health problems related to smokeless tobacco use date back to the eighteenth century. Use of 262
See also Head and neck cancers; Oral and oropharyngeal cancers; Throat cancer; Tobacco-related cancers.
Salem Health: Cancer
u Childbirth and cancer Category: Social and personal issues Definition: Childbirth is an extremely emotional experience that, although often filled with happiness, can also be extremely stressful. Childbirth during cancer treatment, or shortly thereafter, can add more stress for the new mother and her family, as well as causing feelings of fear, anxiety, and depression. Pregnancy during cancer treatment: Cancer treatment is an extremely stressful time for any woman, but pregnancy and childbirth during cancer treatment add many new concerns. Many of the commonly used cancer treatments, such as radiation therapy, are not appropriate for women who are pregnant. In many cases, a woman and her doctor may decide to postpone certain cancer treatments until after the baby is born. Labor may be induced a few weeks early so that cancer treatment can begin as soon as possible. Chemotherapy is not considered safe for women who are in their first trimester of pregnancy. However, some chemotherapy drugs may be appropriate for women who are in their second or third trimesters. Chemotherapy drugs reduce blood counts, so chemotherapy must be stopped for a few weeks before childbirth. This gives the mother’s body time to elevate blood counts back to normal levels and reduces the possibility of complications from childbirth such as infection and excessive bleeding. Childbirth after cancer: For many women who have had successfully treated cancer, pregnancy and childbirth do not pose any special risks. For some women, however, pregnancy and childbirth can be a risk to the mother’s health. If the cancer or cancer treatment caused damage to any of the systems that are affected or stressed by pregnancy or childbirth, such as the lungs or the cardiovascular system, pregnancy or childbirth may cause adverse health effects. Pregnancy and childbirth after cancer can also make it more difficult for the mother and her doctor to be vigilant in watching to make sure the cancer has not returned. Breast cancer, for example, is often much harder to detect in pregnant and nursing women because pregnancy and nursing cause the breasts to swell and become denser. This can disguise small lumps or changes in the breast that may indicate that breast cancer has returned. Mammograms are also harder to read accurately when a woman is pregnant or nursing because of the density of the breast tissue. Research: Research on childbirth and cancer is an active and growing field. It has many complexities and chal-
Childbirth and cancer lenges because of the number of physiological changes that occur during pregnancy and because of the number of different types of cancers and cancer treatments. It also poses special challenges because the health and wellbeing of the mother and developing baby are always of primary importance, so certain types of research cannot be undertaken. For example, it would be unethical to conduct studies on the effects of chemotherapy on the developing baby when the mother is in the first trimester because it is believed that chemotherapy would harm the developing baby. Research has not shown that there is any statistically significant link between childbirth and the recurrence of cancer. Women who have children after successful cancer treatment are believed to be at the same risk of recurrence as women who do not have children. Researchers have, however, begun to uncover a link between childbirth and the prognosis of a breast cancer diagnosis. Swedish researchers did a large study of women in Sweden diagnosed with breast cancer and found that women who were diagnosed shortly after their last childbirth had a worse prognosis than women diagnosed a very long time after their last childbirth. Follow-up research is being done to try to understand what mechanism may account for this and to determine if it may be true of other cancers as well. Emotional considerations: Cancer treatment is an extremely stressful event in anyone’s life, but for a woman who is expecting, it presents even more challenges. After spending days and weeks trying to eat healthy food, do the right amount of exercise, and do everything possible to ensure the best atmosphere for the baby’s development, it can be devastating to consider the implications of a cancer diagnosis and treatment plan. The woman’s cancer care team can help her sort through the various choices and help ensure that she makes the best choices possible both for herself and for her developing baby. Many women will have anxiety about issues such as what will happen to the baby if they are unable to care for it during their cancer treatment or what may happen if the cancer is difficult or impossible to treat. Counseling can help the mother-to-be work through her fears for the future, and many resources are available to help mothers care for their babies if they have to undergo treatments such as chemotherapy shortly after they give birth. Frank discussions with health care team members and the support of family and friends can help ease the difficulty of having a child during cancer treatment. Helen Davidson, B.A.
263
Childhood cancers u For Further Information Harpham, Wendy Schlessel. When a Parent Has Cancer: A Guide to Caring for Your Children. New York: Perennial Currents, 2004. McKay-Moffat, Stella, ed. Disability in Pregnancy and Childbirth. New York: Churchill Livingstone/Elsevier, 2008. Oktay, Kutluk, H., Lindsay Nohr Beck, and Joyce Dillon Reinecke. One Hundred Questions and Answers About Cancer and Fertility. Sudbury, Mass.: Jones and Bartlett, 2008. Pavlidis, N., and F. Peccatori. Cancer and Pregnancy. New York: Springer, 2007. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Breast cancer in pregnant women; Endocrine cancers; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Fertility issues; Gynecologic cancers; Gynecologic oncology; Infertility and cancer; Placental alkaline phosphatase (PALP); Pregnancy and cancer; Uterine cancer; Vaginal cancer.
u Childhood cancers Category: Diseases, symptoms, and conditions Also known as: Childhood neoplasms Related conditions: Leukemia, lymphoma, brain cancer, osteosarcoma Definition: Childhood cancers are cancers that occur in a person from infancy through age nineteen. The twelve major types of childhood cancers vary by type of histology, site of origin, race, sex, and age. They are leukemias, lymphomas, brain and spinal tumors, sympathetic nervous system tumors, retinoblastoma, kidney tumors, liver tumors, bone tumors, soft-tissue sarcomas, gonadal and germ-cell tumors, epithelial tumors, and other and unspecified malignant tumors. The most common types are leukemias and lymphomas. Risk factors: Childhood cancers result from noninherited mutations or changes in the genes of developing cells. Some risk factors have been associated with different types of childhood cancers such as acute lymphocytic leu264
Salem Health: Cancer kemia (ALL) and acute myelogenous leukemia (AML). If a child has an identical twin who was diagnosed with ALL or AML before the age of six, the child has a 20 to 25 percent greater risk of developing the illness. Nonidentical twins and other siblings of children with leukemia have two to four times the average risk of developing the illness. Children with Down syndrome, Klinefelter syndrome, or other genetic syndromes and those who have received drugs following organ transplants also are at greater risk of developing leukemia. Children who have received radiation therapy or chemotherapy for other types of cancer have an increased risk of developing leukemia within an eight-year period following treatment. Etiology and the disease process: In childhood leukemia, an abnormal amount of white blood cells, or leukocytes, is produced in the bone marrow; these cells invade the bloodstream and deplete the body’s ability to fight infection. As the disease progresses, it affects the body’s ability to produce red blood cells and platelets, resulting in anemia, bleeding disorders, and continued risk of infection from the overproduction of white blood cells. Lymphocytes are infection-fighting white blood cells that are made and stored in the lymph nodes (organs in the neck, groin, abdomen, chest, and armpits), spleen, thymus, tonsils, and bone marrow. In lymphoma, the white blood cells of the lymphatic system grow abnormally, producing cancerous cells called Reed-Sternberg cells. Although Hodgkin disease is most often seen in children aged fifteen or older, nodular lymphocyte predominance (LP) is more common in younger children, accounting for about onefifth of the incidence of most Hodgkin disease in children. Non-Hodgkin lymphoma (NHL) occurs more often in boys than girls and most often between the ages of two and ten. Unlike the non-Hodgkin lymphoma seen in adults, most cases of NHL in children are of the fast-growing, aggressive type (such as Burkitt lymphoma, non-Burkitt lymphoma, and lymphoblastic lymphoma). Another common type of childhood cancer, neuroblastomas (solid tumors), often begins in one of the adrenal glands above the kidneys; the tumors can also can arise in nerve tissues in the neck, abdomen, pelvis, or chest. While the cause of neuroblastomas is unknown, they are believed to arise from anomalies during the normal development of the adrenal glands. Incidence: Childhood cancer is the leading cause of death in the United States in children from infancy to fourteen years of age. However, childhood cancer is relatively rare; each year 1 to 2 children per 10,000 children in the United States will be diagnosed with cancer. Childhood cancer is estimated to occur at the rate of 17 per 100,000 children
Salem Health: Cancer
Childhood cancers
Yearly Incidence of Cancers Among Children and Adolescents Under Age Twenty, 1990-1995 Cancer Lymphoid leukemia Acute nonlymphocitic leukemia Hodgkin disease Non-Hodgkin lymphoma Central nervous system malignancies
Incidence per 1 Million Children 29.2 7.6 12.1 10.5 1.9
Source: L. A. G. Ries et al., eds., Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program, 1975-1995, NIH Pub. No. 99-4649 (Bethesda, Md.: National Cancer Institute, SEER Program, 1999)
through the age of nineteen. Incidence is higher for boys than girls, and cancer rates are higher for children under five years of age and those between the ages of fifteen and nineteen. According to a National Cancer Institute (NCI) study from 1975 to 1995, the majority of cancers occurring in childhood were leukemias (25 to 30 percent). Of these, 60 percent were cases of acute lymphocytic leukemia (ALL), and 38 percent were acute myelogenous leukemia (AML). The next most common type was miscellaneous intracranial and intraspinal neoplasms (mostly solid, typically brain tumors involving the cerebellum or brain stem) at 16.7 percent, followed by lymphomas at 15.5 percent. Leukemias are the most common cancer in those under age five (and decrease proportionally in those over age five), and lymphomas are most common in those fifteen to nineteen years old. Hodgkin disease occurs at a rate of 12.6 per 1 million children, while non-Hodgkin lymphoma occurs at a rate of 10.5 per 1 million children. Other types of childhood cancer include Wilms’ tumor, affecting one or both kidneys and seen in children between two and three years of age; neuroblastoma, the most common form of solid tumor occurring outside the brain in children, often diagnosed by one year of age; retinoblastoma, or eye cancer; rhabdomyosarcoma, developing in cells that become mature voluntary muscle (the most common soft-tissue sarcoma seen in children); and primary bone cancer (osteosarcoma). Mortality for childhood cancers has declined significantly in the past thirty years, largely because of early detection and advances in treatment. However, the incidence of invasive cancer in children has increased slightly during the same period. The incidence of all types of invasive cancer in children has increased from 11.5 cases per 100,000 children in 1975 to 14.5 cases per 100,000 in 2004.
The reasons for this increase in incidence are unclear. However, the increase in the incidence of childhood brain tumors may be attributed to advances in early detection, as technologies such as magnetic resonance imaging (MRI) allow more accurate and differential diagnosing of tumors, and advances in neurosurgical techniques allow for biopsies of brain tumors. These advances in detection methods have resulted in an increase in discovery and diagnosis of malignant tumors.
Symptoms: The symptoms of childhood cancer vary by type, may mimic symptoms of other illnesses, and may include unexplained weight loss; headaches and vomiting; increased swelling or pain in bone, joints, back, or legs; a detectable lump or mass in the abdomen, pelvis, chest, armpit, or neck; unusual bleeding, bruising, or rash; recurring infections; sudden and persistent eye or vision changes; nausea or vomiting without nausea; a whitish color behind the pupil; tiredness or pallor; and recurring and persistent fevers. A child in the early stages of leukemia may not have these symptoms but may exhibit other changes in behavior, such as lacking the usual energy to engage in activities. A painless swelling of the lymph nodes, fever, and fatigue are often symptoms of both Hodgkin disease and non-Hodgkin lymphoma. The type of Hodgkin disease most often seen in young adults ages fifteen and older is associated with these symptoms: swollen lymph node in the neck, groin, or armpit; lethargy and weakness; facial swelling; night sweats; unexplained fever and weight loss; abdominal pain or swelling; difficulty breathing; and pain. Non-Hodgkin lymphoma may progress quickly in children, with many initially diagnosed at Stage III or IV, so these children may first complain of abdominal pain, fever, or constipation or decreased appetite originating from an abdominal mass. Neuroblastoma, or a cancer of the sympathetic nervous system, the most common type of cancer in infants, is usually seen as a lump or mass in the abdomen causing swelling, discomfort, pain, or a feeling of fullness. A neuroblastoma can also occur in the pelvis, neck, or eye. Often the neuroblastoma may spread to bone, causing pain, limping, weakness, numbness, or inability to walk. In about one-quarter of cases, the child may develop fever; less common symptoms include rapid heartbeat, flushed skin, sweating, irritability, high blood pressure, and diarrhea. 265
Childhood cancers Screening and diagnosis: There are no tests that screen for childhood cancers such as leukemia or lymphoma; however, there are standard tests for diagnosing. Typically, a parent notices a change in a child’s behavior and brings the child to the doctor, who will conduct a complete physical and examine the child for enlargement of the lymph nodes, liver, or spleen. If a blood cancer such as leukemia is suspected, the doctor will order a complete blood count (CBC) with differential. A fraction of patients with leukemia may have a normal blood test result when diagnosed. Suspicious cases must have a bone marrow test to confirm the diagnosis of leukemia. If Hodgkin disease or non-Hodgkin lymphoma is suspected, the doctor will do a thorough exam and order a CBC and a chest X ray. If the diagnosis of lymphoma is confirmed, the doctor may refer the child to a specialist, such as a pediatric hematologist or oncologist, for further diagnostic tests such as a biopsy of the tumor to differentially diagnose the type of lymphoma, a bone marrow aspirate, or an imaging test such as a computed tomography (CT) scan. Neuroblastomas are relatively rare, and screening for them in children with no symptoms is not believed to decrease mortality from the disease, so no screening test is conventionally used. Most neuroblastomas are detected within the first six months of life. Adoctor who suspects an
Salem Health: Cancer infant of having a neuroblastoma will order a urinalysis, which will reveal a higher-than-normal concentration of metabolites from the body’s breakdown of catecholamine neurotransmitters. If the physical exam and urine chemistry results indicate a neuroblastoma, the doctor will proceed to order other tests, such as an X ray, CT scan, abdominal ultrasound, CBC, blood test of liver and kidney function, bone scan, metaiodobenzylguanidine (MIBG) scan, and bone marrow aspiration. Staging is used to describe the disease at the time of diagnosis and to help the doctor determine the type of therapy, its course, and its prognosis. Leukemia, unlike other childhood cancers, is staged based on its presence and proliferation in organs other than its presence in the bone marrow and blood. Other factors in staging include sex, race, organ spread, types of leukemic cells, presence of abnormal chromosomes, and response to treatment within seven to fourteen days of inception. Staging to assess a child’s prognosis seems to be more important in children with ALL than in those with AML. Age and white blood cell count (WBCC) are important factors in staging ALL, with children younger than one and older than ten at highest risk (having a high white blood cell count of 50,000 cells per cubic millimeter). Lymphoma is staged based on the extent of the disease. Stage I lymphoma is limited to one primary area of the lymph node or organ, while Stage IV indicates the lymphoma has spread to one or more tissues or organs outside the lymphatic system. Neuroblastomas are staged I to IV-S, with Stage I being a tumor that is visible, is localized, and can be removed, and Stage IV being a cancer that has spread to distant lymph nodes or other parts of the body. In Stage IV-S, limited to a child under one year of age, the cancer has spread to skin, liver, or bone marrow but not to bone. Alternatively, neuroblastomas may be staged on the basis of low, intermediate, and high risk, depending on the features of the cancer cells, the age at which the child is diagnosed, and the stage of the disease.
The most common cancers in children are leukemias and lymphomas. (Digital Stock)
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Treatment and therapy: Childhood cancers are treated with surgery, chemotherapy, radiation therapy, or a combination of two or more therapies. Cancers in children, unlike those in many
Salem Health: Cancer adults, typically are fast growing and respond well to chemotherapy. Children are often treated in children’s cancer centers, which tend to offer new therapies and the latest treatment with clinical trials. The NCI recommends that children with cancer be treated by a multidisciplinary team consisting of a pediatric oncologist and other specialists and that all children be considered for clinical trials to test the effectiveness of existing treatments and evaluate the benefits and side effects of experimental treatments. The American Cancer Society (ACS) recommends that parents ask their pediatric cancer team about the potential side effects of treatment before the regimen begins. Side effects include hair loss, fatigue, risk of infection, easy bruising or bleeding, vomiting, diarrhea, bone marrow changes leading to anemia, lower white blood cell counts leading to reduced ability to fight infections, and a reduction in platelet production leading to easy bleeding and bruising. Treatment for the most common forms of cancer seen in children, acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML), consists of three phases: induction, consolidation, and maintenance. Once the cancer is staged by risk group, induction therapy is designed to induce remission such that leukemic cells are no longer present in bone marrow, normal cells return, and blood counts return to normal. The monthlong treatment, often performed in the hospital, is intense because of the risk of serious infection, but more than 95 percent children with ALL who receive this treatment experience remission. Although the cancer is in remission, consolidation treatment lasting four to six months and maintenance therapy lasting at least two years are required to destroy all cancerous cells. These intravenous chemotherapies are coupled with intrathecal chemotherapy (drugs injected into the fluid surrounding the brain and spinal cord) to destroy cancer cells that may have spread to the central nervous system. In addition, radiation therapy may be directed at the brain or spinal cord if the leukemia was present in cerebrospinal fluid at the time of diagnosis; however, the side effects and long-term effects of radiation to the brain are such that this type of radiation therapy is avoided whenever possible. Low-risk ALL has the highest cure rate, 85 to 95 percent of all cases. The three main types of therapy for Hodgkin disease are radiation therapy to decrease tumors and destroy cancerous cells; chemotherapy or systemic drug therapy; and bone marrow and peripheral blood transplants, particularly for those whose disease recurs. The four types of nonHodgkin lymphoma seen in children (Burkitt, lymphoblastic, anaplastic large-cell lymphoma, and large B-cell lymphoma) may be localized in a swollen lymph node, but
Childhood cancers often the disease has spread to other organs at the time of diagnosis. Some neuroblastomas go away without treatment, while others commonly require surgery. Approximately half of the tumors spread to bone and bone marrow, requiring chemotherapy, radiation therapy, stem cell transplantation, or immunotherapy. The location of the tumor, age of the child, and diffusion of the tumor are factors in determining the recommended treatment. Prognosis, prevention, and outcomes: Overall, death rates have declined and five-year survival rates have increased for most types of childhood cancers. The increase in survival rates is attributable to new treatments resulting in cures or long-term remission for many children with cancer. Although the majority of cancers respond well to treatment, some will recur and require the child’s doctor to develop a new treatment plan. The most commonly reported longevity statistic is the five-year survival rate, or the percentage of children with cancer who live at least five years after diagnosis. This survival rate is 79 percent for all sites, 79 percent for leukemia, 95 percent for nonHodgkin lymphoma, and 66 percent for neuroblastoma. The survival rate for chronic lymphoblastic leukemia (CLL) has been reported to approach 90 percent. Children with cancer respond to chemotherapies and tolerate treatment better than adults do, making their prognosis bright. However, children who survive cancer may have long-term effects that require lifelong follow-up. These late or delayed effects can include hormonal disturbances in the endocrine system causing short stature, problems in puberty, thyroid or fertility disturbances, secondary learning difficulties, and other health consequences of the disease or treatment. Published data on long-term survivors of childhood cancers indicate that those most at risk of developing secondary sarcomas (cancers of connective or supportive tissue such as in bone, fat, or muscle) are children whose primary cancer was in soft tissue, bone, or renal tissue, or was Hodgkin disease. Because sarcomas can occur anywhere in the body and are more difficult to detect, long-term aggressive follow-up of childhood cancer patients is critical to their staying healthy. Susan H. Peterman, M.P.H. u
For Further Information Eiser, Christine. Children with Cancer: The Quality of Life. Mahwah, N.J.: Lawrence Erlbaum Associates, 2004. Fromer, Margot Joan. Surviving Childhood Cancer: A Guide for Families. Oakland, Calif.: New Harbinger, 1998. 267
Chlorambucil Keene, Nancy. Chemo, Craziness, and Comfort: My Book About Childhood Cancer. Washington, D.C.: Candlelighters, 2002. Langton, Helen. The Child with Cancer: Family-Centred Care in Practice. New York: Baillière Tindall, 2000. u
Other Resources
Candlelighters Childhood Cancer Foundation http://www.candlelighters.org The Leukemia and Lymphoma Society http://www.lls.org Memorial Sloan-Kettering Cancer Center http://www.mskcc.org See also Acute lymphocytic leukemia (ALL); Bone cancers; Breast cancer in children and adolescents; Craniopharyngiomas; Craniosynostosis; Cryptorchidism; DenysDrash syndrome and cancer; Ependymomas; Family history and risk assessment; Genetics of cancer; Hereditary polyposis syndromes; Hodgkin disease; Juvenile polyposis syndrome; Leukemias; Medulloblastomas; Nephroblastomas; Neuroblastomas; Non-Hodgkin lymphoma; Pediatric oncology and hematology; Peutz-Jeghers syndrome (PJS); Pheochromocytomas; Pineoblastomas; Pleuropulmonary blastomas; RB1 gene; Retinoblastomas; Rhabdomyosarcomas; Rothmund-Thomson syndrome; Spinal axis tumors; Spinal cord compression; Vaginal cancer; Von Hippel-Lindau (VHL) disease; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer; Yolk sac carcinomas; Young adult cancers.
u Chlorambucil Category: Chemotherapy and other drugs; carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1981 Also known as: Leukeran, chloraminophene, Ambochlorin, Ecloril, Linfolysin Related cancers: Acute myeloid leukemia (AML), acute nonlymphocytic leukemia (ANLL) Exposure routes: Inhalation, ingestion, dermal contact Where found: Chemically synthesized; provided as treatment to people with cancer or autoimmune disorders as sugar-coated 2-milligram tablets 268
Salem Health: Cancer At risk: Patients receiving chlorambucil for treatment of cancer or autoimmune disorder; occupational exposure via skin contact or dust inhalation during pharmaceutical processing Definition: Chlorambucil is an alkylating agent of the nitrogen mustard class. As with other agents in this class, chlorambucil undergoes chemical activation to the aziridinium ion, which reacts with deoxyribonucleic acid (DNA) to form a covalent bond. This alkylation damages DNA and leaves it more prone to breakage. When taken up by rapidly dividing cells (such as cancer cells), damaged DNA is unable to repair itself quickly, leading to cell death. Etiology and symptoms of associated cancers: Acute myeloid (or nonlymphocytic) leukemia is a malignancy of blood in which myeloid precursor cells do not mature. These immature cells proliferate rapidly without normal maturation into granulocytes and monocytes. Early signs and symptoms are similar to those of influenza and include fever, weakness, fatigue, loss of appetite, and pain in the bones and joints. Infections, delayed healing of minor cuts, and unusual bruising or bleeding may occur. AML may occur at any age but typically occurs at about age sixty-five. Prognosis varies by age. Overall, 65 to 85 percent of patients achieve complete remission, with 20 to 40 percent achieving five-year survival. Children and adults older than the age of sixty are less likely to achieve complete remission. Alkylating agents such as chlorambucil increase the risk of acute myeloid leukemia, as does exposure to radiation and chemicals, such as benzene. History: Chlorambucil has been used in chemotherapy since the 1960’s, often for long durations. Although it is considered to be the least toxic nitrogen mustard derivative in use, sufficient evidence for carcinogenicity in animals and humans exists. Anecdotal evidence of carcinogenicity has been reported by the International Agency for Research on Cancer (IARC) since the early 1980’s. In most case reports, patients were also receiving radiotherapy or other potential carcinogens. A randomized trial inpolycythemia vera patients showed a thirteenfold increase in the incidence of AML in patients receiving chlorambucil. Risk of development of acute leukemia increased with dose and length of treatment. Karen M. Nagel, Ph.D. See also Antineoplastics in chemotherapy; Myelodysplastic syndromes; Waldenström macroglobulinemia (WM).
Salem Health: Cancer
u 1-(2-Chloroethyl)-3-(4-
methylcyclohexyl)-1nitrosourea (MeCCNU) Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1991 Also known as: Semustine Related cancers: Leukemia, preleukemia Definition: MeCCNU is used to treat various cancers, including some of the brain. A nitrosourea alkylating agent, MeCCNU contains alkyl groups that mainly react with the deoxyribonucleic acid (DNA) in the cell nuclei via a process called interstrand cross-linking. Local side effects of MeCCNU may include blistering of the skin as well as damage to the eyes and respiratory tract. Systemic toxic effects include nausea and vomiting, reduction in both leukocytes and erythrocytes, hemorrhagic tendencies, and nephrotoxicity. Busulfan and cyclophosphamide are among other alkylating agents used in cancer chemotherapy. Exposure routes: Oral (ingestion of capsules) Where found: 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)1-nitrosourea (MeCCNU) is an investigational drug. Patients may be exposed via oral adjuvant chemotherapy for various cancers, including those of the brain, lung, and digestive system. At risk: The National Institute for Occupational Safety and Health (NIOSH) conducted a survey from 1981 to 1983 and determined that approximately 229 workers were potentially exposed to MeCCNU. Etiology and symptoms of associated cancers: Though the exact mechanisms are unclear, it is believed that the most significant actions of alkylating agents are those that disturb cell growth, mitosis, and differentiation of rapidly dividing cells, providing the rationale for use in cancer therapy. However, because alkylating agents such as MeCCNU do not selectively kill cancer cells, they have a toxic effect on normal cells and are considered carcinogenic, mitogenic, and leukemogenic. Symptoms of leukemia may include weakness, fever, bleeding gums, petechiae (small red spots on the skin), lymphadenopathy (swollen glands), splenomegaly (enlarged spleen), and hepatomegaly (enlarged liver). History: Introduced in 1963 because of their lipophilicity and, therefore, ability to cross the blood-brain barrier, nitrosourea alkylating agents such as MeCCNU were designed to treat brain and meningeal cancer. However,
Cholecystectomy based on scientific data, MeCCNU has been shown to be carcinogenic in humans. In 1983 researcher J. D. Boice and colleagues found a twelvefold relative risk of leukemic disorders in 2,067 patients given adjuvant treatment with MeCCNU compared with those given other therapies. In 1987 the International Agency for Research on Cancer (IARC) demonstrated a significant dose-related response to MeCCNU with an adjusted relative risk of approximately fortyfold for patients who received the highest dose of MeCCNU. Also in 1987 the IARC concluded that there was evidence that MeCCNU was carcinogenic in experimental animals. In 1977 researcher J. H. Weisburger had found an increased incidence of tumors and leukemias in animals injected with MeCCNU. Cynthia Racer, M.A., M.P.H. See also Alkylating agents in chemotherapy; Chemotherapy.
u Cholecystectomy Category: Procedures Also known as: Open cholecystectomy, laparoscopic cholecystectomy Definition: Cholecystectomy refers to the surgical removal of the gallbladder. There are two approaches that may be used to remove the gallbladder. An open cholecystectomy involves making a single abdominal incision through which the gallbladder is extracted. This approach is used in complicated cases in which a more thorough exploration of the upper abdomen for cancer spread is anticipated. The minimally invasive laparoscopic cholecystectomy makes use of four abdominal incisions small enough to allow the insertion of a laparoscope and instruments (trocars). The gallbladder is extracted through one of the large ports. This approach is often reserved for uncomplicated gallbladder disease, although gallbladder cancer is found after removal in 1 percent of all patients undergoing liver and biliary tract surgery. Higher recurrence of gallbladder cancer is also reported with this method. Cancers treated: Gallbladder carcinoma, melanoma, metastatic carcinoma Why performed: Cholecystectomy is performed to remove the primary tumor and reduce the possibility of liver tissue invasion, regional lymph node infiltration, and distant spread (metastasis) of tumor cells. Although the main indication for performing a cholecystectomy is for definitive treatment of symptomatic gallbladder stone obstruc269
Cholecystectomy
Salem Health: Cancer
A laparoscopic cholecystectomy. (Custom Medical Stock Photo)
tion of the bile ducts (cholelithiasis), a gallbladder carcinoma is sometimes an incidental finding. Patient preparation: The patient first undergoes several laboratory and imaging tests in order to confirm clinical suspicions of gallbladder cancer based upon the patient’s medical history and physical examination. They include an ultrasound and a computed tomography (CT) scan of the abdomen in order to assess the size and spread of the cancer. A CT scan is particularly helpful in visualizing the liver and bile duct anatomy in relation to the cancer. Once the diagnosis is confirmed, preoperative patient preparation includes surgical risk assessment through a general physical examination, especially of the heart (electrocardiograph, or EKG) and lungs (chest X ray, pulmonary function tests), and temporary discontinuance of drugs that may complicate the patient’s recovery. Another consideration is ensuring that the patient has nothing by mouth at least eight hours before the procedure. Steps of the procedure: The patient is positioned, and the surgical site is sterilized. An incision is made near the border of the lower right ribcage, or a larger abdominal inci270
sion slightly to the right of the umbilicus. After the surgeon cuts through the skin and divides the abdominal muscles, the abdominal cavity is entered and the liver is identified. It is common to encounter some adhesions between the liver, gallbladder, and adjacent bowel; these adhesions are cut away. Once the liver and gallbladder are visualized, the gallbladder outlet (cystic duct), contained in a ligament connecting the liver to the duodenum, is exposed and slightly constricted by silk suture to prevent gallstones from passing. The adjacent gallbladder artery (cystic artery) and right hepatic artery are identified to avoid tying off the latter. The gallbladder is dissected away from the liver, starting from the bottom (fundus) and going toward the cystic duct. The cystic artery is reached, then subsequently tied off and cut. The junction between the cystic duct and the larger common bile duct is identified, and the cystic duct is tied off and cut 3 to 5 millimeters away from the common bile duct. An alternative, retrograde approach involves tying off and cutting the cystic duct and artery first before proceeding to dissect the gallbladder away from the liver.
Salem Health: Cancer In more extensive cancer spread, removal of the gallbladder also involves an extended resection (part of the liver and lymph nodes) or a radical resection of the gallbladder involving adjacent structures such as a margin of underlying liver, the common bile duct, the hepatoduodenal ligament, and nearby lymph nodes from the liver, stomach, bowel, and pancreas. Severe spread may even involve removal of a large section of the liver and affected organs. After the procedure: The patient is monitored in the postanesthesia care unit until fully awake and vital signs are stable. The patient may then be discharged to the surgical ward for postoperative monitoring for yellowing of the skin (jaundice), fever, and abdominal pain or enlargement, among other signs. Laboratory examinations and imaging studies are done if signs of deterioration are suspected. Once the patient is stable, ambulatory, urinating, and eating, the patient may be discharged after a few days. Risks: Some of risks of cholecystectomy are procedurerelated and thus preventable. The main risk involved in cholecystectomy is bleeding from small vessels that were not cauterized or ligated intraoperatively. Another risk is ligation of the common bile duct. Bowel injury may lead to bowel adhesions, leakage, fistulas, or inflammation of the abdominal cavity (peritonitis). Ligation of the right hepatic artery may also occur. Results: During the surgery, surgeons may find the gallbladder filled with an irregular mass or polyps, accompanied by mucus or gallstones. Tumors may extend outside the gallbladder and occasionally “replace” the gallbladder itself and encroach on surrounding structures in similar fashion. Microscopically, the cancerous cells resemble the secreting cells of the gallbladder wall (adenocarcinoma). Aldo C. Dumlao, M.D. u For Further Information Gislason, Stephen J. Food and Digestive Disorders: Irritable Bowel Syndrome, Crohn’s Disease, Celiac Disease, Ulcerative Colitis, Ulcers, Reflux, and Motility Disorders. Sechelt, B.C.: Environmed Research, 2003. Goldberg, Andrew, and Gerard Stansby. Surgical Talk: Revision in Surgery. River Edge, N.J.: Imperial College Press, 2005. Premkumar, Kalyani. Interactive Pathology for Massage Therapists. Baltimore: Lippincott Williams & Wilkins, 2000.
See also Gallbladder cancer; Hepatic arterial infusion (HAI); Nuclear medicine scan; Ultrasound tests.
Chordomas
u Chordomas Category: Diseases, symptoms, and conditions Also known as: Chordocarcinomas, chordoepitheliomas Related conditions: Sarcomas Definition: Chordomas are cancerous bone tumors that can occur anywhere along the spinal cord, most commonly at the base of the skull, at the base of the spine (sacrum), or in the tailbone (coccyx). Risk factors: There are no known risk factors. Bone injury, environment, diet, medications, and genetics do not appear to play a role in the development of chordomas. Etiology and the disease process: Chordomas develop in leftover pieces of cells from the notochord, a flexible, rodshaped structure that forms during early fetal development and precedes the spine. Incidence: Chordomas are rare. Most cases have been reported in persons age forty to seventy. Sacrum chordomas are more common in men; chordomas at the skull base are more common in women. Symptoms: Symptoms develop gradually and depend on the tumor site. Tumors near the skull base can cause headaches, face pain, and vision problems. Tumors in the lower spine and tailbone area may lead to leg weakness, leg or groin numbness, constipation, impotence, and bowel and bladder dysfunction. A tailbone chordoma may manifest with a noticeable mass. Chordomas in the upper part of the spine may cause hoarseness and swallowing problems. Screening and diagnosis: Most chordomas grow slowly and do not spread, and the gradual development of symptoms often results in a delayed diagnosis. Patients often have symptoms for more than a year before diagnosis. Computed tomography and magnetic resonance imaging can reveal bone destruction and tissue damage. Biopsy of the tumor confirms the diagnosis. Treatment and therapy: Surgery to remove the tumor and surrounding tissue is the best option but often difficult because of the tumor’s precarious positioning near the spinal cord and brain. Surgery often results in some type of nerve loss. For example, removing a chordoma from the tailbone can damage the nerves that control bladder and bowel function. Radiation therapy may be used along with surgery to ensure that all cancer cells are destroyed. Chemotherapy does not appear to be an effective treatment for chordomas. 271
Choriocarcinomas
Salem Health: Cancer
Duke University student Josh Sommer, right, who has a chordoma, is researching the disease with Duke oncologist Neil Spector. (AP/ Wide World Photos)
Prognosis, prevention, and outcomes: If cancer cells remain after treatment, a chordoma can recur and spread to other parts of the body, most commonly the lymph nodes, lungs, and liver. The recurrence rate is high. Survival rates depend on the location of the tumor. Persons with chordomas of the skull base tend to have the best prognosis. Overall, about 90 percent of persons with chordomas survive about five to ten years. Kelli Miller Stacy, ELS See also Bone cancers; Spinal axis tumors.
Definition: One of the most dangerous germ-cell cancers, choriocarcinoma is a quick-growing cancer that occurs in a woman’s uterus after a pregnancy, miscarriage, or spontaneous abortion. This cancer arises from trophoblastic cells of the placenta and mimics the development of normal placental tissue. The cancer is usually invasive (metastatic), growing so fast that the original tumor outgrows its blood supply and dies, leaving behind only a small scar. For unknown reasons, it metastasizes early to the lungs, liver, and brain. Risk factors: Pregnant women are at risk.
u Choriocarcinomas Category: Diseases, symptoms, and conditions Also known as: Chorioblastomas, trophoblastic tumors, chorioepitheliomas, gestational trophoblast neoplasia, gestational trophoblastic disease Related conditions: Invasive mole 272
Etiology and the disease process: Choriocarcinoma is an uncommon cancer that is associated with pregnancy. Choriocarcinomas result from genetic damage to a germ cell. The cancer forms in the trophoblast (placental) cells that surround the baby. About half of all choriocarcinomas arise from a hydatidiform mole, also known as a molar pregnancy, in which a nonviable embryo implants and rapidly grows within the mother’s uterus. Approximately one-quarter of choriocarcinomas occur after pregnancy
Salem Health: Cancer has resulted in the delivery of a normal child. The remainder of cases occur after any type of abortion, ectopic pregnancy, or genital tumor. Most choriocarcinomas form inside the reproductive organs, such as the testes or ovaries, especially in young adults. A few choriocarcinomas arise in sites outside the reproductive organs (extragonadal tumors); these are usually found in young adults and are more common in men. Incidence: In North America, choriocarcinoma occurs in approximately 1 in 30,000 to 40,000 pregnancies. Choriocarcinoma is more common in Asian Americans than African Americans, and least common in whites. Choriocarcinoma has been shown to occur following hydatidiform mole (50 percent), normal term pregnancy (25 percent), and spontaneous abortion (25 percent). Symptoms: The symptoms of a choriocarcinoma vary, depending on where the tumor originates and where it spreads. If the cancer is in the uterus, the most common symptom is bleeding. Cancers in the ovary often have only subtle signs such as widening of the waistline or pain. In the testes, choriocarcinomas can often be felt as small painless lumps. Choriocarcinomas that spread to other organs may reveal their presence as a result of the bleeding or complications from bleeding that occur in their presence. In the brain, this bleeding can cause a stroke. Additional symptoms may include irregular vaginal bleeding, uneven swelling of the uterus, persistently high human chorionic gonadotropin (HCG) levels, or localized pain. Screening and diagnosis: Most choriocarcinomas produce human chorionic gonadotropin, a hormone normally found only during pregnancy. The presence of HCG in the blood can help in diagnosing this cancer and monitoring the success of treatment. Choriocarcinomas are usually referred to a doctor who specializes in cancer treatment (an oncologist). To diagnose this tumor, the doctor will do a physical examination and examine the internal organs with X rays or ultrasounds. Choriocarcinomas may not be biopsied before being treated because they tend to bleed heavily. Choriocarcinomas can be detected using ultrasound, X rays, computed tomography (CT), magnetic resonance imaging (MRI) scans, or positron emission tomography (PET) scans. Treatment and therapy: After making the initial diagnosis, the oncologist will take a careful history and perform an examination to rule out metastasis (spread to other organs). Chemotherapy is the treatment of choice. Choriocarcinoma is one of the tumors that is most sensitive to chemotherapy. The cure rate, even for metastatic choriocarcinoma, is about 90 percent. Almost all patients
Choriocarcinomas without metastases can be cured; however, metastatic disease to the kidneys, liver, or brain can be fatal. The chemotherapy regimen is generally EMA-CO: etoposide, methotrexate, actinomycin D, cyclosphosphamide, and vincristine (Oncovin). A hysterectomy (surgical removal of the uterus) is rarely required; however, a hysterectomy may be offered to patients over forty years of age or those desiring sterilization. It may be required for those with severe infection and uncontrolled bleeding. Prognosis, prevention, and outcomes: No known means of prevention exists; however, early detection of the symptoms and prompt medical treatment can improve the odds of survival. Although careful monitoring after the removal of a hydatidiform mole or the termination of pregnancy may not prevent the development of choriocarcinoma, it is essential in early identification of the condition, which improves outcome. The prognosis for choriocarcinomas in the uterus is very good. Although these tumors have often spread throughout the body, chemotherapy results in a cure or remission in at least 85 to 90 percent of cases. Women who have had choriocarcinomas often go on to have normal pregnancies and deliveries. Choriocarcinomas in sites other than the uterus have a poorer prognosis. These tumors tend to spread quickly and do not always respond well to chemotherapy. Although treatment can be effective, the outcome usually depends on how widely the cancer is dispersed. Generally, the prognosis is worse if the cancer can be found in the liver or brain, if HCG levels are high, or if the original tumor developed outside the gonads. However, about two-thirds of women who initially have a poor outlook go into remission (a disease-free state). Thomas L. Brown, Ph.D. u
For Further Information Baker, Vicki V. “Gestational Trophoblastic Disease.” In Clinical Oncology, edited by Martin D. Abeloff et al. 2d ed. Philadelphia: Churchhill Livingstone, 2000. Berkowitz, Ross S., and Donald P. Goldstein. “Gestational Trophoblast Neoplasia.” In Practical Gynecologic Oncology, edited by Jonathan S. Berek and Neville F. Hacker. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Vinay, Kumar, Abul K. Abbas, and Nelson Fausto. Robbins and Cotran Pathological Basis of Disease. 7th ed. Philadelphia: Elsevier/Saunders, 2005.
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Other Resources
Eyes on the Prize.org http://www.eyesontheprize.org/index.shtml 273
Chromium hexavalent compounds My Molar Pregnancy.com http://www.geocities.com/thornfield8998/molar.html See also Germ-cell tumors; Gestational trophoblastic tumors (GTTs); Human chorionic gonadotropin (HCG); Hydatidiform mole; Pituitary tumors; Teratocarcinomas.
u Chromium hexavalent
compounds Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Hexavalent chromium, chromium 6, chromium (Vl), Cr (Vl) Related cancers: Lung cancer, and less commonly, cancer of the nose and nasal sinus cavities Definition: The term “hexavalent” describes how highly oxidized chromium becomes in a chemical compound and means that chromium has combined with six oxygen atoms. It is this fully oxygenated form that is associated with chromium’s greatest industrial use and most serious health concerns.
Salem Health: Cancer ation and perforation, bronchitis, asthma, pneumonia, decreased lung function, and cancers of the nose, sinuses, and lung. Even short-term exposure may manifest in fits of coughing, wheezing, and shortness of breath. Although the respiratory tract is the primary area of concern, injury to the kidneys, liver, teeth, eardrums, eyes, and skin is possible. Although genetic damage following hexavalent chromium exposure is clear, research has not yet described the exact cellular mechanism that results in cancer. History: Shortly after chromium, “the red mineral,” was found in Siberia toward the end of the eighteenth century, it became useful as a paint pigment and leather-tanning product. Although some of its health risks soon became apparent, it was not until 1980 that the U.S. government officially acknowledged its role as a carcinogen. In the twenty-first century, businesses using hexavalent chromium must establish the exposure rates of their workers. The Occupational Safety and Health Administration (OSHA) has mandated strict monitoring and eight-hour exposure limits to hexavalent chromium dust or fumes in targeted job sites. Richard S. Spira, D.V.M. See also Cancer clusters; Cigarettes and cigars; Lung cancers; Nasal cavity and paranasal sinus cancers.
Exposure routes: Primarily inhalation and to a lesser extent skin contact and water intake Where found: Chromate dyes of plastics, inks, and photographic processing compounds; anticorrosive agent in paints, electroplated metal, and welded stainless steel; and also in leather-tanning products, textile dyes, and wood preservatives At risk: Workers in daily contact with hexavalent chromium. There is also concern among people living near contaminated wastewater, people who breathe air polluted with chromium hexavalent compounds, and those who have skin contact with products containing these compounds. Hexavalent chromium became part of the American lexicon following the film Erin Brockovich (2000), a cautionary tale about a cancer cluster seemingly associated with industrial contamination of the local drinking water. In a 2001 report, the Environmental Protection Agency estimated that more than two thousand work sites released 7 million tons of chromium compounds into the environment. The health risk from this discharge is unknown. Etiology and symptoms of associated cancers: The respiratory tract is the most common site for hexavalent chromium damage. This damage may lead to septal ulcer274
u Chromosomes and cancer Category: Cancer biology Also known as: Chromosomal instability, CIN Definition: Cancer is usually conceived of as resulting from a series of mutations in two classes of genes: oncogenes and tumor suppressors. Cancer cells, however, typically exhibit broader changes to their chromosome structure that extend well beyond the deoxyribonucleic acid (DNA) base changes that accompany most mutations. These include changes in chromosome number as well as the deletion, duplication, inversion, and translocation of chromosomal segments. Chromosomal aberrations, however, have historically been more difficult to study than mutations, and no direct evidence of their role in carcinogenesis has been produced. Scientists continue to debate whether these chromosomal changes play a causal role in cancer or are simply an artifact of the mutations that lead to cancerous states. However, some consensus has been reached that mutations and chromosomal instability probably play complementary roles in the formation of cancer and that neither acts completely independent of the other.
Salem Health: Cancer
Chromosomes and cancer
factual role of aneuploidy in cancer includes that aneuploid cells have been found to be associated with certain precancerous lesions and therefore could not have been caused by the formation of a cancerous state, that there are specific chromosomal translocations that are diagnostic of certain forms of cancer (these are often referred to as marker chromosomes when used in this context), and that the degree of aneuploidy in a cancer cell often correlates with the severity of the disease and can even be predictive of clinical outcomes. Aneuploidy has also been suggested to be one of the reasons cancer cells are so well adapted for continuous growth in their particular environment. By displaying a nearly limitElectron micrograph of human chromosomes. (Biophoto Associates/Photo Researchers, Inc.) less number of phenotypes that result from changing the dosage of many different combinations of genes, those cells Etiology and symptoms of associated cancers: Most that are particularly well adapted will be selected for and cancer cells are aneuploid. “Aneuploidy” is the term used will propagate more cells like themselves. However, there to describe the gain or loss of a chromosome in a cell, remains no direct evidence that an aneuploid state causes whether it be an entire chromosome or just a portion of the cellular changes that lead to cancer. one. In the latter case, the gain or loss has also been deAnother chromosomal abnormality that is associated scribed as a DNA insertion, or duplication, respectively. with almost all cancer cells, but which was not evident iniUnlike single mutations, aneuploidy can affect the exprestially using conventional cytological techniques, is the sion of genes by the thousands as large numbers of genes presence of very short telomeres. Telomeres are arrays of have their expression effectively doubled or cut in half by repetitive DNA that are found on the ends of linear chrothe duplication or deletion, respectively, of a chromomosomes. These structures protect genomic DNA from somal segment. Such changes in a gene’s “dosage” may, in the shrinkage that occurs in chromosomes every time they turn, lead to an increased rate of cellular mutation, espeare replicated. DNA polymerase, the enzyme that is used cially if the affected genes are involved in the repair of to copy DNA, is unable to copy a complete linear molecule DNA damage. Aneuploidy and mutation can therefore be of DNA because of its use of a ribonucleic acid (RNA) “primer” to initiate its activity. Telomeres are therefore thought of as complementary processes, with one state ofdegraded each time a cell duplicates and divides, providten leading to the other. ing a distinct limit on the number of divisions any cell can An extreme form of aneuploidy is polyploidy, where undergo. Rapidly dividing cells, such as those associated the entire complement of chromosomes in a cell has been with cancer, quickly reach this limit and enter a stage duplicated, so that there are more than the usual two copies deemed cellular crisis. Most cells that reach this stage stop of each chromosome in the cell. Many solid tumors have dividing, and many die, but cancerous cells overcome this been shown to be made up of polyploid cells. Subtler limitation, called the Hayflick limit after American cell bichanges in gene expression can also result from two other ologist Leonard Hayflick, who first described this phechromosomal aberrations that are seen to occur in cancer nomenon in 1962. To do this, most cancer cells express an cells: inversion and translocation. Here, a chromosomal enzyme called telomerase, which adds DNA repeats to the segment is “flipped around” in a chromosome or is transends of the chromosomes and allows cells to continue diferred to a different chromosome. Although the genes on viding indefinitely. this segment are still present in the cell, they may be differShortened telomeres have been shown to be associated entially expressed, because precisely where a gene is lowith chromosomal instability. Telomeres in this shortened cated on a chromosome often affects its level of activity. state often fuse with one another or to other regions of Evidence that supports a causative rather than arti275
Chronic lymphocytic leukemia (CLL) double-stranded breaks within chromosomes to avoid further degradation. The number of such break sites in cancer cells is often increased because of mutations in the DNA enzymes used to repair such damage. Chromosomes that are fused end-to-end or to another chromosomal segment that contains a centromere are then further jumbled when their DNA is pulled apart during mitosis. The centromere is a region of DNA that typically makes up the center of a chromosome and is the area to which the mitotic spindle attaches when sister chromosomes are separated from one another. The chromosomal abnormalities associated with aneuploidy can result from such cycles of fusion followed by chromosomal breakage. History: The concept that cancer is essentially a chromosomal disease is not a new one. In 1902 Theodor Boveri, a German zoologist, proposed that changes in chromosome number were the cause of tumor formation. He used cytological techniques to view the chromosomes of a tumor cell using a microscope. This is not to say that his aneuploidy theory did not leave room to account for the contributions of changes to specific genes. As the concept of thegene began to take shape during the early twentieth century, Boveri formulated a theory of how aneuploidy caused cancer that incorporated an early notion of mutational changes. He proposed that abnormal mitoses could lead to a combination of “chromatin determinants” that, in turn, would lead to cancer. However, when oncogenes and tumor suppressors were discovered in the 1970’s and 1980’s, the concept of aneuploidy as the causative factor of cancer began to fall out of favor. The notion that the identification of specific mutations in a finite number of genes would lead to a full understanding of cancer was an appealing one. As more and more cancer-causing genes were identified, the goal of understanding cancer at a molecular level seemed attainable. However, as time progressed, the mutational theory failed to explain a number of observations, including that cancer is rare in newborns, something one would not predict if newborns inherited cancer-causing genes from their parents; that certain carcinogens are known to cause cancer without causing mutations; and that a long latency period is always present before cancer develops, even after exposure to fast-acting mutagens. The resurgence of the aneuploidy theory of cancer formation can also be linked to the development of new techniques in the 1990’s, such as microarrays, which allow the expression levels of many genes to be assayed at the same time. Using microarray analysis, cancers were seen to exhibit changes in hundreds, or even thousands, of genes— many more than could be accounted for by a purely 276
Salem Health: Cancer mutational model. As cancer research progresses, the role of both mutations as well as chromosomal aberrations will need to be taken into account to fully understand their contributions to carcinogenesis. James S. Godde, Ph.D. u
For Further Information Deusberg, P., R. Li, A. Fabarius, and R. Hehlmann. “The Chromosomal Basis of Cancer.” Cellular Onocology 27 (2005): 293-318. Maser, R. S., and R. A. DePinho. “Connecting Chromosomes, Crisis, and Cancer.” Science 297 (2002): 565569. Rajagopalan, H., and C. Lengauer. “Aneuploidy and Cancer.” Nature 432 (2004): 338-341. Richards, R. I. “Fragile and Unstable Chromosomes in Cancer: Causes and Consequences.” Trends in Genetics 17 (2001): 339-345. Weaver, B. A. A., and D. W. Cleveland. “Does Aneuploidy Cause Cancer?” Current Opinion in Cell Biology 18 (2006): 658-667.
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Other Resources
National Cancer Institute The Center of Excellence in Chromosome Biology http://ccr.cancer.gov/initiatives/CECB/ National Center for Biotechnology Information Cancer Chromosomes http://www.ncbi.nlm.nih.gov/sites/ entrez?db=cancerchromosomes See also Cancer biology; Childhood cancers; Cytogenetics; Family history and risk assessment; Gene therapy; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Mitochondrial DNA mutations; Oncogenes; Proto-oncogenes and carcinogenesis.
u Chronic lymphocytic leukemia
(CLL) Category: Diseases, symptoms, and conditions Also known as: Chronic lymphoid leukemia Related conditions: Acute lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia Definition: Chronic lymphocytic leukemia (CLL) is a cancer of the white blood cells. A lymphocyte is a type of white blood cell made in the bone marrow that helps fight
Salem Health: Cancer infection. For unknown reasons, the bone marrow begins to make lymphocytes that develop abnormally, causing this fast-growing type of cancer. In this disease name, “chronic” means that the disease does not progress as rapidly as acute lymphocytic leukemia. Risk factors: There are few risk factors for CLL. Past research has concluded that the risk of developing CLL is not affected by environmental factors. However, research is ongoing as to whether exposure to herbicides and insecticides increases the risk of CLL. About half the people who develop CLL have chromosomal abnormalities, such as deletions on a chromosome or an extra chromosome. People with close relatives who have CLL have a slightly increased risk of developing this disease. Risk increases with age; patients with CLL are rarely under the age of forty-five and are generally over the age of sixty. Men are more likely to develop CLL than women, and whites and those of Russian Jewish or Eastern European Jewish descent are more likely to develop it than those of other racial and ethnic backgrounds.
Chronic lymphocytic leukemia (CLL)
Incidence of Chronic Lymphocytic Leukemia per 100,000 People, by Gender 7 Women
Men 6
5.8
5 4.4 4
3
2.9
2.8 2.1
2 1.3 1
1.1 0.6
0 White
Black
Hispanic
Asian/Pacific Islander
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
Etiology and the disease process: CLL starts in a single white blood cell (lymphocyte). These CLL cells begin to multiply and crowd out the normal white blood cells. The CLL cells accumulate in the bone marrow, but they do not stop normal blood cell production quite as much as some other types of leukemia. Slow-growing CLL may cause only minimal changes in the blood for years. Some patients begin to produce an antibody during the CLL disease process that works against their body’s own red blood cells and causes a severe type of anemia. In a small number of CLL patients, the disease changes and begins to act like a more aggressive type of lymphoma or leukemia. In a very small number of CLL patients, throughout the disease process, CLL begins to act like acute lymphocytic leukemia (ALL). Incidence: About 15,340 people in the United States were diagnosed with CLL in 2007. Most with CLL are more than fifty years old. Symptoms: Symptoms of CLL usually develop slowly. Patients may find out they have this type of slow-growing
cancer after getting blood tests for another condition. Symptoms may include anemia, bleeding easily, bone pain, bruising easily, fever, joint pain, loss of appetite, night sweats, pain or a feeling of fullness below the ribs, shortness of breath, swollen liver, swollen lymph nodes, swollen spleen, tiredness, unexplained or repeated infections, and weight loss. Screening and diagnosis: There is no screening test for CLL. Blood and bone marrow tests are necessary to diagnose CLL. These tests look for abnormal lymphocyte cells. A bone marrow aspirate test (using a long needle to take marrow out of the bone) and a bone marrow biopsy (surgical removal of some bone marrow) are two possible tests. The bone marrow aspirate test looks for abnormal cells in the bone marrow and can also be used for other types of analysis. A bone marrow biopsy can show how much disease is already in the bone marrow. The results of these tests help determine which type of drug therapy to use and how long treatment should last. Another test that may be performed, immunophenotyping, helps determine 277
Chronic lymphocytic leukemia (CLL)
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whether the increased lymphocytes in the blood are monoclonal (came from a single malignant cell). This can help distinguish CLL from other types of diseases that cause increased lymphocytes in the blood. Depending on where the cancer started and the results of testing, CLL may be categorized into B-cell CLL (the most common type), T-cell CLL (which generally behaves more like other T-cell cancers than like CLL), or NK-cell CLL. B-cell CLL may be divided into further subtypes based on whether genetic mutations have occurred. As these mutations may affect how rapidly the disease progresses, this further division may help doctors determine treatment and which patients will benefit from earlier treatment. These subdivisions may also give a general idea of the progression and outcome of the disease, such as what effect the disease will have on marrow and blood cell development and what other organs, such as kidneys, bowels, or liver, may be affected. Researchers are investigating whether these subdivisions of CLL are actually different types of cancer. Staging of CLL involves evaluating the number of CLL cells; whether the liver, lymph nodes, or spleen are enlarged; and whether the red blood cell or platelet counts are low. In the Rai system, used commonly in the United States, CLL is divided into five stages: • Stage 0: Large numbers of lymphocytes in the blood but no other symptoms • Stage I: Large numbers of lymphocytes in the blood and enlarged lymph nodes • Stage II: Large numbers of lymphocytes in the blood, enlarged liver or spleen, possibly enlarged lymph nodes • Stage III: Large numbers of lymphocytes in the blood, too few red blood cells (anemia), possibly enlarged lymph nodes, liver, or spleen • Stage IV: Large numbers of lymphocytes in the blood, too few platelets, possibly too few red blood cells, and possibly enlarged lymph nodes, liver, or spleen
lower, anemia becomes worse, the lymph nodes or spleen have enlarged, or symptoms have become bothersome to patients. Treatment involves slowing the growth of CLL cells, keeping patients well enough to carry out daily activities, and protecting patients from infections, because the abnormal white cells are not able to fight infection. CLL is usually treated with chemotherapy or monoclonal antibody therapy. Both these therapies involve the use of certain drugs or drug combinations to kill abnormal lymphocytes. A bone marrow or cord blood transplant may help some CLL patients. A transplant is a high-risk procedure, however, and probably will not be used unless a patient has a fast-growing type of CLL, is younger than fifty-five years of age, and has a close relative who is a good transplant match. Older patients or patients with slow-growing CLL are not good transplant candidates. CLL is not usually treated with radiation therapy. However, radiation may be used if a large mass of lymphocytes is blocking an important part of the body, such as the kidneys, stomach, intestines, or throat. In a small number of CLL patients, surgery to remove the spleen (splenectomy) can help relieve pressure if the spleen is filled with too many CLL cells. If patients with CLL have problems fighting infections, they may be treated with antibiotics. If infections become a chronic problem, patients may be treated with injections of a protein found in the blood that fights infections (immunoglobulin). Follow-up treatment for CLL involves regular doctor visits and continuing lab tests to make sure the CLL cells are not beginning to increase rapidly. These doctor visits also help find any side effects from treatment. Patients who have had CLL are at increased risk for developing some other cancers, such as lung, colon, or skin cancer, and patients should be screened for these conditions during follow-up visits.
Treatment and therapy: Patients diagnosed with CLL may not need treatment immediately. They may have good health for several years without any treatment at all. However, doctors will want to watch and wait—closely follow patients with CLL to ensure that the CLL is not getting worse. This allows patients to avoid the side effects of treatment until treatment is necessary. However, some patients will need treatment near the time of diagnosis because these patients have had the disease for some time and it is progressing or because they have a faster-growing type of CLL. Treatment may become necessary when the number of CLL cells rapidly becomes higher, the number of normal cells becomes
Prognosis, prevention, and outcomes: There is no cure for CLL and no known way of preventing the disease. However, many patients, especially those with slowgrowing forms of this disease, may live for many years in good health. Survival rates range from one year to more than twenty or thirty years depending on stage and form of disease. The five-year survival rate of CLL patients is greater than 70 percent. Marianne M. Madsen, M.S.
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For Further Information Caligaris-Cappio, F., and R. Dalla-Favera, eds. Chronic Lymphocytic Leukemia. New York: Springer, 2005.
Salem Health: Cancer Faguet, G. B. Chronic Lymphocytic Leukemia: Molecular Genetics, Biology, Diagnosis, and Management. Totowa, N.J.: Humana Press, 2003. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Chronic Lymphocytic Leukemia: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. u
Other Resources
Chronic Lymphocytic Leukemia Foundation http://www.cllfoundation.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute Chronic Lymphocytic Leukemia Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ CLL See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Agent Orange; Blood cancers; Chronic myeloid leukemia (CML); Hairy cell leukemia; Hemolytic anemia; Immunoelectrophoresis (IEP); Leukemias; Lymphocytosis; Monoclonal antibodies; Richter syndrome; Side effects; Staging of cancer.
u Chronic myeloid leukemia
(CML) Category: Diseases, symptoms, and conditions Also known as: Chronic granulocytic leukemia, chronic myelocytic leukemia, chronic myelogenous leukemia Related conditions: Acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelomonocytic leukemia, chronic neutrophilic leukemia, juvenile myelomonocytic leukemia, other myeloproliferative disorders such as essential thrombocythemia, myelofibrosis, and polycythemia vera Definition: Chronic myeloid leukemia (CML) is one of the four types of leukemia, cancers of the white blood cells. Patients with CML have a growth of malignant bone marrow cells, and these bone marrow cells begin to accumulate in the blood. Usually, these patients have a chromosome abnormality called the BCR-ABL cancer gene. “Chronic” means this cancer is more slow growing than an acute type of cancer. “Myeloid” is the type of white blood cell that is affected.
Chronic myeloid leukemia (CML) Risk factors: About 95 percent of people with CML have a chromosome abnormality called the Philadelphia chromosome (named after the city where it was first documented). The Philadelphia chromosome occurs when a piece of chromosome 22 breaks off at a gene called BCR. If a piece of chromosome 9 breaks at a gene called ABL and switches with the break in chromosome 22, the BCR-ABL cancer gene forms. This gene somehow instructs cells to make a protein that leads to CML. This gene appears only in the cells that form blood and is not passed on to other family members. This switch in chromosomes may be affected by very high levels of radiation (such as in atomic bomb survivors) or high-dose radiation therapy for other kinds of cancers. However, most people with CML do not have these risk factors, and others who have these risk factors do not develop CML. Etiology and the disease process: Like all leukemias, CML begins with a change in a single cell. At diagnosis, patients may be feeling well. Usually, the body makes more white blood cells only when fighting an infection, and when the infection has passed, the number of white blood cells returns to normal. However, if this disease is not treated, the white blood cells begin to increase rapidly and start to circulate in the blood, causing swelling of the liver and spleen. The number of BCR-ABL cancer genes in the body increases. The disease may progress to a phase in which the patient has a low red blood cell count (anemia) and the platelets are not able to function properly. Eventually the ability of the white blood cells to fight infection is affected. Incidence: About 4,500 people in the United States were diagnosed with CML in 2007. Though children may have CML, it is very uncommon; only about 2 percent of CML patients are children. Most CML occurs in adults. It is slightly more common in men than women. The risk of getting this cancer increases with age; most patients are adults older than age sixty. Symptoms: Symptoms of CML usually develop slowly. Patients may find they have this type of cancer after getting blood tests for another condition. Symptoms may include anemia (low red blood cell count), bleeding easily, bone pain, bruising easily, fever, loss of appetite, night sweats, pain or a feeling of fullness below the ribs (especially in the upper left abdomen), paleness, shortness of breath, stomach pain, swollen liver, swollen spleen, tiredness, unexplained or repeated infections, weakness, and weight loss. Screening and diagnosis: There is no screening test for CML. Generally, CML can be diagnosed from an exami279
Chronic myeloid leukemia (CML) nation of the blood cells. However, bone marrow tests may be done to look for changes not seen in the blood. Cytogenetic tests (tests that analyze a cell’s chromosomes) may also be used to confirm the diagnosis by looking for the BCR-ABL cancer gene. The results of these tests help determine which type of drug therapy to use and how long treatment should last. CML has three phases that are determined by how many immature leukemia cells (blasts) are in the bone marrow and blood: • Chronic phase: Most patients, about 85 percent, are in this stage when their CML is diagnosed. During this time, the blood and bone marrow have less than 5 percent blasts. Red blood cells and platelets are affected; however, white blood cells are still fighting infection. This stage may last for years. • Accelerated phase: During this phase, there are more than 5 percent but less than 30 percent blasts in the blood and bone marrow. Patients may begin to feel ill. They may have anemia, the number of platelets in the blood may drop, and the white cells may either increase or decrease. The number of blast cells begins to increase, and the
Salem Health: Cancer spleen may swell. At this phase, the disease is progressing, and patients are likely to move into the next phase. • Blast crisis phase: In this phase, there are more than 30 percent blasts in the blood and bone marrow. Patients in this phase often have infections. They may also be short of breath or tired and have stomach pain, bone pain, or bleeding. The number of blast cells in the blood and bone marrow increases, and the number of red cells and platelets drops. At this phase, CML may begin to act more like an acute leukemia.
Treatment and therapy: Drugs or chemotherapy are usually used to achieve treatment goals for patients with CML. These goals include bringing the red blood cell and platelet counts back to normal and eliminating all the cells with the BCR-ABL gene. This treatment also helps shrink the spleen back to normal size. Treatment does not cure CML. However, patients usually achieve remission, during which they feel well and are able to return to normal activities. If treatment is stopped, the symptoms are likely to flare up again. This may also happen if a patient becomes resistant to the drug treatment. Another possible treatment for CML is to have white blood cells removed from the blood (leukapheresis). This Incidence of Chronic Myeloid Leukemia may help if a patient has a very high per 100,000 People, by Gender white blood cell count, so high that the white blood cells are interfering with 2.5 blood flow to parts of the body, such as Women Men the brain. Monitoring whether treatment is 2.0 2.0 1.9 working is important with this disease. Patients will continue to have blood tests to see if red blood cell, white blood 1.5 1.5 cell, and platelet counts are returning to 1.5 normal. A blood test or bone marrow bi1.2 opsy (surgically removing some bone 1.1 1.0 marrow) can show whether the BCR1.0 ABL gene count is decreasing. Cytoge0.8 netic tests such as fluorescent in situ hybridization (FISH) or polymerase chain 0.5 reaction (PCR) may be used to monitor the level of BCR-ABL genes. Other tests, such as computed tomography (CT) scans or ultrasounds, may be used to see 0.0 how this cancer is affecting other parts White Black Hispanic Asian/Pacific of the body, such as the spleen. Islander A bone marrow or cord blood transSource: Data from National Cancer Institute, Surveillance Epidemiology and End plant may help some CML patients. A Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004 transplant is a high-risk procedure but is the only cure for CML. Whether a pa-
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Salem Health: Cancer tient is a good candidate for a bone marrow transplant depends on the patient’s age and overall health, how the patient is responding to treatment with drugs, and how well donor cells and patient cells match. Transplants are generally more successful in younger patients and in those patients who are still in the chronic phase. Prognosis, prevention, and outcomes: There is no known way to prevent CML, though promising drugs are being tested. A bone marrow transplant is currently the only cure for CML; however, many patients can control CML with drug therapy. Outcomes for this disease depend on many factors, including age, size of spleen, and blood cell counts. The median survival rate for CML is four to six years. However, when the disease has moved into the accelerated phase, survival is usually less than one year. When this disease has moved into the blast crisis phase, survival rates drop to only a few months. Marianne M. Madsen, M.S. u For Further Information Cortes, Jorge, and Michael Deininger, eds. Chronic Myeloid Leukemia. New York: Informa Healthcare, 2007. Lackriz, Barb. Adult Leukemia: A Comprehensive Guide for Patients and Families. Cambridge, Mass.: O’Reilly, 2001. Talpaz, Moshe, and Hagop M. Kantarjian, eds. Medical Management of Chronic Myelogenous Leukemia. New York: Dekker, 1998. u
Other Resources
CMLHelp.org http://www.cmlhelp.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute Chronic Myelogenous Leukemia Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ CML See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Biological therapy; Bone marrow transplantation (BMT); 1,4-Butanediol dimethanesulfonate; Chronic lymphocytic leukemia (CLL); Computed tomography (CT) scan; Genetics of cancer; Leukapharesis; Leukemias; Myeloproliferative disorders; Tyrosine kinase inhibitors.
Cigarettes and cigars
u Cigarettes and cigars Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Smoking tobacco Definition: Cigarettes and cigars are made from dried tobacco leaves, to which manufacturers add hundreds of substances to enhance flavor and other properties. The primary difference between cigars and cigarettes is that cigars are wrapped in leaf tobacco or other substances that contain tobacco, whereas cigarettes are wrapped in paper or other substances that do not contain tobacco. Also, cigars typically do not have filters. According to the American Cancer Society, a single large cigar can contain as much tobacco as an entire pack of cigarettes. Tobacco and tobacco smoke contain more than 4,000 chemicals, of which as many as 250 are known to be toxic or carcinogenic. The composition of smoke varies depending on the product, tobacco blend, chemical additives, and other factors. Some of the toxic compounds found in tobacco smoke include ammonia, tar, cyanide, carbon monoxide, and the carcinogens benzene, aromatic amines, arsenic, and chromium. Sidestream (second-hand) smoke contains many of the same carcinogens as mainstream smoke, sometimes in higher concentrations. Because cigars contain more tobacco than cigarettes and usually burn longer, they give off more sidestream smoke with higher concentrations of carcinogens. Related cancers: Cancers of the lung, oral cavity, larynx, pharynx, esophagus, bladder, stomach Exposure routes: Inhalation is the primary route of exposure to the carcinogens found in cigarettes and cigars. Smoking tobacco produces mainstream smoke that is inhaled by the smoker. Secondhand exposure via sidestream smoke (also called secondhand smoke, passive smoke, or environmental tobacco smoke) can also occur. Cigarettes are the primary source of tobacco smoke exposure; cigars are less common. Direct exposure through the mouth, gums, and swallowed saliva can also occur during smoking. Where found: Legally sold in the form of cigarettes and cigars At risk: All users of smoking tobacco are at risk of developing cancer. As of 2007, approximately 21 percent of adults in the United States (45.3 million people) were smokers. In 2006, about 371 billion cigarettes were consumed. The use of tobacco products varies with gender, age, and racial and ethnic background. More men smoke (23.9 percent) than women (18.0 percent). Smoking is 281
Cigarettes and cigars much more common among adults ages eighteen to fortyfour (48.5 percent) and forty-five to sixty-four (21.9 percent) than among those over age sixty-five (8.6 percent). In addition, of high school students, 23 percent smoke cigarettes and 14 percent smoke cigars. Overall smoking rates are highest among American Indians and Alaska natives (32 percent), whites (21.9 percent), and blacks (21.5 percent). Each year, approximately 438,000 people in the United States die prematurely from smoking or sidestream smoke exposure; another 8.6 million suffer from smoking-related illnesses. Cancer was among the first diseases causally linked to smoking, and cigarette smoking is the primary cause of cancer mortality in the United States (responsible for at least 30 percent of all cancer deaths). It is the leading risk factor for lung cancer and causes approximately 90 percent of lung cancer deaths in men and almost 80 percent in women. Smoking light cigarettes or those with less tar does not substantially reduce lung cancer risk.
Salem Health: Cancer Inhalation of sidestream smoke also increases cancer risk. More than 126 million nonsmoking Americans, including children, are regularly exposed to secondhand smoke, and more than 3,000 nonsmoking Americans die of lung cancer each year, primarily because of exposure to sidestream smoke. Cigar smoking is a popular habit in the United States. Rates more than doubled in the 1990’s, and approximately 5.1 billion cigars were consumed in 2005. Cigar smoking is most common among men ages thirty-five to sixty-four who have higher incomes and educational backgrounds. Most new cigar users are teenagers and younger males (ages eighteen to twenty-four). In addition, in 2004, about 18 percent of students (grades six to twelve) smoked at least one cigar in the past thirty days. Etiology and symptoms of associated cancers: Toxic ingredients in cigarette smoke travel throughout the body, causing damage in several different ways. Some carcinogens in tobacco smoke produce substances called epoxides when they undergo oxidation (burning). These epoxides bind to and damage the deoxyribonucleic acid (DNA) in cells, causing them to grow abnormally or divide quickly and uncontrollably, resulting in tumor development. Although nicotine is not considered carcinogenic, it can inhibit cell death, thereby promoting tumor development. Symptoms vary with the type of cancer. History: Based on the findings of hundreds of scientific articles, the U.S. Surgeon General first reported a causal association between cigarette smoking and cancer in 1964. The health risks associated with sidestream smoke were first published by the Surgeon General in 1972. Cigarettes are subject to several state and federal regulations. The 1964 Surgeon General’s report led to laws requiring warning labels on tobacco products; however, those laws were only applied to cigars much later. Television advertising of cigarettes has been prohibited since 1971 and has since been expanded to include advertising on radio and other electronic media; these regulations do extend to cigar advertising. Cigarettes and cigars are also subject to taxes, which vary from state to state. In addition, it is currently illegal to sell tobacco products to minors, and in many states it is illegal for a minor to possess any form of tobacco. Many states also prohibit smoking in restaurants and in some public places. Jaime Stockslager Buss, M.S.P.H., ELS u
Cigarette smoking is the primary cause of cancer mortality in the United States; it is the cause of at least 30 percent of all cancer deaths. (PhotoDisc)
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For Further Information Brandt, A. M. The Cigarette Century: The Rise, Fall, and Deadly Persistence of the Product That Defined America. New York: Basic Books, 2007.
Salem Health: Cancer Lapointe, Martin M., ed. Adolescent Smoking and Health Research. New York: Nova Biomedical Books, 2008. U.S. Department of Health and Human Services. The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. Washington, D.C.: Author, 2006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Wesley, Merideth K., and Ingrid A. Sternbach, eds. Smoking and Women’s Health. New York: Nova Science, 2008. u
Other Resources
American Cancer Society Tobacco and Cancer http://www.cancer.org/docroot/PED/PED_10.asp American Lung Association What Is the Connection Between Tobacco Use and Lung Disease? http://www.lungusa.org/site/c.dvLUK9O0E/ b.4061173/apps/s/content.asp?ct=5328919 Centers for Disease Control and Prevention Smoking and Tobacco Use http://www.cdc.gov/tobacco See also Chewing tobacco; Lung cancers; Oral and oropharyngeal cancers; Smoking cessation; Tobacco-related cancers.
u Clinical breast exam (CBE) Category: Procedures Definition: A clinical breast exam (CBE) is a screening test for cancer and other breast conditions intended to detect palpable masses and other indications of possible malignancy at an early stage of progression. ACBE is done by a clinician (physician, nurse practitioner, or physician’s assistant). It includes the inspection and palpation of the axillary and supraclavicular lymph nodes and breasts for masses and tenderness, examination for skin changes of the breast, and evaluation for nipple discharge. Cancers diagnosed: Breast cancer, including cancer in the milk ducts or lobules and cancer that is invasive to surrounding breast tissue; less commonly, breast cancer may originate outside the ducts or lobules, as with inflammatory breast cancer and Paget disease of the breast.
Clinical breast exam (CBE) Why performed: Breast cancer is the most commonly diagnosed cancer in U.S. women. It is estimated that in the United States, one out of seven or eight women will develop breast cancer at some time in their lives, and early diagnosis is key to effective treatment. Breast cancer is the second leading cause of cancer death in U.S. women. In 2006, over 212,000 women in the United States were diagnosed with breast cancer. Positive findings on a clinical breast exam that may be indicative of cancer require further tests. A clinical breast examination can find cancers that are missed by mammography up to 10 percent of the time, and 5 percent of breast cancers are found by the clinical breast examination alone. Mammography is used for screening in women who are forty years and older and diagnostically in younger women who are symptomatic. Clinical breast examination has not been found to be valuable for screening younger women because of limitations posed by their denser breast tissue. Ultrasonography has been used along with clinical breast examination for screening of high-risk young women, as has magnetic resonance imaging (MRI), but this use of MRI is controversial because of its high cost. Patient preparation: Before conducting a breast examination, the clinician reviews the patient’s history and any concerns, including whether she performs breast selfexamination (BSE), any history of lumps or nipple discharge, any history of breast surgeries, and family history of breast cancer. Family medical history is most significant if a first-degree relative (or relatives) developed breast cancer while premenopausal. Some women may come for a CBE with a known high risk for breast cancer, including a diagnosis of high-risk status from genetic screening for the BRCA1 and BRCA2 genetic defects. Steps of the procedure: Before the CBE, the clinician informs the patient that many of the steps to be performed are the same ones that she can herself in a self-exam, as the best time to teach BSE is while performing an examination. Clinical breast examination begins with visual inspection of the breasts. Adequate lighting is important to distinguish subtle changes. Flexation of the pectoral muscles with the patient’s hands on her hips, followed by examination of the breasts as the patient lifts her hands high above her head, will help determine the presence of dimpling or retractions, inverted nipples, and other skin changes. Following visual examination, the lymph nodes should be palpated for any swelling, masses, or tenderness, including those above and below the clavicle and the axillary nodes. It is recommended that this be done while the patient is sitting. Following examination of the lymph nodes, 283
Clinical breast exam (CBE)
Salem Health: Cancer biopsy, mammography, and, for women younger than thirty-five years old, diagnostic breast ultrasound. Mammography can help to evaluate the need for follow-up, but accurate diagnosis of a mass requires biopsy. A biopsy may be done in the office as a needle biopsy (either fine-needle or core needle) or surgically as an excisional biopsy (lumpectomy) that is both diagnostic and may provide treatment. A fine-needle biopsy produces the fastest results, but a negative result for a needle biopsy is nondiagnostic, meaning that because of the high rate of false negatives, further surgical evaluation is needed. After the procedure: The clinician will reinforce the need for breast self-exam and, for negative examinations, discuss intervals for regular screening mammography and make referrals if necessary. If any positive findings occur, then the need for further testing is discussed. Many patients need help arranging for additional testing, and many clinician offices will assist with scheduling of appointments rather than leaving patients to coordinate care when they may be emotionally distraught by the possibility of a cancer diagnosis.
This breast exhibits the skin change known as peau d’orange, which looks like the surface of an orange with regularly spaced, shallow pitting. (©Scott Camazine/ Phototake—All rights reserved)
the patient lies supine with her arm high above her head to flatten out the breast tissue and facilitate examination. Palpation should include the full margins of the breast tissue, including the tail of Spence, the area of breast tissue that extends from the upper outer quadrant toward the axilla, which is the site where most malignancies develop. It is important that the entire breast margin be palpated with the flats of the fingers moving in dime-size circles in a systematic fashion so that no area is missed. Common areas that are missed in self and clinical breast exams include the tissue that extends up to the clavicle and the area directly underneath the nipple. Each area should be palpated using light, medium, and then firm pressure. A well-done clinical breast examination takes at least several minutes. Studies have documented increased success in finding lesions when a minimum of five minutes is spent doing an examination, although studies have also documented that many clinicians spend less than two minutes, an inadequate amount of time, examining the breasts. Patients who are not used to examinations that take longer may be anxious and require reassurance that this is being done in order to be thorough, not as a result of suspicious findings. When a new breast lump is detected in a patient who is premenopausal, she will often be counseled to wait through one menstrual cycle and then return to the clinic for evaluation. In many cases, the lumps are benign and will spontaneously resolve. If a lump persists, the patient is referred to a breast surgeon who will evaluate the lump using 284
Risks: Clinical breast examinations are associated with no direct physical risk. False negative results, however, can be misleading and delay diagnosis, while false positive results are very common and can result in invasive testing and significant emotional distress and anxiety as well as expense. Results: The results of a clinical breast examination may be negative (no findings), in which case no action other than continuation of regular clinical screening and breast self-examination is warranted. Findings that are positive may include a discrete mass, a thickened area, breast tenderness or pain, nipple discharge, and skin changes. Discrete masses may be fixed or mobile and tender or nontender, and they may be in the breast tissue itself or in the axillary lymph nodes. They are carefully described as to shape, size, and location in the breast, including depth. A thickened area of breast tissue may be detected bilaterally (in both breasts) or unilaterally (in one breast only). It will be evaluated further but is less likely than a discrete mass to be a cause for concern. Breast tenderness may be bilateral or unilateral. It may
Salem Health: Cancer be hormonal and vary over the course of a month, but if associated with skin changes it can be related to infection or possible malignancy. Breast tenderness is common with some hormonal contraception and with pregnancy. Episodic sharp breast pain has been found to be responsive, in many cases, to a decrease in caffeine intake. Nipple discharge may be bilateral or unilateral and may be clear, reddish or bloody, milky, or greenish. It may occur spontaneously or only with manual expression. It may or may not have an odor. History of recent pregnancy as well as some medications (in particular, many antipsychotics) may cause a bilateral, nonsticky milky discharge called galactorrhea. Bilateral discharge is usually benign. Secretions may be collected on a slide and examined under a microscope to help determine the need for further evaluation, including mammography, other imaging methodologies, and biopsy. Skin changes may include uneven fullness or flattening, asymmetry that was not previously present, rashes and discoloration, areas of warmth and redness, retraction or dimpling of the skin, inversion of the nipple, crusting and erosion or ulceration of the nipple and areola, and the skin change described as peau d’orange, which looks like the surface of an orange with regularly spaced, shallow pitting. Skin changes are particularly associated with inflammatory breast cancer, which may cause red and swollen skin and a peau d’orange appearance, and Paget disease, which may cause an eroded and/or retracted nipple. Nipple inversion is of clinical concern only if it has not been present previously. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP) u
For Further Information Fenton, J. J., et al. “Specificity of Clinical Breast Examination in Community Practice.” Society of General Internal Medicine 22 (January 9, 2007): 332-337. Grobstein, Ruth H. The Breast Cancer Book: What You Need to Know to Make Informed Decisions. New Haven, Conn.: Yale University Press, 2005. Knutson, D., and E. Steiner. “Screening for Breast Cancer: Current Recommendations and Future Directions.” American Family Physician 75, no. 11 (June 1, 2007): 1660-1666. McDonald, S., D. Saslow, and M. H. Alciati. “Performance and Reporting of Clinical Breast Examination: A Review of the Literature.” CA: A Cancer Journal for Clinicians 54 (2004): 345-361. Weiss, N. S. “Breast Cancer Mortality in Relation to Clinical Breast Examination and Breast Self-Evaluation.” Breast Journal 9, suppl. 2 (May/June, 2003): S86-S89.
Clinical trials u
Other Resources
American Cancer Society Detailed Guide: Breast Cancer—Can Breast Cancer Be Found Early? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_3X_Can_breast_cancer_be_found_early_5 .asp?sitearea= Susan G. Komen Foundation http://cms.komen.org See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Breast self-examination (BSE); Calcifications of the breast; Mammography; Needle biopsies; Nipple discharge; Palpation; Screening for cancer.
u Clinical trials Category: Medical specialties Also known as: Clinical studies, clinical research studies, clinical investigational studies Definition: According to the U.S. Food and Drug Administration (FDA), a clinical trial is the systematic investigation of the impact of materials (such as investigational drugs and medical devices) or methods (such as surgery and radiation) on a disease state, conducted according to a formal trial protocol. The main objective of a clinical trial is evaluating the safety and efficacy of new materials or new methods in humans before approving these materials or methods for commercial use. To ensure the safety of all involved, clinical trials are strictly regulated by the FDA. The trial design can be controlled or uncontrolled, randomized or nonrandomized, and nonblinded, singleblinded, or double-blinded. Controlled means that the group receiving the new treatment is compared with a control group, whose members can be receiving a placebo, a different dose, no treatment, or standard-of-care treatment, or be historical subjects. Randomized means that patients who are selected to take part in a specific trial are randomly assigned to either the treatment or the control group. Single-blinded means that only the investigator, not the patient, knows whether the patient is in the treatment or control group. Double-blinded means that neither the investigator nor the patient knows to which group the patient has been assigned. FDA-regulated clinical trials are prospective, meaning that clinical data are collected forward according to a trial plan, in contrast to retrospective studies, where clinical data are retrieved from existing 285
Clinical trials sources, such as medical charts. Controlled, randomized, double-blind trials have the strongest scientific value. Starting a clinical trial has to be approved by the FDA and the Institutional Review Board after thorough scientific and ethical review of the mandatory regulatory documents (namely, investigational new drug application or investigational device exemption) for the new drug or medical device submitted by the clinical trial sponsor, which is normally a pharmaceutical or medical device company. Also, conducting, monitoring, inspecting, recording, and analyzing a clinical trial must be based on national FDA regulations and the International Conference on Harmonisation’s Good Clinical Practice (ICH-GCP) guidelines to ensure proper ethical conduct of a clinical trial (such as voluntariness of participation). Participants in a clinical trial are either healthy subjects (also called probands) or subjects with a specific target disease (such as breast or prostate cancer) and the clinical trial team, consisting of the (principal) trial investigators, the trial coordinator, and other health care professionals. For any drug, multiple trials in three phases must be conducted. In phase I trials, normally healthy subjects are involved, and these trials mainly focus on the trial’s feasibility. In addition, pharmacokinetic and pharmacodynamic data on the new drug are collected, and the maximal tolerable dose is determined (therefore, phase I trials are also called dose-finding trials). Phase I trials are usually shortterm (two weeks or less) and limited to ten or fewer individuals. Phase II trials are conducted to confirm the effective dose and regimen of the investigational new drug and to provide early efficacy and safety information. These trials are usually short-term (two months or less) and include approximately fifty to three hundred subjects with the primary target disease. Phase III trials normally include patients with the primary disease but also allow for associated conditions. These trials are normally longer-term and involve one hundred to thousands of patients, depending on the target disease. The goals of these trials are to determine efficacy for the main indication (such as breast cancer), the rates of adverse events (side effects), and, for drugs, the optimal dose. Phase IV trials, also called postmarketing trials, are conducted according to the product label in a very large patient population after FDA approval of the new drug, medical device, or method. The goal of these trials is normally further therapy optimization. Cancers addressed: Clinical trials are offered for patients with many kinds of cancers to evaluate new treatment options or altered treatment options or new indications for existing cancer therapies. 286
Salem Health: Cancer Training and certification: The required qualification and obligations of a clinical investigator to conduct a clinical trial are outlined in the regulations of the Food and Drug Administration and the Good Clinical Practice (GCP) guidelines. According to these regulations and guidelines, the principal clinical investigator (PI) of a clinical trial must, for example, submit a detailed curriculum vitae showing that the person is qualified by training and experience to investigate a new drug or method. The person should have at least two years’ experience in conducting clinical trials. The PI is trained in detail about the new drug or method before the beginning of a clinical trial. This training is provided by the clinical trial sponsor, which is normally a pharmaceutical company developing the drug. The training includes reviewing the clinical investigator’s brochure, a document prepared by the trial sponsor and containing all known relevant information on the investigational product, including preclinical, pharmacokinetic, and pharmacodynamic data in animals and in humans as well as data from earlier clinical trials. The training also includes how to properly report potential side effects in the patients according to the regulatory requirements. In addition, the PI has to train the trial team (trial coordinator, coinvestigators, and others) on the investigational product, including its proper use or administration according to the trial protocol, which must be strictly followed. Services and procedures performed: Participants in a clinical trial can possibly benefit from being treated with an investigational new drug or method or a commercially available drug used for a new indication, particularly if standard treatments are not effective or do not exist for the patient’s disease. Patients do not have to pay for the new treatment, and their overall health is generally more closely and thoroughly monitored than in nontrial settings. However, the new treatment is not guaranteed to work, and patients’ health may deteriorate during or after completion of the clinical trial. Also, patients may be part of the control group and not receive the new drug. Before patients can be included in a clinical trial, the investigator has to make sure that they meet strict inclusion criteria that have been outlined in the clinical protocol. If a patient meets all inclusion criteria and none of the exclusion criteria, the person must be thoroughly informed about the trial, and all questions must be answered satisfactorily. The investigator has to make sure that the patient has understood all benefits and potential risks involved with the trial, as well as the procedures performed at each trial visit and the patient’s obligation to complete the trial visits and to comply with all instructions given by the
Salem Health: Cancer investigator. The patient must also understand the alternative treatment options. Then, if the patient is still willing to participate in the trial, the individual has to sign and date a patient consent form stating that participation in the clinical trial is voluntary and that the patient can withdraw at any time without compromising the standard care to which the patient is otherwise entitled. The patient consent form must have been previously approved by an investigational review board (IRB), an independent group of medical and nonmedical professionals whose goal is to ensure that the clinical trial is performed safely, with integrity, and with respect to the rights of the participating subjects. After signing the informed consent, patients will be screened to ensure they are eligible for the trial. Screening visits generally include taking an anamnesis (a case history), performing a physical exam and lab tests, and documenting all medications the patient is currently taking. After the screening visit, eligible patients are randomly assigned to either the treatment or the control group, if the design of the trial requires patient randomization. After performing the trial procedure, which can include, for example, taking a specific investigational new drug or undergoing a surgical procedure, the patient will be closely monitored during the subsequent, predefined follow-up visits. Depending on the protocol, the patient procedures during these visits may include another physical exam, lab tests, an electrocardiograph (ECG), filling out questionnaires, and the recording of all side effects that may have occurred since the last visit, whether they may be associated with the trial treatment or not. All patient data collected are documented on case report forms by the clinical trial personnel. If any serious side effects occur between trial visits, the patient must inform the trial personnel immediately, seek immediate medical help, or both. The investigator’s responsibility is to report immediately any serious side effects (those that are life-threatening, lead to hospitalization, or are fatal) to the trial sponsor, which will take all required actions. All patient personal data are encoded before transferring them to any third party so the patients’ identities are concealed. After completion of an individual trial, which can take weeks or years depending on the trial phase and design, the trial data are analyzed, typically by the trial sponsor. The outcome of the analysis may influence the design of the next trial phase. The trial results may be published in a scientific journal. In many cases, however, analyses are performed at predetermined times during a clinical trial, which may lead to continuation or discontinuation of the trial (for example, if the trial results show a significant benefit). Use of so-called open-label trials after phase III
Clinical trials trials is relatively common. They typically follow a doubleblind, randomized, placebo-controlled trial of a new drug, and patients may be invited to enroll because this kind of trial allows gathering of further data about safety and tolerability of the new drug or device in long-term, day-today use. Treatment schedules, drug treatment, and doses are known to both the investigator and the patient in these trials. To apply for marketing approval of a new drug (or medical device) that has been tested in clinical trials, the sponsor must prepare a new drug application (NDA) or a corresponding marketing application for the medical device for submission to the FDA. This document contains all information on preclinical and clinical trials, as well as other knowledge about the drug or device. The FDA’s review of a standard new drug application typically takes just over a year. Silke Haidekker, Ph.D. u
For Further Information Blichert-Toft, M., H. Mouridsen, and K. W. Andersen. “Clinical Trials.” International Seminars in Surgical Oncology 12 (1996): 32-38. Friedman, L. M., C. D. Furberg, and D. L. DeMets. Fundamentals of Clinical Trials. 3d ed. New York: Springer, 1998. Jenkins, V., and L. Fallowfield. “Reasons for Accepting or Declining to Participate in Randomized Clinical Trials for Cancer Therapy.” British Journal of Cancer 82 (2000): 1783-1788. Olver I., et al. “The Adequacy of Consent Forms for Informing Patients Entering Oncological Clinical Trials.” Annals of Oncology 6 (1995): 867-870. Thornton, H. “Clinical Trials: A Brave New Partnership.” Journal of Medical Ethics 20 (1994): 3-4. Verheggen, F., R. Jonkers, and G. Kok. “Patients’ Perceptions on Informed Consent and the Quality of Information Disclosure in Clinical Trials.” Patient Education and Counseling 29 (1996): 137-153.
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Organizations and Professional Societies
Association of Clinical Research Professionals http://www.acrpnet.org 500 Montgomery Street, Suite 800 Alexandria, VA 22314 Society of Clinical Research Associates http://www.socra.org 530 West Butler Avenue, Suite 109 Chalfont, PA 18914 287
Coal tars and coal tar pitches u
Other Resources
Abramson Cancer Center of the University of Pennsylvania Oncolink/Emerging Med Cancer Clinical Trials Matching Service http://www.oncolink.com/treatment/matching.cfm CenterWatch Clinical Trial Listings Service http://www.centerwatch.com International Conference on Harmonisation of Technical Requirement for Registration of Pharmaceuticals for Human Use http://www.ich.org/cache/compo/276-254-1.html National Cancer Institute Finding Clinical Trials http://www.cancer.gov/clinical_trials U.S. Food and Drug Administration http://www.fda.gov See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Chemoprevention; Chemotherapy; Complementary and alternative therapies; Dana-Farber Cancer Institute; Dietary supplements; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Informed consent; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Medical oncology; Medicare and cancer; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Coal tars and coal tar pitches Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Coal tar pitch volatiles (CTPVs) Related cancers: Skin cancer, scrotal cancer, lung cancer, bladder cancer, kidney cancer, leukemia, digestive tract cancers including the esophagus, as well as cancers of the oral cavity and larynx Definition: Coal tar is a product of bituminous coal distillation and is composed mainly of aromatic hydrocarbons. 288
Salem Health: Cancer Coal tar pitch is the residue produced by the distillation or heat treatment of coal tar. Continued distillation of the coal tar yields a variety of products, including benzene, toluene, xylene, naphthalene, anthracene, acridine, benzopyrene, chrysene, pyrene, and phenanthrene. The many coal tar distillates are central to the synthesis of dyes, drugs, explosives, flavorings, perfumes, preservatives, synthetic resins, paints, and stains. The remaining pitch left after distillation finds uses in paving, roofing, waterproofing, and insulation materials. Exposure routes: Inhalation, ingestion, skin contact Where found: Pesticides, roofing materials, pipe coatings, enamels, plastics, dyestuffs, synthetic fibers, synthetic rubbers, varnishes, paints, electrodes, binders used in aluminum smelting, epoxy resins, denatured alcohol, carbon brushes, graphites, road-paving materials, naphthalene, pharmaceuticals, high-temperature-resistant materials At risk: Those at risk include workers exposed to coal tars or coal tar pitches. Additionally, patients using therapeutic levels of coal tar preparations may be at risk for skin cancer. Especially vulnerable are workers exposed to coal tar fumes found in coal gasification and coke production. Etiology and symptoms of associated cancers: Coal tars and coal tar pitches contain several carcinogens, which include such known offenders as benzene and naphthalene. The resulting cancers include skin cancer (notably scrotal cancer), digestive tract cancers, lung cancer, bladder and kidney cancers, and leukemia. The cancer type is often associated with the workers’ exposure. For example, millwrights and welders are prone to digestive tract cancers and leukemia, while workers exposed to tar distillates show an increased risk of bladder cancer, and rates of kidney cancer climb with exposure to petroleum or coal tar pitches. History: Since 1775, when scrotal cancer was first described in chimney sweeps, industrial exposure to coal tar has been targeted as an important carcinogen. From coal tar pitch volatiles at coke ovens to pharmaceuticals used in the home, the carcinogenic potential is fully recognized. Richard S. Spira, D.V.M. See also Air pollution; Carcinogens, known; Carcinogens, reasonably anticipated; Coke oven emissions; Melanomas; Photodynamic therapy (PDT); Polycyclic aromatic hydrocarbons.
Salem Health: Cancer
u Cobalt 60 radiation
Coenzyme Q10
Category: Procedures
shrink or eliminate a tumor, then success is determined by the presence or absence and size of the tumor. Robert Bockstiegel, B.S.
Definition: Cobalt 60 is a radioactive isotope that is used to provide radiation therapy during cancer treatment.
See also External beam radiation therapy (EBRT); Gamma Knife; Radiation oncology; Radiation therapies.
Cancers treated: Many cancers, including breast, bladder, oral, and brain cancers Why performed: Cobalt 60 radiation is used to shrink or destroy tumors or to kill residual cancer cells left after surgical removal of a tumor. Patient preparation: Patient preparation will vary depending on the type of radiation therapy being administered and the type and location of the cancer. Before therapy is begun, the doctor works with other members of the cancer care team to develop a plan that will provide the maximum dose of radiation to the tumor or cancerous area while creating as little harm as possible to healthy cells in the surrounding area. Steps of the procedure: Cobalt 60 radiation can be administered in many ways. One way is to use a machine to aim the beam of radiation at the desired area from outside the body. Cobalt 60 can also be administered internally. Small capsules containing cobalt 60 can be inserted into the desired area to release radiation at close range. A device known as a Gamma Knife is a machine that uses 201 separate, stationary beams of cobalt 60 radiation to treat cancers that occur in the brain. After the procedure: Aftercare varies depending on the type of therapy performed. For most uses of cobalt 60, no specific aftercare is required unless the patient experiences significant side effects. Risks: The risks of cobalt 60 radiation vary depending on the type of radiation treatment being done, the strength of the radiation dose, the length and frequency of treatment, and the area of the body being targeted. Side effects of cobalt 60 radiation can include fatigue and nausea. If the radiation is delivered from an external source, then the patient may experience skin redness, tenderness, peeling, or discoloration. If the radiation is delivered internally, then there may be soreness around the cite of the delivery device(s). Results: The way in which success is determined when cobalt 60 is administered depends on the goal of the treatment. If the goal was to eliminate residual cancer cells, such as after surgical tumor removal, then the treatment is usually considered a success if the cancer does not return for five or more years. If the goal of the procedure was to
u Coenzyme Q10 Category: Lifestyle and prevention; complementary and alternative therapies Also known as: Co Q 10, ubiquinone, vitamin Q 10 Definition: Coenzyme Q10 is a fat-soluble vitamin or vitamin-like substance sometimes used in cancer treatment and prevention. A vitamin is an organic compound needed in very small amounts for the body to function normally. Vitamins serve as coenzymes or precursors to coenzymes that are normally present in food or may sometimes be generated in the body. Coenzyme Q10 is produced in all bodily tissues and is present in tiny quantities in food. Coenzyme Q10 has been shown to significantly reduce the cardiotoxicity of cancer chemotherapy drugs such as Adriamycin (doxorubicin). Studies of coenzyme Q10 used as an adjuvant to boost therapeutic outcome following standard treatment for breast cancer showed good results in a small number of patients; the studies, however, were neither randomized nor controlled. Cancers treated or prevented: All, particularly breast cancer Delivery routes: Orally as a pill (capsule or tablet) or intravenously (IV injection), the latter in animal studies How this substance works: Coenzyme Q10 was first isolated from beef heart mitochondria (energy-producing structures in the cell) by Dr. Frederick Crane in 1957. A year later, Karl Folkers determined the exact structure of coenzyme Q10. Coenzymes are cofactors upon which the relatively large and complex enzymes absolutely depend in order to function. Coenzyme Q10 acts as a coenzyme for at least three mitochondrial enzymes in addition to enzymes in other areas of the cell. Mitochondrial enzymes are crucial for the production of high-energy adenosine triphosphate (ATP), upon which all cellular activities depend; coenzyme Q10 acts as a coenzyme for several of the key enzymatic energy-generating steps in the cell. It also serves as an antioxidant vital to its clinical effects. Studies in animals found that coenzyme Q10 boosts the immune system and may be helpful in fighting certain infections and cancer. Since some conventional cancer therapies 289
Cognitive effects of cancer and chemotherapy such as drugs and radiation therapy destroy cancer cells by producing free radicals, researchers are trying to find out whether coenzyme Q10 in conjunction with traditional cancer treatments may affect the outcome. Side effects: While no serious side effects have been reported with coenzyme Q10 usage, the most frequently reported side effects include insomnia, higher-than-usual levels of liver enzymes, upper abdomenal pain, sensitivity to light, irritability, headache, dizziness, heartburn, and extreme fatigue. It should be kept in mind that coenzyme Q10 is a dietary supplement; it has not been approved for use as a cancer treatment by the Food and Drug Administration (FDA) and is regulated not as a drug but as a food. Cynthia Racer, M.A., M.P.H. See also Anthraquinones; Antioxidants.
u Cognitive effects of cancer and
chemotherapy Category: Social and personal issues Definition: Cancerous brain tumors often lead to neurological problems such as difficulties with memory, attention span, speed of mental processing, and reasoning skills. Chemotherapy for all types of cancer also can cause deficits in normal, healthy cognitive functioning. The drugs used can interfere with mental processing and produce what some refer to as “chemobrain” or “chemofog,” but the problems typically subside shortly after the treatment is terminated. However, for some individuals, the difficulties will remain for months or even years after chemotherapy has ended. Diagnosing cognitive deficits: Cognitive functioning refers to a host of processes that are performed by the brain that allow people to adapt to their environment and make informed judgments. Cognitive skills refer to the ability to attend to and concentrate on one or more tasks at the same time, to initiate and plan future actions, to engage in verbal or written language, and to have the ability to learn and recall information. All of these skills help people cope in a complex world. When one or more of these processes are short-circuited, mild or even devastating consequences can ensue. People with cognitive problems are likely to find it difficult to return to work or school and to function as well as they did in the past. In more severe cases, people might find it difficult to fully manage their normal daily activities. Their ability to maintain social relationships, to man290
Salem Health: Cancer age a household, and to monitor their own self-care during treatment can be significantly diminished. Because healthy cognitive functioning is so important, any dysfunction regarding cognitive processes brought on by cancer directly or due to chemotherapy must be diagnosed, assessed, and followed closely. The preponderance of evidence reveals that chemotherapy in standard-dose ranges can bring on cognitive impairments in approximately 20 percent of cancer patients. If high-dose treatments are used, research has shown that there is a significantly greater likelihood that normal functioning will be adversely affected. Neuropsychological testing with instruments such as the Halstead-Reitan Neuropsychological Battery, the Mini-Mental Status Exam, and the Weschler Adult Intelligence Scale is commonly done to diagnose and assess cognitive problems. These tests are crucial not only for providing an initial benchmark regarding how well an individual is functioning but also for long-term tracking of cognitive performance during and after cancer treatment. Behavioral symptoms: Patients undergoing chemotherapy often report that their ability to think is clouded and that they feel as if their heads are in a fog. Their ability to think and process information efficiently seems slowed and compromised. Neurological and neuropsychological testing reveals that some chemotherapy patients will have difficulty concentrating or paying attention. For others, the primary cognitive deficits emerge in terms of memory processing. Although long-term memory appears to be spared, short-term memory, including the manipulation of concepts that are present in the immediate consciousness, can be severely affected. Problems with comprehension, combined with language difficulties, can make it very difficult for a person to engage in multitasking, an ability that is very important for adequate functioning in the workplace or in school. Almost any combination of cognitive symptoms can result in problems with decision making and reasoning. Fortunately, the cognitive symptoms experienced by most cancer patients are usually mild to moderate. Although the literature contains reports of severe cases of delirium (mental confusion) due in part to chemotherapy, these instances are rare. In addition, in the vast majority of people with deficits brought on by cancer-fighting drugs, particularly adults, the chemo-induced cognitive problems are usually transient. Young children undergoing chemotherapy are more susceptible to long-term cognitive deficits. This is most likely because their central nervous systems are still immature and the drugs are affecting the development of
Salem Health: Cancer critical brain structures that are involved in mental processing. Long-term consequences for young children include an increased risk for developing a learning disability or attention-deficit disability, a general lowering of the intelligence quotient, and overall lowering of academic success in school. Possible causes and mechanisms involved: Although numerous studies have been conducted on the effects of chemotherapy agents on cognitive functioning, relatively little is known about the specific mechanisms that create the deficits. It is known that most chemotherapy drugs do not easily cross the blood-brain barrier. This protective barrier controls the types of substances that can leave the blood supply and enter the central nervous system. Because most chemotherapy drugs have difficulty crossing the barrier, they appear to exert their effect on the brain by influencing multiple secondary mechanisms that ultimately produce cognitive impairments. Several chemotherapy agents have been implicated in a neurological impairment called leukoencephalopathy, which is characterized by profound changes in the brain’s white matter. This condition could be caused by drugs coming into contact with the brain’s glial cells, which form the protective myelin sheath that covers some neurons. If the drugs are toxic to the glial cells, resulting in cell death, this could lead to abnormal neural signaling and ultimately influence cognitive processing. Another possible mechanism could be chemotherapy-induced anemia, which has long been associated with poor mental functioning, as is the case with vascular dementia. When the brain is not getting enough oxygen, it can result in deficiencies in alertness, attention, concentration, and memory. Brain tumors can lead to deleterious effects on cognition through several mechanisms. First, as brain tumors begin to grow, they can displace healthy structures adjacent to the cancer and alter the functional properties of neurons. Typically, as the tumor grows, more and more healthy tissue will be displaced, leading to more cognitive deficits. One explanation for the problems that develop is that the tumor growth squeezes adjacent structures to the point that the brain tissue that makes up the structure is no longer able to function normally. If this squeezing occurs over a long period of time, it could result in massive cell destruction, leading to permanent cognitive impairment. Management and treatment: Usually, chemotherapyinduced cognitive deficits begin to subside shortly after treatment has ended. If the deficits do not go away, there are ways to manage the impairments. Neurocognitiveenhancing drugs can be prescribed to help counteract whatever mechanisms might be involved in maintain-
Cognitive effects of cancer and chemotherapy ing the cognitive deficiencies. Behavioral stimulants, such as methylphenidate, commonly used in children with attention-deficient disorder, have been found to increase alertness, concentration, and energy levels in adults who have suffered from cognitive problems brought on by chemotherapy. Another treatment alternative involves cognitive rehabilitation therapy. This form of therapy targets specific areas of need, such as multitasking, organizational skills, or short-term memory, and teaches patients to practice mental exercises that force them to use their brains in a way that strengthens these areas. In some instances, patients are able to develop new coping strategies that compensate for cognitive processes that have become compromised. Bryan C. Auday, Ph.D. u
For Further Information Corrigan, Patricia, Humberto Fagundes, and Alan P. Lyss. Chemotherapy and Radiation for Dummies. Hoboken, N.J.: John Wiley & Sons, 2005. Kelvin, Joanne F., and Leslie Tyson. One Hundred Questions and Answers About Cancer Symptoms and Cancer Treatment Side Effects. Sudbury, Mass.: Jones and Bartlett, 2005. Magee, Sherri, and Kathy Scalzo. Picking Up the Pieces: Moving Forward After Surviving Cancer. Piscataway, N.J.: Rutgers University Press, 2007. Perry, Michael C., and James E. Wooldridge. Companion Handbook to the Chemotherapy Source Book. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2004.
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Other Resources
Cancer Symptoms.org Cognitive Dysfunction http://www.cancersymptoms.org/ cognitivedysfunction Cancer.Net http://www.cancer.net/portal/site/patient National Cancer Institute http://www.cancer.gov See also Anxiety; Brain and central nervous system cancers; Depression; Elderly and cancer; Leukoencephalopathy; Living with cancer; Neurologic oncology; Omega-3 fatty acids; Opioids; Personality and cancer; Psychooncology; Psychosocial aspects of cancer. 291
Coke oven emissions
u Coke oven emissions Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1981 Also known as: 3,4- benzopyrene, benzanthracene, chrysene, phenanthrene, benzene, toluene, and xyglenes Related cancers: Respiratory cancers including tracheal, bronchial, and lung cancers as well as cancers of the skin, prostate, scrotum, large intestine, pancreas, bladder, and kidneys Definition: Coke oven emissions are produced when bituminous coals are heated in the absence of oxygen to produce coke, tars, and light oils. Roughly 60 percent of the coal is converted to coke; the remainder is emitted in the form of by-products including light oils and gases and vapors of methane, ethane, ethylene, propylene, formaldehyde, ammonia, nitrogen oxides, cadmium, arsenic, and carbon monoxide. Tar acids, naphthalene, creosote, and pyridine are also emitted as coke oven gas tar. These various gases and vapors fall under the category of coke oven emissions and are the source of concern as potential carcinogens. Exposure routes: Inhalation, dermal contact Where found: Coke oven emissions occur when coal is processed to produce coke, or when the coke is combusted as fuel for making steel and processing ores, and in the manufacturing of substances such as graphite products. At risk: Workers in coke oven plants that produce coke from coal, at coal tar plants, and in the aluminum, steel, graphite, electrical, and construction industries are especially at risk. Residents in the immediate vicinity of cokeproducing plants and coal tar industries are also at risk of higher-than-normal exposure to vapors and gases. Etiology and symptoms of associated cancers: Coke oven emissions are related to respiratory cancers that can develop from inhalation or ingestion of toxic substances. These cancers typically interfere with speaking and breathing and often affect taste and smell. Skin cancer may result from dermal contact with toxic substances and is characterized by a tumor on or just below the skin surface, which may become red and irritated. Cancers of the prostate, scrotum, pancreas, bladder, kidney, and large intestine can develop if toxic substances are ingested and pass through the blood or urinary system. They may affect urine flow, frequency, and strength or may disable ejaculation. Pancreatic, kidney, and intestinal cancer can cause extreme abdominal discomfort as well as hinder the digestion and blood-cleansing processes. 292
Salem Health: Cancer History: Coke, or pure carbon, is used as a fuel reductant in the manufacture or synthesis of steel, iron, calcium carbide, graphite, and electrodes. The chemicals given off as coke oven emissions can be used in making plastics, solvents, dyes, drugs, paints, roads, roofing, insulation, pesticides, and sealants. Coke production in the United States began to decrease around 1950 because of a seemingly strong relationship between exposure to coke oven emissions and cancer rates. A number of studies conducted in the United States, Japan, Sweden, and the United Kingdom have produced significant evidence linking coke oven emissions with increased cancer rates among coke oven workers, especially cancers of the skin, lungs, and prostate. One study with 15,818 cohorts showed that occupational exposure to coke oven emissions was associated with significant excess mortality from cancer of the respiratory system and of the prostate. Another study found higher rates of lung cancer among topside coke oven workers and among those working near the tops, or lids, of the ovens, where exposure rates were greatest. Additional studies have shown significant links between exposure to coke oven emissions and incidence rates of malignant skin tumors and kidney, large intestine, and pancreatic cancers. Because of the studies confirming the relationships between coke oven emissions and cancers, numerous safety regulations are in place, including limitations on exposure levels to coke oven emissions and the use of respirators and protective clothing for coke oven workers. Still, use of coke as a fuel remains high in certain industries. Regulations require that coke oven emissions be collected, but structural defects, including loose-fitting doors and lids on coke ovens and poor engineering controls, result in continued release of varying amounts of potentially carcinogenic coke oven gases and vapors. Dwight G. Smith, Ph.D. See also Air pollution; Benzene; Coal tars and coal tar pitches.
u Cold nodule Category: Diseases, symptoms, and conditions Also known as: Hypofunctioning thyroid nodule Related conditions: Thyroid cancer, Hashimoto or de Quervain’s thyroiditis Definition: A cold or hypofunctioning nodule is a focal area of decreased uptake of radiotracer on a nuclear medicine thyroid scan that may correlate with a thyroid nodule
Salem Health: Cancer
Colectomy
felt on routine physical examination of the thyroid gland performed by a doctor.
u Colectomy
Risk factors: The risk factors for a cold nodule are the same as those for thyroid cancer, including previous radiation to the neck area as therapy for acne or for enlarged tonsillar tissue, a family history of thyroid cancer, and exposure to radioiodine in childhood.
Category: Procedures Also known as: Colon resection, large bowel resection, large intestine surgery
Etiology and the disease process: About 80 to 90 percent of solitary thyroid nodules are hypofunctioning. Although malignant thyroid tumors do not concentrate radioisotopes well and can therefore manifest as cold thyroid nodules, only about 10 to 20 percent of cold thyroid nodules occurring in young patients and about 5 percent of cold nodules occurring in adult patients are malignant. The remainder consist of cysts, inflammatory nodules of either Hashimoto or de Quervain’s thyroiditis, hemorrhagic benign nodules, or degenerative nodules. Incidence: The annual incidence of cold thyroid nodules in the general population is 5.2 per 100,000 young people and 55.9 per 100,000 adults. Symptoms: Symptoms include enlargement of the thyroid gland or a palpable lump or nodule within the gland. Physical findings suggestive of a malignant nodule in the thyroid include lymphadenopathy in the neck, size of the nodule, fixation to adjacent structures, or tracheal deviation. Screening and diagnosis: A cold nodule on a nuclear medicine scan may be composed of solid or cystic material or a combination of both as shown by thyroid ultrasound. Ultrasound is not especially useful for differentiating benign from malignant nodules of the thyroid unless multiple tiny echogenic foci are seen throughout the nodule, suggestive of microcalcifications. However, it is useful in guiding fine needle aspiration of the nodule. Neither computed tomography (CT) nor magnetic resonance imaging (MRI) helps distinguish benign from malignant thyroid nodules unless there is cervical adenopathy or local invasion. Treatment and therapy: Biopsy of the nodule is usually recommended using fine needle aspiration under ultrasound guidance to obtain tissue for pathologic evaluation. If the pathology from the biopsy shows malignant cells, then surgical removal of the nodule is warranted. Prognosis, prevention, and outcomes: If the nodule is benign, the prognosis is excellent. If the nodule is found to contain cancerous cells, then the prognosis depends on the stage and type of thyroid cancer found at surgery. Debra B. Kessler, M.D., Ph.D. See also Thyroid nuclear medicine scan.
Definition: Colectomy is the surgical removal of part or all of the colon. Either the two remaining ends of the bowel are connected (anastomosis) or the lower end is sealed and the upper end is rerouted to a new opening (ostomy) in the abdomen, forming a stoma. The ostomy may be temporary or permanent. Cancers treated: Colon cancer Why performed: For patients at high risk for colon cancer, colectomy is performed to remove precancerous lesions or to prophylatically remove the entire colon, thereby preventing the disease. For patients with colon cancer, colectomy is performed to remove the diseased colon segment with a margin of healthy tissue and all draining lymph nodes, as well as other lesions and involved structures, thereby curing or controlling the disease. For patients with advanced colon cancer, colectomy is performed to manage obstructions, perforations, hemorrhages, or other symptoms. Patient preparation: Medical tests are completed to plan effective treatment and to evaluate the patient’s fitness for major surgery. If an ostomy is needed, then a specialist counsels the patient and helps choose the location for the stoma. For the colectomy, certain patient medications may need to be stopped, the patient’s bowel must be cleaned, and the patient’s stomach must be emptied. In an emergency, patient evaluation and preparation may be limited. If the patient’s colon is partially obstructed, then the obstruction is relieved before the colectomy. If the patient’s colon is completely obstructed, perforated, or bleeding profusely, then the bowel cannot be prepared, and emergency surgery (colectomy or an alternative) is performed once the patient is stabilized. Steps of the procedure: Colectomy is performed in an hospital. Before the surgery, sensors are placed to monitor the patient’s condition. An intravenous (IV) line is started, and an antibiotic is infused. General anesthetic is administered, and a breathing tube is placed. The patient is positioned, a urinary catheter is inserted, and the incision site is prepared. Colectomy has four steps: opening and evaluation, tissue removal, anastomosis or stoma formation, and inspection and closure. Details vary with the part(s) of the colon involved (ascending, transverse, descending, or sigmoid); 293
Coloanal anastomosis
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why the colectomy is needed (prevention, cure/control, or relief); and the surgical approach chosen (open or laparoscopic). In an emergency, these steps may be reordered or performed as separate procedures. To begin, the surgeon opens the abdomen with one large incision; four to five small incisions, when using a laparoscope; or a combination of these approaches. Within the abdomen, the surgeon looks for cancer and other abnormalities, then evaluates the colon segment to be removed. If the colon segment cannot be removed safely, then a bypass procedure is performed instead. If the colon segment is removable, then the colectomy continues. To remove tissue, first the major blood vessels to that colon segment are tied. The colon segment is freed from attachments. The mesentery for that colon segment is clamped and divided; the tied blood vessels are divided and sealed; and then that colon segment is divided and removed, as well as any adjacent tissues that are diseased. All tissues are taken to the laboratory for histopathologic evaluation. Either the remaining ends of the bowel are connected, forming an anastomosis (colo-colo, colo-rectal, or coloanal), or the lower end is sealed and the upper end is rerouted. When rerouting, first an ostomy opening is made in the abdomen. The upper end is passed through the ostomy opening; the bowel segment is sized to an appropriate length; and the edge of the cut end is folded back and stitched to the abdomen, forming a stoma. Finally, the inside of the abdomen is inspected and cleaned, and the incision is closed.
bleeding, perforation, abscess, fecal contamination, incisional hernia, bowel obstructions, and peritoneal seeding.
After the procedure: Anesthesia is stopped, and the breathing tube is removed. The urinary catheter and the IV line are kept. If an ostomy was needed, then a clear collection pouch (ostomy appliance) is fitted over the stoma. The patient is transferred to the recovery room and then to a hospital room. Medications are given to control pain and infection. The patient slowly progresses to a normal diet and learns to regulate bowel function. If an ostomy was needed, then it is monitored; once the stoma starts functioning, the patient learns to care for it and to empty and change pouches. At home, the patient follows the physician’s instructions about medications, activities, and diet. Additional treatment with radiation therapy, chemotherapy, or both may be recommended.
See also APC gene testing; Colorectal cancer; Colostomy; Gardner syndrome; Hereditary polyposis syndromes; Pancolitis; Turcot syndrome.
Risks: Colectomy is moderately safe, with low mortality, but it is riskier in emergencies. The risks relate to anesthesia, infection, and inadvertent damage to structures. Side effects are common, with the most frequent ones being urinary infection, wound infection, and problems related to anastomosis or ostomy. Less frequent side effects are 294
Results: Long-term outcome varies with patient-specific factors (such as life-threatening condition, disease stage, and overall health) and therapeutic combinations (such as type of radiation therapy, chemotherapy, or both after surgery). Curative removal is possible for many first-time patients, but otherwise recurrence rate is high. Five-year survival is excellent for patients with localized cancer but is poorer for patients with more advanced disease. Patricia Boone, Ph.D. u
For Further Information Levin, Bernard, et al., eds. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006.
u
Other Resources
American Cancer Society Colon and Rectum Cancer Surgery http://www. cancer.org Patient Education Institute Colon Cancer Surgery: Interactive Tutorial http://www.nlm.nih.gov/medlineplus Society of American Gastrointestinal and Endoscopic Surgeons Laparoscopic Colon Resection http://www.sages.org
u Coloanal anastomosis Category: Procedures Also known as: Low anterior resection of the rectum; ileal pouch anal anastomosis Definition: Coloanal anastomosis is the surgical removal of a portion of a diseased rectum or the entire rectum and the attachment of the colon to the remaining rectum or to the anal muscle. This technique preserves anal function so that, in the long term, the process of eliminating stool remains nearly the same. Cancers treated: Rectal and colon cancer Why performed: Coloanal anastomosis is performed to treat colorectal cancer or severe dysplasia with inflamma-
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Coloanal anastomosis anal muscle. The surgeon also creates a temporary loop ileostomy during the first surgery to divert stool into an external colostomy bag outside the body to allow the bowel to heal. In some cases, the side of the colon is attached to the anus (side-to-end coloanal anastomosis), and a small pouch is created from a section of the colon (about 2 inches long) to store stool until it is eliminated. With the J-pouch coloanal anastomosis procedure, a larger, J-shaped pouch is created. About six to eight weeks after the first surgery, a second surgery is performed to reverse the loop ileostomy and restore anal function. Recent studies have suggested that there is no need for a temporary diverting stoma, so patients should discuss the surgical technique with their surgeon.
Coloanal anastomosis. (Custom Medical Stock Photo)
tory bowel diseases when other medical therapies have not been effective. It is also performed when a malignant stricture or fistula is suspected. Patient preparation: Before surgery, the patient’s medical status must be optimized by managing malnutrition, treating infection, and correcting anemia and dehydration. In some cases, total parenteral nutrition (tube feeding) may be required before surgery to rest the bowel and reduce symptoms that may be occurring as a result of eating solid foods. Tests before surgery may include biopsy, endoscopic evaluation, and radiography. Patients should receive thorough education regarding the risks, benefits, and expected outcomes of the proposed surgery. The health care team should discuss the patient’s expectations after surgery as well as the care of the temporary ostomy. One week before the procedure, patients must stop taking anticoagulants, as directed by the physician, to reduce the risk of increased bleeding during surgery. The patient uses a bowel preparation the day before surgery to cleanse the bowel. In many cases, antibiotics are given to reduce the risk of infection. The day before surgery, the patient follows a clear liquid diet and should not eat or drink anything after midnight the evening before surgery. Steps of the procedure: The procedure is usually performed in two stages. During the first surgery, the diseased portion of the rectum or the entire rectum is removed and the bowel is reconnected to the remaining rectum or the
After the procedure: Medications are given to manage pain, and an intravenous line delivers fluids and medications as needed. In some cases, nutrients are delivered intravenously until the patient is well enough to take foods orally. A urinary catheter removes urine and is removed about two to three days after surgery. Tubes may be in place to remove fluids and bloody drainage from the wound. Anal leakage is common after surgery and occurs as a result of the stress on the anal muscles during surgery. It may occur for several weeks and can be managed by wearing a cotton pad. The patient is not able to eat or drink until bowel function is restored, as indicated by the passage of liquid waste. Bowel function usually returns within twenty-four hours up to a few days after surgery. The patient gradually progresses to a clear liquid diet and advances to full liquids and soft, bland foods. The hospital stay is about five to seven days, depending on the patient’s recovery. The patient is encouraged to get out of bed and walk the day after surgery, and activity gradually progresses to several daily walks in the hall. Before going home, the patient receives instructions from an enterostomal therapy (ostomy) nurse who teaches the patient about caring for the temporary ostomy, obtaining ostomy supplies, and managing potential complications such as stomal blockage. The patient receives specific activity and dietary guidelines. A follow-up schedule is provided, and home care nursing services are scheduled as necessary. The patient can gradually return to regular activities, with a full return to normal activities within five to six weeks after being discharged from the hospital. Risks: The most frequent complication is pouchitis, an inflammation of the pouch characterized by increased stool frequency, urgency, incontinence, abdominal cramps and pain, and flulike symptoms. Other risks include wound infection, urinary tract infection, poor postoperative ano295
Colon polyps
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rectal function, stricture of the anastomosis, anal fistula or abscess, and reduced fertility. Results: Coloanal anastomosis surgery prevents the longterm need for a colostomy bag, maintains anal sensation, and improves continence after the rectum has been removed. Angela M. Costello, B.S.
Colon
u For Further Information Berndtsson, Ina, et al. “Long-Term Outcome After Ileal Pouch-Anal Anastomosis: Function and HealthRelated Quality of Life.” Diseases of the Colon & Rectum 50 (2007): 1545-1552. Heppell, Jacques. “Surgical Management of Inflammatory Bowel Disease.” UptoDate, January, 2008. Huh, Jung Wook, et al. “A Diverting Stoma Is Not Necessary When Performing a Handsewn Coloanal Anastomosis for Lower Rectal Cancer.” Diseases of the Colon & Rectum 50 (2007): 1040-1046. Kiran, R., and V. Fazio. “Inflammatory Bowel Disease: Surgical Management.” In Fecal and Urinary Diversions: Management Principles, edited by J. Colwell, M. Goldberg, and J. Carmel. St. Louis: Mosby, 2004. u
Polyps
Worms
Diverticular disease
Other Resources
American Society of Colon and Rectal Surgeons http://www.fascrs.org National Cancer Institute General Information About Rectal Cancer http://www.cancer.gov/cancertopics/pdq/treatment/ rectal/Patient National Digestive Diseases Information Clearinghouse (NDDIC) http://digestive.niddk.nih.gov/index.htm See also Colectomy; Colorectal cancer; Enterostomal therapy; Exenteration; Hereditary polyposis syndromes; Ileostomy; Stent therapy.
u Colon polyps Category: Diseases, symptoms, and conditions Also known as: Colorectal polyps Related conditions: Familial adenomatous polyposis (FAP), Gardner syndrome, colon cancer Definition: Colon polyps are extra clumps of tissue that grow inside the large intestine. Most polyps are benign, but some can turn into cancer. 296
Ulcerative colitis Crohn’s disease Polyps Bowel cancer Appendicitis
Ulcerative colitis
Polyps and other intestinal disorders.
Risk factors: People older than age fifty and those with a family or personal history of colon polyps or colon cancer are more likely to develop these growths. Ulcerative colitis and Crohn disease increase a person’s risk of polyps. Genetic mutations play a role in a small number of colon polyp cases. A high-fat diet, alcohol consumption, smoking, excess weight, and a lack of exercise have also been linked to an increased risk for colon polyps. Etiology and the disease process: Polyps are caused by abnormal cell growth. They may be smaller than a pebble or larger than a golf ball. Some are flat; others have a domelike shape. The larger the polyp, the more likely it will turn cancerous.
Salem Health: Cancer There are three types of colon polyps: adenomatous, hyperplastic, and inflammatory. Adenomatous polyps may turn into cancer if they grow larger than a quarter inch wide. Hyperplastic polyps are rarely cancerous. Inflammatory polyps may develop after a flare-up of inflammatory bowel disease. Incidence: Persons over age sixty with normal risk factors have a 1 in 4 chance of developing a polyp. Colon polyps afflict more men than women. Symptoms: There may be no symptoms. However, some polyps, particularly larger ones, can cause constipation or diarrhea, blood in the stool, rectal bleeding, or crampy abdominal pain. Screening and diagnosis: A doctor may feel a rectal polyp during a rectal exam, but a physical exam is usually normal. Other tests used to screen for polyps include barium enema, sigmoidoscopy, or colonoscopy. Cancer experts recommend that persons age fifty and older at normal risk be screened every ten years with a colonoscopy. Alternatively, screening with sigmoidoscopy or barium enema may be done every five years. People at increased risk for polyps may need screenings more often. Treatment and therapy: Polyps can be removed during a colonoscopy or sigmoidoscopy or surgically through the abdomen. A biopsy of the polyp determines if it is cancerous. Prognosis, prevention, and outcomes: A low-fat diet rich in fruits and vegetables and foods high in calcium and folate may reduce the risk of colon polyps. Other forms of prevention include regular exercise, losing excess weight, avoiding alcohol, and not smoking. Kelli Miller Stacy, ELS See also Adenomatous polyps; Cholecystectomy; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Desmoid tumors; Duodenal carcinomas; Gastric polyps; Gastrointestinal cancers; Gastrointestinal oncology; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Juvenile polyposis syndrome; Polypectomy; Polyps; Rectal cancer; Sigmoidoscopy.
Colonoscopy and virtual colonoscopy
u Colonoscopy and virtual
colonoscopy Category: Procedures Also known as: Endoscopy, CT colonoscopy Definition: These procedures employ either a colonoscope (a flexible tube inserted into the colon with a light and camera at the tip) or computerized imaging to examine the large intestine for precancerous, cancerous, and other conditions. Cancers diagnosed: Cancers of the large intestine and rectum, precancerous adenomas, polyps Why performed: These procedures are intended for the prevention and early detection of colon cancer for people over the age of fifty, or earlier when indicated. They are also a necessary component in the management of inflammatory bowel diseases (Crohn disease and ulcerative colitis) or for individuals who have a family history of polyps or diseases of the large intestine. Many patients resist the procedure as a result of embarrassment and/or concern over the bowel preparation, which is the same for both traditional and virtual colonoscopy. Neither procedure replaces the need for yearly testing for blood in the feces with a fecal occult blood test (FOBT) or a fecal immunochemical test (FIT). There are several considerations in deciding on the appropriate procedure. Patients should discuss family history of any bowel disease, increasing age, existing medical problems, and other personal issues with a physician when deciding the most appropriate procedure. Both forms of colonoscopy are considered the most thorough and accurate in examining the entire large intestine, but there are differences in how they are performed and what happens if a test is abnormal. Patient preparation: Patients should not stop taking any medications (such as insulin, aspirin, or blood thinners) to prepare for a colonoscopy unless approved by their physicians. Three days before either procedure, the patient should stop eating a high-fiber diet or taking fiber supplements and iron-containing vitamins or iron tablets. The day before the procedure, all three meals should consist only of clear liquids, such as tea, broth, gelatin, clear juices, tea, or coffee. The doctor will provide bowel preparation information and laxatives, either tablets or liquid, to take the day before the procedure and possibly again four hours before the procedure. The large intestine must be completely empty and free of all fecal matter in order to clearly see any abnormal growths or changes in the wall of the intestine. The 297
Colonoscopy and virtual colonoscopy patient may not eat or drink anything after midnight before the procedure unless it is water to take approved medication. Steps of the procedure: Traditional colonoscopy is usually performed in an outpatient surgery suite. Patients are moderately sedated and given pain medication through an intravenous catheter. It is common for patients to sleep through the procedure, which can take thirty to sixty minutes. The patient lies on the left side, and a colonoscope is inserted through the anus and rectum. The doctor watches a video screen as the tube is guided through the large intestine. Examination includes visualization during slow withdrawal of the tube, as some growths can be hidden in folds in the intestine. The gastroenterologist is looking at the actual lining of the intestine—not a computerized image. The following can be done during this procedure: removal of polyps, sampling of abnormal tissue (biopsy), removal of small growths, stopping of small areas of bleeding, laser treatment of abnormal tissue or growths, and the introduction of certain medicines. Virtual colonoscopy is performed by a radiologist in a radiology suite. No sedation is necessary. The patient is
Salem Health: Cancer asked to lie on the back on a table. A thin tube is inserted into the rectum introducing air to inflate the large intestine for better visualization. The table passes through the scanner as three-dimensional computerized images of the large intestine are made and immediately viewed on a video screen. The patient is instructed to periodically hold the breath to be sure that the images taken are clear. The procedure is repeated with the patient lying on the stomach and is completed in ten to fifteen minutes. Identification of anything abnormal might require traditional colonoscopy. Repeat bowel preparation will be necessary if the procedure cannot be performed the same day. After the procedure: The patient will need to be driven home after traditional colonoscopy, as the sedation used during the procedure makes it unsafe to drive. It can take one to two hours after traditional colonoscopy for the patient to be alert enough to be driven home. There can be some abdominal cramping and feelings of gas. Normal activities can be resumed the following day. Virtual colonoscopy does not require medication, and patients are free to leave immediately after the procedure. Some cramping might occur following virtual colonoscopy because of the introduction of air during the procedure. Risks: Perforation and/or infection of the large intestine, while very uncommon, is a possible complication from traditional colonoscopy. The doctor will provide an information sheet that describes what is normal and not normal following colonoscopy. Symptoms that should indicate calling the doctor include bloody diarrhea, blood coming from the rectum, dizziness, fever, severe abdominal pain, and weakness. There is radiation exposure with virtual colonoscopy.
Colon cancer detected by colonoscopy. (Brian Evans/Photo Researchers, Inc.)
298
Results: Both procedures are considered the most thorough in examining the entire large intestine. Traditional colonoscopy is better at finding growths smaller than 10 millimeters and has the advantage of permitting biopsies of abnormal growths, removal of polyps, treatment of inflammation or disease, and laser treatment during the examination. Virtual colonoscopy is a much newer procedure and has been widely embraced by those who are fearful of traditional colonoscopy. Traditional colonoscopy is required following virtual colonoscopy if any abnormalities
Salem Health: Cancer are found. Some studies have found that certain abnormalities on virtual colonoscopy were normal when traditional colonoscopy followed. Studies continue comparing the benefits and drawbacks of each procedure. Janet R. Green, M.S.P.H. u For Further Information Cotterchio, M., et al. “Colorectal Screening Is Associated with Reduced Colorectal Cancer Risk: A Case-Control Study Within the Population-Based Ontario Familial Colorectal Cancer Registry.” Cancer Causes & Control 16, no. 7 (2005): 865-875. Waye, Jerome D., Douglas K. Rex, and Christopher B. Williams, eds. Colonoscopy: Principles and Practice. Malden, Mass.: Blackwell, 2003. Yee, Judy. Virtual Colonoscopy. Philadelphia: Lippincott Williams & Wilkins, 2008. u
Other Resources
American Cancer Society http://www.cancer.org Mayo Clinic http://www.mayoclinic.org National Cancer Institute http://www.cancer.gov See also Adenomatous polyps; Barium enema; Colon polyps; Colorectal cancer; Colorectal cancer screening; Crohn disease; Digital rectal exam (DRE); Diverticulosis and diverticulitis; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; Laxatives; Polypectomy; Polyps; Rectal cancer.
u Colony-stimulating factors
(CSFs) Category: Chemotherapy and other drugs ATC code: BO3XA01-erythropoietin, BO3XA02darbepoetin alfa, LO3AA02-filgrastim, LO3AA03molgramostim, LO3AA09-sargramostim, LO3AA10lenograstim, LO3AA12-ancestim, LO3AA134pegfilgrastim Also known as: Hematopoietic growth factors Definition: Colony-stimulating factors (CSFs) are glycoproteins that stimulate the production of blood cells. Several recombinant CSFs have achieved widespread clinical use. Others have been identified but have not been as-
Colony-stimulating factors (CSFs) sessed in clinical trials or have not been approved for use by the Food and Drug Administration (FDA). Cancers treated: Colony-stimulating factors are not used to treat cancers per se. Rather, they are used as supportive care to increase red blood cell, white blood cell, and hematopoietic stem cell counts that are depleted during some forms of chemotherapy or radiation therapy. CSFs generally are administered only to patients with nonmyeloid malignancies and usually as primary prophylaxis to prevent febrile neutropenia or to allow dose intensity with specific chemotherapy regimens. CSFs are administered after chemotherapy or radiation therapy. They also may be used before bone marrow or stem cell transplantation to increase the number of cells available for transplant or after transplantation to assist in bone marrow recovery. Delivery routes: Because colony-stimulating factors are proteins and are subject to digestion and degradation in the stomach, they are administered either as intravenous (IV) infusions or subcutaneous injections, depending on the specific formulation used. Some CSFs are presented in prefilled syringes, allowing patients to inject themselves at home without the need to go to a hospital or doctor’s office. How these drugs work: Hematopoiesis, the formation of blood cells, is the process by which early hematopoietic stem cells in the bone marrow with potential for renewal, proliferation, and differentiation give rise to large numbers of mature cells through a series of intermediate cells. As the stem cells mature, they lose their ability to selfrenew and become specialized. Stem cells produce cells that belong to one of three lineages: erythroid cells (red blood cells), lymphoid cells (white blood cells, including T cells and B cells), and myeloid cells (white blood cells such as granulocytes and macrophages, and platelets or thrombocytes). The process of proliferation, differentiation, and maturation is complex, with many interacting steps, and is controlled by CSFs, alone or in combination. To date, more than twenty CSFs have been identified. They are active in very small amounts. Once CSFs were discovered in experimental models, the genes for them were identified and cloned. Many of the endogenous CSFs have been produced as recombinant human forms and have received marketing approval from the FDA. The recombinant human forms of CSFs can be used to replace or supplement the endogenous proteins after chemotherapy or radiation therapy or in the case of anemia caused by kidney failure or the anemia of chronic disease, which includes cancer. 299
Colorectal cancer Erythropoietin or epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) increase the number of red blood cells by causing committed erythroid progenitor cells to proliferate and differentiate. Filgrastim (Neupogen) and pegfilgrastim (Neulasta) are granulocyte CSFs that increase the number of neutrophils, white blood cells specific to fighting infection. Another white cell factor, lenograstim (Granocyte), is available in Europe and other countries. The granulocyte CSFs increase the circulating half-life of neutrophils and enhance their ability to attack bacteria. Sargramostim (Leukine) is a granulocyte-macrophage CSF used to increase several types of white blood cells; molgramostim (Leucomax) is another version that is available in Europe. Granulocyte-macrophage CSFs are locally active and remain at the site of infection to recruit and activate neutrophils. Ancestim (Stemgen) is a CSF that promotes the development of stem cells, which can differentiate into the other types of blood cells; it is not available in the United States. Interleukin-11 (oprelvekin, Neumega; LO3AC02) is not a CSF but is used to increase platelet counts in patients with cancer who are receiving myelosuppressive chemotherapy. Side effects: All drugs and biologic products that are effective have side effects, and each type of CSF has side effects specific to it. Patients who are receiving CSFs should consult their health care professionals and the package insert for specific information concerning side effects. In general, however, the side effects from use of CSFs are much less intense than those from chemotherapy or radiation therapy. Common side effects are bone pain, flulike symptoms, fever, fatigue, and loss of appetite. MaryAnn Foote, M.S., Ph.D. u
For Further Information Armitage, J. O. “Emerging Applications of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor.” Blood 92 (1998): 4491-4508. Molineux, G., M. A. Foote, and S. G. Elliott, eds. Erythropoietins and Erythropoiesis: Molecular, Cellular, Preclinical, and Clinical Biology. Basel, Switzerland: Birkhäuser Verlag, 2003. Morstyn, G., M. A. Foote, and G. J. Lieschke, eds. Hematopoietic Growth Factors in Oncology: Basic Science and Clinical Therapeutics. Totowa, N.J.: Humana Press, 2004. Welte, K., et al. “Filgrastim (r-metHuG-CSF): The First Ten Years.” Blood 88 (1996): 1907-1929. 300
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Other Resources
Epogen http://www.epogen.com Leukine http://www.leukine.com Neulasta http://www.neulasta.com Neupogen http://www.neupogen.com Procrit http://www.procrit.com See also Biological therapy; Bone marrow transplantation (BMT); Cytokines; 5Q minus syndrome; Gene therapy; Immunotherapy; Interleukins; Leukopenia; Myelofibrosis; Myeloproliferative disorders; Neutropenia; Soots; Stem cell transplantation; Thrombocytopenia; Umbilical cord blood transplantation.
u Colorectal cancer Category: Diseases, symptoms, and conditions Also known as: Colon cancer, rectal cancer, intestinal cancer Related conditions: Familial polyposis Definition: Colorectal cancer (CRC) is cancer of the colon, which is also called the large intestine, and the rectum. The cells of the colon and rectum become abnormal and lose the defining characteristics of normal intestinal cells and their ability to divide in a controlled way. These cells grow rapidly and form tumors. The large intestine includes the ascending colon, transverse colon, and sigmoid colon. The rectum and anus follow the sigmoid colon, where solid waste (feces or stool) exits the body. Carcinoma, a type of cancer derived from epithelial cells, is the most common cell type found in CRC. Epithelial cells normally line the digestive system, glands, and make up the top layers of skin. Intestinal epithelial cells vary somewhat from those in other parts of the body. Risk factors: Increasing age, a family history of colorectal cancer, familial polyposis, ulcerative colitis, and Crohn disease increase risk. A high-fat, low-fiber diet and inactivity can play a role, but the mechanism of this association is not known. Etiology and the disease process: Some changes take place in the colon before cancer develops. A small area of
Salem Health: Cancer
Colorectal cancer
Incidence of Colorectal Cancer per 100,000 People, by Gender 80 72.6
Men
Women
70 60.4
60 55.0
49.1
50
47.5
44.0
42.1
40
35.3
39.6
32.9
30 20 10 0 Black
White
Asian/Pacific Islander
Hispanic
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
precancerous cells will begin to form on the surface of the intestine. These cells can mutate into cancerous cells and will continue to grow in both directions—outward from the surface and inward though deeper layers of tissue that form the multiple layers of the intestinal wall. As the abnormal growth invades these layers, it can encroach on blood vessels and lymph nodes, from which cancer cells can travel to the liver or other organs. Liver metastases are common with advanced disease. The most common large intestine abnormality is noncancerous growths called polyps. Polyps grow into the intestine from its walls. Some polyps have a stalk. Polyps usually grow in the sigmoid colon and the rectum. Adenomatous polyps (derived from glandular tissue) are more likely to become malignant (cancerous). Approximately 25 percent of people with colon cancer have polyps somewhere else in the large intestine. Familial polyposis is a hereditary condition. There is a genetic predisposition to grow many—even one hundred or more—precancerous adenomatous polyps in the large intestine. Cases of colorectal cancer due to this condition appear before the age of forty, unlike colorectal cancers
due to other causes, which have a higher rate of incidence with advancing age. Polyps are removed unless there are so many of them that it is better to remove a section of the large intestine containing the polyps. Frequent examination of the large intestine is necessary to watch for new growth. The most extreme measure to prevent the growth of more polyps is the surgical removal of the rectum and anus. A surgical opening is made in the abdominal wall (ileostomy), where solid waste can be collected in a pouch. Incidence: Colorectal cancer is the third most common cancer for men and women in the United States and other Western countries. It is also the third leading cause of death. In 2007, there will be approximately 79,600 new cases of colon cancer in men and 75,000 cases in women. Approximately 26,000 men and women will die each year from this disease. From 2000 to 2004, the median age at diagnosis for colorectal cancer was seventy-one years. The median age at death was seventy-five years. Men, in general, have higher incidence rates per 100,000 people than women: Black men have the highest rate at 72.6 per 100,000; whites, 60.4; Asian/Pacific Is301
Colorectal cancer landers, 49.1; Hispanics, 47.5; and American Indian/ Alaska natives, 42.1. Among women, black women have the highest incidence rates at 55 per 100,000, followed by white women, 44.0; American Indian/Alaska natives, 39.6; Asian/Pacific Islanders, 35.3; and Hispanics, 32.9. Trends in colorectal cancer incidence for men and women from 1975 to 2004 show a decline for all races and ethnicities. Symptoms: There are no symptoms of early colorectal cancer. Screening is the most important component in prevention and early detection. Symptoms such as weight loss, constipation, blood in the stool, and liver disease indicate a more advanced stage of disease. Screening and diagnosis: There are several tests for screening and diagnosis. The type and frequency of testing depend on the patient’s age and medical history. A yearly fecal occult blood test/fecal immunochemical test (FOBT/ FIT) is recommended in people age fifty or older. A physician decides which additional test—double-contrast barium X ray, flexible sigmoidoscopy, or colonoscopy— should be given to each person, starting at age fifty and every five to ten years after for those without new symptoms. • Fecal occult blood test (FOBT): Three fecal samples taken at different times are placed on special cards that are
Salem Health: Cancer sent to the laboratory for testing. The presence of blood in the sample indicates that further testing is required. A positive FOBT does not necessarily mean cancer. Blood can come from hemorrhoids, a noncancerous polyp, or inflammatory bowel diseases such as Crohn disease or ulcerative colitis. • Fecal immunochemical test (FIT): A relatively new test, also known as an immunochemical fecal occult blood test (iFOBT), to detect blood in the feces. The advantage to this test is that the patient is not required to restrict certain foods and medications before collecting the sample. Also, early evidence indicates that the FIT might be more specific in detecting blood than the FOBT. • Double-contrast barium X ray: An X ray of the colon and rectum using barium for contrast. Growths, narrowing of the colon, and evidence of inflammation can be seen, as the barium outlines the large intestine. Biopsies and polyp removal are not possible with this procedure. • Flexible sigmoidoscopy: The sigmoidoscope is a flexible tube with a light and a tiny camera at the tip. The instrument is introduced into the rectum. Polyps, other growths, and evidence of inflammation can be seen in the lower one-third of the intestine and rectum. Biopsies (tiny samples of abnormal tissue) can be taken of tissue that appears abnormal. • Colonoscopy: The colonoscope is a flexible tube with a light and tiny camera at the tip. The patient is given “conscious sedation” and frequently sleeps though the procedure. The tube is introduced through the rectum and is passed into all three sections of the large intestine. Biopsies of abnormalities can be taken. The colonoscopy is the only test that visualizes the entire colon and allows for biopsy of abnormalities. If a biopsy is positive for cancer, further testing is required to see if the cancer has spread. The process is called staging. • Stage 0: Very early cancer is present on the innermost layer of the intestine. • Stage I: Cancer is in the inner layers of the colon. • Stage II: Cancer has spread through the muscle wall of the colon. • Stage III: Cancer has spread to the lymph nodes. • Stage IV: Cancer has spread to other organs.
Colon cancer. (David M. Martin, M.D./Photo Researchers, Inc.)
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Treatment and therapy: Treatment options vary according to disease stage and the age
Salem Health: Cancer and general health of the patient. The main treatment categories are surgery, chemotherapy, radiation therapy, and targeted therapy (specifically targeting cancer cells by stimulating the immune system). More than one of these treatments may be used. Many patients choose to get a second opinion, which allows them to have increased confidence in the treatment option that they have chosen with their physician or to explore other options. It is very important that colorectal cancer patients ask questions necessary to feel confident that they understand the disease and treatment. Patients are advised to take a trusted friend or family member to appointments and write down questions at home to ask their physician. Surgery is the primary treatment. The type of surgery depends on the stage of disease. Laparoscopic surgery, which involves a small incision in the abdomen, can remove some Stage 0 and Stage 1 tumors and cancerous polyps (polypectomy). Surgery in the early stages can be curative. Surgical procedures range from polypectomy, often performed during a colonoscopy, to resection (removal) of major sections of the large intestine or rectum. When resection is performed, up to one-third of the intestine is removed. The ends of each section are then attached (anastomosis) where there is healthy tissue on each side. Cancer of the rectum and anus may require colectomy, a process in which the surgeon removes part or all of the colon, brings a normal section of the large intestine through an opening in the abdomen, and attaches a bag to collect solid waste. Radiation therapy focuses high-energy beams directly into the tumor from outside the body, killing the cancer cells. Radiation usually follows surgery to remove a large mass or tumor. Radiation therapy is very precise and can be focused on small areas of tumor cells not seen during surgery. There are times when radiation is used before surgery to shrink a tumor and ease removal. Radiation for colon cancer is performed with a linear accelerator. Precision calculations determine the most direct path to the tumor cells while damaging the fewest normal cells. Treatment lasts only a few minutes per day and might continue for several weeks. Endocavitary radiation treatment for cancer of the rectum and anus is performed internally. A small, handheld device is introduced into the rectum, where the dose of radiation can more directly reach the cancer cells. Side effects from radiation include skin irritation, nausea, bladder irritation, bowel incontinence, diarrhea, rectal irritation, and fatigue. Sexual dysfunction can occur in men and women. Chemotherapy involves several strategies. It can be used after surgery when all evidence of cancer is gone, or it
Colorectal cancer can work to prevent a return of the cancer, which is called adjuvant chemotherapy. Drugs used to treat colorectal cancer include fluorouracil (5-FU), capecitabine (Xeloda), oxaliplatin (Eloxatin), and irinotecan (Camptosar). Systemic chemotherapy is the introduction into the body of toxic, cancer-fighting chemicals, which find cancer cells and kill them. Cancer cells divide more rapidly than normal cells. Chemotherapy drugs get inside the cancer cells more rapidly and kill them. A targeted variation is injecting chemotherapy drugs directly into an artery supplying blood to an organ (liver) that contains tumor cells. Side effects of chemotherapy are due to the toxicity of the drugs, which kill cancerous and noncancerous cells. Common side effects are severe diarrhea, low blood counts, nausea, and vomiting. Newer medications are available to control the nausea and vomiting. Targeted therapy exploits unique abnormalities of cancer cells other than just rapid cell division. Proteins called monoclonal antibodies selectively find the cancer cells and kill them. There are fewer side effects, possibly from less damage to normal cells. Targeted therapy is not without side effects or danger. Lung scarring, rashes, fatigue, infection, and allergic reactions are all realities with this therapy. Monoclonal antibody and target therapy drugs include bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix). Prognosis, prevention, and outcomes: People who are aware of their family history for colorectal cancer or polyps are in a good position to lessen their chances for contracting colorectal cancer. High-fat, low-fiber diets are implicated in higher rates of CRC, but the mechanism is not known. People who eat lean meat, smaller portions of meat, and more vegetables and grains have lower rates of CRC. Physical activity also seems to be important. It is imperative that beginning at age fifty, yearly FOBT/FIT testing is performed and that colonoscopy, flexible sigmoidoscopy, or double-contrast barium X ray is also performed every five to ten years. The main reason people do not have these screening tests are concerns about the colon-cleansing procedure before testing, unease about taking fecal samples for the FOBT, and embarrassment. Excellent prognosis or cure is associated with early detection. Stages 0, I, II, and III are potentially curable. Colorectal cancer that has not spread (metastasized) or invaded the intestinal wall has a greater chance for cure. More than 90 percent of patients receiving treatment during the early stages will survive at least five years. Some 39 percent of colorectal cancer is found in the early stages. Stage IV cancer has spread to organs such as the liver, 303
Colorectal cancer screening ovaries, lungs, or peritoneum. Surgery is performed not to cure the cancer but to prevent the colon from becoming blocked by the tumor. Liver metastases have been successfully removed through surgery. There have been some cures from this procedure, but this stage of disease is difficult to cure. Multiple therapies are used with Stage IV disease and include targeted therapies, chemotherapy, freezing tumors, and radiation. Janet R. Green, M.S.P.H. u For Further Information Brown, Gina. Colorectal Cancer. New York: Cambridge University Press, 2007. Cassidy, Jim, Patrick Johnston, and Eric van Cutsem, eds. Colorectal Cancer. New York: Informa Healthcare, 2007. Holen, Kyle, and Ki Young Chung. Dx/Rx: Colorectal Cancer. Sudbury, Mass.: Jones and Bartlett, 2008. u
Other Resources
American Cancer Society http://www.cancer.org
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u Colorectal cancer screening Category: Procedures Also known as: Fecal occult blood test (FOBT), immunoassay, or immunochemical, fecal occult blood test (iFOBT), flexible sigmoidoscopy, doublecontrast barium X ray, colonoscopy, or virtual colonoscopy Definition: Colorectal cancer screening tests are performed to detect abnormalities in the large intestine and rectum. The tests vary in accuracy, ease of performance, and invasiveness. Cancers diagnosed: Colorectal cancers Why performed: Early-stage colorectal cancers do not cause symptoms. The treatment of polyps or precancerous lesions can prevent the development of cancer, and the early detection of colorectal cancer can result in a cure. Testing is also performed as surveillance for chronic inflammatory conditions such as Crohn disease, ulcerative colitis, and familial polyposis.
Susan Cohan Kasdas Colon Cancer Foundation http://www.coloncancerfoundation.org
Patient preparation: Preparation varies with the test being performed. FOBT and iFOBT do not require patient preparation. However, FOBT restricts the eating of red meat and the taking of aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs), except acetaminophen, for three days before the samples are taken. Flexible sigmoidoscopy, double-contrast barium X ray, and colonoscopy require that the colon be free of all fecal material so that the lining of the intestine can be visualized. This preparation necessitates taking strong laxatives the day and evening before the examination, eating a clear liquid diet the day before the examination, and not eating any food after midnight of the day of the examination. Some preparation protocols also call for a selfadministered enema prior to the procedure.
See also Adenomatous polyps; Anal cancer; APC gene testing; Bethesda criteria; Colon polyps; Crohn disease; Cyclooxygenase 2 (COX-2) inhibitors; Desmoid tumors; Diverticulosis and diverticulitis; DPC4 gene testing; Duodenal carcinomas; Enteritis; Enterostomal therapy; Epidermoid cancers of mucous membranes; Gardner syndrome; Gastric polyps; Gastrointestinal cancers; Hemorrhoids; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; MLH1 gene; MSH genes; PeutzJeghers syndrome (PJS); PMS genes; Polyps; Rectal cancer.
Steps of the procedure: The fecal occult blood test (FOBT), a test for the presence of blood in the feces, is the simplest test for colorectal cancer and is performed by the patient at home. It is never normal to have blood in the feces, but the presence of blood does not mean cancer. Preparation begins three days prior to the collection of a fecal sample. Patients are instructed to avoid ingesting red meat, beets, other red foods or food containing red dye, aspirin, vitamin C, or iron tablets. The collection kit contains small wooden sticks to obtain stool samples and place on the cards provided. Two samples from different parts of the stool are placed on the card provided and allowed to dry
Centers for Disease Control and Prevention http://www.cdc.gov Colon Cancer Alliance http://www.ccalliance.org MayoClinic.com http://www.mayoclinic.com National Cancer Institute http://www.cancer.gov
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Salem Health: Cancer before the card is closed with a flip-over cover (similar to a matchbook). Two samples are required from three separate stool samples on three cards. The cards are then placed in a envelope enclosed with the collection kit and sent to the laboratory. This test is performed yearly beginning at age fifty. The newer immunoassay (or immunochemical) fecal occult blood test (iFOBT) also detects blood in the feces, but it does not require food or medication restriction prior to sample collection (hence minimizing inaccurate results from lack of proper preparation). Only a single sample is required. There is evidence that the iFOBT might be more accurate at specifically detecting human blood in the stool, but if the result is positive, then further testing is necessary. This test is performed yearly beginning at age fifty. The double-contrast barium enema is an X ray of the colon and rectum following the introduction of a barium contrast material. After the colon is completely emptied, a barium sulfate solution and air are introduced through the rectum so that the outline of the colon is clear. Following the exam, the patient expels the barium solution and might experience abdominal cramping for up to twenty-four hours. This test should be done every five years unless flexible sigmoidoscopy or colonoscopy is performed. Flexible sigmoidoscopy allows the visual examination of the rectum and lower third of the intestine with a flexible tube lighted at the end. The physician is able to see a polyp, inflammation of the intestinal walls, or other growths. Biopsies (tiny samples of abnormal tissue) can be taken for diagnosis. This test is quick and has few complications. No sedation is required. The doctor can view only the lower third of the colon, however, so polyps or precancerous lesions beyond this point cannot be seen. If signs of disease are detected, then further testing might be necessary. This test is performed every five years unless doublecontrast barium X ray or colonoscopy has been performed. The most invasive yet most thorough examination for colorectal cancer is colonoscopy. A colonoscope is a flexible tube with a light and a tiny camera at the tip. The patient is usually given “conscious sedation” and sleeps though the procedure. The tube is introduced through the rectum and is passed through the entire colon. Biopsies and removal of polyps are performed as indicated. Virtual colonoscopy uses computerized images to see the entire colon, but biopsies cannot be performed. After the procedure: Patients have no special instructions to follow after FOBT, iFOBT, virtual colonoscopy, or sigmoidoscopy. Following a colonoscopy, which requires thirty to sixty minutes, the patient will be monitored while waking. Because sedation has been administered,
Colorectal cancer screening the patient will need to be driven to and from the procedure. Doctors will not allow a patient to drive or go home alone. Patients are told to rest for the remainder of the day and can resume normal activities the next day. Sometimes gas (air used during the procedure to make it easier to view the colon) is expelled for several minutes or hours following a sigmoidoscopy or colonoscopy. Risks: The FOBT and iFOBT tests involve no risks, and risks for the double-contrast barium enema and flexible sigmoidoscopy, which require no sedation, are rare. The flexible sigmoidoscopy may, rarely, result in small tears in the colon or rectum. The risks of colonoscopy include bleeding, the possibility of tears in the colon or rectum, and perforation of the colon or rectum. However, these are rare complications. The test should be performed at age fifty and every ten years thereafter if no polyps or other signs of disease are detected. Results: A negative FOBT result means that no blood was found in the stool samples. A positive test means that blood was found in one or more samples, and further testing will be necessary to determine the source of bleeding. FOBT should be repeated yearly but will not detect polyps or tumors that are not bleeding. The double-contrast barium enema can miss some small polyps and cancers. Biopsy and polyp removal cannot be performed. Therefore, additional diagnostic procedures might be necessary. Because sigmoidoscopy examines only the lower third of the colon, polyps or precancerous lesions to that point will be detected and removed; if found, additional procedures (colonoscopy) will be needed. Lesions beyond the lower third of the colon cannot be detected by sigmoidoscopy. Colonoscopy and virtual colonoscopy are the most sensitive and thorough tests available, although some small polyps and precancerous growths still might be missed. Janet R. Green, M.S.P.H. u
For Further Information Cotterchio, M., et al. “Colorectal Screening Is Associated with Reduced Colorectal Cancer Risk: A Case-Control Study Within the Population-Based Ontario Familial Colorectal Cancer Registry.” Cancer Causes & Control 16, no. 7 (2005): 865-875. Imperiale, T. F., et al. “Fecal DNA Versus Fetal Occult Blood for Colorectal Cancer Screening in an AverageRisk Population.” New England Journal of Medicine 351, no. 26 (2004): 2704-2714. Segnan, N., et al. “Randomized Trial of Different Screen305
Colostomy ing Strategies for Colorectal Cancer: Patient Response and Detection Rates.” Journal of the National Cancer Institute 97, no. 5 (2005): 347-357. u
Other Resources
American Cancer Society http://www.cancer.org American College of Gastroenterology Colorectal Cancer Screening http://www.acg.gi.org/patients/gihealth/colon.asp National Cancer Institute Colorectal Cancer Screening: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ detection/colorectal-screening See also Barium enema; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Digital rectal exam (DRE); Diverticulosis and diverticulitis; Endoscopy; Fecal occult blood test (FOBT); Hemorrhoids; Immunochemical fecal occult blood test (iFOBT); Polyps; Rectal cancer; Sigmoidoscopy.
u Colostomy Category: Procedures Also known as: Ostomy surgery Definition: Colostomy is the surgical rerouting of the colon through a new opening (ostomy) in the abdomen, forming a stoma. A colostomy is described by the part of the colon involved (ascending, transverse, descending, or sigmoid); the type of stoma constructed (end-type or looptype), and the type of ostomy (temporary or permanent). Cancers diagnosed or treated: Colon cancer, rectal cancer, advanced anal cancer Why performed: Colostomy is performed to reroute the waste in the colon, either as a temporary diversion or as a permanent new path for waste to leave the body. Temporary diversion may be needed so that newly connected tissues in the lower bowel can heal, to stage an operation for a patient who has a partial obstruction or is too frail to undergo extensive surgery, or in an emergency to relieve an obstructing tumor or to allow an infection to clear before removing diseased tissue. Later, the temporary ostomy may be reversed to restore normal bowel function. Permanent colostomy is needed when the anal sphincter is removed, when the rectum and part or all of the colon are removed and it is not possible or optimal to connect the 306
Salem Health: Cancer remaining ends, or when an obstructing tumor cannot be bypassed or an unremovable tumor is likely to obstruct. Patient preparation: A series of medical tests are completed to plan treatment and to evaluate the patient’s fitness for this surgery. A specialist (ostomy nurse or enterostomal therapist) counsels the patient and helps choose the location for the stoma. For the procedure, certain patient medications may need to be stopped, the patient’s bowel must be cleaned, and the patient’s stomach must be empty. In an emergency, patient evaluation and preparation may be limited. Steps of the procedure: Colostomy is performed in a hospital as part of or as the first stage of a larger operation. For the procedure, sensors are placed to monitor the patient’s condition. An intravenous (IV) line is started, and an antibiotic is infused. General anesthesia is administered, and a breathing tube is placed. The patient is positioned, a urinary catheter is inserted, and the incision sites are prepared. Most commonly, a colostomy constructs either an endtype or a loop-type stoma. Details for each procedure vary with the larger operation needed, the parts of the bowel involved, and the surgical approach chosen (open or laparoscopic). With an end-type stoma, this procedure temporarily or permanently connects the upper end of the colon to an opening on the abdomen. First, an ostomy opening is made in the abdomen. The colon is freed from attachments and divided. The upper end is passed through the ostomy opening, the colon segment is sized to an appropriate length, and the edge of the cut end is folded back and stitched to the abdomen, forming an end stoma. The lower end may be totally removed, permanently sealed, temporarily sealed, or temporarily formed into a mucous fistula by connecting it to a second abdominal opening. With loop-type stoma, this procedure temporarily opens a loop of colon onto the abdomen and constructs either one stoma (end-loop) or two stomas (double-barrel). First, an ostomy opening is made in the abdomen. A loop of colon is freed from attachments and is brought through the ostomy opening. Then, either an end-loop stoma or a doublebarrel stoma is constructed. To construct an end-loop stoma, the loop is divided. The lower end is sealed and anchored with one stitch near the ostomy opening, and the cut edge of the upper end is folded back and stitched to the abdomen, forming one stoma. To construct a doublebarrel stoma, the loop is slit lengthwise. A small bridge is placed underneath the loop, bisecting the slit and raising the middle of the loop. The edges of the split are stitched to the abdomen on both sides of the bridge, forming two stomas.
Salem Health: Cancer
Colostomy
After the procedure: After the surgery anesthesia is stopped, and the breathing tube is removed. The urinary catheter and the IV line are kept. A clear collection pouch is fitted over the stoma. The patient is transferred to the recovery room and then to a hospital room. Medications are given to control pain and infection. The ostomy is closely monitored; once it starts functioning, the patient learns how to care for the stoma, empty and change pouches, and manage bowel function. At home, the patient follows the physician’s instructions for medications, activities, and diet. Risks: Colostomy is relatively safe. Stomal side effects are very common, but most are not serious. Early side effects are irritation and leakage. Later side effects are hernia, prolapse, fistula, obstruction, ischemia, necrosis, re-
traction, separation, and narrowing. When an ostomy is temporary, overall risk includes that of reversing the colostomy. Results: After colostomy, waste previously collected in the rectum and pushed through the anus now flows through the ostomy into a flat plastic pouch (ostomy appliance) that fits securely over the stoma. Many types and sizes of ostomy appliances are available, depending on the type of colostomy and patient-specific factors. Some patients benefit from minor changes in diet and alterations in clothing. All patients can perform the same activities as before. In recent years, patients’ quality of life has greatly improved with advances in ostomy management and stomal care. Patricia Boone, Ph.D.
The Results of Colostomy
Abdominal wall
Front view
Stoma
Closed section of the colon Side view Colostomy is performed to reroute the waste in the colon, either as a temporary diversion or as a permanent new path for waste to leave the body.
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Colposcopy
Salem Health: Cancer
u For Further Information Levin, Bernard, et al., eds. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006. u
Normal Squamous Epithelium Transformation Zone Columnar Epithelium
Other Resources
American Cancer Society Colostomy Guide http://www.cancer.org
Keratosis Saline
American Society of Colon and Rectal Surgeons Ostomy http://ascrs.affiniscape.com
Lesion
United Ostomy Associations of America http://www.uoaa.org
Saline
See also Colectomy; Coloanal anastomosis; Diverticulosis and diverticulitis; Enterostomal therapy; Exenteration; Gastrointestinal cancers; Hereditary polyposis syndromes; Self-image and body image.
Mosaic Pattern with Punctation
3% Acetic Acid
u Colposcopy Category: Procedures Also known as: Colposcopy-directed biopsy Definition: A colposcopy is a diagnostic procedure in which the cervix is examined using a microscope and any abnormal tissue is biopsied.
3% Acetic Acid
Normal and abnormal colposcopy results. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Cancers diagnosed: Cervical cancer or its precursor, cervical intraepithelial neoplasia (CIN) Why performed: Colposcopy is performed as a follow-up to an abnormal Pap smear. It is also performed on a patient exposed to diethylstilbestrol (DES), with repeated inflammation of the cervix or an abnormal-appearing cervix, or with repeated atypical squamous cells of undetermined significance (ASCUS). Patient preparation: Patients should avoid placing anything in the vagina before the exam—including medicines for yeast infections, douches, and spermicides—and should abstain from sexual intercourse. The physician will provide specific instructions. Some physicians advise patients to take an over-the-counter pain medication, such as ibuprofen. Steps of the procedure: Colposcopy is performed in the office and takes ten to fifteen minutes. The patient lies on 308
an exam table in the same position as for a Pap smear. A speculum is used to open the vagina and view the cervix. The physician stains the cervix with acetic acid and iodine using a cotton swab. The physician examines the cervix using a microscope placed about 30 centimeters from the vagina and notes variations in the normally smooth, pink appearance of the cervix, including areas of disordered growth of cells (dysplasia), abnormal patterns of blood vessel growth (punctation), and acetowhite areas (patches of tissue that are white after staining with acetic acid). Biopsies of abnormal areas are taken using biopsy forceps and sent to a laboratory for examination by a pathologist. After the procedure: The patient may feel mild cramps or pinching and may have dark-colored vaginal discharge after the procedure if biopsies are taken. The physician may recommend that the patient avoid activities such as sexual intercourse, treating for vaginal yeast infections, and douching after the exam.
Salem Health: Cancer
Complementary and alternative therapies
Risks: There is little risk associated with this procedure; however, heavy vaginal bleeding, foul-smelling discharge, or a high fever should be reported to the physician.
DCIS has dead cells (necrosis) that plug the center of the breast duct. It tends to grow fast and has a higher risk of invasive cancer than noncomedo DCIS.
Results: A normal cervix is smooth and pink with no unusual patterns of blood vessels, turns dark with iodine staining, and has only mild acetowhite areas. Abnormal cervical tissue is rough or “humped up,” intensely acetowhite, includes patterns of blood vessel growth described as “punctuation” or “mosaic,” and is iodine-negative (yellow). The biopsies are graded as CIN I, CIN II, or CIN III, or carcinoma in situ. CIN I findings often resolve themselves and are usually followed with additional colposcopy and Pap smears. CIN II, CIN III, or carcinoma in situ is usually treated. Michele Arduengo, Ph.D., ELS
Incidence: Ductal carcinoma in situ is becoming increasingly common, accounting for 22 to 45 percent of newly diagnosed cases of breast cancer. The comedo type represents about 40 percent of the cases and carries a poorer prognosis.
See also Cervical cancer; Conization; Endoscopy; Gynecologic oncology; Hysterectomy; Loop electrosurgical excisional procedure (LEEP); Pregnancy and cancer; Virusrelated cancers; Vulvar cancer.
u Comedo carcinomas Category: Diseases, symptoms, and conditions Also known as: Ductal carcinoma in situ (DCIS), high nuclear grade or poorly differentiated DCIS Related conditions: Spontaneous nipple discharge, Paget disease Definition: Comedo carcinoma is a type of ductal carcinoma in situ (very-early-stage breast cancer), which accounts for approximately 22 to 45 percent of all breast cancers diagnosed with mammography. Most cases appear after the age of fifty-five and may persist for years without a palpable abnormality. Ductal carcinoma in situ (DCIS) refers to a family of cancers that occur in the breast ducts. There are two categories of DCIS, noncomedo and comedo. The high grade or comedo type represents 40 percent of all DCIS and on pathologic evaluation appears as pluglike necrotic material that can be expressed from the ducts of the cut pathology specimen. On mammography, often a linear branching or casting pattern of microcalcifications is visible. Risk factors: Risk factors include increasing age, having few children and the first child after the age of thirty, obesity, a history of atypical hyperplasia or of breast carcinoma, and having a mother or sibling with breast cancer. Etiology and the disease process: In comedo carcinoma, cancer forms in the breast ducts. The comedo form of
Symptoms: Most patients are asymptomatic. Less commonly, DCIS appears as a mass with ill-defined or lobulated borders on a mammogram, which may or may not be associated with malignant microcalcifications. Screening and diagnosis: On a mammogram, comedo carcinoma manifests as clusters of pleomorphic (manyformed), ductally oriented microcalcifications. In the staging system used to classify cancer, DCIS is known as Stage 0 and is sometimes called precancer. It may also be referred to as tumor in situ (Tis), which means that the cancer is noninvasive. Treatment and therapy: The standard treatment is needle localization and lumpectomy with radiation or simple or modified mastectomy. Prognosis, prevention, and outcomes: Some 20 to 50 percent of women with comedo carcinoma develop invasive cancer five to ten years after initial diagnosis if the cancer is not removed surgically. Debra B. Kessler, M.D., Ph.D. See also Duct ectasia; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas.
u Complementary and
alternative therapies Category: Complementary and alternative therapies Also known as: Complementary and alternative medicine (CAM) Definition: Complementary and alternative medicine (CAM) is defined by the National Center for Complementary and Alternative Medicine (NCCAM) as a group of diverse medical and health care systems, products, and practices not presently considered part of conventional medicine. Differences between complementary and alternative medicine: Complementary medicine is used along with conventional medicine. Conventional medicine includes 309
Complementary and alternative therapies allopathic (medical doctor, M.D.) and osteopathic (doctor of osteopathy, D.O.) medicine. Allied conventional health professionals include nurses, respiratory therapists, and psychologists. Examples of complementary therapies include using aromatherapy or massage to lessen discomfort following surgery or chemotherapy. Alternative medicine is used instead of conventional medicine. Treating cancer with the compound containing amygdalin (trademark Laetrile) in place of undergoing surgery, radiation, or chemotherapy is an example of an alternative therapy. Little reliable evidence exists for Laetrile’s efficacy as a cancer drug, and the U.S. Food and Drug Administration has not approved the use of this compound for cancer treatment. The NCCAM, part of the National Institutes of Health (NIH), defines integrative medicine as a combination of mainstream medicine and those parts of complementary and alternative medicine that have high-quality scientific evidence of safety and effectiveness. The NIH has placed complementary and alternative medicine modalities into five major categories: alternative medical systems, biologically based therapies, manipulative and body-based methods, mind-body interventions, and energy therapies. These provide a useful framework for understanding many different therapeutic approaches to health care. Alternative medical systems: Alternative medical systems are complete care systems, much as conventional medicine is a complete system of theory and practice. These complete systems have central philosophies, such as the healing power of nature, and use therapies in line with these philosophies. These systems include traditional Chinese medicine and other medical systems formulated outside of Western culture, such as American Indian, Tibetan, and Indian (Ayurvedic) systems, as well as homeopathic and naturopathic medicine, formulated within Western culture. Although considered alternative medicine in the United States, traditional Chinese medicine and Ayurvedic medicine are part of the culture and heritage of China and India, respectively, and in these countries they have been practiced for millennia and coexist with conventional medicine. According to the NIH, scientific evidence supports the use of acupuncture, a technique from traditional Chinese medicine, to treat postoperative and chemotherapy-associated nausea and vomiting. Acupuncture may be useful as an adjunct for treating pain-related conditions and other maladies. Naturopathy is a healing system initiated in Europe. It views disease as alterations in the body’s natural healing 310
Salem Health: Cancer processes. Naturopaths believe that the body can heal itself if it is in a healthy environment. They take a holistic approach to the body, looking at the patient’s mind, body, and spirit, and use therapies such as nutrition and herbal medicine, physical medicine, hot/cold compresses, massage, lifestyle and psychological counseling, and detoxification. Scientific evidence does not support naturopathy’s claims. Homeopathy was founded by Samuel Christian Hahnemann in Germany about two hundred years ago. Hahnemann believed that effective remedies must contain substances that produce effects similar to those produced by the diseases they cured, and he called this the principle of similars. Conventional medicine uses a thought process not unlike this principle in vaccine development. Homeopathy emphasizes the careful examination of all aspects of an individual’s health, including mental and emotional states, as well as distinctive physical and personality characteristics. Homeopathy employs liquids or pills that have been diluted from the original substance to the point that sometimes no detectable trace of the original molecule may be found. The manufacturing process involves vigorous shaking between dilution steps, purportedly producing the vital essence of the substance. Homeopathy contends that the memory of the original molecule is retained after the homeopathic dilution process and that the end product is therapeutic even when the original molecule is thinned out of measurable existence. Scientific and clinical evidence of the efficacy of homeopathy is lacking. Biologically based therapies: Biologically based therapies use natural substances such as herbs, vitamins, foods, and other dietary supplements. These substances are formulated in many ways, including tablets, capsules, gel caps, powders, teas, oils, and syrups. Although the idea of a natural substance is very attractive to many consumers, natural products can have serious side effects. Some biologically based therapies, such the use of shark cartilage or Laetrile (a compound containing amygdalin) to treat cancer, lack scientific support, while others have some scientific studies that show their efficacy. Amygdalin is a chemical found in the pits of many fruits. In the presence of certain enzymes, Laetrile breaks down and produces cyanide, a known poison. In addition to lacking effectiveness, Laetrile creates many side effects, mostly related to cyanide poisoning, including cyanosis (bluish skin secondary to oxygen deprivation), uncoordinated walking, liver damage, low blood pressure, and droopy upper eyelids. The essential oils used in aromatherapy are extracted
Salem Health: Cancer from fragrant plants such as chamomile, lavender, lemon, and cedarwood. These oils are inhaled or applied to the skin. Although aromatherapy does not cure cancer, it can help patients with quality-of-life issues. Studies have shown that odors can improve mood, enhance perceptions of health, and reduce anxiety. Allergic reactions and dermatitis have been reported as side effects of aromatherapy. The seeds of milk thistle, a plant native to Europe but also found in North and South America, have been harvested for more than two thousand years for use primarily as a treatment for liver disease. Silymarin, the chemical compound identified as the active ingredient in milk thistle seeds, is a potent antioxidant. It has been shown to help in cases of chronic hepatitis and cirrhosis, and some laboratory studies have indicated that it may increase the ability of some chemotherapeutic agents to treat cancer and decrease the drugs’ toxicity. More research must be done before its true efficacy is known. Few side effects are reported regarding milk thistle. Dietary supplements include vitamins, minerals, herbs, amino acids, enzymes, and organ tissues. Although many people take these types of compounds for health reasons, these supplements are not regulated the same way as are over-the-counter and prescription medications. Prescription medications, in particular, must go through extensive testing and clinical trials and have proven efficacy before they are allowed on the market. Dietary supplements are regulated in a manner closer to the production of salt and pepper than that of prescription medication. Manufacturers of herbs, vitamins, minerals, and other biologically based dietary supplements follow manufacturing guidelines for the production of food. Medications require Food and Drug Administration approval before they can be placed on the market, whereas individual manufacturers of dietary supplements are responsible for the safe production of their products. The Federal Trade Commission monitors dietary supplements for accuracy in advertisement, whereas the Food and Drug Administration regulates the production of prescription medications. These differences in oversight are not usually evident to the consumer, but consumers should be aware that supplements are much different from medications. Manipulative and body-based methods: Body-based therapies are based on movement or manipulation of body parts. Chiropractic or osteopathic manipulation and massage therapy are examples of manipulative and body-based therapies. Rolfing, reflexology, Trager bodywork, Alexander and Bowen techniques, the Feldenkrais method, and many other techniques and therapies are included in this category. The NCCAM reports that appointments with
Complementary and alternative therapies chiropractors and massage therapists represent 50 percent of all visits to complementary and alternative health practitioners. These practices focus on the body’s structural elements, such as bones and joints. Circulatory and lymphatic systems are often emphasized in manipulative and bodybased practices. Some of these techniques were developed over the past two thousand years in traditional systems from China and India, whereas others, such as chiropractic and osteopathic manipulations, arose in the last 150 years. Although many practitioners are formally trained in anatomy and physiology, considerable variability exists in the education and approaches of these providers. For example, osteopaths and chiropractors use manipulations involving rapid movements, whereas massage therapists use techniques involving slower force applications. Manipulative and body-based modalities share some principles, including the body’s ability to heal itself, self-regulation by the human body, and the interdependence of parts of the human body. These characteristics, along with the laying on of hands, are attractive to some health care consumers seeking relief from various ailments. Studies have shown massage to be useful in the short-term relief of pain, anxiety, depression, fatigue, and stress in cancer patients, but there is no scientific support for claims that massage slows the growth or spread of cancer. Mind-body interventions: Mental, emotional, spiritual, and behavioral factors affect an individual’s health. Mindbody therapies focus on these powerful factors and on the interaction between mind, brain, body, and behavior. The therapies are generally based on respecting and enhancing the human capacity for self-care and individual knowledge. Techniques included in this category include hypnosis, meditation, visual imagery, biofeedback, yoga, tai chi, spirituality, support groups, and therapies tapping creative channels such as music, writing, art, or dance. Some of these therapies, such as patient support groups, have become part of integrated or even conventional medicine. Evidence exists that a number of the mind-body therapies have been shown to help strengthen the immune system and reduce pain, anxiety, stress, and depression, thus improving the quality of life for cancer patients. Energy therapies: Energy therapies use two major types of energy fields, biofield and bioelectromagnetic. Biofield therapies claim to manipulate energy fields surrounding and penetrating the body. These energy fields have not been adequately measured or scientifically proven. Some energy therapy techniques try to change biofields by ma311
Complete blood count (CBC)
Salem Health: Cancer
nipulating the body or applying pressure in, on, or through these biofields. Examples include Reiki and Therapeutic Touch. Bioelectromagnetic-based techniques involve using electromagnetic fields, including pulsed, magnetic, alternating-current, or direct-current fields in unconventional manners. Their efficacy for cancer has not been proved.
National Cancer Institute Complementary and Alternative Medicine http://www.cancer.gov/cancertopics/treatment/cam
Perspective and prospects: Conventional health care is disease oriented, tends toward specialty-based care, and is often used after an acute event (a major accident or illness). Allopathic and osteopathic (conventional) medicine becomes more specialty oriented as more scientific mechanisms for disease are discovered. Many people using complementary and alternative therapies are more concerned with maintaining health and optimizing defenses against disease. These people do not reject conventional health care but see conventional health care as an important part of their overall care plan, particularly for acute disease. Those who turn to complementary and alternative therapies after becoming ill typically want to optimize their chances for becoming well. Many therapies previously considered a part of complementary or alternative medicine—such as support groups for cancer patients, hypnosis for smoking cessation, aspirin for reducing inflammation, or digitalis for heart conditions—have become part of mainstream or integrative medicine. Science does not support all modalities of complementary and alternative medicine, but it supports some aspects. The NCCAM, part of the U.S. Department of Health and Human Services, conducts and funds scientific research into nonconventional medicine in an attempt to help medical professionals and the public understand which therapies have been shown to be safe and effective. Richard P. Capriccioso, M.D.
See also Anthraquinones; Antioxidants; Cancell; Carotenoids; Cartilage supplements; Coenzyme Q10; Curcumin; Delta-9-tetrahydrocannabinol; Dietary supplements; Electroporation therapy; Essiac; Ginseng, panax; Green tea; Herbs as antioxidants; Integrative oncology; Laetrile; Mistletoe; PC-SPES; Phenolics; Saw palmetto; Sun’s soup.
u For Further Information Keegan, L. Healing with Complementary and Alternative Therapies. Albany, N.Y.: Delmar, 2001. Peters, David, and Anne Woodham. Encyclopedia of Natural Healing. London: Dorling Kindersley, 2000. Zhang, Qunhao. “Complementary and Alternative Medicine in the United States.” Asia Pacific Biotech News 8, no. 23 (December 1, 2004): 1274-1277. u
Other Resources
MayoClinic.com Complementary and Alternative Medicine http://mayoclinic.com/health/alternative-medicine/ PN00001 312
National Center for Complementary and Alternative Medicine http://nccam.nih.gov
u Complete blood count (CBC) Category: Procedures Also known as: Hemogram Definition: A complete blood count (CBC) is a group of blood tests that provides information about red cells, white cells, and platelets. The tests included are white cell count (WBC); white cell differential (the percentage of each of the white cell types—neutrophils, lymphocytes, monocytes, eosinophils, and basophils); red cell count (RBC); hemoglobin (HGB); hematocrit (HCT); platelet count (PLT); mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC); mean platelet volume (MPV); and red cell distribution width (RDW). The test is performed using whole blood on an automated hematology analyzer. The HCT, MCH, and MCHC are calculated from the measured results of the RBC, HGB, and MCV. MPV is the average size of the platelets. RDW is a calculation based on the red cell indicating the variation in red cell size. A technologist may make a thin smear of the sample on a glass slide, stain it with special dyes, and examine the cells using a microscope. Cancers diagnosed: All Why performed: The CBC is a common screening test. It does not determine a specific type of cancer. The results may lead the physician to order other blood tests and imaging studies that determine the presence of cancer. Chemotherapy and radiation treatments may affect any or all of the tests that make up a CBC. Therefore, a CBC or any part of it is used to monitor treatment.
Salem Health: Cancer
Computed tomography (CT)-guided biopsy
A complete blood count is a common screening test that provides information about red cells, white cells, and platelets. (PhotoDisc)
Patient preparation: No special preparation is needed. Steps of the procedure: A small sample of blood is collected from a vein and placed in a tube. In children, blood may be obtained from a capillary in the heel or finger. After the procedure: A small gauze or cotton ball is applied at the site of needle insertion. The patient is asked to apply pressure. The person collecting the blood observes the site for bleeding and may apply a bandage. The bandage may usually be removed in thirty to sixty minutes. Risks: The risks of CBC include bleeding, bruising, hematoma (bleeding under the skin), fainting, light-headedness, or multiple needlesticks to obtain a sample. Results: Normal CBC levels vary by the patient’s sex and age and the analyzer used. Each laboratory establishes a set of normal ranges based on this information. The physician receives a report of the test results with the normal values. CBC results may be higher or lower than normal depending on the type of cancer, treatment, any bleeding, or infectious processes taking place. Wanda E. Clark, M.T. (ASCP)
See also Aleukemia; Bone cancers; Cachexia; Childhood cancers; Crohn disease; Embryonal cell cancer; Fanconi anemia; Germ-cell tumors; Hairy cell leukemia; Herpes zoster virus; Hodgkin disease; Lambert-Eaton myasthenic syndrome (LEMS); Leukapharesis; Leukemias; Lymphocytosis; Myelodysplastic syndromes; Myeloproliferative disorders; Nephrostomy; Neutropenia; Pneumonia.
u Computed tomography
(CT)-guided biopsy Category: Procedures Definition: A biopsy is needed when a mass has been found on physical examination or from an X ray, magnetic resonance image (MRI), or CT scan. In a CT-guided biopsy, a very thin needle is inserted into the mass while it is being visualized with the CT to withdraw fluid or tissue to be used to determine a diagnosis. CT-guided biopsy can allow a patient to avoid having to go to an operating room 313
Computed tomography (CT)-guided biopsy to have the biopsy completed. Many oncology patients are unable to tolerate an operation, so this procedure is a valuable diagnostic tool. Cancers diagnosed: CT-guided biopsy can be used to help diagnose many different masses located in various organs in the body, such as the lung, liver, kidney, and adrenal glands. Solid tumors are frequently biopsied to determine the type of tumor and how fast it is growing. This information will then be used by the oncologist to determine what type of chemotherapy to use and whether radiation would benefit the patient. Why performed: A biopsy is done to achieve a definitive diagnosis for tumors and masses. In order to ensure that proper treatment is given to the patient, the exact type of cancer must be determined. A mass in the kidney may be kidney cancer or another type of cancer that has spread to that organ. The biopsy can determine what type of cells are present and then what type of therapy would be best to treat that diagnosis. ACT-guided biopsy is done on masses located on internal organs or in deep tissue. Often these
Salem Health: Cancer masses cannot be felt on examination but are found through imaging. Patient preparation: This procedure can be done on both an inpatient and an outpatient basis. Preparation will depend on in what organ or area the mass is located. The patient may receive a sedative or pain medication before the procedure and may also be connected to a cardiac monitor to ensure that no cardiac abnormalities occur. The patient may be asked not to eat anything in the eight hours before the procedure. It is important to identify patients who have claustrophobia, as they may experience anxiety with the CT itself and need medication to decrease this anxiety. Patients may have their blood levels monitored to ensure that they have the ability to clot after a biopsy has been completed. Patients should give informed consent prior to having the biopsy done. Steps of the procedure: The procedure can take as little as twenty minutes to complete. The patient is positioned as comfortably as possible on the back, side, or abdomen to allow for proper access to the area requiring biopsy. The
A patient undergoes a CT scan. (Digital Stock)
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Salem Health: Cancer patient should remain in the same position during the whole procedure. A preliminary CT scan is performed to locate the site for needle insertion for the biopsy. Once this site is determined, the skin is properly cleaned and a numbing medication is injected. The biopsy needle is then inserted through the skin into the mass. Another CT is done to determine where the tip of the needle is resting. When the tip of the needle is in the correct location, then the biopsy, or sample, is taken and prepared for pathology. After the needle is removed, an additional CT is done to ensure that there are no air bubbles or bleeding. After the procedure: After completion of the procedure, the patient is monitored either in the hospital or the recovery room for a few hours and then discharged home. The patient may still be drowsy or dizzy from the medication and should not drive. Risks: CT-guided biopsies are not recommended for patients who have a bleeding disorder or thrombocytopenia. If the patient is or may be pregnant, then special precautions will need to be taken. Risks related to CT-guided biopsies are minimal and include bleeding and infections. It is not recommended that a needle biopsy be done on the spleen because of the tendency of that organ to bleed. There is also a 25 percent risk of a pneumothorax, or collapsed lung, when a biopsy of the lung has been done. Pneumothorax may also occur when biopsies of the liver or adrenal glands have been done. Results: A preliminary evaluation may be done by the physician prior to sending the sample to pathology. Not all physicians may do so. Many times the sample is sent straight to the pathologist for diagnosis and evaluation. The pathologist will be able to determine what the mass consists of and give a diagnosis so that treatment may begin. If the sample size was not sufficient or the pathologist is unable to determine a diagnosis, then a repeat biopsy may need to be done. Katrina Green, R.N., B.S.N., O.C.N. u For Further Information Cooper, Geoffrey M. The Cancer Book: A Guide to Understanding the Causes, Prevention, and Treatment of Cancer. Boston: Jones and Bartlett, 1993. Finn, William G., and LoAnn C. Peterson, eds. Hematopathology in Oncology. Boston: Kluwer Academic, 2004. Klag, Michael J., et al., eds. Johns Hopkins Family Health Book. New York: HarperCollins, 1999.
See also Computed tomography (CT) scan; Cordotomy; Dukes’ classification.
Computed tomography (CT) scan
u Computed tomography (CT)
scan Category: Procedures Also known as: Computed axial tomography (CAT) scan, abdominal CT, brain CT, chest CT, contrast CT scan, conventional CT, cranial CT, CT-guided biopsy, electron-beam CT scan, full body CT scan, helical CT scan, lumbosacral CT, multislice CT scan, orbit CT, pelvic CT, spiral CT, thoracic CT, 3D CT, virtual bronchoscopy, virtual colonography, virtual colonoscopy, virtual CT, virtual endoscopy, volumetric CT scan Definition: A computed tomography (CT) scan is a radiological imaging test used to create cross-sectional slice images of a portion of or the entire body. The slice images are stacked to create three-dimensional images. CT images provide more anatomical detail than X rays. Cancers diagnosed: Most Why performed: CT is a valuable tool for screening for cancer, locating tumors, performing guided biopsy, identifying cancer that has spread, staging cancer, planning and monitoring cancer treatment, and checking for cancer recurrence. CT can identify blood vessels that support a tumor, as well as the tumor’s shape, size, location, and volume. CT scans are used with procedures to diagnose cancer, such as needle-guided biopsies. They are used in cancer treatments, such as radiofrequency ablation and interstitial therapy. CT images are archived in computers or printed form. Images are printed on film or with laser imaging. They can be sent and viewed online within a facility and can be compared for changes over time. Conventional CT was developed in the early 1970’s. CT uses controlled amounts of thin, high-energy radiation beams. Images are taken from a variety of angles. A computer calculates information about the images and produces a slice image of a specific area of the body. CT can be taken of the entire body or a specific section. Dye is used to enhance images to show more detail and contrast. The contrast dye can be swallowed, received intravenously, or administered in an enema. CT has evolved to become faster and to use lower doses of radiation. Spiral or helical CT allows images to be collected quickly. The rapid process helps compensate for movements or breathing that otherwise can blur images. Additionally, spiral CT produces thinner slices of images that show even greater detail. A computer stacks the images to create three-dimensional, rotational pictures of a 315
Computed tomography (CT) scan tumor. Spiral CT is especially useful for imaging liver, lung, and pancreatic cancer. Recent technology allows doctors to use CT with endoscopy to create virtual endoscopy, virtual bronchoscopy, and virtual colonoscopy or CT colonography. The process uses a computer to create and manipulate threedimensional images to create a “fly-through” view of an organ, as seen on endoscopy. CT is used to guide surgeons precisely during procedures. CT is used with needle aspiration biopsy for tumors, such as for breast cancer biopsies. The CT guidance eliminates the need for invasive exploratory surgery. CT is used to guide certain radiation treatments. For example, interstitial therapy uses CT guidance to insert radioactive material into a tumor. CT is also used to create a three-dimensional image of a tumor to allow external beam radiation to precisely target the tissue and spare as much healthy tissue as possible. Patient preparation: CT scans may not be appropriate for some people. Patients should let their doctor know if they have diabetes or kidney disease or if they are pregnant. Some facilities conduct a pregnancy test on all women prior to scanning because the radiation can be dangerous to a developing fetus. Children, patients with movement disorders, or patients that are claustrophobic may receive a mild sedative prior to the test. In extreme situations, people may be sedated if they are not able to remain still while the images are taken. Some CT machines may not be used for people that weigh more than three hundred pounds because of size parameters of the machinery. About 5 percent of patients are allergic to contrast dye. Patients should let their doctor know if they are allergic or sensitive to contrast dye, iodine, or shellfish. CT scans are outpatient procedures performed at a hospital radiology department or freestanding radiology center. Patients will receive instructions prior to their procedure, which vary depending on which procedure is conducted. Patients may be instructed not to eat or drink for several hours before the CT. Some patients need to use an enema or laxatives. Patients may need to drink a liquid contrast agent before arriving at the clinic or upon arriving at the clinic. Patients wear an examination gown or robe for the procedure. They must remove metal objects that can interfere with the imaging process, such as jewelry, hearing aids, hair clips, glasses, or dentures. Steps of the procedure: Patients are led into the imaging room. A radiology technologist conducts the CT. Patients lie on a narrow table. The technologist may use positioning devices to help patients maintain specific postures for 316
Salem Health: Cancer the test. Head-stabilizing devices may be used for brain scans. Patients may be instructed to change positions throughout the procedure. During the CT scan, the radiologist technician steps into a room that is separated by a glass partition. The radiologist is in constant contact with the patient via a microphone and intercom system. The radiologist technician operates the CT machine. To take a CT, the table slides into the doughnut-shaped hole of the scanner. Patients must remain motionless while the images are taken. Patients are instructed to take a deep breath and hold it until they are told to exhale. The CT scanner has an X-ray component that emits beams at specific angles. The beams pass through the body and are detected by equipment on the opposite side. The equipment makes buzzing or clicking noises while the scanner is employed. Patients receiving a contrast material may have a CT scan first, receive the contrast material, and then receive a final CT scan. An intravenous (IV) line is inserted into the hand or forearm to deliver injected contrast material. Contrast material may be swallowed. An enema is also used to insert contrast material for gastrointestinal-related CT scans. The contrast material may make patients feel temporarily warm or flushed. The actual CT scan is short, but the preparation and positioning time makes the procedure last from about ten to thirty minutes. Spiral CTs are shorter in length. Patients are asked to wait until it is confirmed that the images are clear. Patients are observed for allergic reactions for a short time following the procedure. After the procedure: There are usually no aftercare procedures following CT. If the patient has received sedating medication, a friend or relative must drive the patient home. Risks: Patients may experience an allergic reaction to the contrast dye. The symptoms include hives, shortness of breath, nausea, wheezing, itching, or a bitter taste in the mouth. Severe allergic reaction or anaphylactic shock is a rare risk. Radiation from CT is higher than that of standard X rays. CT is not recommended for pregnant women; the risks to others are minimal. Results: CT images are read by a radiologist and conveyed to the ordering doctor. The doctor may view the images as well. CT images depict anatomical structures in black, white, and shades of gray. Air, soft tissue, hard tissue, fluids, and the contrast agent show details that otherwise cannot be seen. Abnormal results show different characteristics from what is expected, such as tumors,
Salem Health: Cancer
Conization
cysts, cancer metastasis, tumor density, tumor composition, enlarged lymph nodes, or atypical fluid accumulations. In some cases, CT can help differentiate between types of tumors. Mary Car-Blanchard, O.T.D., B.S.O.T. u For Further Information Applegate, K. “Pregnancy Screening of Adolescents and Women Before Radiologic Testing: Does Radiology Need a National Guideline?” Journal of American College of Radiology 4, no. 8 (August, 2007): 533-536. Ishikawa, S., et al. “Mass Screening of Multiple Abdominal Solid Organs Using Mobile Helical Computed Tomography Scanner: A Preliminary Report.” Asian Journal of Surgery 30, no. 2 (April, 2007): 118-121. Sone, S., et al. “Long-Term Follow-up Study of a PopulationBased 1996-1998 Mass Screening Programme for Lung Cancer Using Mobile Low-Dose Spiral Computed Tomography.” Lung Cancer, August 3, 2007.
See also Angiography; Bone scan; Brain scan; Bronchography; Computed tomography (CT)-guided biopsy; Cystography; Ductogram; Endoscopic retrograde cholangiopancreatography (ERCP); Gallium scan; Hysterography; Imaging tests; Lymphangiography; Magnetic resonance imaging (MRI); Mammography; Nuclear medicine scan; Percutaneous transhepatic cholangiography (PTHC); Positron emission tomography (PET); Radionuclide scan; Thermal imaging; Thyroid nuclear medicine scan; Urography; X-ray tests.
u Conization Category: Procedures Also known as: Cone biopsy, cold-knife conization, loop electrosurgical excision procedure (LEEP) Definition: Conization is the surgical excision of an en bloc section of the cervix to diagnose suspicious lesions that may be precancerous or overt cancer. Cancers diagnosed: Precancerous lesions, such as highgrade suspicious intraepithelial lesions (HGSIL) or cervical intraepithelial neoplasia II or III; cervical cancer Why performed: Conization of the cervix is performed when complete microscopic visualization (colposcopy) of all lesions is inadequate or inconclusive or reveals inconsistent results when compared to a Pap smear. Although a Pap smear and colposcopy detect 58 to 89 percent of all precancerous and cancerous lesions, conization can pro-
Cervical conization, showing the area to be excised. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams & Wilkins. All rights reserved.)
vide a definite pathological diagnosis. Conization can also be therapeutic if the entire lesion is removed and frank involvement of other organs (vagina, uterus bladder, or rectum) is absent. Patient preparation: The patient undergoes preoperative evaluation, including blood workups to determine her fitness to undergo surgery and general anesthesia. Patients are instructed to take nothing by mouth the night before the procedure. Steps of the procedure: After the patient is anesthetized and prepared, the cervix is visualized. Local anesthesia is administered if the patient is not under general anesthesia. The cone base area is determined by applying Lugol’s solution. The uterine depth is determined prior to incising. Incision is done in a circular, centrally angled fashion. A suture at the twelve o’clock position of the specimen is placed. Curettage of the remaining ectocervix is done to detect any lesions above the cone tip. Cautery or ligation of any bleeding vessels and vaginal packing is done. After the procedure: The patient is monitored in the postanesthesia care unit until she is fully awake and ambulatory and her vital signs are stable. Once stable in unit, the 317
Continuous hyperthermic peritoneal perfusion (CHPP) patient may be discharged on the same day. Admission for overnight observation is warranted if the patient is unstable or other medical problems need to be managed. Risks: The most significant risk is miscarriage in women (10 percent) who intend to become pregnant after conization. Only specialists experienced in managing the potential complications should care for these patients. Other risks include excessive intraoperative or postoperative bleeding for as many as ten to fourteen days (30 percent), cervical narrowing as a result of scarring, perforation of adjacent organs, and infertility. Results: A benign histologic examination of the specimens may reveal increased but orderly normal cell growth within the lesion but no elements of disordered growth of abnormal cells. Histologic examination of the specimens that reveals disordered proliferation and abnormal cellular characteristics is suggestive of cervical cancer. Aldo C. Dumlao, M.D. See also Biopsy; Cervical cancer; Colposcopy; Endoscopy; Gynecologic cancers; Hysterectomy; Loop electrosurgical excisional procedure (LEEP); Pap test; Pregnancy and cancer; Vulvar cancer.
u Continuous hyperthermic
peritoneal perfusion (CHPP) Category: Procedures Also known as: Intraperitoneal hyperthermic perfusion, intraperitoneal hyperthermic chemotherapy Definition: Continuous hyperthermic peritoneal perfusion (CHPP) is a procedure that delivers highly heated fluid containing chemotherapeutic agents directly to the abdominal cavity, often during or immediately after abdominal surgery. Cancers treated: Primary mesothelioma; primary stomach cancers; recurrent or widely spread ovarian cancers; recurrent colon cancer; cancers in the lung, breast, or appendix that have spread Why performed: The benefits of CHPP are twofold. First, hyperthermia increases cancer cell sensitivity to other treatments (radiotherapy and chemotherapy) and increases the effectiveness of some chemotherapy (such as mitomycin-C) through improved pharmacokinetics. Second, regional administration allows for the direct treatment of errant cancer cells that remain after tumor excision while preserving noncancerous cells. 318
Salem Health: Cancer Patient preparation: Preparation is similar to that of any abdominal surgery. The patient’s bowel must be cleansed, and the patient must fast on the day of the procedure. Before surgery and CHPP, intravenous lines are inserted, and general anesthesia is administered. During surgery, the body temperature may be allowed to drop by 3 to 5 degrees Fahrenheit to accommodate impending hyperthermia. Steps of the procedure: The effectiveness of CHPP is related to the maintenance of a narrow temperature range for a prescribed time, so administration must be monitored closely. First, fluid-delivery tubing and thermometer probes are inserted into the abdominal cavity. Fluid is heated outside the body and is pumped in via catheter to bathe the area, usually at 106 to 108 degrees Fahrenheit, for forty-five minutes to two hours. Then, the fluids are removed with draining tubes. After the procedure: After CHPP, the patient’s incision is closed as with any abdominal surgery. Initial recovery in the intensive care unit (ICU) involves the evaluation of surgical recovery and may require temporary feeding tubes. Risks: Because surgery and CHPP are often performed together, it is difficult to separate their complications, which include bleeding, infection, and wound-healing problems. Although most normal tissue remains intact to 111 degrees Fahrenheit, the death of normal cells is possible with hyperthermia. Most adverse effects of CHPP are temporary and include local pain, local blood clots, and burns or blisters to the skin, muscles, and nerves. More seriously, damage to blood vessels or to the lungs and heart may occur. Results: Like systemic chemotherapy, the goal of CHPP is to destroy cancer cells in the peritoneal cavity. Unlike systemic therapy, CHPP aims to eradicate lingering cancer cells directly without affecting normal cells. Nicole M. Van Hoey, Pharm.D. See also Hyperthermic perfusion.
u Cordectomy Category: Procedures Also known as: Vertical hemilaryngectomy, partial laryngectomy Definition: A cordectomy is a surgical procedure for treating laryngeal cancer. It entails resection of an entire vocal cord, the surrounding soft tissue, and the inner lining of the thyroid cartilage. Cancers treated: Laryngeal (glottic) carcinoma
Salem Health: Cancer Why performed: In defining treatment protocols, the larynx is divided into three anatomical regions: supraglottis, glottis, and subglottis. The distribution of carcinoma among these regions is estimated at 40:59:1. Glottic carcinomas are the most common and readily detected because of the prompt development of symptoms (hoarseness, sore throat, and dysphagia). Early-stage glottic carcinoma can be treated effectively by a single modality, utilizing surgery or radiation. Radiation therapy will provide 85 percent local control for T1 (Stage 1) glottic cancer and local control in 65 percent of T2 (Stage 2) lesions. Vertical hemilaryngectomy (cordectomy) can achieve local control rates of 95 percent for T1 lesions and 80 percent for T2 lesions. Overall, surgery provides better local control, but the potential benefit of radiation therapy has been voice preservation. Patient preparation: A routine preoperative workup and assessment of anesthetic risks are required. Prior to any surgery for laryngeal cancer, physical examination of the larynx is accomplished with indirect mirror visualization or by direct laryngoscopy. Magnetic resonance imaging (MRI) scans are employed to evaluate tumor size, location, airway patency, and cartilage involvement. Steps of the procedure: With the patient under general anesthesia, surgical exposure is performed through a traditional transcervical incision. Exposure of the vocal cords is achieved through a laryngofissure approach (a midline incision through the thyroid cartilage). Carbon dioxide (CO2) laser cordectomy is now an alternative surgical option. Carried out as an endoscopic procedure, it can be performed on an outpatient basis. The single disadvantage with this procedure is the problem of evaluating free (healthy) tissue margins, especially on frozen section. After the procedure: With traditional cordectomy, the patient stays in the hospital for a few days so that vital signs, incision site, and respiratory status can be monitored. Patients undergoing laser cordectomy are required to stay only for observation (three to four hours) to detect any signs of airway obstruction. Postoperatively, an adult companion should remain with the patient for the first twenty-four hours. Risks: The specific risks of cordectomy involve speech problems, airway obstruction, and aspiration. General surgery risks include postoperative infection, scarring, and potential neurologic-vascular compromise to the operative area.
Cordotomy Results: The success of postoperative rehabilitation depends on anatomic and patient factors. The extent of the surgery, the type of reconstruction, and the utilization of radiation are important anatomical factors. Patient factors include motivation, dexterity, and access to speech therapy. John L. Zeller, M.D., Ph.D. See also Electrolarynx; Esophageal speech; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy; Throat cancer; Tracheostomy.
u Cordotomy Category: Procedures Also known as: Open or closed cordotomy, unilateral or bilateral cordotomy Definition: Cordotomy is a surgical procedure that disables selected sensory tracts contained within the spinal cord (interruption of the lateral spinothalamic tract). The procedure is commonly performed on patients experiencing severe pain as a result of cancer. Anterolateral cordotomy is effective in relieving unilateral, somatic pain while bilateral cordotomy may be required for visceral or bilateral limb pain. Cordotomy is usually done percutaneously (stereotactic technique) with fluoroscopic guidance while the patient is under local anesthesia. Open cordotomy is not recommended for patients with unstable medical conditions but may be required if percutaneous cordotomy is not feasible or a previous attempt has failed. Cancers treated: This surgical technique addresses the management of cancer pain that does not respond to oral analgesics. Why performed: Pain is experienced by up to 75 percent of patients with advanced cancer. Between 25 and 30 percent of these patients report the pain as severe or excruciating. Intraspinal procedures are the last of a long treatment continuum that includes the following: • systemic regimens utilizing medications and physical therapy • direct operations for spinal decompression or stabilization • psychological protocols • chemotherapy and/or radiation therapy • regional anesthetics and opioids The extensive number of available drugs has resulted in adequate control of discomfort from most malignant cancers. For a small number of cancer patients, however, re319
Cordotomy ferral for anesthetic or neurosurgical procedures for pain management is still needed. The optimal candidate for this operation should have unilateral, severe pain in the fifth cervical vertebra (C5) or lower dermatomes that is not treated adequately by less invasive methods. Cordotomy appears to be more effective in the treatment of intermittent shooting pains rather than distressing dysesthesias (burning, prickling pain, or aching). It is indicated for localized, not general, pain and is not usually indicated for pain in the upper torso because of the risk of respiratory complications. Patient preparation: The procedure is usually done on an outpatient basis. Patients are instructed not to eat or drink anything for five hours prior to the procedure. In cases where open surgery is required, patients should not eat or drink for twenty-four hours prior to the surgery. In both cases, someone should drive the patient to and from the procedure and stay with the patient for at least eighteen to twenty-four hours afterward. Steps of the procedure: The patient is placed in a supine position with the upper cervical spine in a horizontal position. The patient is given light intravenous sedation. Using local infiltration of anesthesia between the first and second cervical vertebrae, the physician introduces a cordotomy needle in the side of the neck on the side opposite that of the perceived pain. An image intensifier is used to define the point of the dural puncture. Once the needle has been introduced into the subarachnoid space of the spinal cord, a contrast medium is injected to visualize the surrounding anatomy. A special insulated electrode is inserted through the needle. With monitoring, the electrode is directed into the spinal cord. An electrical cable line is attached to the electrode, and the tip is stimulated with an electrical current. During each stimulation, the patient is closely questioned about sensory changes and motor twitching. In this setting, portions of the spinothalamic tract are destroyed to result in a desired level of analgesia. Disturbances in temperature sensation are usually seen as a result of these cordotomy lesions. The CT-guided cordotomy technique is similar to this traditional percutaneous method except that the cordotomy electrode needle is inserted with the patient in a computed tomography (CT) machine. In selected cases, an open cordotomy is needed. The patient is completely anesthetized, placed in a prone position, and undergoes a traditional surgical exposure. A laminotomy is performed at the level of the first and second thoracic vertebrae (T1 and T2), and the spinal cord is directly visualized. Placement of the electrode is accom320
Salem Health: Cancer plished with C-arm fluoroscopy, and disruption of the spinothalamic tract is electrically monitored. After the procedure: Postoperative care consists of observation for ipsilateral leg weakness, changes in bladder control, significant lower medication requirements, and possible respiratory depression. Hospitalization is usually for one or two days. Risks: The complication rate from unilateral cordotomy is low, with a mortality rate between 0.6 and 6.0 percent. Bowel incontinence and bladder dysfunction can be seen in 2 to 10 percent of patients. Although information relative to sexual function is difficult to obtain, reports of impotency are rare. Transient hypotension can occur in 2 to 8 percent of cases. Permanent muscle weakness with ataxia (difficulty in walking) can be a major concern in 1 to 6 percent of patients. Respiratory problems are mild and transient, but respiratory failure has been documented in 1 percent of patients. Postcordotomy dysesthetic syndromes (burning distress throughout the entire area that was made analgesic) can occur in 1 to 10 percent of patients. Their pathophysiologic mechanisms are unknown. Open surgical cordotomy seems to be less effective and certainly has a higher risk of complication than do percutaneous techniques. Results: Cordotomies are performed to treat cancer pain, often from lung or gastrointestinal malignancies. The procedure has been rarely employed in the treatment of lumbar radiculopathy or peripheral neuropathy. The target sites are the lower body as opposed to the upper body in about two-thirds of patients. In the hands of experienced surgeons, the spinothalamic tract can be located in 95 percent of patients. Adequate levels of pain relief are found in as high as 95 percent of patients on discharge from the hospital. At last follow-up, the success rate drops to 84 percent. Review of the literature realistically suggests longterm success rates of 50 to 75 percent. Repeat cordotomies may be necessary in 10 percent of patients. John L. Zeller, M.D., Ph.D. u
For Further Information Crul, B., L. Blok, and J. van Egmond. “The Present Role of Percutaneous Cervical Cordotomy for Treatment of Cancer Pain.” Journal of Headache Pain 6, no. 1 (February, 2005): 24-29. Giller, C. A. “The Neurosurgical Treatment of Pain.” Archives of Neurology 60 (2003): 1537-1540. Jones, B., et al. “Is There Still a Role for Open Cordotomy in Cancer Pain Management?” Journal of Pain and Symptom Management 25, no. 2 (2003): 179-184.
Salem Health: Cancer
Corticosteroids
Loeser, John D., ed. Bonica’s Management of Pain. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2001. Raj, P. Prithvi., ed. Pain Medicine: A Comprehensive Review. 2d ed. St. Louis: Mosby, 2003.
After the procedure: Either a suture (stitch) or Steri-Strip (adhesive paper) is applied to close the edges of the incision. A sterile dressing is applied over the biopsy site. The patient is monitored for one hour after the biopsy.
See also Infusion therapies; Pain management medications; Palliative treatment.
Risks: The risks of core needle biopsy are bleeding from the biopsy site, local nerve damage, infection, and, for lung biopsies, pneumothorax (collapse of a lung).
u Core needle biopsy Category: Procedures Also known as: Stereotactic (exact) biopsy, Mammotome biopsy, Advanced Breast Biopsy Instrument (ABBI) biopsy Definition: A core needle biopsy is a procedure in which a sample of a tumor is extracted by using a wide-gauge hollow needle, a Mammotome, or an ABBI. The Mammotome and the ABBI are used for breast biopsies only. A core needle can range in size from 0.25 to 1.0 centimeter in diameter. It has a spring-loaded device that suctions out the tissue sample. The Mammotome suctions in breast tissue and cuts it with a rotating blade. The ABBI extracts a cylinder of breast tissue about the size of the tumor. Cancers diagnosed: Breast, prostate, kidney, musculoskeletal, and skin cancers Why performed: Needle biopsies are performed to obtain tissue samples from a tumor that is suspected of being cancerous. Patient preparation: If a core needle biopsy is performed in a physician’s office, then ultrasonic guidance is used to localize the tumor, unless it is palpable. If it is palpable, no radiologic guidance is required. Needle biopsies that require the use of radiologic imaging to visualize the tumor or that are high risk are performed in an outpatient surgical center or hospital. The preparation for these procedures may include a physical examination, blood work, and possibly an electrocardiogram (EKG). The patient would need to fast for two to four hours before the procedure. Steps of the procedure: The patient is positioned so that the area to be biopsied is exposed. This area is then scrubbed and disinfected. A local anesthetic is injected into the area. If the tumor is not superficial, then a small incision (0.125-inch to 0.25-inch long) is made into the tissue above the tumor. The core needle is inserted through the incision, and several tissue samples are taken.
Results: The biopsied tissue is sent to a pathologist to be examined under a microscope. The surgeon receives a report that describes the size, shape, and activity of the cells and their nuclei and states whether the tumor is cancerous. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Biopsy; Breast cancer in pregnant women; Calcifications of the breast; Clinical breast exam (CBE); Computed tomography (CT)-guided biopsy; Needle biopsies; Needle localization; Pleural biopsy; Progesterone receptor assay; Stereotactic needle biopsy.
u Corticosteroids Category: Chemotherapy and other drugs ATC code: H02-systemic, D07-dermatological, S02sensory organs, M01-musculoskeletal Definition: Corticosteroids are synthetic forms of the naturally occurring hormones produced by the cortex of the adrenal gland. Cancers treated: Brain cancer, lymphomas, leukemias, lung cancer, renal cancer, bone cancer Subclasses of this group: Systemic-short-acting, systemicintermediate-acting, systemic-long-acting, inhaled, topical, intranasal, ophthalmic, intra-articular (into a joint) Delivery routes: These drugs can be taken orally as tablets. There are solutions that may be administered intravenously. They can also be inhaled from metered dose or disk inhalers, instilled into the nostrils, applied to the skin, or dropped into the eyes. In addition, steroids may be injected into inflamed joints in the body. How these drugs work: Corticosteroids are used primarily to suppress the immune response of the body in instances when this response is causing troublesome symptoms and/or damaging the tissues of the body. They accomplish this by decreasing the activity of white blood cells and the production of the chemicals that are involved in the symptoms of inflammation. By decreasing inflammation, corticosteroids can often decrease the symptoms of cancer and chemotherapy. 321
Coughing
Salem Health: Cancer
Common Corticosteroids Drug
Brands
Subclass
Delivery Mode Cancers Treated
Beclomethasone
Vanceril, QVAR
Inhaled
Inhalation
Lung cancer
Betamethasone
Celestone
Long-acting
Oral, IV
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Dexamethasone
Decadrol, Decadron
Long-acting
Oral, IV
Brain tumors
Fluticasone
Flovent
Inhaled
Inhalation
Lung cancer
Hydrocortisone
Solu-Cortef, Cortef, Hydrocortone
Short-acting
IV
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Methylprednisolone Medrol, Solu-medrol
Intermediate-acting Oral, IV
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Prednisolone
Delta-cortef, Hydeltrasol, Intermediate-acting Oral, IV Predacort, Prednisol
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Prednisone
Deltasone
Intermediate-acting Oral
Lymphomas; leukemia; multiple myeloma; gastrointestinal, ovarian, bone, liver, and renal cancers
Triamcinolone
Azmacort
Inhaled
Lung cancer
Side effects: Systemic corticosteroids have many side effects, including increased appetite, weight gain, insomnia, mood swings, muscle weakness, increased growth of body hair, easy bruising, swollen face, acne, stomach irritation, restlessness, cataracts, glaucoma, and water retention. They can cause medical problems such as osteoporosis, worsening of diabetes, and high blood pressure, as well as psychiatric problems such as depression and anxiety. Because they depress the immune response, corticosteroids can increase a patient’s susceptibility to infections. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Antinausea medications; Chemotherapy; Pain management medications.
u Coughing Category: Diseases, symptoms, and conditions Also known as: Hacking, barking, expectorating, hawking, whooping, tussis Related conditions: Asthma, pneumonia, lung cancer, melanoma, lymphomas, thyroid cancer, sarcomas, leuke322
Inhalation
mia, and cancer metastasis (spread of cancer) from primary locations such as the breast, kidney, colon, stomach, rectum, prostate, testis, and bones Definition: Coughing is the sudden and noisy expulsion of air from the chest in response to an irritation in the airway or respiratory tract. Coughing causes a repetitive contraction of the thorax. Etiology and the disease process: The purpose of coughing is to naturally clear the airway and throat of irritants or foreign bodies. Coughing is usually a reflex triggered by irritants that stimulate the cough receptors of the respiratory system. A cough starts with a deep breath and occurs when the diaphragm and chest muscles press on the lungs, forcing the air out through the throat. Coughing clears the airway or lungs of phlegm (sputum). Sometimes a dry cough occurs with postnasal drip, asthma, gastroesophageal reflux disease, or in response to medications such as beta-blockers for blood pressure or aspirin. Smoking is a common cause of coughing. Chronic or persistent coughing lasting two to three weeks with no obvious source usually indicates underlying disease. A cough that lasts months may indicate lung cancer or metastatic cancer.
Salem Health: Cancer Incidence: Coughing is a natural response to respiratory irritants, so almost everyone coughs at some time. When seen by a health care provider for a cough, nonsmokers with a normal chest X ray will receive a benign diagnosis about 93 percent of the time. However, one of the primary signs of lung cancer is persistent or chronic coughing over an extended time, often with bloody sputum. Over 90 percent of lung cancers start in the bronchi or large tubes that branch off the trachea (the airway that allows air to enter the lung). Lung cancer is the leading cause of cancer death in both women and men, causing an estimated 160,440 deaths in 2004. About 90 percent of lung cancer in men and 80 percent in women occurs in smokers. Coughing is often a symptom. Symptoms: Any persistent cough lasting over two weeks should be evaluated by a health care provider. Coughing up bloody or rust-colored mucus (hemoptysis) from the lungs may indicate metastasis of the primary cancer for a cancer patient. Lung cancer can result in narrowing of the bronchial tubes, causing wheezing and coughing. Screening and diagnosis: Several tests can be used to determine the cause of persistent coughing. A chest X ray is a noninvasive screening tool that takes a picture of the chest, heart, lungs, ribs, arteries, and diaphragm. A radiologist examines the X ray to determine if the patient has conditions such as infections from pneumonia or bronchitis, scarred lung tissue, collapsed lung, tuberculosis, lung cancer, or lung tumor. Acomputed tomography (CT) scan will show smaller tumors or nodules undetected by a screening X ray. Another diagnostic tool is the sputum specimen. The patient produces a deep cough and collects the mucus in a cup. Cultures are collected from the sputum and examined for bacteria or blood. A positive culture confirms abnormal results and indicates a disease is present. A bronchoscopy is a diagnostic procedure using a flexible or rigid tube put down the nose or throat into the lungs. The health care provider can extract samples of tissue (biopsy) or fluids and lung cells for further examination. This is usually an outpatient procedure. Lung cancer is diagnosed through this procedure and the accompanying biopsy examination. Treatment and therapy: Treatment for coughing depends on the underlying cause. Coughing is generally treated with medications such as cough suppressants and expectorants to loosen the mucus so that it can be expelled. Some cough medications are over the counter (OTC), while others such as codeine require a doctor’s prescription.
Coughing Surgery or chemotherapy may be indicated for a lung tumor. In secondary lung cancer, the malignancy has spread (metastasized) from a primary or distal site to the lungs; radiation therapy may alleviate the coughing by reducing the size of the cancer. If the irritation is coming from a blocked airway, laser therapy can sometimes burn the tumor out of the airway; a tube (stent) is inserted to relieve the pressure and hold the airway open. Prognosis, prevention, and outcomes: The prognosis for coughing depends on the underlying cause. Because research has confirmed that smoking can cause lung cancer, prevention translates into not smoking. If the coughing is benign or nonmalignant (not cancer related), coughing can be prevented by minimizing exposure to the offending cause. The outcome should be positive if the irritant is removed. Avoiding fumes and toxic chemicals as well as known allergens can decrease the incidence of coughing and possible lung cancer. If the coughing is related to lung cancer, treatment of the cancer may decrease the respiratory irritation from the cancer. Marylane Wade Koch, M.S.N., R.N. u
For Further Information Homsi, Jade, Declan Walsh, and Kristine A. Nelson. “Important Drugs for Cough in Advanced Cancer.” Supportive Care in Cancer 9, no. 8 (November, 2001). Meuser, T., et al. “Symptoms During Cancer Pain Treatment Following WHO Guidelines: A Longitudinal Follow-up Study of Symptom Prevalence, Severity, and Etiology.” Pain 93, no. 3 (September, 2001): 247257. Redington, Anthony E., and Alyn H. Morice, eds. Acute and Chronic Cough. Boca Raton, Fla.: Taylor and Francis, 2005. Roth, Jack A., James D. Cox, and Waun Ki Hong, eds. Lung Cancer. 3d ed. Malden, Mass.: Blackwell, 2005.
u
Other Resources
American Cancer Society http://www.cancer.org American Lung Association http://www.lungusa.org Lung Cancer Alliance http://www.alcase.org National Cancer Institute http://www.cancer.gov See also Bronchial adenomas; Bronchoalveolar lung cancer; Bronchoscopy; Hemoptysis; Lung cancers; Pneumonia; Smoking cessation; Sputum cytology. 323
Counseling for cancer patients and survivors
u Counseling for cancer patients
and survivors Category: Social and personal issues Definition: Counseling involves the services and service providers available to help people with cancer, those who have survived cancer, and their families cope with the physical and psychological effects of the illness, during and after medical treatment. Why counseling might be needed: Those diagnosed with cancer, and their families, face many complex issues at all stages of the illness. The experience of being diagnosed with, and treated for, cancer changes every aspect of life: The person suddenly is faced with combating a disease with an uncertain outcome. Patients must strive to cope with the physical aspects of cancer, including pain, fatigue, and treatment side effects, as well as psychological and emotional issues, such as fear, stress, anger, denial, change in physical appearance, loss, death, anxiety, and even guilt. Families and caregivers also experience intense emotional reactions. In addition, the person with cancer may need to address financial and legal issues, spiritual issues, and the practical aspects of living with cancer. Together, these emotional and practical concerns often are referred to as psychosocial issues. Thus, a person who has cancer (and his or her family members) may seek counseling for help with a specific issue or feeling (such as death), for support in working through the many emotions encountered throughout treatment, or simply to “talk through” the experience with someone else and to retain a sense of meaning in life. It is important for both the patient and family to understand that seeking help to address these issues can be beneficial and requires a great deal of courage. Emotional and psychological problems: Some patients might encounter psychological problems resulting from cancer treatment. Depression, for example, can be caused by some types of chemotherapy. In addition, patients inevitably experience emotional reactions to physical changes created by some types of cancer therapy, such as hair loss or weight changes. Sometimes, emotional or psychological problems can create physical reactions, such as a rapid heartbeat, tense muscles, or insomnia. Further emotional difficulty is created if a patient must face the disease and treatment without any emotional support. In contrast, other patients may be surrounded by family and friends but nevertheless feel isolated and lonely. The person’s “developmental stage” will affect how he or she feels about, and deals with, the emotions surround324
Salem Health: Cancer ing cancer. Children and teenagers, for example, experience different emotions from adults. In short, every patient experiences different emotions and reacts differently. These emotions, as well as an overwhelming feeling of helplessness and lack of control over life, may affect the person’s ability or motivation to seek medical or psychological treatment. The emotions themselves often feel very foreign to the person experiencing them, and this alone can introduce additional fear and anxiety. Reactions of family and caregivers: Family, friends, spouses, parents, and colleagues—indeed, everyone involved with the person who has cancer—is affected by it and responds in his or her own way. It is important that those involved understand that everyone’s reactions affect one another, including the patient. For instance, family members may experience fear and anxiety, just like the patient, but may keep it to themselves in an effort to “protect” the patient. Often, this lack of communication between caregivers and patient may be more damaging than helpful. It is equally important to address the emotions experienced by the family in order to benefit both the patient and family. Problems with practical issues: Many practical aspects of life may be affected by cancer. These include financial difficulties, as well as problems with employment, education, and obtaining health care services. Addressing these problems can help patients and families feel some sense of control in their lives, despite the uncertainty of cancer. Types of counselors and what they do: Many types of counselors and counseling services are available to help cancer patients and their families. Yet, there now is so much information available, it can be difficult to know where to begin to find help and what type of help different service providers can offer. • Medical staff involved in the patient’s care may help patients address some of the issues listed above. Yet, there are many people who are trained specifically to address the emotional, psychological, and practical issues that patients face. These service providers may be employed by hospitals, government agencies, or private organizations, or they may work in private practice. • Genetic counselors help people who are concerned about inherited forms of cancer and their family’s or their own risk for certain types of cancer. Training includes a master’s degree with work in medical genetics and counseling. Many genetic counselors also are certified by a professional board. • Medical social workers help patients find and access various services (such as financial advice or at-home care)
Salem Health: Cancer needed during and after treatment. Some social workers also may be trained to help patients and families address emotional issues. Training includes a bachelor’s degree and usually a master’s degree in social work (M.S.W.) and state licensure. • Mental health counselors work specifically with the emotional and psychological issues affecting patients and families. The counselor may work individually with the patient and/or with the patient’s family members. Some counselors specialize in working with illness-related issues. Training usually includes a master’s degree in psychology or a related area (M.S. or M.A.P.) and state licensure. • Nurse practitioners are registered nurses who have completed additional training (usually a master’s degree) in managing specific medical conditions, including cancer. The nurse usually provides medical services but also may advise patients on psychosocial issues. Often, nurses talk through issues with patients during medical checkups or treatments. • Oncology nurses are registered nurses (with advanced certification or a bachelor’s degree in nursing) who spe-
Counseling for cancer patients and survivors cialize in working with cancer patients. These nurses provide a broad range of medical services, which also may include addressing psychosocial issues. • Pastoral counselors address emotional and psychological issues affecting patients and families within the context of a specific religious orientation (usually Christian). Training includes a master’s degree in psychology or divinity (M.Div.), with further state licensure (often in marriage and family therapy) and certification by a professional board. • Psychologists are trained specifically to address emotional and psychological issues and to diagnose psychological problems (for example, major depressive disorder). Training includes a doctorate (Ph.D.) in psychology or related area with state licensure. • Psychotherapists are trained specifically to address emotional and psychological issues, through talking with the client. Psychotherapists often work with patients primarily to address aspects of meaning and emotion in the patient’s life, and work secondarily with specific psychological or behavioral symptoms. The psychotherapist is not licensed to prescribe medication but often works with
Counseling helps patients deal with changes associated with being diagnosed with and treated for cancer. (Digital Stock)
325
Cowden syndrome people who are taking medication for mental health problems. Training includes a master’s degree, usually in psychology (M.A.P.), and state licensure. • Psychiatrists usually focus specifically on psychiatric and/or psychological disorders that require medication and are caused by a physical process (for example, brain cancer that is creating behavioral difficulties). These providers are medical doctors (M.D.’s) who specialize in mental health. Some psychiatrists focus mainly on diagnosing conditions and prescribing medication, rather than on counseling. • Volunteers are key in many organizations, providing services such as support groups or telephone hotline services. Often, the sponsoring organization provides brief training for these volunteers, and in many cases the volunteers have had some personal involvement with cancer or with cancer patients. Types of counseling services: Counseling services can include individual sessions with the providers mentioned above; group sessions with other patients or family members, led by a mental health professional; support networks available by phone or by computer; and organized activities or classes led by volunteers or by trained professionals. Amy J. Neil, M.S., M.A.P. u
For Further Information Cousins, Norman. Anatomy of an Illness as Perceived by the Patient. New York: W. W. Norton, 1979. Fiore, Neil. The Road Back to Health: Coping with the Emotional Aspects of Cancer. Berkeley, Calif.: Celestial Arts, 1990. Granet, Roger. Surviving Cancer Emotionally: Learning How to Heal. New York: John Wiley & Sons, 2001. Holland, Jimmie, and Sheldon Lewis. The Human Side of Cancer. New York: HarperCollins, 2000. Siegel, Bernie. Love, Medicine, and Miracles. New York: Harper & Row, 1986. u
Other Resources
Salem Health: Cancer CancerCare http://www.cancercare.org National Cancer Institute http://www.cancer.gov Patient Advocate Foundation http://www.patientadvocate.org See also Anxiety; Cancer care team; Cancer education; Caregivers and caregiving; Case management; Elderly and cancer; End-of-life care; Family history and risk assessment; Financial issues; Genetic counseling; Grief and bereavement; Home health services; Hospice care; Informed consent; Karnofsky performance status (KPS); Living with cancer; Long-distance caregiving; Medicare and cancer; Oncology social worker; Overtreatment; Palliative treatment; Personality and cancer; Prayer and cancer support; Psycho-oncology; Psychosocial aspects of cancer; Relationships; Self-image and body image; Singlehood and cancer; Stress management; Support groups; Watchful waiting.
u Cowden syndrome Category: Diseases, symptoms, and conditions Also known as: Multiple hamartoma syndrome Related conditions: PTEN hamartoma tumor syndrome (PHTS), Lhermitte-Duclos disease Definition: Cowden syndrome is an inherited disorder characterized by the presence of multiple tumorlike growths, termed hamartomas. Although these hamartomas are generally benign, or noncancerous, individuals with hamartomas have a predisposition to the development of certain cancers. Risk factors: Cowden syndrome is inherited in an autosomal dominant pattern and therefore may be inherited from just one parent.
Association of Oncology Social Work http://www.aosw.org
Etiology and the disease process: Cowden syndrome is linked to mutations in the PTEN gene. PTEN is a tumorsuppressor gene, which normally functions to control cell growth and division. The mutations in PTEN may either be inherited or occur spontaneously. Approximately 80 percent of patients with Cowden syndrome have identified mutations in the PTEN gene. However, the cause of the condition in the other 20 percent of patients is unknown.
Cancer Hope Network http://www.cancerhopenetwork.org
Incidence: The exact incidence of Cowden syndrome is not known but is estimated at 1 in 200,000 individuals.
American Cancer Society http://www.cancer.org American Psychosocial Oncology Society http://www.apos-society.org
326
Salem Health: Cancer
Craniopharyngiomas
Symptoms: The major defining symptom of Cowden syndrome is the presence of multiple hamartomas. These growths are generally small and most often occur on the skin and on mucous membranes such as the inside of the nose and mouth. However, hamartomas may also occur on the inner lining of the intestines and within other parts of the body. Also, patients with Cowden syndrome often develop noncancerous breast and thyroid diseases. Another common symptom of Cowden syndrome is macrocephaly, or an enlargement of the patient’s head.
1 to 4 inches in size. They grow by expansion and can cause compression of structures such as the optic chiasm and nerves and the pituitary stalk and gland. The three subtypes are adamantinomatous or pediatric type, which is the classic and most common form of this tumor, having primarily a cystic composition, usually with a solid component; papillary or adult type, which has a more encapsulated, solid component that typically has no calcifications; and mixed type, which is composed of transitional features between the adamantinomatous and papillary variants.
Screening and diagnosis: Cowden syndrome is typically diagnosed through recognition of the extensive hamartomas. To help confirm a diagnosis, the PTEN gene can be sequenced to identify any mutations.
Risk factors: The cause of craniopharyngioma is not known, and there are no known environmental or infectious risk factors. More than 50 percent of people with craniopharyngiomas are younger than eighteen (adamantinomatous type), and most cases occur in children between the ages of five and ten. The second most common age range in which craniopharyngioma occurs is between forty and sixty years (papillary). Craniopharyngiomas do not appear to be more prevalent in a particular gender or ethnicity, nor do they appear to be inherited.
Treatment and therapy: The hamartomas and other symptoms related to Cowden syndrome are typically not treated; however, the main recommendation is for these patients to continue to be screened to watch for the early development of cancerous lesions. Prognosis, prevention, and outcomes: Because Cowden syndrome is often an inherited disorder, little can be done to prevent the disease. Patients with Cowden syndrome have a heightened risk of developing certain cancers. These include breast cancer, thyroid cancer, and uterine cancer. However, with routine screening, these tumors may be diagnosed in early stages and therefore often respond well to therapy. Lisa M. Cockrell, B.S. See also Family history and risk assessment; Thyroid cancer; Trichilemmal carcinomas.
u Craniopharyngiomas Category: Diseases, symptoms, and conditions Also known as: Rathke pouch tumors, adamantinomas Related conditions: Endocrinological and neurological dysfunctions Definition: A craniopharyngioma is a slow-growing, histologically benign tumor that has been found above and below the sella turcica (depression in the upper surface of the sphenoid bone) and in ectopic locations in the brain. Most craniopharyngiomas are found in the sella turcica and the area above it, home to the pituitary gland and hypothalamus. Although generally benign, craniopharyngiomas, like malignant tumors, can metastasize to areas outside the brain. When discovered, they typically range from
Etiology and the disease process: Although the etiology of craniopharyngiomas has not been determined with certainty, several theories exist as to their origin. One theory is that craniopharyngiomas are another form of a congenital tumor known as an epidermoid cyst. (Epidermoid cysts can arise anywhere in the body and are proven to be congenital.) Another theory suggests that they arise from embryonic dental or jaw tissue (dental anlage). A third theory, and the one that seems to be the most popular, purports that craniopharyngiomas are remnants of Rathke’s pouch (a depression in the roof of the developing mouth that gives rise to the anterior pituitary) and arise from squamous cell nests found at the junction of the pituitary stalk and the distal portion of the anterior pituitary. Craniopharyngioma appears as a single, large cyst or multiple cysts filled with a cloudy, proteinaceous, brownishyellow material that glitters because it contains floating cholesterol crystals. This kind of tumor most frequently arises in the pituitary stalk and projects into the hypothalamus. Craniopharyngioma causes symptoms in three different ways: first, as it grows it increases the pressure on the brain; second, as it enlarges it interferes with the normal function of the pituitary gland; and third, as it grows upward, it damages the optic nerve. Incidence: Craniopharyngioma is a rarely occurring, nonheritable cancer. According to the National Cancer Data Base, the overall incidence of craniopharyngioma in the United States is 0.13 per 100,000 persons per year. Craniopharyngiomas account for 1 to 3 percent of all 327
Craniopharyngiomas intracranial tumors and 4.2 percent of all childhood intracranial tumors. The incidence does not vary by sex or race. Approximately 340 cases of craniopharyngiomas occur annually in the United States, with 96 occurring in children between birth and fourteen years of age. Recurrences usually occur at the primary site. Ectopic and metastatic recurrences are extremely rare and have been reported after surgical removal. Recurrence rates can be as high as 20 percent. Symptoms: Symptoms frequently develop slowly and become obvious only after the tumor enlarges to about 1.5 inches in diameter. Craniopharyngiomas produce symptoms by compression of adjacent neural structures, leading to endocrine and visual problems; they obstruct cerebrospinal fluid pathways, causing hydrocephalus and increased intracranial pressure, which lead to headaches and nausea. The most common symptoms are headache (55 to 86 percent of patients), endocrine dysfunction (66 to 90 percent of patients), and visual disturbances (37 to 68 percent of patients). Headaches are slowly progressive, dull, continuous, and positional, becoming severe when endocrine symptoms become obvious. Endocrine dysfunction includes hypothyroidism, adrenal failure, and diabetes insipidus; young patients typically display growth failure and delayed puberty. Nearly three-quarters of patients suffer some sort of damage to the optic pathway. Other manifestations relate to the various connections of the hypothalamic-pituitary complex and surrounding structures. Tumors located in the thalamus and frontal lobes are often accompanied by corresponding endocrine, autonomic, and behavioral problems, such as hyperphagia and obesity, short-term memory deficits, psychomotor retardation, emotional immaturity, and lethargy. Screening and diagnosis: Computed tomography (CT) scanning and magnetic resonance imaging (MRI) are the screening methods of choice for craniopharyngioma. MRI, with or without administration of contrast enhancement, is generally preferred over CT scanning but may not be as readily available. Although CT can clearly demonstrate the characteristic calcifications and size of the tumor, MRI can demonstrate the size and extent of the tumor as well as any ventricular involvement. MRI results can confirm cystic features of the tumor. Various MRI sequences, such as fluid-attenuated inversion recovery (FLAIR), gradient echo, and diffusion-weighted imaging, can aid in making the correct diagnosis. The diagnostic workup for craniopharyngioma also includes complete endocrinological and neuroophthalmological evaluation with visual-field examination and neuro328
Salem Health: Cancer psychological assessment. The endocrinological tests will include serum electrolytes, serum and urine osmolality, thyroid studies, morning and evening cortisol levels, growth hormone levels, and luteinizing and follicle-stimulating hormone levels. Postoperatively, CT scanning is performed to establish a baseline from which follow-up scans will be judged. MRI is often performed to determine whether there is any residual tumor. Treatment and therapy: There is no medical therapy per se for craniopharyngioma. There is little debate that the standard treatment of this tumor is surgical excision followed by adjuvant radiotherapy; however, controversy does exist about the optimal degree of excision. Some physicians believe that complete resection is the best treatment and that every effort should be made to remove as much of the tumor as possible. Others advocate a planned partial tumor excision, leaving radiotherapy or radiosurgery to complete the removal. The controversy stems from the fact that nearly all craniopharyngiomas are located in eloquent areas of the brain; removal necessitates maneuvering around very delicate anatomical structures, which, if damaged during the course of tumor removal, could fail to perform normally, leaving the patient with severe deficits. Craniopharyngiomas tend to adhere to the structures and tissues that surround them, making them difficult to excise without disturbing or damaging these other entities. It is especially challenging to resect a craniopharyngioma that is adhering to the pituitary gland, the hypothalamus, or the optic chiasm and nerves. For example, damage to the pituitary gland, which controls the activity of many other endocrine glands, such as the thyroid, the ovaries, and the adrenal glands, can result in a cascade of endocrine-related disorders including hypothyroidism, obesity, diabetes, and, in children, failure to thrive. Damage to the hypothalamus, which controls the activity of the pituitary by releasing various hormones to regulate it, can result in a host of problems from interrupted circadian rhythm to impaired immune system function. Damage to the optic chiasm and optic nerves can cause visual disturbances ranging from mild hemianopsia (in which each eye is able to send images from only half its field of vision to the brain) to complete blindness. Because of these issues, treatment of craniopharyngioma is complex. The surgical approach used is dictated by the tumor’s location. If the predominant portion of the tumor is intrasellar, the approach is usually transsphenoidal (through the sphenoid bone). The transsphenoidal approach is less invasive than craniotomy (in which part of the skull is re-
Salem Health: Cancer moved to provide access to the brain) and therefore preferable. Craniotomy is necessary when the predominant component is suprasellar. Certain suprasellar masses may be approached through an extended transsphenoidal craniotomy. The pterional craniotomy is the standard approach to suprasellar lesions because it allows the surgeon to see the optic nerves and chiasm. A subfrontal approach is used for lesions that are anterior to the optic chiasm, but this may be difficult to determine preoperatively. Cyst aspiration combined with instillation of radioactive isotope phosphorus-32 is the alternative to traditional resection; however, a tumor with significant solid components is not likely to respond to this type of treatment. Prognosis, prevention, and outcomes: The survival rate for patients who undergo surgery for craniopharyngioma is estimated to be 86 percent at two years and 80 percent at five years postdiagnosis. Survival varies by age group, with excellent survival rates for patients younger than twenty years old and poorer survival rates for those older than sixty-five. Molecular and genetic studies focusing on the treatment and prevention of craniopharyngioma are ongoing. Keller Kaufman-Fox, B.A. u For Further Information Chakrabarti, I., A. P. Amar, W. Couldwell, and M. H. Weiss. “Long-Term Neurological, Visual, and Endocrine Outcomes Following Transnasal Resection of Craniopharyngioma.” Journal of Neurosurgery 102 (2005): 650-657. Chiou, S. M., et al. “Stereotactic Radiosurgery of Residual or Recurrent Craniopharyngioma, After Surgery, with or Without Radiation Therapy.” Neuro-oncology 3 (2001): 159-166. Garrè, M. L., and A. Cama. “Craniopharyngioma: Modern Concepts in Pathogenesis and Treatment.” Current Opinions in Pediatrics 19 (2007): 471-479. Merchant, T. E., et al. “Craniopharyngioma: The St. Jude Children’s Research Hospital Experience, 19842001.” International Journal of Radiation Oncology, Biology and Physics 53 (2002): 533-542. Rekate, Harold L. “Craniopharyngioma.” Journal of Neurosurgery (Pediatrics 4) 103 (2005): 297-298. u
Other Resources
MedlinePlus Craniopharyngioma http://www.nlm.nih.gov/medlineplus/ency/article/ 000345.htm
Craniosynostosis National Cancer Institute Childhood Craniopharyngioma http://www.cancer.gov/cancertopics/pdq/treatment/ childbrain/Patient/page10 See also Brain and central nervous system cancers.
u Craniosynostosis Category: Diseases, symptoms, and conditions Related conditions: Craniofacial syndromes Definition: Craniosynostosis is a process resulting in premature closure or fusion of the cranial sutures. The most common site is the sagittal suture, followed by the coronal, lambdoidal, and metopic. This condition results in an abnormally shaped skull and occurs with a male-to-female ratio of 3:1. Approximately 10 percent are familial, resulting from an autosomal dominate inheritance. Other cases are the result of chromosome deletions, duplications, translocations, breaks, missense, or splice-site abnormalities. Prenatal head constraint is hypothesized as a causative factor in some cases. In utero human development proceeds in a normal fashion, with abnormalities becoming apparent at birth or shortly thereafter. The phenotypic presentation is variable. More than one hundred syndromes have been associated with craniosynostosis. Risk factors: Primary cases of craniosynostosis, in the majority of cases, is the result of spontaneous genetic mutations, although it can also be transmitted genetically from a parent. Children with microcephaly (poor brain growth) are at risk of developing craniosynostosis. Normal brain growth pushes the cranial bones apart at the sutures, but with impaired brain growth, sutures may prematurely fuse. Etiology and the disease process: Mutations in fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3), TWIST, and MSX2 genes are associated with craniosynostosis development. Fibroblast growth factor receptors affect animal growth, development, and homeostasis. They regulate cell growth, differentiation, migration, and survival. They exert direct influence on the formation of various tissues, organs, and blood vessels and are responsible for wound healing. FGFR mutations are directly associated with specific growth and development abnormalities, including the inability to control cell growth leading to tumor formation. Currently, four FGFR mutations have been identified. These mutations produce a variety of results. Germline 329
Craniosynostosis mutations cause skeletal dysplasia (hypochondroplasia, achondroplasia) and craniosynostosis syndromes (Apert, Beare-Stevenson, Crouzon, Pfeiffer, Jackson-Weiss), while somatic mutations cause a variety of cancers. Oncogenes and tumor-suppressor genes are located near recombination sites on chromosomes. Thus, when breaks, translocations, deletions, and amplifications occur in these regions, tumor-suppressor genes can be excluded or oncogenes can be amplified. These processes lead to the development of various cancers. FGFR mutations have been identified in endometrial, breast, gastric, colorectal, bladder (urothelial), cervical, endometrial, and glial tumors and multiple myeloma. In addition, FGFR mutations are implicated in the formation of benign skin lesions such as epidermal nevi and seborrheic keratoses. Saethre-Chotzen syndrome, an autosomal dominantly inherited form of craniosynostosis, is caused by the mutation of the transcription factor gene TWIST1. The protein encoded by this gene is a transcription factor that regulates metastasis and is overexpressed in Saethre-Chotzen syndrome. This abnormality is highly associated with early breast cancer development. An autosomal dominant MSX2 defect has been identified as the causative agent in Boston-type craniosynostosis. Incidence: Craniosynostosis occurs in 1 in 3,000 live births. The association with different syndromes varies from 1 in 25,000 to 1 in 150,000. Symptoms: Normally, bone growth in the skull occurs at its edges, where the initial skull bones are approximated by fibrous connective tissue. When premature fusion of approximated skull bones occurs, the skull assumes an abnormal shape. Palpation of the sutures, fontanels, and skull bones; measurement of the skull circumference; and observation of the skull shape are performed by the care provider during a physical examination of the individual. Premature suture closure may result in additional symptoms, such as increased intracranial pressure and developmental delay. The individual may exhibit bulging eyes, widespaced eyes, a beaked nose, low-set ears, and a small jaw. Certain syndromes may also be associated with hand and limb abnormalities. Screening and diagnosis: Detection is through physical examination and radiographic techniques including X rays and three-dimensional computed tomography (CT) scans. A CT scan not only can detect suture fusion but also can evaluate the brain for underlying structural abnormalities, thereby assisting the surgeon in planning corrective surgery. 330
Salem Health: Cancer Individuals with craniosynostosis are at risk for having an associated syndrome and for developing various cancers. Because of the high incidence of chromosomal defects, duplications, deletions, and substitutions associated with craniosynostosis, affected individuals are candidates for genetic counseling and chromosomal analysis. Early and consistent screening for cancer leads to diagnosis and treatment in earlier stages of the disease, making a cure more possible. Treatment and therapy: Surgery is performed to reopen closed sutures and provide a more normal-appearing skull. An open surgical technique is used with multiple suture fusions or if the surgery is performed after the first year of life. This method involves an ear-to-ear incision, removing, reshaping, replacing, and securing the affected bones. For a single fused suture or if surgery is done in the first few months of life, surgical instruments called endoscopes are inserted through small scalp incisions, and small pieces of bone are removed, releasing the suture fusion. These patients then wear a custom-molded helmet for several months. The helmet provides a template for normal skull growth and shape. For other cosmetic issues, the individual may require orthodontic and orthognathic (jaw) surgery to restore normal facial features. Prognosis, prevention, and outcomes: The prognosis for craniosynostosis is good and improves with early detection and treatment. The morbidity and mortality depend on associated defects as part of a syndrome. Currently, there is no method to prevent autosomal dominant transmission to offspring or to prevent new mutations. FGFR mutations produce a variety of results. Research is necessary to determine how mutations result in different consequences. If it can be determined how mutations affect outcomes, definitive targeted therapies can be developed. One such proposal is anti-FGFR therapy, designed to target the upregulated FGFR genes. Because of the associated risk for a variety of cancers, the individual will require ongoing evaluation and screening for carcinogenesis. Wanda Todd Bradshaw, R.N.C., M.S.N. u
For Further Information Cohen, M. Michael. “Malformations of the Craniofacial Region: Evolutionary, Embryonic, Genetic, and Clinical Perspectives. American Journal of Medical Genetics 115 (2002):245-268. Coumoul, Xavier, and Chu-Xia Deng. “Roles of FGF Receptors in Mammalian Development and Congenital Diseases.” Birth Defects Research 69 (2003): 286-304. Hansen, Ruth, et al. “Fibroblast Growth Factor Receptor 2,
Salem Health: Cancer
Craniotomy
Gain-of-Function Mutations, and Tumourigenesis: Investigating a Potential Link.” Journal of Pathology 207 (2005): 27-31. Ridgway, E. B. “Skull Deformities.” Pediatric Clinics of North America 5, no. 2 (2004): 359-387. u
Other Resources
Children’s Craniofacial Association http://www.ccakids.com March of Dimes Birth Defects Foundation http://www.marchofdimes.com National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/index.htm See also Craniotomy; Dry mouth; Mucosa-associated lymphoid tissue (MALT) lymphomas; Nasal cavity and paranasal sinus cancers.
u Craniotomy Category: Procedures Also known as: Brain surgery Definition: Craniotomy is a surgical procedure in which an incision is made into the skull to gain access to the brain. Cancers treated: Brain cancers, such as glioma, astrocytoma, medulloblastoma, and ependymoma Why performed: Craniotomy is performed for cerebral artery aneurysm clipping, arteriovenous malformation repair, increased intracranial pressure control, hematoma drainage, ventricular shunting, and abscess or tumor excision. Patient preparation: Before surgery, the patient undergoes a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain to determine tumor location and size and to evaluate brain tissue swelling. Other routine studies are performed to check for abnormalities and establish a baseline for postoperative comparison. These studies include a chest X ray, an electrocardiogram (EKG), bleeding time, and blood tests to check kidney function, clotting times, white blood cell count, and electrolyte, hemoglobin, and oxygen levels. A blood sample is also drawn to check the patient’s blood type in case a transfusion is needed during surgery. The patient must not eat or drink for at least eight hours before surgery. An intravenous (IV) catheter is inserted for
A patient’s head is readied for a craniotomy. (Custom Medical Stock Photo)
fluids and medications. Depending on the tumor’s location, the patient may also receive a bolus dose of an antiseizure medication, such as phenytoin, to prevent seizure activity during and after surgery. An indwelling urinary catheter is also inserted so that urine output can be monitored closely during and after the procedure. Sequential compression devices are applied to the patient’s legs and worn during and after surgery to prevent blood clot formation. Steps of the procedure: Immediately before the procedure, an arterial catheter is inserted into the patient’s wrist to monitor blood pressure continuously during surgery. This catheter also permits blood sampling so that oxygen and electrolyte levels can be monitored. A central venous catheter may also be inserted to monitor the patient’s fluid status and to administer IV fluids and medications during surgery. After the patient is anesthetized, the neurosurgeon makes an incision into the skin and the skin is retracted. 331
Crohn disease Next, an incision is made into the muscle and the muscle is retracted. Special tools are used first to make holes in the skull bone and then to cut through the bone to make a bone flap. The bone flap is then separated from the protective layer that surrounds the brain and removed. It is kept moist during the procedure. Next, the neurosurgeon exposes the brain tissue and removes the tumor, if possible. Depending on the tumor location, a ventricular drain may be inserted to prevent hydrocephalus and monitor intracranial pressure. If a ventricular drain is not needed, then an intracranial pressure monitor sensor may be inserted. After the tumor is excised, the neurosurgeon ties off bleeding vessels and then replaces the bone flap and secures it using plates and screws. Next, the neurosurgeon closes the incision and covers it with a sterile dressing. This procedure typically takes several hours. After the procedure: The patient is transferred to the intensive care unit (ICU) and attached to a monitor that displays heart rhythm, blood pressure, oxygen saturation, central venous pressure, intracranial pressure, and cerebral perfusion pressure. These devices help the ICU nurses monitor the patient’s condition closely. The patient may have an endotracheal tube (breathing tube) connected to a mechanical ventilator to assist with breathing or may breathe independently with supplemental oxygen. A patient who is able to breathe without help from a ventilator will be encouraged to breathe deeply and use an incentive spirometer frequently to prevent pneumonia. The head of the patient’s bed is maintained at a prescribed elevation based upon the tumor’s location. Every two hours, nurses may gently roll the patient to prevent the development of pressure ulcers and pneumonia. If the patient’s neurologic status becomes unstable, however, then the patient may be unable to tolerate turning. Nurses closely monitor the patient’s vital signs, respiratory, and neurologic status to detect signs of increased intracranial pressure. If such signs are detected, then nurses administer diuretics, such as furosemide and mannitol, to decrease brain swelling. The patient will also receive a corticosteroid, such as dexamethasone, to combat inflammation. Medications such as codeine will also be administered to control pain. If a ventricular drain was inserted during the procedure, then the nurses will maintain the drain as ordered and closely monitor the type and amount of drainage. Nurses also monitor urine output frequently. A sudden increase in urine output without diuretic use may signal diabetes insipidus, a complication of craniotomy. During the immediate postoperative period, it is important to keep the patient’s environment calm and quiet to minimize anxiety and to avoid increasing intracranial 332
Salem Health: Cancer pressure. A drug-induced coma is sometimes necessary to control intracranial pressure that is unresponsive to other therapy; the need is rare, however, following brain tumor resection. When the patient’s condition is stabilized and ventricular drainage is minimal, the ventricular drain is removed and the patient’s activity level is increased. The length of hospital stay varies by the tumor location, extent of surgery, and the patient’s rate of recovery. Depending on the tumor’s extent and location, physical therapy, chemotherapy, or radiation therapy may be needed after surgical recovery. Risks: There are many risks associated with craniotomy, including increased intracranial pressure, surgical site infection, hydrocephalus, meningitis, intracerebral hemorrhage, air embolism, seizures, stroke, cranial nerve damage, syndrome of inappropriate antidiuretic hormone (SIADH), and diabetes insipidus. Results: Pathologic examination of the brain tumor specimen reveals the type of cancer. Collette Bishop Hendler, R.N., M.S. u
For Further Information Greenberg, Mark S. Handbook of Neurosurgery. 6th ed. New York: Theime Medical, 2006. Hickey, Joanne V. The Clinical Practice of Neurological and Neurosurgical Nursing. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Surgical Care Made Incredibly Visual. Philadelphia: Lippincott Williams & Wilkins, 2007.
u
Other Resources
American Cancer Society http://www.cancer.org See also Astrocytomas; Brain and central nervous system cancers; Craniopharyngiomas; Neurologic oncology.
u Crohn disease Category: Diseases, symptoms, and conditions Also known as: Crohn’s disease, ileitis, ileocolitis, regional enteritis, enteritis Related conditions: Aphthous ulcers, episcleritis, scleroconjunctivitis, recurrent iritis, uveitis, erythema nodosum, pyoderma gangrenosum, spondyloarthropathy or spondyloarthritis-ankylosing spondylitis and sacroiliitis, peripheral arthritis, hypercoagulability, secondary amyloidosis,
Salem Health: Cancer primary sclerosing cholangitis, gallstones, perianal disease, malnutrition, malabsorption, osteoporosis, anemia, lymphoma, cholangiocarcinoma, adenocarcinoma of the gastrointestinal tract, colorectal cancer
Crohn disease Crohn Disease
Definition: Crohn disease is a chronic inflammatory condition of the gastrointestinal tract, anywhere from the mouth to the anus, but most commonly in the end of the small intestine called the ileum and in the adjoining large colon. Risk factors: Those with a family history of Crohn disease, a genetic predisposition, or a history of smoking are at greatest risk for this disease. Etiology and the disease process: Crohn disease (CD) belongs to the group of diseases known as inflammatory bowel disease (IBD), a generic term for diseases characterized by inflammation in the small and large bowels. Other IBDs are ulcerative colitis (UC) and indeterminate colitis (lymphocytic colitis and collagenous colitis). There are many theories about the etiology of Crohn disease, but the exact cause is unknown. It is known to run in families and be more common in certain ethnicities, suggesting a genetic predisposition. However, no specific reason or factor consistently explains the origin of the disease. The current belief relates Crohn disease to an inflammatory process. The human immune system protects people from harmful foreign substances (referred to as antigens) such as bacteria, viruses, and parasites. This protection is provided by cells and various proteins (such as antibodies) through an inflammatory reaction that is a response toward antigens or cell injuries. In Crohn disease, the immune system reacts abnormally against the affected part of the gastrointestinal tract and causes damage. This inappropriate inflammation leads to the clinical manifestations of Crohn disease. Studies have shown that the inflammation related to Crohn disease is multifactorial and may depend on genetic factors, immune reactions, and environmental cues. A region on the human chromosome 16 was found to possibly contain genes that are involved in the abnormal inflammatory response in Crohn disease. One such gene, known as NOD2/CARD15, was found to be more common in Crohn disease patients than in the general population. An abnormality in this gene causes a mutation in the gene product (protein) that ultimately weakens the immune system’s ability to recognize harmful bacteria. The immune reaction may be a response to antigens or to modified parts of the gastrointestinal tract associated with the inflammation. Antitumor necrosis factor-alpha (TNF-alpha) is a protein produced by the immune system that enhances the
Crohn disease is associated with colorectal cancer.
white blood cells’ ability to defend against infections and other foreign substances. TNF-alpha may be a cause of the inflammation associated with Crohn disease; it is abnormally elevated in Crohn disease, causing excessive inflammation and its adverse effects. IBDs (Crohn disease and ulcerative colitis) have similar symptoms, but they also have significant differences. Crohn disease can affect any part of the gastrointestinal tract, cause inflammation deeply penetrating through the tract linings (full thickness), and show radiographic results suggestive of Crohn disease. Ulcerative colitis affects the 333
Crohn disease colon and rectum; it can also cause a “backwash” ileitis in the junction of the small and large intestines. Ulcerative colitis inflammation is mainly in the superficial linings of the affected gastrointestinal tract. Tissue sampling further identifies the difference between Crohn disease and ulcerative colitis. Incidence: The incidence of Crohn disease is 7 new cases per 100,000 people per year, and the prevalence is 162 cases per 100,000 people per year. About 20 percent of Crohn disease cases run in families. Men and women are affected equally. Crohn disease is more common in people of European and Jewish heritage than those of other ethnicities. The onset of Crohn disease has two peaks: between the ages of fifteen and thirty and the ages of sixty and eighty. However, most patients are diagnosed before the age of thirty. Symptoms: The manifestations of Crohn disease are heterogeneous, including symptoms within the gastrointestinal tract and outside of it (extraintestinal). Constitutional symptoms of Crohn disease are fatigue, fever, loss of appetite, and weight loss. Most common gastrointestinal tract symptoms are prolonged diarrhea, with or without rectal bleeding, and abdominal pain (tenderness), usually in the lower right area, which can be mistaken for appendicitis. Malabsorption in the gastrointestinal tract can lead to malnutrition and weight loss, which is related to delayed development and poor growth in children. Mouth ulcers may manifest along with pain in the mouth and gums. Problems of the throat such as pain or difficulty with swallowing can occur if the esophagus is involved. Patients with Crohn disease may develop perianal diseases such as fissure in ano (fissures or tears in the lining of the anus) and fistula-in-ano (abnormal connection between the anal intestinal lining and another part of the body, such as the skin, bladder, vagina, or another part of the gastrointestinal tract). Fistulas are most common in the anal region; abscesses (pockets of pus) may be present as a complication. Blockage (obstruction) and perforation of the gastrointestinal tract may occur. Extraintestinal symptoms include eye disorders, skin problems, arthritis, and liver and gallbladder diseases. Screening and diagnosis: Screening is done through a comprehensive physical examination and a complete blood count to evaluate for anemia and infection. A stool test will be performed if there is gastrointestinal tract bleeding or infection. Special tests for antibodies, such as antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibodies, may be used if the diagnosis of Crohn disease is uncertain. Radiographic studies can in334
Salem Health: Cancer clude upper and lower gastrointestinal series (barium enema). Upper or lower gastrointestinal endoscopy can identify the affected site, allow tissue sampling (biopsy), and confirm the diagnosis of Crohn disease. The severity of Crohn disease is diverse, and its activity is described as mild-moderate, moderate-severe, severe-fulminant, and remission. Treatment and therapy: Crohn disease has no cure; however, symptoms can be alleviated. Management of Crohn disease and its complications may include medications for treatment of symptoms such as antidiarrheal agents (loperamide and diphenoxylate), nutritional support, surgery, or a combination of these modalities. Medications for Crohn disease include antibiotics such as ciprofloxacin and metronidazole; anti-inflammatory drugs such as corticosteroids, sulfasalazine, and 5-aminosalicylate (5-ASA); immunomodulators that inhibit the immune response such as azathioprine, 6-mercaptopurine, and methotrexate; and biological therapies such as infliximab (Remicade) and adalimumab (Humira), which are antibodies that block TNF-alpha activity. All of these medications may have side effects ranging from nausea, vomiting, and headaches to infection susceptibility. The risks and benefits of medications are assessed and modifications implemented on an individual basis. Regular nutritional assessments are necessary to prevent malnutrition, which can result from malabsorption in the inflamed small and large bowels. Surgical intervention is needed in some cases, such as failure of medical treatment and complications such as obstruction, perforation, nonstop bleeding, abscess, and fistula. Prognosis, prevention, and outcomes: Crohn disease is a chronic medical condition. It can manifest in recurrent episodes of the active disease (flares) or remain in remission for variable time periods. Patients with Crohn disease are monitored closely for related conditions such as associated cancers. Regular cancer screening using colonoscopy is recommended for patients with Crohn disease because of its association with colorectal cancer. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. u
For Further Information American Gastroenterological Association. Clinical Practice Committee. “Perianal Crohn’s Disease.” Gastroenterology 125, no. 5 (November, 2003): 1503-1507. Eyre, Harmon J., Dianne Partie Lange, and Lois B. Morris. Informed Decisions: The Complete Book of Cancer, Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002.
Salem Health: Cancer Hanauer, Stephen B., William Sandborn, and the Practice Parameters Committee of the American College of Gastroenterology. “Management of Crohn’s Disease in Adults.” American Journal of Gastroenterology 96, no. 3 (March, 2001): 635-643. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003. u
Other Resources
American Academy of Family Physicians http://familydoctor.org/online/famdocen/home/ common/digestive/disorders/252.html American College of Gastroenterology http://www.acg.gi.org American Gastroenterological Association http://www.gastro.org Crohn’s & Colitis Foundation of America http://www.ccfa.org/ Crohn’s and Me—Make the Connection http://www.crohnsandme.eu European Crohn’s and Colitis Organisation http://www.ecco-ibd.eu
Cruciferous vegetables
u Cruciferous vegetables Category: Lifestyle and prevention Also known as: Brassicaceae family, glucosinolates, isothiocyanates, indole-3-carbinol Definition: Cruciferous vegetables are edible plants from the Brassicaceae family that include broccoli, cauliflower, brussels sprouts, cabbage, arugula, watercress, bok choy, turnip and mustard greens, kale, kohlrabi, turnips, rutabagas, and radishes. Cruciferous vegetables contain a variety of healthful substances such as vitamin C, selenium, fiber, and sulfur-containing compounds called glucosinolates. The sulfur compounds give cruciferous vegetables their pungent taste and aroma. Cancers treated or prevented: Colorectal cancer, lung cancer, prostate cancer Delivery routes: Oral by diet How these compounds work: Cruciferous vegetables are rich sources of glucosinolate compounds, which may be the source of their cancer-fighting effects. When the vegetables are chopped or chewed, bioactive hydrolysis products of glucosinolates, such as isothiocyanates and indole-3carbinol, are formed. These compounds may help prevent certain cancers by eliminating dietary carcinogens from
European Federation of Crohn’s and Ulcerative Colitis Associations http://www.efcca.org Irish Society for Colitis and Crohn’s Disease http://www.iscc.ie MedlinePlus http://www.nlm.nih.gov/medlineplus/ crohnsdisease.html National Association for Colitis and Crohn’s Disease (UK) http://www.nacc.org.uk National Digestive Diseases Information Clearinghouse Crohn’s Disease http://digestive.niddk.nih.gov/ddiseases/pubs/crohns/ See also Bacteria as causes of cancer; Cholecystectomy; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Duodenal carcinomas; Enteritis; Gastrointestinal cancers; Ileostomy; Inflammatory bowel disease; Leiomyosarcomas; Pancolitis; Small intestine cancer.
Cruciferous vegetables such as broccoli are rich sources of glucosinolate compounds, which may be the source of their cancerfighting effects. (©Irochka/Dreamstime.com)
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Cryoablation the body or by preventing normal cells from becoming cancerous. Cooking or boiling cruciferous vegetables decreases the amount and bioavailability of glucosinolates, so raw vegetables provide much higher levels of the compounds than do cooked vegetables. Higher intakes of cruciferous vegetables have been linked to a lower risk of lung, prostate, and colorectal cancer in epidemiological studies. Current evidence is limited, however, and the effects are not consistent. In addition, it is not clear whether the beneficial effects of cruciferous vegetables come from the glucosinolate compounds or from other phytochemicals that act synergetically. Genetic variability may influence the effects of cruciferous vegetables on cancer risk. For example, individuals may vary in their capacity to absorb, metabolize, and eliminate glucosinolate compounds from the body. Thus, genetic differences that affect how long these compounds or their metabolites remain in the body may influence how protective they are against cancer. The National Cancer Institute recommends the daily consumption of five to nine servings of fruits and vegetables; human epidemiological studies suggest five weekly servings of cruciferous vegetables are beneficial. Side effects: Very high intakes of cruciferous vegetables may cause hypothyroidism. In addition, some of the isolated metabolites of glucosinolates in cruciferous vegetables, such as indole-3-carbinol, have produced mixed results in animal studies. For example, depending on when the compound is administered or the length of exposure, indole-3-carbinol can prevent or promote the development of cancer in animals. These studies highlight the disadvantages of isolating potentially beneficial compounds from food, as isolated compounds may produce unwanted effects, and the synergy of many compounds may be critical in cancer prevention. Linda Hart, M.S., M.A. See also Beta-carotene; Chemoprevention; Folic acid; Indoles; Lutein; Nutrition and cancer prevention; Polyps; Prevention; Stomach cancers; Thyroid cancer.
u Cryoablation Category: Procedures Also known as: Cryosurgery, targeted cryoablation therapy, ablation therapy Definition: Cryoablation is a minimally invasive method of treating tumors using extremely cold temperatures to destroy cancer cells or precancerous cells in a localized 336
Salem Health: Cancer area. Cryoablation uses liquid nitrogen, alcohol, or an argon gas-based system delivered through probes that are inserted through a small incision in the skin to freeze a particular area of the tumor and kill the cancerous tissue. Cancers diagnosed or treated: Prostate, kidney, skin, liver, lung, bone, soft-tissue, and pelvic cancers; also being studied for use in certain types of breast tumors and used for some heart rhythm disturbances Why performed: Cryoablation is often used when a tumor is not operable or removable because of the late stage of the cancer or its difficult location near major blood vessels or other organs not affected by the cancer. It may be used as a primary treatment for some cancers such as prostate cancer or as a palliative treatment for liver or other cancers to relieve pain and control cancer-related symptoms. Progress has been made in treating kidney cancers with cryoablation. Sometimes cryoablation is added to other traditional treatments (radiation therapy or chemotherapy) for cancer. Cryoablation is also used to remove precancerous lesions, such as precancerous moles. Patient preparation: Minimal preparation is needed for cryoablation. An intravenous (IV) line is started in the patient for sedation, and the patient’s blood work is checked. Some physicians may also prescribe an antibiotic as a preventive measure. Steps of the procedure: The procedure may take one to two hours. If the patient will have cryoablation during an operation as an added treatment for the tumor, then general anesthesia will be used and a hospital stay will be required. Most cryoablation procedures, however, can be done under local anesthesia and require only an overnight stay in the hospital. An interventional radiologist performs cryoablation using image guidance. A computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI) helps the interventional radiologist guide the probe (usually multiple probes) into the tumor and avoid damage to any healthy tissue surrounding the tumor. A local anesthetic is given in the area overlying the tumor where the probe will enter. The agent used (liquid nitrogen, alcohol, or argon gas) is then delivered through the probes to freeze the tissue. During freezing, an ice ball or crystals form inside and outside the cell spaces of the tumor tissue. The ice forming inside the cell space leads to cell death by injury to the cell membrane, structures within the cell, or both. Ice that forms outside the cell space, where freezing is slower, causes death by creating a rush of the fluid moving in the space outside the cell. This causes the cell to burst and re-
Salem Health: Cancer
Cryoablation
A doctor uses cryoablation to remove skin growths from a woman’s stomach. (Antonia Reeve/Photo Researchers, Inc.)
sults in cell death by a deprivation of oxygen to the cell and the cell membrane. After the procedure: The patient is monitored for a few hours and usually will have to stay overnight in the hospital. A drug such as ibuprofen may be given to relieve a patient’s discomfort from having to remain in one position during the procedure. Although there may be a few restrictions suggested by the physician, most patients can resume their daily activities within one or two days. Risks: Depending on the type of tumor, side effects from cryoablation vary. The most common minor side effects are pain or bruising at the site, fever, nausea, local infection, fatigue, and temporary low platelet count not requiring transfusion. Most resolve within a week. Major risks include freezing injury to organs near the tumor, fluid collection within the organ being treated, and puncture of the colon or other organs near the tumor that can result in major bleeding or infection.
For prostate cancer, impotence and loss of bladder control can be a major complication. A more recent cryoablation procedure for prostate cancer, called nerve-sparing cryoablation and focal prostate cryoablation, is being used to reduce the possibility of impotence and urinary incontinence. Results: The advantages of cryoablation are low complication rates, ability to destroy local tumor tissue with minimal discomfort to the patient, reduction in hospital stay, shortened patient recovery time, less scarring, and lower cost (compared to surgery). It is an especially useful treatment for cancers that are otherwise untreatable and can enhance an individual’s quality of life through better symptom control. For some cancers, such as lung and bone cancer, cryoablation is considered investigational, and health care insurance companies may not cover the procedure. Jo Gambosi, M.A., B.S.N. 337
Cryptorchidism u For Further Information Bahn, Duke, et al. “Focal Prostate Cryoablation: Initial Results Show Cancer Control and Potency Preservation.” Journal of Endourology 20, no. 9 (2006): 688692. Centeno, Arthur S., and Gary Onik. Prostate Cancer: A Patient’s Guide to Treatment. Omaha, Nebr.: Addicus, 2004. Chung, Leland. Prostate Cancer: Biology, Genetics, and New Therapeutics. Totowa, N.J.: Humana Press, 2001. VanSonnenberg, Eric, William McMullen, and Luigi Solbiati. Tumor Ablation: Principles and Practice. New York: Springer, 2005. u
Other Resources
American Cancer Society http://www.cancer.org Galil Medical Cryotherapy http://www.galil-medical.com/galil-medicalcryotherapy.html See also Adenoid cystic carcinoma (ACC); Basal cell carcinomas; Birt-Hogg-Dubé syndrome (BHDS); Carcinoid tumors and carcinoid syndrome; Cervical cancer; Dermatology oncology; Eyelid cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Kidney cancer; Radiofrequency ablation; Skin cancers; Surgical oncology.
u Cryptorchidism Category: Diseases, symptoms, and conditions Also known as: Undescended testicles, hidden testis, obscure testis, maldescended testis Related conditions: Reduced fertility, testicular cancer Definition: Cryptorchidism refers to a condition in which one or both testes are absent from the scrotum, having failed to descend into the scrotum before birth. It has been associated with development of testicular cancer later in life. Risk factors: There is a strong link between low birth weight and cryptorchidism. Additionally, premature infants can be born before descent of the testes takes place. Studies have shown that regular alcohol consumption during pregnancy is associated with a threefold increase in this abnormality. Those with cryptorchidism have between a four- and fortyfold greater risk of developing testicular cancer, most often in the third through fifth decades of life. 338
Salem Health: Cancer Etiology and the disease process: The testes remain high in the abdomen until the seventh month of gestation, when specific hormones initiate the movement of the testes from the abdomen into the two sides of the scrotum. The movement, controlled by hormones, occurs in two phases. The first phase involves movement across the abdomen to the entrance of the inguinal canal, and the second phase involves movement of the testes through the inguinal canal into the scrotum. Incidence: About 30 percent of premature and 3 percent of full-term infant boys are born with at least one undescended testis, making cryptorchidism the most common birth defect of male genitalia. However, most testes descend by the first year of life, making the true incidence of cryptorchidism around 1 percent overall. Symptoms: A manual exam of the scrotum determines if one or both testes are not present. For associated testicular cancer, a painless testicular mass is the most common symptom; a few young men may also experience diffuse testicular pain or swelling. Screening and diagnosis: Screening for cryptorchidism takes place immediately after birth as part of a routine physical exam. Diagnosis is generally confirmed by a manual exam, resulting in the determination of only one testicle (or none) in the scrotal sac. Treatment and therapy: A surgery known as orchiopexy is primarily performed in infancy for boys who have a testis still within the inguinal canal. When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and is occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin. A series of injections (ten injections over five weeks is common) is given, and the status of the testis or testes is reassessed at the end. The most common argument for orchiopexy as opposed to hormone treatment is to lower the risk of developing testicular cancer. For men with only one undescended testis, that risk is higher in the descended testis as well. Prognosis, prevention, and outcomes: The prognosis for correction of cryptorchidism is excellent. Currently there are no preventive measures for this disease, as it usually occurs during fetal development. Men who experienced cryptorchidism as infants, particularly if there is a family history of testicular cancer, have a 2.5- to 11-fold increased risk of developing testicular cancer and should be regularly screened starting at puberty. Boys typically are taught how to examine the testes and advised to report lumps or other abnormal characteris-
Salem Health: Cancer tics. Cancers (most commonly seminomas) caught early in this fashion are treatable. Semen and blood tests may begin in the late teenage years, and biopsy of the testes may be recommended in adults. Robert J. Amato, D.O. See also Spermatocytomas; Teratocarcinomas; Testicular cancer; Testicular self-examination (TSE); Yolk sac carcinomas.
u Culdoscopy Category: Procedures Also known as: Flexible culdoscopy Definition: A culdoscopy is a minimally invasive surgical procedure for visualizing the female pelvic organs through an endoscope (or culdoscope). The endoscope, a rigid viewing tube, is passed through the vagina into the cul-desac or retrouterine pouch (the pouch of Douglas), the part of the peritoneal cavity between the rectum and the uterus. The procedure can be used for the diagnosis of diseases such as cancer or the diagnosis of other conditions such as infertility or endometriosis. Cancers diagnosed: Cancer of the uterus, ovaries, or Fallopian tubes Why performed: Culdoscopy allows examination of the female pelvic organs and collection of a biopsy (tissue sample) for diagnosing cancer, with minimal discomfort for the patient. Patient preparation: The procedure is minimally invasive and is usually a hospital procedure with a short stay. Gas distension may be required for visualization but may not be necessary if the procedure is done in the knee-tochest position. Anesthesia required for the procedure may vary from local or regional to general anesthesia, depending on various factors. If a flexible tube is used, then the patient may stay awake during the procedure. The patient is informed of the risks involved, as well as the benefits of this type of diagnostic procedure. Steps of the procedure: The patient can be positioned in the knee-to-chest position or lying down (lithotomy) for this procedure. The endoscope, or culdoscope, is inserted into the female pelvic cavity via a small incision or puncture in the top of the posterior (back) vaginal wall. After the surgeon visualizes the pelvic cavity, a tissue sample may be taken and sent to the laboratory to determine the presence of cancer.
Curcumin After the procedure: The patient may be positioned on her abdomen to help expel any air used in the procedure. The patient is assessed and monitored for bleeding from the vagina. The patient should abstain from sexual intercourse, tampon use, or douches for at least two weeks or until cleared through her health care provider. Risks: Bowel injury and sepsis are possible risks of culdoscopy. Complications are estimated at 2 percent of patients and include bleeding at the puncture site, infection or peritonitis, or hypersensitivity or allergic reaction to the anesthetic used in the surgery. Results: Though culdoscopy is still useful as a diagnostic tool, many health care providers have replaced this procedure with a laparoscopy. Marylane Wade Koch, M.S.N., R.N. See also Endoscopy; Fallopian tube cancer; Gynecologic oncology; Pelvic examination; Uterine cancer; Vaginal cancer.
u Curcumin Category: Complementary and alternative therapies Also known as: Diferuloylmethane Definition: Curcumin is the active principle of turmeric, which is used as a common food additive in Asian cooking. It has been used for many centuries in ancient Chinese and Ayurvedic medical treatments. Curcumin has been selected, along with other promising diet-derived compounds, for testing as a chemopreventive agent for cancer targets in the NCI Chemoprevention Drug Development Program in the United States. Cancers treated or prevented: Supplemental treatment for chemical carcinogenesis caused by pesticides, breast cancer, metastatic melanoma, and lymphoma Delivery routes: Oral by capsule How this substance works: Curcumin is the active component of turmeric, a common spice found in the kitchen cabinets of Asia. Turmeric is a yellow powder obtained from the dried rhizomes of a flowering plant belonging to the ginger family. Curcumin is present in turmeric along with related yellow compounds called curcuminoids. It belongs to a chemical family of compounds known as polyphenols, which are antioxidants that destroy harmful tissue-damaging substances called free radicals. Curcumin has been reported to possess a wide range of medicinal properties, including the ability to inhibit can339
Cushing syndrome and cancer cerous tumors in the breast, colon, and skin in mice, rats, guinea pigs, and hamsters. Curcumin is being investigated for the prevention of colon cancer in a phase I clinical trial at the University of Michigan sponsored by the National Cancer Institute (NCI). One study reported that it reverses the negative effects of Taxol (paclitaxel), a breast cancer drug that can cause breast cancer cells to spread. Additionally, it is being tested against multiple myeloma and advanced pancreatic cancer. Based on experimental findings, curcumin has also been postulated to enhance detoxification of carcinogens such as DDT and dioxin by blocking their access to cells. The proposed hypothesis of the way curcumin inhibits cancerous cell growth is through its ability to block certain kinds of growth factors that are activated by chemical messengers called cytokines and kinases present in the cancer cells, sending signals to the cells to multiply. The structure of curcumin enables it to inhibit multiple kinases, thereby blocking the signals to the cells and effectively stopping the growth of certain types of cancer cells. Side effects: Ingesting large quantities of curcumin can cause ulcers. Curcumin, when used in conjunction with anticoagulants and thrombolytic agents, could enhance their activity and increase the risk of bleeding. Lalitha Krishnan, Ph.D. See also Antioxidants; Chemoprevention; Herbs as antioxidants.
u Cushing syndrome and cancer
Salem Health: Cancer the inflammatory response, balances the activity of insulin, and regulates the metabolism of proteins, sugars, and fats. It also helps the body respond to stress and is found in high levels in women in their last three months of pregnancy, highly trained athletes, and people suffering from depression. Cortisol secretion by the adrenal glands is tightly regulated. A peptide hormone called corticotropin-releasing hormone (CRH) is released into the bloodstream by a portion of the brain called the hypothalamus. CRH signals to the anterior lobe of the pituitary gland, which lies just below the hypothalamus, to release a protein hormone called adrenocorticotropin (ACTH). Circulating ACTH signals to the adrenal cortex cells to release cortisol. Normal blood cortisol levels shut off CRH and ACTH release by the hypothalamus and anterior lobe of the pituitary gland, respectively. Perturbation of this negative feedback control loop can abnormally increase blood cortisol levels. Particular tumors of the anterior lobe of the pituitary (pituitary adenomas) that secrete increased amounts of ACTH cause most cases of Cushing syndrome (Cushing disease). Tumors outside the pituitary also can secrete increased amounts of ACTH (ectopic ACTH syndrome). Lung tumors cause more than half these cases. Sometimes adrenal gland tumors can cause Cushing syndrome. Adrenocortical carcinomas cause high blood cortisol levels and rapid onset of symptoms. Incidence: The majority of Cushing syndrome cases are due to exogenous glucocorticoids. The annual incidence of endogenous Cushing syndrome is estimated at 10 to 15 cases per 1 million individuals.
Risk factors: People who take exogenous steroids, like arthritics or organ transplant patients, and families that show an inherited tendency to develop endocrine gland tumors are at risk of developing Cushing syndrome.
Symptoms: Symptoms of Cushing syndrome include rapid weight gain concentrated around the face (moon face) and trunk; excessive sweating; thinning of the skin that causes easy bruising, poor healing, and stretch marks; muscle weakness, particularly in the shoulders and hips; excessive hair growth in women; and fat pad deposition on the back of the neck and collar bone (buffalo hump). Excess cortisol also causes insomnia, infertility, and psychological disturbances that range from euphoria to psychosis and also commonly include depression, anxiety, and panic attacks. Complications include bone loss and osteoporosis, high blood pressure, kidney stones, type II diabetes, and unusual infections as a result of suppression of the immune system.
Etiology and the disease process: The adrenal glands lie on top of the kidneys, and the hormone cortisol is made by the outer layer (cortex) of the adrenal glands. Cortisol maintains blood sugar levels and blood pressure, reduces
Screening and diagnosis: The urinary free cortisol (UFC) test determines free cortisol concentrations in the urine over a twenty-four-hour period. Urinary cortisol concentrations higher than three to four times the normal level
Category: Diseases, symptoms, and conditions Also known as: Cushing’s syndrome, hypercortisolism, hyperadrenocorticism Related conditions: Polycystic ovary syndrome, pseudoCushing’s syndrome Definition: Cushing syndrome is an endocrine disorder that results from prolonged exposure of the body to high levels of the hormone cortisol.
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Salem Health: Cancer (50 to 100 micrograms a day) are highly suggestive for Cushing syndrome. However, measuring cortisol in saliva at nighttime has become more popular. High salivary cortisol levels are also indicative of Cushing syndrome. The dexamethasone suppression test determines the location of the abnormality. Dexamethasone mimics the physiological effects of cortisol, inhibiting ACTH release by the anterior lobe of the pituitary gland and decreasing cortisol production. If an ectopic source of cortisol production exists, then dexamethasone administration should not decrease blood or urine cortisol levels. Low-dose and high-dose dexamethasone tests are combined, and if there is no change in cortisol levels before and after dexamethasone administration for either test, an adrenal or ectopic ACTH-producing tumor is indicated. No change for the low-dose test and normal suppression in the high-dose test indicate a pituitary tumor. The CRH stimulation test further distinguishes between pituitary and ectopic ACTHproducing tumors. After an injection of CRH, patients with pituitary adenomas usually experience a rise in blood levels of ACTH and cortisol, but those with ectopic ACTH syndrome and cortisol-secreting adrenal tumors show no such response. If the endocrine tests are positive for Cushing syndrome, computed tomography scans of the chest and abdomen or magnetic resonance imaging of the pituitary gland can detect tumors of the adrenal glands or pituitary gland that might be producing excessive cortisol or ACTH. Treatment and therapy: Reducing the use of corticosteroid drugs can ameliorate the symptoms of exogenous Cushing syndrome. In the case of endogenous Cushing syndrome, surgery is recommended for tumors producing ACTH or cortisol. Radiation therapy is sometimes required to completely extirpate the tumor. Drugs that reduce cortisol production such as ketoconazole (Nizoral), mitotane (Lysodren), or metyrapone (Metopirone) can normalize cortisol blood levels and are given before surgery for those who are quite ill or to those for whom surgery and radiation were not completely successful. Prognosis, prevention, and outcomes: If left untreated, Cushing syndrome is lethal, but with treatment, most patients experience some relief of symptoms and cortisol normalization. Michael A. Buratovich, Ph.D. u
For Further Information Blevins, Lewis, S., ed. Cushing’s Syndrome. New York: Springer, 2002. Gaillard, Rolf C., ed. The ACTH Axis: Pathogenesis, Diagnosis, and Treatment. New York: Springer, 2003.
Cutaneous breast cancer Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Cushing’s Syndrome: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. Walsh, Mary. Cushing’s Syndrome, A Patient Guide: One Woman’s Journey. Rye, N.Y.: New Mill Press, 2001. Zuckerman, Eugenia, and Julie R. Ingelfinger. Coping with Prednisone (and Other Cortisone-Related Medicines): It May Work Miracles, but How Do You Handle the Side Effects? 2d ed. New York: St. Martin’s Griffin, 2007. u
Other Resources
MedlinePlus Cushing Syndrome http://www.nlm.nih.gov/medlineplus/ency/article/ 000410.htm National Endocrine and Metabolic Diseases Information Services Cushing’s Syndrome http://www.endocrine.niddk.nih.gov/pubs/cushings/ cushings.htm See also Adrenal gland cancers; Adrenocortical cancer; Carney complex; Endocrine cancers; Hepatomegaly; Hormonal therapies; Neuroendocrine tumors; Paraneoplastic syndromes; Pituitary tumors; Urinanalysis.
u Cutaneous breast cancer Category: Diseases, symptoms, and conditions Related conditions: Inflammatory breast cancer (IBC), melanoma of the breast, Paget disease of the breast Definition: Cutaneous breast cancer is the metastatic spread of a primary breast cancer to the skin. The most common site of skin metastases is to the affected breast, but it may also metastasize to the axilla, back, scalp, face, neck, extremities, around the ear, and above the clavicle. Risk factors: Although cutaneous cancer can occur with many types of cancer, it is most common with breast cancer and is associated with a history of breast cancer. It is not known why some breast cancers metastasize to the skin. Etiology and the disease process: Cutaneous breast cancer develops when the cancer cells invade the bloodstream or lymphatic system. For cutaneous cancer to develop, the 341
Cutaneous T-cell lymphoma (CTCL) cancer cells must evade the body’s immune defenses and then settle on the skin, where they invade the tissue. Incidence: Cutaneous breast cancer is relatively rare. It is estimated that from 0.7 to 10.4 percent of breast cancer patients will develop skin metastases. Symptoms: The symptoms of cutaneous breast cancer are changes in the skin, most commonly over the site of the primary breast cancer or on the mastectomy incision. There are several types of cutaneous lesions that can develop. The most common are reddened nodules (lumps) and papules (pimple-like lesions). There may also be purple papules, nodules, and plaques (flat, raised patches). Sometimes only a reddened, raised patch develops. The patch appears inflamed and has a defined margin. The last type is a large, purple plaque that has infiltrated the tissue. Screening and diagnosis: There is no screening in particular for cutaneous breast cancer. A diagnosis of cutaneous breast cancer is verified by skin biopsy. Cutaneous breast cancer is not staged as a separate entity because it is a sign of metastases of breast cancer and indicates Stage III or IV breast cancer. Treatment and therapy: Cutaneous breast cancer may be surgically excised, treated with photodynamic therapy, or cryotherapy (freezing). Systemic chemotherapy may be administered, or a topical cream called imiquimod 5 percent (Aldara) may be applied. Treatment is performed to improve the patient’s quality of life. Prognosis, prevention, and outcomes: Because it is a sign of advanced breast cancer, the presence of cutaneous breast cancer is indicative of a poor prognosis. There is no way to prevent it. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Breast cancer in men; Clinical breast exam (CBE); Comedo carcinomas; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas; Nipple discharge.
u Cutaneous T-cell lymphoma
(CTCL) Category: Diseases, symptoms, and conditions Also known as: Anaplastic large-cell lymphoma, cutaneous anaplastic large-cell lymphoma, granulomatous slack skin, lymphomatoid papulosis, lymphoproliferative disorder, pagetoid reticulosis, reticulum cell sarcoma of the skin, Woringer-Kolopp disease 342
Salem Health: Cancer Related conditions: Adult T-cell leukemia and lymphoma, follicular mucinosis, mycosis fungoides, nonHodgkin lymphoma, peripheral T-cell lymphoma, Sézary syndrome Definition: Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin lymphoma that mainly affects the skin. It is an uncontrolled growth of T cells, a type of white blood cell. “Cutaneous” means that this disease affects the skin. Sézary syndrome is a type of CTCL in which the skin, lymph nodes, and blood are all affected. Mycosis fungoides is another kind of CTCL in which only the skin and lymph nodes are affected. Risk factors: What causes CTCL is not known. Usually people with lymphomas have some type of gene mutation; however, if there is an exact mutation associated with this type of cancer, it is still unknown. In some patients, this disease may be associated with a preexisting allergic condition or a viral infection. Currently, researchers are investigating whether there is a connection between this disease and viruses and whether environmental factors have any association with this disease. Etiology and the disease process: Most types of nonHodgkin lymphoma do not affect the skin. However, CTCL is different in that it mostly affects skin cells. This disease often starts with a rash that itches, sometimes to the point of interrupting sleep, or very dry skin. It may progress to red, scaly patches on the skin, called plaques, that spread to larger areas of skin. The skin may also have tumors that may become infected or turn into bloody sores. This disease may progress to the lymph nodes and, in advanced cases, can spread to the spleen, liver, and intestines. In some cases, this type of lymphoma may begin to act like a more aggressive Hodgkin lymphoma. Incidence: CTCL is quite rare. In the United States, only about 1,500 new cases of CTCL are diagnosed each year. People between the ages of forty and sixty are most likely to get this type of cancer, and children rarely have it. Men are twice as likely as women to develop CTCL, and it is slightly more common in African Americans than in those of other racial backgrounds. Symptoms: Symptoms of CTCL include a rash; red, scaly, itchy skin; and skin tumors. Screening and diagnosis: A physical examination is helpful in diagnosing CTCL. However, since CTCL’s effect on the skin is similar to that of many other conditions, a diagnosis of CTCL involves a biopsy of the affected skin. This skin is then examined under a microscope to determine if T cells are growing abnormally. Diagnosis may
Salem Health: Cancer also involve blood tests to determine if the cancer has spread to the blood system. Computed tomography (CT) or magnetic resonance imaging (MRI) scans may be used to look at lymph nodes to determine if the disease has spread to them. One type of staging of CTCL involves three stages; however, the disease does not always progress through these stages. • Pretumor stage: Small raised patches appear on the skin, usually on the breast or buttocks, though they may appear anywhere. These patches may resemble eczema. Most patients never progress beyond this stage. • Plaque stage: Red patches appear on the skin, and sometimes there is no hair growth in these patches. These irregularly shaped patches, called plaques, may appear anywhere on the body but are usually on the face or buttocks or in the skin folds. • Tumor stage: Tumors, or raised lumps, begin to appear on the skin. These tumors and the plaques may become ulcers (bleeding sores). Sometimes the lymph nodes are affected at this stage, and occasionally, the cancer affects internal organs such as the spleen, liver, or lungs at this stage. This disease may also be called Sézary syndrome, especially if it progresses to the point of having many abnormal lymphocytes in the blood. Sometimes in Sézary syndrome, the entire skin is red, thick, swollen, and itchy. Non-Hodgkin lymphomas are often graded into low grade (slow growing) or high grade (fast growing). CTCL is a low-grade non-Hodgkin lymphoma. Another type of staging of the disease, associated particularly with Sézary syndrome, is as follows: • Stage I: Only parts of the skin are affected with a red, scaly rash. There are no tumors, and lymph nodes are normal. • Stage II: The lymph nodes are normal or enlarged but have no cancerous cells, and the skin has red, scaly rash but no tumors, or the lymph nodes are normal or enlarged but do not contain cancerous cells, and the skin has tumors. • Stage III: Most of the skin is affected by the red, scaly rash, but the lymph nodes, either normal or enlarged, do not contain cancerous cells. • Stage IV: In addition to the skin rash, either cancer cells are in the lymph nodes or cancer cells have spread to other organs.
Cutaneous T-cell lymphoma (CTCL) If only small areas of the skin are affected, the disease can be treated by radiotherapy or electronic beam radiation. High-energy rays are directed at the affected skin, killing the abnormal lymphocytes while minimizing the damage to the healthy cells. This treatment is most effective during the early stages of the disease. It may also be used on the entire body if the cancer has not spread below the outer layer of the skin. Another type of topical therapy is UVB (ultraviolet light B) therapy. The patient’s skin is exposed to UVB, which can help slow down the growth of skin cells. CTCL can also be treated by a type of chemotherapy in which drugs are applied directly to the skin using a cream, gel, or ointment. If the cancer becomes much worse or is not responding to other types of therapy, conventional chemotherapy, where drugs are injected into the bloodstream, may also be used. Photochemotherapy, a combination therapy, may be used if the cancer affects a large area of skin. A patient takes certain drugs that make the skin very sensitive to a type of ultraviolet light called ultraviolet light A. After the drugs have had time to affect the tumors, the skin is exposed to ultraviolet light A, which kills the tumors in the skin. Researchers are investigating oral drugs and immunotherapy (therapy that uses the body’s own immune system to fight the disease) that may be useful for CTCL patients. Prognosis, prevention, and outcomes: CTCL may stay only in the skin for several years, and many patients can lead normal lives for quite some time while controlling the disease with treatment. Outcomes for CTCL depend on the type of disease the patient has, how quickly the disease is progressing, and how well the patient is responding to therapy. Prognosis for patients with mycosis fungoides is usually good, as this type of CTCL usually affects only the skin, and patients are generally diagnosed early in the disease process. These patients have a median survival rate of more than twelve years. Those with Sézary syndrome generally have a more limited prognosis with a median survival of five years as this disease extends into the blood system. Patients whose internal organs are affected have a median survival of two to four years. Marianne M. Madsen, M.S. u
Treatment and therapy: Treatments for CTCL involve treating the skin either topically (on the surface), systemically (through the blood), or a combination of both. Treatment may control the disease, but if a patient does not continue treatment, the disease may recur.
For Further Information Greer, John P., et al., eds. Wintrobe’s Clinical Hematology. 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Souhami, Robert, et al., eds. Oxford Textbook of Oncology. 2d ed. New York: Oxford University Press, 2002. 343
Cyclin-dependent kinase inhibitor-2A (CDKN2A) Zackheim, Herschel, ed. Cutaneous T-cell Lymphoma: Mycosis Fungoides and Sézary Syndrome. Boca Raton, Fla.: CRC Press, 2005. u
Other Resources
Cutaneous Lymphoma Foundation http://www.clfoundation.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Lymphoma Information Network http://www.lymphomainfo.net See also Mycosis fungoides; Sézary syndrome.
u Cyclin-dependent kinase
inhibitor-2A (CDKN2A) Category: Cancer biology Also known as: CDKN2, CDK4 inhibitor, multiple tumor suppressor 1 (MTS1), TP16, p16INK4a, p14ARF Definition: Cyclin-dependent kinase inhibitor-2A (CDKN2A) is a tumor-suppressor gene located on chromosome 9p21. The gene’s role: As a tumor-suppressor gene, CDKN2A plays a major role in regulating cell division. The loss of function of a tumor-suppressor gene is a key event in the multistep process that transforms a normal cell into a cancer cell. In normal cells, the proteins that arise from these genes play a role in regulating cell growth and proliferation. A loss of function of these genes by mutation results in uncontrolled cell growth that leads to cancer. The chromosomal region where CDKN2A is located is often mutated in cancer cells. The CDKN2A gene locus on chromosome 9p21 codes for two proteins, p16INK4a and p14ARF, both of which inhibit the cell cycle. Cyclin-dependent kinases (CDKs) have two subunits: a kinase subunit (cdk) and a cyclin that activates the kinase. Regulating the function of CDKs is another group of proteins known as the cyclin kinase inhibitors. The protein coded for by CDKN2A belongs to the cyclindependent kinase inhibitor family of proteins. It binds to CDKs and acts as an inhibitor of cell division. Disruption of the function of the CDKN2A gene, therefore, has major consequences on the normal functioning of a cell. Cancer and the gene: Unlike other tumor-suppressor genes that are inactivated by point mutations, inactivation 344
Salem Health: Cancer of CDKN2A occurs through homozygous deletions, mutations, or promoter methylation. Mutations in the CDKN2A gene are known to occur in patients with multiple primary myelomas. Inactivation of CDKN2A has also been reported in numerous primary tumors, including bladder carcinoma, glioma, mesothelioma, gastrinomas, T-cell acute lymphoblastic leukemia, melanoma, prostate adenocarcinoma, and renal cell carcinoma. Some gene alterations that have been observed in different cancers related with alteration in the structure or function of CDKN2A include hypermethylation of CDKN2A in gastrinomas, germ-line mutation in CDKN2A in pancreatic cancer and melanoma, and inactivation of CDKN2A in sporadic pancreatic cancers. An increased risk of melanoma and pancreatic cancer exists in individuals with CDKN2A mutations. Clinical observations such as detection of germ-line mutations in CDKN2A in melanoma-prone families, increased risk of pancreatic cancer among melanoma-prone families with CDKN2A mutations, and zero occurrence of pancreatic cancer in melanoma-prone families without the CDKN2A germ-line mutation suggest a link between CDKN2A mutations and occurrence of melanoma and pancreatic cancer. Families with co-occurrence of pancreatic cancer and melanoma should participate in clinical screening programs for CDKN2A mutations. This would enable identification of high-risk family members and a more improved individual risk assessment for better outcomes for CDKN2A mutation carriers. Banalata Sen, Ph.D. See also BRCA1 and BRCA2 genes; Hereditary cancer syndromes; MYC oncogene; TP53 protein.
u Cyclooxygenase 2 (COX-2)
inhibitors Category: Chemotherapy and other drugs ATC code: 101XX, M01AH Definition: Cyclooxygenase 2 (COX-2) inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that inhibits the COX-2 enzyme, which is involved in inflammation and cancer. Cancers treated: Primarily colorectal cancers, such as familial adenomatous polyposis (FAP); others under investigation, including breast, head and neck, lung, and pancreatic cancers
Salem Health: Cancer Delivery routes: These drugs are administered orally as either capsules or tablets and can be taken on an at-home basis.
Cyclophosphamide
Cyclooxygenase 2 (COX-2) Inhibitors Drug
Brand
Delivery Mode
Cancers Treated
Celecoxib
Celebrex
Oral
Familial adenomatous polyposis (FAP); others under investigation
How these drugs work: The COX Rofecoxib Vioxx Oral None (removed from market in enzymes catalyze the production of 09/2004) hormones called prostaglandins, which Valdecoxib Bextra Oral None (removed from market in stimulate cells to produce inflamma05/2005) tory responses. COX-1 is always expressed and is found in many tissues. Its inhibition can reduce inflammation but may also cause serious gastrointestinal side effects. In contrast, COX-2 is expressed only u Cyclophosphamide in response to stimulation signals and is present in a limited number of tissues. COX-2 is overexpressed, however, Category: Carcinogens and suspected carcinogens; in several cancers, correlating with poorer overall surchemotherapy and other drugs vival. Therefore, COX-2 inhibitors are being investigated RoC status: Known human carcinogen since 1980 for the treatment and prevention of cancer. Also known as: Cytoxan, Neosar COX-2 contributes to tumor growth by enhancing tumor cell proliferation and survival, inhibiting the body’s Related cancers: Bladder cancer, myeloproliferative and immune response to cancer, and inducing the development lymphoproliferative malignancies (leukemias) of new blood vessels that feed a tumor and help it spread to Definition: Cyclophosphamide is a highly toxic, antiother parts of the body. Because the active sites of the cancer drug that belongs to a family of drugs known as COX enzymes differ, COX-2 inhibitors can form tight alkylating agents. It is a derivative of nitrogen mustard. complexes with COX-2 that dissociate slowly, thereby blocking enzyme activity. These inhibitors only loosely Exposure routes: Orally or by intravenous injection as and reversibly bind to COX-1, however, with no effect on part of medical treatment. Skin contact or dust inhalation its activity. Blocking only COX-2 may reduce tumor is possible during the manufacturing process and in hancell growth and survival and improve immune responses dling of the drug during preparation and administration. against tumor cells without the risk of severe gastrointestinal complications as seen with COX-1 inhibition. Where found: Cyclophosphamide is used in the treatment of various cancers, including lymphoma and leukemia, in Side effects: The major side effects of COX-2 inhibitors bone marrow transplant as part of a peripheral stem cell are cardiovascular, such as increased risks of blood clots, mobilization or preparative regimen, as an immune supheart attack, stroke, and high blood pressure. This has led pressive agent following bone marrow or solid organ to two drugs, Vioxx (rofecoxib) and Bextra (valdecoxib), transplant, and to treat autoimmune disorders such as being removed from the market by the Food and Drug Adrheumatoid arthritis. ministration (FDA). COX-2 inhibitors may also cause indigestion, stomach bleeding, ulcers, and perforation of the At risk: People who have been previously treated with stomach or intestines. Long-term administration may recyclophosphamide alone or in association with other chesult in kidney toxicity and (rarely) liver toxicity. Allergic motherapy drugs; health professionals (nurses, pharmaskin rashes may also occur with celecoxib (Celebrex). cists, physicians) who handle the drug during preparation, Elizabeth A. Manning, Ph.D. administration, and cleanup; and workers involved in the See also Angiogenesis; Bone pain; Desmoid tumors; Hereditary polyposis syndromes; Nonsteroidal anti-inflammatory drugs (NSAIDs); Pain management medications; Premalignancies.
manufacturing process. An estimated 500,000 patients are treated with cyclophosphamide annually. The general population is not considered to be at risk. Etiology and symptoms of associated cancers: Cyclophosphamide is used to treat cancer, but studies show that it can cause a secondary cancer as a long-term side effect. 345
Cyclosporin A It is a cytotoxic drug that affects the growth of cancer cells by interfering with the deoxyribonucleic acid (DNA) within the cells. Normal, noncancerous cells are affected as well, causing side effects that may include inflammation and bleeding from the bladder (hemorrhagic cystitis), bone marrow suppression, nausea and vomiting, and hair loss (alopecia). It is the damage to cellular DNA that can lead to a secondary cancer months or years after treatment with cyclophosphamide. Patients who experience hemorrhagic cystitis during treatment with cyclophosphamide have been shown to be at a higher risk of bladder cancer after treatment. Signs and symptoms of bladder cancer include blood in the urine (hematuria), pelvic pain, pain during urination, and a frequent urge to urinate. Patients who are treated with cyclophosphamide for primary myeloproliferative or lymphoproliferative malignancies (leukemia) are at a higher risk for a secondary hematologic malignancy (leukemia) as a long-term side effect of treatment. The symptoms of secondary acute leukemia include recurrent infections, bone and joint pain, swollen lymph nodes, and shortness of breath. History: Cyclophosphamide was first synthesized in 1958. The first clinical trials were published at the end of the 1950’s. It has been in widespread use as a chemotherapeutic agent since the 1960’s. Melanie Hawkins, B.S.N., R.N., O.C.N. See also Adrenal gland cancers; Bladder cancer; Burkitt lymphoma; Carcinoid tumors and carcinoid syndrome; Estrogen-receptor-sensitive breast cancer; Myeloproliferative disorders; Nasal cavity and paranasal sinus cancers.
u Cyclosporin A Category: Chemotherapy and other drugs; carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1998 Also known as: Cyclosporin, ciclosporin, cyclosporine, CsA, CYA, Sandimmune, Neoral, Restasis, Gengraf, Cicloral Related cancers: Lymphoma, skin cancer Definition: Cyclosporin A is a drug approved by the U.S. Food and Drug Administration, now marketed as an immunomodulator. It is a short polypeptide with eleven amino acids, eight of which form a ring. Exposure routes: Oral, intravenous, or topical administration 346
Salem Health: Cancer Where found: Commercially available in pharmacies At risk: People given the drug for therapeutic immunosuppression Etiology and symptoms of associated cancers: Cyclosporin A modifies the immune response by inhibiting calcineurin in lympocytes (primarily T cells); calcineurin is then unable to normally activate transcription of interleukin-2. It also inhibits release of the important proapoptotic factor cytochrome C from mitochondria. Although not important in modulating the immune response, the deficit of cytochrome C may slow or prevent normal apoptosis and act as a pro-survival factor for malignant cells. Another mechanism by which cyclosporin A promotes cancer progression is independent of immune cell inhibition; this direct carcinogenicity involves activation of transforming growth factor beta (TGF-β). Tumors in transplant recipients may arise from the recipient’s cells or from cells brought in with the transplanted organ, whereby premalignant donor cells are no longer subject to the surveillance of an intact immune system. Symptoms of lymphoma include fatigue, enlarged and painful lymph glands, and elevated white blood cell counts. Skin cancer is usually detected by visual inspection. In some patients, tumors become apparent within a few weeks of treatment initiation, and in some cases discontinuation of the drug is followed by tumor remission. History: As part of a drug discovery effort, soil samples from Norway were tested and found to have immunosuppressive activity in the early 1970’s; the active component was found to be a small peptide produced by the fungus Tolypocladium inflatum Gams. The drug was first administered to prevent transplanted organ rejection in 1980 and was approved for this indication in 1983. Transplant recipients were soon found through registry data to have a threefold to fivefold increased risk of cancer compared with the general population, with more aggressive malignancies and overall poorer prognosis. Despite the increased risk of cancer, cyclosporin A has since been approved for other indications, including prevention of graftversus-host disease (GVHD), psoriasis, rheumatoid arthritis, nephrotic syndrome, and keratoconjunctivitis sicca (dry eyes). The drug continues to be widely used, and efforts to minimize post-transplant malignancies continue. John B. Welsh, M.D., Ph.D. See also Aplastic anemia; Edema; Fibroadenomas; Graftversus-host disease (GVHD); Myasthenia gravis; Pancolitis; Paraneoplastic syndromes; Sjögren syndrome.
Salem Health: Cancer
u Cystography Category: Procedures Definition: Cystography is a procedure in which dye is injected into the bladder and X rays are taken to examine the organ. Cancers diagnosed: Cancers of the bladder and urinary system, prostate cancer Why performed: Cystography is performed to allow doctors to get a detailed picture of the bladder to check for problems such as cancerous growths. Patient preparation: Before the procedure, the patient may be asked to refrain from eating solid food for a period of time. The patient may be asked not to drink any fluids or may be asked to drink an increased amount of fluids, depending on the type and purpose of the procedure. Steps of the procedure: The patient is asked to urinate to empty the bladder as the first step of the procedure. Then a catheter is inserted into the bladder. Through the catheter, a contrast dye is injected into the bladder, until the bladder is full. The patient will experience the feeling of a need to urinate as a result of the fullness of the bladder. Once the dye has been injected, X rays are taken of the bladder. If the patient is male, then a lead shield will be used to protect the testes from the X-radiation. The patient may be asked to move into several different positions to allow for different views of the bladder. Once all the X rays needed have been taken, the catheter is removed and the patient is allowed to expel the dye. After the procedure: After the procedure, the patient may be advised to drink a large amount of clear fluids for a few days to help flush the dye out of the bladder. Because of the dye, the patient’s urine may be an unusual color. Risks: Some risks are associated with cystography. There is a small risk of infection because of the insertion of the catheter, as well as a small risk of allergic reaction to the injected dye. This procedure is generally not advised for women who are pregnant because exposure to X-radiation can harm the fetus. Results: The cystography will provide the health care team with detailed pictures of the patient’s bladder to use in evaluating the presence of cancerous growths and other bladder problems. Patients generally do not experience any long-term side effects from the procedure. Robert Bockstiegel, B.S.
Cystoscopy See also Bladder cancer; Cystoscopy; Prostate cancer; Transitional cell carcinomas; Urethral cancer; Urinary system cancers; Urography; Urologic oncology; Urostomy.
u Cystoscopy Category: Procedures Also known as: Cystourethroscopy Definition: During urination, urine moves from the bladder, through the urethra tube, and to the outside of the body. Cystoscopy uses a cystoscope (a thin tube with a miniature camera and light) to allow a doctor to see, examine, and biopsy abnormal tissues inside the urethra and bladder. This procedure is used to check for possible cancer cells. Cancers diagnosed: Bladder and urethral cancer; followup for renal pelvis and ureter cancer Why performed: Cystoscopy is primarily a diagnostic procedure used to view the inside of the bladder and urethra. Suspicious tissues are biopsied with a clipper on the end of the cystoscope. The tissue samples are examined in a laboratory for the presence of cancer cells. Patient preparation: Cystoscopy is performed with general or local anesthesia. Patients receiving general anesthesia should not eat or drink after midnight prior to the day of the procedure. Patients may be asked to provide a urine sample prior to the cystoscopy. The urine sample is tested for the presence of infection. Patients will wear an examination gown for the procedure. Steps of the procedure: The patient is usually positioned on the back with the knees spread. The lower body is covered with a sheet. The opening of the urethra is cleansed, and a pain-relieving medication is applied. The cystoscope is inserted through the urethral opening and into the bladder. Sterile fluid travels through the cystoscope into the bladder to expand the folds in the bladder and provide the doctor with a good view of the bladder lining. A biopsy is taken of any abnormal-looking tissue. The procedure is short, usually lasting only a few minutes, after which time the fluid and cystoscope are removed. The patient can empty the bladder when the cystoscopy is complete. After the procedure: Patients may experience a burning sensation while urinating or blood in their urine for about twenty-four hours after the procedure. Antibiotics may be prescribed. Patients should drink plenty of water. 347
Cytogenetics
Salem Health: Cancer breakage of chromosomes is used to diagnose cancers. Many cancers are defined by cytogenetic test results. Subspecialties: Oncology cytogenetics, reproductive cytogenetics, molecular cytogenetics Cancers treated: All
A doctor uses a cytoscope to examine a patient. (©Yoav Levy/ Phototake—All rights reserved)
Risks: There is a slight risk of bladder perforation during the procedure or infection following the procedure. Men should contact their doctors immediately if testicular swelling occurs. Results: A healthy bladder wall appears smooth. Suspicious growths are biopsied to determine whether cancer is present. Mary Car-Blanchard, O.T.D., B.S.O.T. See also Bladder cancer; Cystography; Hematuria; Renal pelvis tumors; Transitional cell carcinomas; Urinary system cancers; Urography; Urologic oncology; Urostomy.
u Cytogenetics Category: Medical specialties Also known as: Chromosome analysis, karyotyping Definition: Cytogenetics is the study of chromosomes as seen under the microscope. Observation of gain, loss, or 348
Training and certification: Technologists perform cytogenetic analysis under the direction of laboratory directors and technical supervisors. Laboratory directors and technical supervisors are medical doctors or scientists with doctoral degrees experienced in cytogenetics and certified by the American Board of Medical Genetics; in addition, they may be required to pass state board examinations. Supervisors and technologists are certified by the National Credentialing Agency (NCA). NCA certification is not required to practice in the United States. California, Florida, and New York require professional licensing for cytogeneticists to practice. The licenses very closely follow the requirements of the NCA certification. NCA certification as a clinical laboratory specialist in cytogenetics, or CLSp (CG), is available to those who have appropriate educational backgrounds, including a bachelor’s degree, specialized training in cytogenetics, one year of experience in a cytogenetics laboratory, and satisfactory completion of an exam. Supervisors must take an additional exam to qualify as supervisors. NCA certification must be maintained through continuing education. Those with a bachelor’s degree may participate in training programs available at cytogenetics laboratories before applying for NCA certification. College-based programs also exist at Kennesaw State University, the University of Connecticut, the University of Texas M. D. Anderson Cancer Center, Northern Michigan University, Texas Tech University, the University of Kansas, and the University of Texas, San Antonio. Services and procedures performed: In cytogenetic analysis, cells are collected from a patient and then grown in cell culture. The cells are chemically treated so that the chromosomes are visible. The cells are grown in culture media that support the growth of that particular cell type. A chemical that stops cells during cell division is used to arrest the dividing cells at the metaphase stage, when the chromosomes are most condensed. Depending on the specimen type, the chromosomes may be grown on or dropped onto microscope slides. The resulting slides are then stained using various special techniques. The staining results in a unique banding pattern for each of the chromosomes. This allows the identification of the chromosomes and enables cytogeneticists to identify
Salem Health: Cancer
Cytogenetics
abnormal chromosomes. Multiple cells are analyzed by the technicians. The entire process—from collecting the sample at the physician’s office or hospital to processing, analysis, and reporting the results to the physician—varies depending on the tissue type. The cell growth can take a few days to more than a week. The results are given in the form of a photograph of the chromosomes (a karyotype) and a written report. The karyotype shows the chromosomes aligned and paired by their numerical classification. After the metaphase cells are karyotyped, it is much easier to compare the bands and to identify abnormalities. Typical abnormal results include the loss of a chromosome, the gain of additional chromosomes, the loss of part of a chromosome, inversions (when a middle piece of one chromosome is turned upside down), and translocations (when two or more chromosomes break and exchange parts). One or many changes may happen in any one tumor cell, and the cancer can be complicated by having many different, related cancer cell lines that are mutating and changing continuously. The changes can include loss or gain of different abnormal chromosomes and structural abnormalities. Doctors can interpret the kinds of cancer and the severity based on the results of cytogenetic tests. After successful treatment, subsequent cytogenetic testing should show normal chromosomes.
somes can be “probed” with tiny pieces of fluorescently labeled DNA. DNA will attach to other DNA of the same kind (complementary sequences). For example, a fluorescent probe for the TP53 cancer oncogene (also known as p53) may be used to identify the presence or absence of the TP53 gene on a patient sample. If the TP53 gene is present, the probe will attach. A fluorescent microscope will reveal a visible signal in the location of the TP53 gene. An abnormal specimen would be lacking that signal, indicating a deletion of the TP53 gene. Christopher Pung, B.S., C.L.Sp. (CG)
Related specialties and subspecialties: In addition to studying cancer, cytogeneticists can identify birth defects such as Down syndrome, in which an extra chromosome 21 can be observed. This use of chromosome analysis is referred to as reproductive cytogenetics. Amniocentesis specimens are most commonly used in reproductive cytogenetics. Beginning in the 1990’s, a new branch of cytogenetics, molecular cytogenetics, began to develop. Deoxyribonucleic acid (DNA) based tests are being applied to samples processed by cytogeneticists. Molecular cytogenetics is rapidly becoming its own specialty as new tests are being developed in conjunction with the growing understanding of the molecular basis of chromosome abnormalities. Most molecular cytogenetic tests are being performed with the fluorescence in situ hybridization (FISH) technique, which uses the complementary nature of DNA to answer specific questions about particular regions of the DNA. FISH can be used to identify abnormalities that may be too small to be seen using conventional cytogenetic methods. Microscope slides prepared to analyze chromo-
National Credentialing Agency http://www.nca-info.org P.O. Box 15945-289 Lenexa, KS 66285
u
For Further Information Harper, Peter S. First Years of Human Chromosomes: The Beginnings of Human Cytogenetics. Bloxham, England: Scion, 2006. Heim, Sverre, and Felix Mitelman. Cancer Cytogenetics. 2d ed. New York: Wiley-Liss, 1995. Mark, Hon Fong L., ed. Medical Cytogenetics. Boca Raton, Fla.: CRC Press, 2000.
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Organizations and Professional Societies
Association of Genetic Technologists http://www.agt-info.org P.O. Box 15945-288 Lenexa, KS 66285
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Other Resources
Mountain States Genetic Foundation Molecular Cytogenetics (FISH) http://mostgene.org/gd/gdvol13c.htm NCI-Frederick Comparative Molecular Cytogenetics Core Facility http://www.ncifcrf.gov/research/cytogenetics/ default.asp See also Blood cancers; Chromosomes and cancer; Chronic myeloid leukemia (CML); Genetics of cancer; Klinefelter syndrome and cancer; Leukemias; Myelodysplastic syndromes; Myeloproliferative disorders; Neuroblastomas; Nijmegen breakage syndrome; Pathology.
349
Cytokines
u Cytokines Category: Cancer biology; chemotherapy and other drugs ATC code: LO3-LO3AX Also known as: Lymphokines, monokines, interleukins and interferons, tumor necrosis factors, chemokines, granulocyte colony-stimulating factor Definition: Cytokines are a class of (mainly water-soluble) proteins or glycoproteins produced by white blood cells (immune system cells). Cytokines carry chemical messages between cells and are of particular importance in both the innate and the adaptive immune response. Immune cell activity can be stimulated or inhibited, or can stimulate or inhibit the activity of other cells. There are many cytokine subclasses. Cytokines are produced naturally by immune cells in the body and can also be produced in the laboratory.
Salem Health: Cancer syndrome, low blood pressure, high cardiac output. liver toxicity, renal toxicity, pulmonary edema, fever, chills, gastric acidity, and infection. Most of the toxic side effects can be reversed. Fever and chills are treated with acetominophen and antibiotics are used for infection. Cytokine storm is a syndrome that can occur with the overstimulation of cytokines and can result in severe adverse effects and death. Janet R. Green, M.S.P.H. See also Anthraquinones; Appetite loss; Bacillus Calmette Guérin (BCG); Beryllium and beryllium compounds; Biological therapy; Exercise and cancer; Fever; Gene therapy; Human growth factors and tumor growth; Immune response to cancer; Immunotherapy; Interferon; Interleukins; Tumor necrosis factor (TNF); Vaccines, therapeutic.
Cancers treated: Renal cell carcinoma, melanoma, lymphoma, Kaposi sarcoma, chronic myelogenous leukemia, and hairy cell leukemia; being studied as a treatment for breast cancer and other solid tumors
u Cytology
Delivery route: Subcutaneous or intravenous (IV) injection
Definition: Cytology is the microscopic study of the structure of cells. A cytotechnologist examines cells collected from patients. The purpose is for detection (screening) or diagnosis of cancer, precancerous states, or other diseases.
How these agents work: Cytokines are unique in that they bind to individual cell receptors. They can regulate several parts of the immune system by stimulating the production of cellular molecules that can attach themselves to the surface of tumor cells and have antitumor activity. Other cytokines suppress the activity of cells and thus inhibit their action. Cytokines do not have one mechanism of action, and many aspects of their cellular signaling are being actively researched. They are being investigated for their ability to kill tumor cells and for their potential to act as vaccines or adjuvant stimulants against the development of cancer cells by presensitizing the immune system to kill cancer cells if they develop. Immunotherapy is still being aggressively studied for mechanisms of action, stimulation, and suppression, and it is believed that it will work in conjunction with other therapies rather than alone. The attractiveness of immunotherapy is the specificity of attacking only cancer cells and not harming normal cells, finding small numbers of cancer cells not identified though other treatment modalities, and using the existing immune system to treat cancer. Side effects: Common side effects of cytokine treatment include nausea, vomiting, acute toxicity, capillary leak 350
Category: Medical specialties Also known as: Cytotechnology, cytopathology
Subspecialties: Molecular diagnostics, immunocytochemistry Cancers diagnosed: Primarily cancers of the cervix, uterus, lungs, breast, and urinary tract Training and certification: Cytotechnologists must obtain a baccalaureate degree from an accredited college or university. This includes a twelve-month cytotechnology program accredited by the American Medical Association’s Commission on Accreditation of Allied Health Education Programs (CAAHEP). Students must take classes in biology, chemistry, mathematics, and statistics and must meet general education requirements. Their clinical training may be in a hospital or university. Students learn how to collect and prepare samples for examination, how to use a microscope, how to recognize normal cells, and how to recognize changes in the cells that indicate the presence of disease. After completing course work, students take the American Society for Clinical Pathology (ASCP) Board of Registry (BOR) national certification exam for cytotechnology. If they pass the exam, students receive a certificate
Salem Health: Cancer
Cytology
and can use the initials CT (ASCP) after their name. Some states require state licensure of cytologists. These states are California, Florida, Hawaii, Louisiana, Montana, New York, Rhode Island, Tennessee, and West Virginia. Georgia and Nevada require state certification. Once certified, cytotechnologists must maintain competency through continuing education. The credits earned enable the cytotechnologist to renew certification every three years. In addition, cytotechnologists performing gynecological testing must pass an annual proficiency test. A cytotechnologist may go on to earn certification as a specialist in cytotechnology. A combination of education and work experience in an accredited laboratory under the
supervision of a certified pathologist qualifies the cytotechnologist to take the specialist exam. Cytotechnologists may obtain CT certification and work five years, earn a master’s degree and work four years, or earn a doctorate and work three years. Upon passing the exam, the cytotechnologist is certified as a specialist in cytotechnology and has the right to use the designation SCT (ASCP). Services and procedures performed: Cytologists work in the laboratory, where patients do not usually see them. However, the work they perform and the decisions they make play a major role in the diagnosis and treatment of cancer.
The Methods of Cytology
Cytologists use microscopes to examine cells and fluids obtained through biopsy and separated by centrifugation.
351
Cytology The majority of work performed by cytotechnologists is the screening test for cervical cancer, called a Pap test or smear. Physicians or other health care providers collect the samples by using a small spatula or brush to scrape cells from the cervix. The cells are either spread on a glass slide and a fixative sprayed on the sample, or are placed in a liquid preservative and sent to the cytology laboratory. Relevant patient clinical information is also sent with the sample. The cytotechnologist or an assistant assigns the sample a number. The samples are registered by number in a logbook or computer program. Samples collected in liquid are filtered and the cells are spread evenly on a glass slide. The cytotechnologist or an assistant places the slides in a series of solutions that stain the nuclei and cytoplasm of the cells. A cover slip is placed on the slide and permanently bound to the slide with mounting media. The cytotechnologist works in a quiet environment. Using a microscope, the cytotechnologist examines the slide using a low-power (ten-power, or ×10) objective and a ×10, ×12, or ×10 wide field ocular. The cytotechnologist systematically examines the slide by starting in one corner and going back and forth in a horizontal or vertical direction to ensure that the entire sample is observed. The cytotechnologist looks at the cell structure, including the nucleus (center of the cell) and the cytoplasm that surrounds the nucleus. Changes in the nucleus or cytoplasm may indicate the presence of cancer or precancerous conditions. If unusual cells are noted, a high-power (×40) objective is used to see more detail. These cells are then marked using one of several marking systems. Along with determining if the cells are normal or abnormal, the cytologist determines if there are adequate cells present. If the preparations are adequate and all cells are normal, the cytologist reports the results. All samples with unusual cells are further examined by a pathologist for final reporting of screening results or diagnosis. If the preparations contain an inadequate number of cells, the cytologist will contact the health care provider to collect another sample. Some labs may use an automated imaging system to examine the slides. However, a cytotechnologist must still examine samples that have abnormal findings on the automated system. The cytologist also prepares slides from body fluids such as urine, cerebrospinal fluid, and effusions. Effusions are abnormal accumulations of fluid and may be peritoneal (ascites or abdominal fluid), pleural fluid (fluid surrounding the lungs), or pericardial fluid (fluid surrounding the heart). The fluids are centrifuged to prepare a concentration of cells. The excess fluid is removed, and the cytologist makes a thin preparation of the cells on a glass slide. 352
Salem Health: Cancer The slide is then stained and examined under the microscope. The cytologist may assist radiologists, endocrinologists, or other physicians collecting cellular samples from patients by a technique called fine needle aspiration. The cytologist may examine the material microscopically to determine if an adequate sample was taken before the patient leaves the exam room. The cytologist prepares the slides and stains and examines them in the same manner that the Pap smears are examined for the presence or absence of cancer cells. Related specialties and subspecialties: Cytologists work not only independently but also as part of a team. In a screening or diagnostic cytology laboratory, cytologists always work with a pathologist. Pathologists are medical doctors with specialized training in the examination of tissues, cells, and body fluids. In addition to a medical degree, pathologists complete a three- to four-year residency program. The pathologist examines not only abnormal cytology smears but also tissue samples removed during surgery, directs the clinical laboratory, may perform autopsies, and consults with other physicians. Cytology labs must have a system to obtain both surgical samples and clinical confirmation of cytology results for comparison. Because of this close relationship between cytology and surgical specimens, cytologists also work with histotechnologists (histotologists). Histotechnologists prepare slides from surgical samples for the pathologist to examine under the microscope. A histotechnologist has a baccalaureate degree plus one year of histology laboratory training under the direction of a pathologist. In smaller laboratories, cytotechnologists and histotechnologists may share some functions, such as logging in samples, staining slides, and filing reports. Clinical laboratory scientists (CLS’s) work in the clinical laboratory. They perform cell counts and chemical and microbiology tests on the same types of fluids that the cytology lab may receive. When CLS’s see abnormal cells in a fluid, they check to see if cytology has been ordered. If not, the smear and remaining fluid as well as a copy of the results are sent to the cytology lab for further study. In large laboratories, an assistant under a cytotechnologist’s supervision may perform repetitive work such as assigning sample numbers, recording samples in a logbook, entering data into a computer, staining and adding the cover slip, and filing reports and slides. Cytotechnologists, particularly in specialty or research laboratories, may also work with molecular diagnostics and immunocytochemistry techniques. Wanda E. Clark, M.T. (ASCP)
Salem Health: Cancer u For Further Information Abeloff, Martin D., et al. Clinical Oncology. 3d ed. Philadelphia: Churchill Livingstone/Elsevier, 2004. American Medical Association. Health Professions Career and Educational Directory 2007-2008. 35th ed. Chicago: AMA Press, 2007. Cibus, Edmund S., and Barbara S. Ducatman. Cytology: Diagnostic Principles and Clinical Correlates. 2d ed. Philadelphia: Saunders, 2003. Keebler, Catherine M., and Theresa M. Somrak. The Manual of Cytotechnology. 7th ed. Chicago: ASCP Press, 1997. Koss, Leonard G., and Myron R. Melamed. Koss’ Diagnostic Cytology and Its Histopathologic Bases. 5th ed. Philadelphia: Lippincott/Williams and Wilkins, 2006. Rushing, Lynda, and Nancy Joste. Abnormal Pap Smears: What Every Woman Needs to Know. Amherst, N.Y.: Prometheus Books, 2001. Swanson, Barbara M. Careers in Health Care. New York: McGraw Hill Professional, 2005. u
Cytology American Society for Cytotechnology http://www.asct.com 1500 Sunday Drive, Suite 102 Raleigh, NC 27607 American Society of Cytopathology http://www.cytopathology.org 400 West 9th Street, Suite 201 Wilmington, DE 19801 u
Other Resources
American Cancer Society Testing Biopsy and Cytology Specimens for Cancer http://www.cancer.org/docroot/PED/content/ PED_2_3X_Testing_Biopsy_and_Cytology_ Specimens_for_Cancer.asp?sitearea=PED Papanicolaou Society of Cytopathology http://www.papsociety.org See also Cytogenetics; Hematologic oncology; Molecular oncology; Pathology; Sputum cytology.
Organizations and Professional Societies
American Society for Clinical Pathology http://www.ascp.org 33 West Monroe, Suite 1600 Chicago, IL 60603
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Dana-Farber Cancer Institute
u Dana-Farber Cancer Institute Category: Organizations Definition: The Dana-Farber Cancer Institute, a regional center for basic and clinical cancer research located in Boston, Massachusetts, is a Harvard Medical Schoolaffiliated institution. The institute, along with Massachusetts General Hospital and Brigham and Women’s Hospital (the Data-Farber/Harvard Cancer Center) and Children’s Hospital Boston, work together to provide comprehensive cancer care and treatment. Founding and history: In 1947 Sidney Farber, a Harvard Medical School graduate of the class of 1928, founded the Children’s Cancer Research Foundation. Farber, a pathologist at Children’s Hospital in Boston, was interested in finding a cure for leukemia. He conducted early chemotherapy studies with children who were seriously ill with leukemia and in 1948 published promising results in the New England Journal of Medicine. Funding for Farber’s research came from a charitable organization (the Variety Club of New England) made up of entertainers who wanted to support a local scientist. In 1948 “Jimmy,” a young patient of Farber, was introduced on Truth or Consequences, a popular radio program, and as a result of his appearance on the show, many contributions were made to support Farber’s research. The Variety Club’s patronage project was renamed the Jimmy Fund, a charitable organization for children’s cancer research. The scope of the research foundation was widened in 1969 to include cancer research and treatment for patients of all ages, and the name of the institution was changed to the Sidney Farber Cancer Center (and later modified slightly to the Sidney Farber Cancer Institute) in honor of Farber, who died in 1973. An industrialist, Charles A. Dana, supported the Children’s Cancer Research Foundation with major grants beginning in 1962, and the institution was renamed the Dana-Farber Cancer Institute in 1983 to reflect his generous support. Farber was a pioneer of the concept of total care, believing that all patient and family services, such as clinical care, nutrition counseling, and social work, should be provided in one place. Further, he believed that decisions about the care of a patient should be made by a team consisting of everyone involved in taking care of that patient. Through the years, the Farber family, including siblings, children, and grandchildren of Sidney Farber, have been involved with the Sidney Farber Cancer Institute in roles such as members of the Board of Governors or in initiating new programs. 354
Salem Health: Cancer Current facilities: The Dana-Farber Cancer Institute (DFCI), along with Brigham and Women’s Hospital and Massachusetts General Hospital, provide adult cancer treatment. All three institutions are affiliated with Harvard Medical School, and the program is one of thirty-nine centers nationwide designated by the National Cancer Institute as a comprehensive cancer care center. In 1996, the DFCI, Brigham and Women’s and Massachusetts General formed the Dana-Farber/Partners CancerCare system, and it is the largest such system in the United States. Adult patient care is provided at two locations: the Massachusetts General Hospital Cancer Center and the Dana-Farber/ Brigham and Women’s Cancer Center. Treatment of pediatric cancer patients is provided through a collaboration of the Dana-Farber Cancer Institute and Children’s Hospital Boston. Children’s Hospital is the pediatric teaching hospital for Harvard Medical School. Pediatric outpatient treatment is provided at the Dana-Farber Cancer Center, and pediatric inpatients are treated at Children’s Hospital. There are twelve cancer treatment programs for adults: breast cancer, endocrine cancer, gastrointestinal cancer, genitourinary cancer, gynecological cancer, head and neck cancer, hematologic malignancies, hematology, melanoma, neurologic cancer, sarcoma, and thoracic oncology. Pediatric programs and specialty services include bone and soft-tissue tumors, brain tumors, histiocytosis, Hodgkin disease, kidney tumors, leukemia, neuroblastoma, non-Hodgkin lymphoma, stem cell transplantation, and a pediatric advanced care team. The Dana Farber/Children’s Hospital Cancer Center recognizes the need to address potential late effects of pediatric cancers and has several childhood cancer survivor programs for long-term follow-up of patients. The Dana-Farber Cancer Institute is involved in a wide range of community outreach programs and has a mission to reach underserved and minority groups. Research: Research at Dana-Farber began in 1947 with Farber’s research on chemotherapy for children with cancer and continues today under the Dana-Farber/Harvard Cancer Center (DF/HCC). The DF/HCC comprises the Dana-Farber Cancer Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Children’s Hospital Boston, Massachusetts General Hospital, and Harvard School of Public Health. In 2000 the designation of the DFCI as a comprehensive cancer care center was redefined to include the DF/HCC. Research at the DF/HCC is carried out at eighteen core facilities by hundreds of researchers; the collaborative research programs have made significant contribu-
Salem Health: Cancer tions in areas such as basic cancer cell biology, genetic epidemiology, tumor immunology, and clinical/translational cancer research.
Delta-9-tetrahydrocannabinol pot, reefer, sinsemilla, weed; there are also many names signifying different growing regions and qualities of marijuana
Specialization: The bone marrow transplantation program is one of the nation’s oldest programs of its kind. The Pediatric Brain Tumor Program is the largest such program in the eastern region of the United States. The Quality of Life Clinic at DFCI provides comprehensive follow-up for adult survivors of pediatric cancers. Dana-Farber is a member of the Multiple Myeloma Research Consortium. Vicki Miskovsky, B.S., R.D.
Definition: Delta-9-tetrahydrocannabinol (THC), the psychoactive substance that is the active ingredient in the plant Cannabis sativa (marijuana), is debated as a viable medical treatment. Cancer patients use substances containing THC and its synthetic and derivative forms to relieve nausea and vomiting. Patients with human acquired immunodeficiency syndrome (AIDS) also use these substances to combat weight loss.
u
Delivery routes: Drugs such as Marinol capsules and Cesamet pills are taken orally. Dried forms of marijuana, including buds of flowers and leaves, pieces of leaves, seeds, and stems, are smoked in marijuana cigarettes or pipes; burned and vaporized using other means; or ingested in foods such as baked cookies. Cannabis sativa also may be used to produce the drug hashish, or hash, a resinous substance typically found in either block or oil form. Hash can be smoked or consumed orally. Oral forms are often used to mitigate nausea, which may accompany all forms of cancer and the chemotherapeutic drugs used to treat them. Non-oral forms (such as smoking) may be contraindicated for some types of cancer, such as lung cancers. Use also may be contraindicated in the presence of other medical and psychiatric conditions.
For Further Information Dollinger, M., et al. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 4th ed. Kansas City, Mo.: Andre McMell, 2002. Eyre, Harmon, and Dianne Partie Lange, eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002. Wisnia, Saul. The Jimmy Fund of Dana-Farber Cancer Institute. Charleston, S.C.: Arcadia, 2002. u
Other Resources
Dana-Farber/Brigham and Women’s Cancer Center http://www.cancercare.harvard.edu Dana-Farber Cancer Institute http://www.dfci.harvard.edu See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Delta-9-tetrahydrocannabinol Category: Complementary and alternative therapies; chemotherapy and other drugs Also known as: THC, dronabinol (Marinol), nabilone (Cesamet), Cannabis sativa, medical marijuana; slang terms include bud, ganja, grass, hemp, herb,
How this compound works: The human body has a cannabinoid system including receptors called CB1 and CB2 receptors. CB1 receptors are located in the central nervous system and peripherally. To date, there is a presumption that CB2 receptors are located in peripheral areas of the body only. Both CB1 and CB2 receptors are involved in nausea and vomiting, interacting with other neurotransmitters affecting both the central nervous system (CNS) and gastrointestinal system. Products containing THC, its derivatives, and synthetic forms are understood to affect the cannabinoid system as a whole and via these CB1 and CB2 receptors. Cannabis sativa is a plant whose history spans centuries across diverse cultures. The plant itself has many purposes, so its worldwide presence is understandable. It has been used for its spiritual and religious ceremonies in some cultures, for its medicinal purposes in others, and as a recreational drug in others. In some cultures, it is an illicit substance or highly controlled or regulated, depending on its form. In the United States, marijuana is the most widely used illicit drug. Effects may be substantially different de355
Delta-9-tetrahydrocannabinol pending on the presence of other substances used at the same time (whether they are legal, illicit, or medicinal) and the presence of physical or mental illnesses. For many years, marijuana use was thought to be associated with cancers, particularly those of the head, neck, and lungs, such as those commonly associated with tobacco products. Contemporary scientific reviews (Reena Mehra et al., 2006) and studies (Mia Hashibe et al., 2007) suggest, however, that such assertions are more cautionary and tentative. In fact, no studies have shown a definitive link between long-term marijuana use and cancer. As with other smoking, however, it is associated with increased respiratory infections and other physical changes. In addition, risks associated with secondhand smoke are still suspect. Marijuana and tobacco contain many of the same carcinogens. Therefore, caution is recommended regarding any marijuana use. Hashibe and colleagues point out that the current findings regarding marijuana and health deserve continued study. For instance, scientists need better methods to estimate dosages of marijuana smoked. Such methods would provide a way to allow scientists to more formally evaluate dose-response issues. This is problematic for epidemiologic and naturalistic studies of marijuana use because marijuana is a street drug. The quality of street drugs is not set at a known standard and does not have a certain amount of active ingredients per amount of the drug. There is also a need for studies of the effects of marijuana over longer periods to ensure that observation periods have been long enough to see long-term health impacts. For instance, studies evaluating longitudinal effects over a lifetime, or substantial portion of a lifetime, and potentially accounting for dose effects and method of administration will have benefit. Side effects: Short-term effects may vary by user but include things such as changes in sensory experiences, increases in appetite, relaxation, increased feelings of pleasure, decreases in feelings of nausea, memory and learning difficulties, panic, anxiety, coordination problems, and impaired problem solving. Long-term effects may include
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Salem Health: Cancer problems related to addiction, such as abuse or dependence, motivational problems, daily cough, phlegm problems, respiratory problems, and impact to the immune system. It is noteworthy that these effects are what would be observed in normal users—that is, individuals without other significant physical or mental health problems who are not using any other substances. In individuals with other characteristics, such as other physical or psychiatric problems, the effects might differ in important ways. Nancy A. Piotrowski, Ph.D. u
For Further Information Earleywine, Mitch. Understanding Marijuana: A New Look at the Scientific Evidence. New York: Oxford University Press, 2002. Faupel, Charles, Alan M. Horowitz, and Gregory Weaver, eds. The Sociology of American Drug Use. New York: McGraw-Hill, 2004. Grotenhermen, Franjo, and Ethan Russo, eds. Cannabis and Cannabinoids: Pharmacology, Toxicology, and Therapeutic Potential. Binghamton, N.Y.: Haworth Press, 2002. Hashibe, Mia, et al. “Marijuana Use and the Risk of Lung and Upper Aerodigestive Tract Cancers: Results of a Population-Based Case-Control Study.” Cancer, Epidemiology, Biomarkers, & Prevention 15, no. 10 (2006): 1829-1834. Mehra, Reena, et al. “The Association Between Marijuana Smoking and Lung Cancer: A Systematic Review.” Archives of Internal Medicine 166 (July 10, 2006): 13591367. Rosen, Winifred, and Andrew T. Weil. From Chocolate to Morphine: Everything You Need to Know About MindAltering Drugs. Rev. ed. Boston: Houghton Mifflin, 2004. Russo, Ethan B., and Franjo Frotenhermen, eds. Handbook of Cannabis Therapeutics: From Bench to Bedside. Binghamton, N.Y.: Haworth Press, 2006. See also Antinausea medications; Medical marijuana; Nausea and vomiting.
Salem Health: Cancer
u Denys-Drash syndrome and
cancer Category: Diseases, symptoms, and conditions Also known as: DDS Related conditions: Wilms’ tumor (WT), Frasier syndrome, WAGR syndrome Definition: Denys-Drash syndrome is a rare disorder that usually causes kidney failure by the age of three, malformed sex organs, and often Wilms’ tumor. It is caused by a WT1 gene mutation and was named for two pediatricians, Pierre Denys and Allan Drash, who initially described this condition. Risk factors: The primary risk factor is having a relative with a WT1-related disorder. Etiology and the disease process: Denys-Drash syndrome originates with the mutation of the WT1 gene’s chromosome 11, band p13. Children with Denys-Drash syndrome are usually born with kidney disease, which becomes apparent several weeks after birth through eighteen months. Malignant Wilms’ tumor growth in one or two kidneys occurs in approximately 90 percent of DenysDrash patients. Cancer occasionally extends from the kidneys into the livers, lungs, and lymph nodes. Incidence: The precise number of Denys-Drash syndrome cases is uncertain, with an estimated 160 cases from the late 1960’s through the early twenty-first century. U.S. physicians diagnose approximately 500 children annually with Wilms’ tumors, which represent 95 percent of kidney cancers affecting children and 6 percent of pediatric cancers. Symptoms: Denys-Drash syndrome patients often exhibit symptoms commonly associated with kidney disorders and Wilms’ tumors, including swollen abdomens, elevated blood pressure, and bloody urine. Both male and female Denys-Drash syndrome patients have abnormal external or internal genitalia. Screening and diagnosis: Physicians test young children born with genitalia irregularities for Denys-Drash syndrome. Chromosome analysis verifies WT1 gene mutations. During infancy, biopsies and blood tests detect problems with kidneys. Computed tomography (CT) scanning, magnetic resonance imaging (MRI), or ultrasounds of abdomens locate tumors. Pediatricians apply the National Wilms’ Tumor Study Group (NWTS) staging system’s five stages to determine effective treatments.
Depression Treatment and therapy: Medical strategies to combat Denys-Drash syndrome primarily consist of surgery, radiation, or chemotherapy, either separately or combined to impede growth and eliminate malignancies. Some DenysDrash syndrome patients undergo kidney transplantation and dialysis. Additional pharmaceutical and dietary therapies reduce blood pressure and aid kidney functioning. Prognosis, prevention, and outcomes: Denys-Drash syndrome patients often develop infections, circulatory problems, and additional cancers that exacerbate their condition. Preventive options include replacing kidneys with healthy transplants and routine screening for malignancies. Kidney failure causes the death of approximately two-thirds of Denys-Drash syndrome patients by age three. In contrast, approximately 90 percent of patients treated solely for Wilms’ tumor survive. Elizabeth D. Schafer, Ph.D. See also Nephroblastomas; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Depression Category: Diseases, symptoms, and conditions; social and personal issues Also known as: Major depression, major depressive disorder, reactive depression, adjustment disorder with depressed features, depression with psychotic features, first episode depression, chronic depression, depression in remission Related conditions: Anxiety disorder, mood disorder, substance abuse, seasonal affective disorder, borderline personality disorder, schizoaffective disorder Definition: Depression is a common emotional state that can be conceptualized along a continuum ranging from transient, nonclinical periods of low mood and sadness that remit quickly on their own, to a serious, life-threatening, clinical disorder requiring aggressive psychiatric intervention. Depression can lead to significant impairment of an individual’s ability to function and is a leading cause of disability worldwide. Clinical depression often occurs with cancer because of its chronic and life-threatening nature, but it is not considered typical or expected, which is counter to a common yet erroneous belief that depression and cancer “understandably” go hand in hand. Depression nonetheless is one 357
Depression
Salem Health: Cancer
is based on a complex interaction of factors. These include genetic predisposition to aberrant neurochemical states that precede or result from • The type of cancer, its stage, and prognosis an inadequate stress response combined with a Whether they are newly diagnosed, in treatment, in remission, or • experiencing a recurrence distorted, negatively biased cognitive style or • How well developed their coping strategies are worldview that is learned and reinforced early • Their support group, including friends and family in life. This multidimensional framework indi• Their age cates need for a combined psychopharmaco• The availability of treatment logic and psychotherapeutic treatment approach • Their beliefs about why they got cancer that is well supported in the medical literature. Clinical depression can present as a single epiSource: National Cancer Institute sode, be chronic and unremitting, or occur over time with periods of remissions and exacerbations. of the most common psychiatric complications in cancer A crisis framework is often used to describe the occurpatients. rence of depression in the context of cancer. The acute crisis response (ACR) typically occurs at transitions in the Risk factors: Depression is most common among cancer disease trajectory (diagnosis, treatment initiation, recurpatients with advanced disease and with symptoms and rence, treatment failure, disease progression). The ACR is discomfort that are not treated or inadequately treated. It characterized by symptoms of anxiety and depression that commonly coexists with anxiety and is common in indiusually resolve within a short time period. Time frames are viduals with substance abuse problems and other chronic variable, but the ACR usually resolves when individuals physical and mental disorders. Most cancer patients maniknow what to expect in terms of treatment, receive reasfest transient symptoms of depression that are responsive surance that discomfort can be controlled, and mobilize to support, reassurance, and information about what to exusual coping strategies and support systems. When symppect regarding the course, treatment, and prognosis of toms worsen rather than resolve over time or coping mechtheir disease. Others experience unremitting or recurrent anisms are insufficient, treatment for depression must be depression requiring aggressive monitoring and intervenconsidered regardless of whether diagnostic criteria for a tion. The following list depicts risk factors that favor the clinical diagnosis are met. development of clinically significant depression within the context of a cancer diagnosis: Incidence: Prevelance rates vary and depend on the population studied, site and stage of disease, and method used • Family history of depression to measure depression. Prevalence rates among cancer pa• Past history of depression, depression treatment, psychiatric hospitalization, or significant psychiatric/persontients range from 5 percent (lower than general population ality disorder rates) to 90 percent. In general, studies that use established diagnostic criteria report rates of depression of about 25 • History of unusual, eccentric behavior percent. Rates of depression are highest among patients • Confusion (may be indicative of an organically based depression) with advanced cancer and in studies in which stringent diagnostic guidelines are not used. • Maladaptive coping style • Dysfunctional family coping or complex family issues Symptoms: Symptoms of depression in cancer popula• Limited social support tions include the following: • Financial problems including lack of insurance • Persistent sad mood • Multiple roles, obligations, and stressors • Loss of interest or pleasure in typically pleasurable ac• Advanced cancer tivities • Treatment resulting in disfigurement or loss of function Feelings of guilt, worthlessness, helplessness • • Presence of dependent children Crying, not easily comforted • • Inadequate symptoms management Frequent thoughts of death or suicide • • Treatment that has a depressionogenic effect (certain Trouble concentrating, indecisiveness • chemotherapies, steroids, narcotics) • Appetite change Etiology and the disease process: Simplistically stated, • Diminished energy that may be mixed with restlessness the etiology of clinical depression, cancer related or not, and anxiety
Factors Affecting How People Adjust to Cancer
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• •
Fatigue, loss of energy Insomnia or hypersomnia Diagnosis of cancer-related depression relies heavily on the presence of affective symptoms (the first five symptoms in the list). Neurovegetative symptoms (the last five symptoms in the list) that characterize depression in physically healthy individuals are not good predictors of depression in cancer patients because cancer and its treatment produce similar symptoms. Additional behaviors suggestive of depression include refusal, indecisiveness, or noncompliance with treatment; persistent anxiety and sadness, unresponsive to usual support; unremitting fear associated with procedures; excessive crying, hopelessness that does not diminish over time; an abrupt change in mood or behavior; eccentric behavior or confusion; and excessive guilt or self-blame for illness. Screening and diagnosis: A formal diagnosis of depression is based on fulfillment of criteria outlined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR (2000). The diagnostic subtypes of depression include major depressive disorder (severe depression that lasts for more than two weeks and is particularly amenable to pharmacologic treatment), adjustment disorder with depressed features (depression that occurs in response to a clearly defined event or stressor), dysthymia (chronic, low-level depression that pervades an individual’s personality and daily life), and bipolar disorder (a genetically determined severe form of depression that may or may not alternate between depressive lows and manic highs and is responsive to mood-stabilizing, pharmacologic agents). Major depression and adjustment disorder are common diagnoses among individuals with cancer. Dysthymia and bipolar disorder usually precede a cancer diagnosis or occur for the first time following cancer diagnosis in those genetically predisposed. Depressive symptoms not severe enough or of sufficient duration to achieve diagnostic status are the most common type of depressive phenomena in individuals with cancer. Because a formal diagnosis is not present, these symptoms are often ignored despite a common, negative impact. More research on the simultaneous occurrence of cancer and depression is needed, including symptom profiles, clinical treatment trials, and related outcomes. A number of tests screen for depression, but they have not been consistently incorporated into clinical care. Nonpsychiatric providers fail to diagnose and treat depression in as many as 50 percent of cancer patients with depressive disorders. Obstacles to recognizing depression
Depression include inadequate provider knowledge of diagnostic criteria, competing treatment priorities in oncology settings, time limitations in busy offices, concern about the stigma associated with a psychiatric diagnosis, limited reimbursement, and uncertainty about the value of screening mechanisms for case identification. In general, regardless of whether screening measures are used, if symptoms do not remit in a reasonable time frame, evaluation of depressive symptoms by a psychiatric specialist should be sought. Treatment and therapy: Psychosocial interventions can exert an important effect on the overall adjustment of patients and their families to cancer and its treatment. Factors contributing to the diagnosis of depression should influence the treatment approach. Treatments include psychopharmacologic treatment, individual psychotherapy, group therapy, family therapy, marital therapy, or some combination of these. Antidepressant medication should be chosen on the basis of diagnostic subtype, treatment response, and side effect profile. Bipolar disorder is usually treated with a mood stabilizer, requiring careful monitoring and adjustment, especially during active treatment, as therapeutic blood levels are narrow and can shift dramatically in response to electrolyte and metabolic changes. Major depression is commonly treated with one of several classes of antidepressant medication, commonly a selective serotonin reuptake inhibitor (SSRI) or a a selective serotonin and norepinepherine reuptake inhibitor (SSNRI). Dosages are typically lower than required in healthy individuals and can positively affect other symptoms that the patient might be experiencing, such as pain and anxiety. In the oncology setting, a multimodal treatment approach is most effective in treating depression and can have a positive impact on a range of psychosocial and medical outcomes. Prognosis, prevention, and outcomes: Left untreated, depression can produce a range of negative outcomes from diminished quality of life to noncompliance with treatment to diminished survival. Depression can be prevented in some individuals by providing preemptive counseling, education, support, and information about resources. Early recognition and treatment offer the best hope for rapid remission. Modern therapies are effective in treating depression even among cancer patients who are in progressive and terminal stages of illness. Treatment can vastly improve quality of life and diminish suffering; thus routine screening and treatment should be a universal aspect of comprehensive cancer care . Jeannie V. Pasacreta, Ph.D., A.P.R.N. 359
Dermatofibrosarcoma protuberans (DFSP) u For Further Information Akechi, Tatsuo, et al. “Major Depression, Adjustment Disorders, and Post-traumatic Stress Disorder in Terminally Ill Cancer Patients: Associated and Predictive Factors.” Journal of Clinical Oncology 22, no. 10 (May 15, 2004): 1957-1965. Carr, D., et al. Management of Cancer Symptoms: Pain, Depression, and Fatigue. Evidence Report/Technology Assessment 61. AHRQ Publication No. 02-E032. Rockville, Md.: Agency for Healthcare Research and Quality, 2002. Fleishman, S. “Treatment of Symptom Clusters: Pain, Depression, and Fatigue.” Journal of the National Cancer Institute: Monographs 2004, no. 32 (2004): 119-123. Lloyd-Williams M. “Screening for Depression in Palliative Care Patients: A Review.” European Journal of Cancer Care 10 (2001): 31ff. Parker, P. A., W. F. Baile, C. de Moor, and L. Cohen. “Psychosocial and Demographic Predictors of Quality of Life in a Large Sample of Cancer Patients.” Psychooncology 12, no. 2 (2003): 183-193. Patrick, D. L., et al. “National Institutes of Health State-ofthe-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 1517, 2002.” Journal of the National Cancer Institute 95 (2003): 1110ff. u
Other Resources
Abramson Cancer Center of the University of Pennsylvania Oncolink http://www.oncolink.org/resources American Psychosocial Oncology Society http://www.apos-society.org Cancer Care http://www.cancercare.org National Institute of Mental Health Depression http://www.nimh.nih.gov/health/topics/depression/ index.shtml Substance Abuse and Mental Health Services Administration http://www.samhsa.gov See also Anxiety; Appetite loss; Benzodiazepines; Elderly and cancer; End-of-life care; Exercise and cancer; Fatigue; Grief and bereavement; Hormonal therapies; Integrative oncology; Living with cancer; Medical marijuana; Opioids; Pain management medications; Palliative treat360
Salem Health: Cancer ment; Personality and cancer; Psycho-oncology; Psychosocial aspects of cancer; Self-image and body image; Survivorship issues.
u Dermatofibrosarcoma
protuberans (DFSP) Category: Diseases, symptoms, and conditions Also known as: Bednar tumor, familial dermatofibrosarcoma protuberans, fibrosarcomatous tumors with attenuated dermal surfaces, fibrosarcomatous progression, fibrosarcoma of the skin, metastatic dermatofibrosarcoma protuberans, progressive and recurring dermatofibroma Related conditions: Dermatofibroma, epidermal inclusion cyst, fibrosarcoma, giant cell fibroblastoma, fibrous histiosytoma, keloid and hypertrophic scar, lymphoma, malignant melanoma, metastatic carcinoma of the skin, morphea Definition: Dermatofibrosarcoma protuberans (DFSP) is a rare type of skin cancer that affects the inner layer of the skin (dermis). “Derma” means that it affects the skin. “Protuberans” means that it sticks out (protrudes) above the skin. Risk factors: There is no known cause of DFSP. In a minority of patients, about 10 percent, some type of trauma, such as a burn, scar, or injection site, has occurred at the site where the disease develops. Laboratory studies seem to show that a type of chromosome mutation tends to help the previous skin damage evolve into this type of cancer. In this chromosome mutation, material from chromosomes 17 and 22 somehow combine to form another chromosome or switch material from one chromosome to another. However, many people with this chromosome mutation do not develop DFSP, and many who have DFSP do not have this chromosome mutation. Etiology and the disease process: DFSP is a very slowgrowing cancer. It usually starts as a small, hardly noticeable lump on the skin, which may remain that way for several years. It may then get larger and develop into a sore, or plaque, that is irregularly shaped, can vary in color (it may be red-brown, red-blue, or simply a bit darker than the surrounding skin), and bulges out. This lump may be tender or bleed, or it may be painless. This type of cancer most often occurs on the body, arms, or legs. It very rarely occurs on the neck or head. Rarely, DFSP may appear as a thickened area of skin or
Salem Health: Cancer a soft depressed area of skin. This type of DFSP may go unnoticed for quite some time, until it has grown big enough for a patient to notice, and so may have spread far underneath the skin. This type of DFSP is difficult to diagnose as it looks very similar to other skin diseases. DFSP does not generally spread beyond the original tumor site. However, the tumors are very aggressive in that they move out underneath healthy skin. The tumor may be much larger under the surface than it appears to be from the top of the skin. This makes DFSP a difficult cancer to completely eliminate because the distance the tumor has spread underneath the top layer of skin may make it difficult to remove the entire tumor, and cells that are left behind tend to grow into another tumor. In rare cases, this cancer may spread to lymph nodes or into the bloodstream, where it may spread to the lungs, heart, brain, or bones. Incidence: This type of cancer is relatively rare, having a rate of about 4 new cases per 1 million people each year. DFSP occurs slightly more often in men than in women. Though it may occur in persons of any race, blacks develop this cancer at almost twice the rate whites do. An uncommon variant called Bednar tumor occurs mostly in
Dermatofibrosarcoma protuberans (DFSP) black patients. This cancer occurs most often in people between the ages of twenty and fifty. It is very rarely found in newborns, children, or the elderly (those over eighty years old). Symptoms: DFSP appears as a small, red-brown or redblue tumor on the skin that may develop into a larger, irregularly shaped lump. This lump may feel rubbery or firm. It is attached under the skin so it does not move around when touched. Usually, the lump is not painful. It may develop into a patch of several lumps or nodules. Screening and diagnosis: There is no screening test or staging system for DFSP. Because the appearance of the skin in a patient with DFSP can be similar to that of a patient with many other conditions, a diagnosis involves a biopsy of the affected skin. This skin is examined under a microscope to determine if cells are growing abnormally. There is no blood test available for determining whether a patient has DFSP. Usually, imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) are not used in diagnosis unless the tumors are suspected to have spread into the lymph system or into other body areas.
Dermatofibrosarcoma protuberans on a patient’s back. (©ISM/Phototake—All rights reserved)
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Dermatology oncology Treatment and therapy: Surgery is generally the first line of treatment for this type of cancer. Usually, the tumor itself and a large amount of skin around it must be removed to ensure that the entire tumor, growing under the skin where it cannot be seen, is removed. This type of surgery is called wide excision. Mohs micrographic surgery (MMS) is often used because this type of surgery allows a surgeon to view the edges of the skin through a microscope during surgery. While removing the tissue around the edges of the tumor, the surgeon can keep checking to make sure the skin around the tumor site has no more cancerous cells. Once no more cancerous cells are present in the tissue at the edges of the surgery site, the surgeon can stop removing skin. This can help ensure removal of the entire tumor. When surgery is used to remove DFSP tumors, the surgical site is often large. Depending on the amount of skin removed, a patient may need skin grafts to close the surgery site. The tumors often have ragged edges and unusual shapes, making removal of the entire tumor difficult. As a result, DFSP has a high rate of recurrence. Any cancerous cells left behind tend to grow into another tumor. If the cancer is large or its removal would cause serious cosmetic damage, such as a scar on the face or in another exposed area, radiation therapy may be used. In radiation therapy, the skin is exposed to high-energy rays that destroy the cancerous cells while doing as little damage as possible to the surrounding healthy tissues. Radiation therapy may also be used as a follow-up to surgery. Chemotherapy is rarely used with DFSP, as it has proven to be relatively ineffective. Researchers are developing oral medications and molecular-level therapies to treat this type of cancer. Oral medications may be able to target the specific cancerous cells and kill them while causing few, if any, side effects to the rest of the body. Molecular-level therapies use the body’s own natural defenses to target and kill cancerous cells. Prognosis, prevention, and outcomes: This type of cancer usually does not spread, but it has a high rate of recurrence: In about 20 percent of DFSP patients, the cancer returns in the same place. Usually, this is because the first occurrence of the cancer was not completely removed. Because of this high rate of recurrence, it is important that patients continue to receive follow-up care. Recurrence usually happens within three years, and patients should be seen regularly during that period to assess any tumor sites to ensure that cancerous cells left behind during surgery have not begun to grow. If the cancer has spread into the lymph nodes or bloodstream, as it does in only about 3 percent of cases, the prog362
Salem Health: Cancer nosis is much worse than if the cancer has been contained to tumors in the skin, with death usually occurring within two years. Prognosis is even worse with the variation of this cancer called fibrosarcomatous progression, because this variation is a much more aggressive type of cancer. Older patients (over fifty years old) are more likely to have a poorer outcome than those who are younger. Marianne M. Madsen, M.S. u
For Further Information Agnew, Karen L., Barbara A. Gilchrist, and Christopher B. Bunker. Skin Cancer. Oxford, England: Health Press, 2005. Du Vivier, Anthony, and Phillip H. McKee. Atlas of Clinical Dermatology. 3d ed. Edinburgh: Churchill Livingston, 2002. Hunter, John, John Savin, and Mark Dahl. Clinical Dermatology. 3d ed. Malden, Mass.: Blackwell, 2002.
u
Other Resources
DermNet NZ http://www.dermnetnz.org/lesions/dfsp.html Skin Cancer Foundation http://www.skincancer.org See also Fibrosarcomas, soft-tissue; Sarcomas, soft-tissue.
u Dermatology oncology Category: Medical specialties Also known as: Dermatological oncology, dermatologic oncology, cutaneous oncology Definition: Dermatologic oncology is the medical specialty dealing with the diagnosis and treatment of skin cancers. Dermatologic oncologists may provide services and treatment in an office or hospital setting. They receive special education after medical school in dermatology, then additional training specific to oncology diagnosis, procedures, and surgeries. Often dermatologic oncologists can treat skin cancers, but for cancers that have spread to the lymph nodes or other areas of the body, they will enlist the assistance of other specialized medical professionals, such as medical or surgical oncologists. Subspecialties: Although there are no formal subspecialties in dermatologic oncology, many dermatologic oncologists specialize in particular types of cancer or treatments. Some dermatologic oncologists may specialize in rarer forms of skin cancer or in skin cancers that have
Salem Health: Cancer
Dermatology oncology
A doctor administers local anesthesia before removing a skin lesion from a man’s face. (©Pulse Picture Library/CMP Images/ Phototake—All rights reserved)
significantly metastasized. Others may have special training in a particular treatment or procedure and may focus their practice on it. Some dermatologic oncologists may concentrate on performing clinical research into experimental techniques or procedures and writing articles for journals. Cancers treated: Dermatologic oncologists diagnose and treat the three main types of skin cancers: basal cell carcinoma, squamous cell carcinoma, and melanoma. Basal cell carcinoma very rarely spreads beyond the skin and can most often be treated by in the office or on an outpatient basis. Squamous cell carcinoma also only rarely spreads to other areas of the body, although it does have a somewhat higher incidence of spreading than basal cell carcinoma. It too can usually be treated in the office or on an outpatient basis. Melanomas are the most common cause of death from skin cancer. This type of skin cancer is very treatable if found early, but if diagnosed later, it can be aggressive and
has a high incidence of spreading to the lymph nodes and other parts of the body. If found early, melanoma can usually be treated successfully in the office or on an outpatient basis. If melanoma has spread over a large portion of the skin or to other organs, dermatologic oncologists will work with other health care professionals such as medical and surgical oncologists, radiologists, and chemotherapists to treat the cancer. Dermatologic oncologists also treat rare forms of skin cancer such as Kaposi sarcoma, which develops in the skin’s blood vessels, and sebaceous gland carcinoma, which originates in the skin’s oil glands. Training and certification: Dermatologic oncologists must complete a residency in dermatology after successfully completing medical school. Residencies are generally at least four years in duration. After completion of the residency, doctors may take an American Board of Dermatology exam for board certification in general dermatology. The next step is usually a fellowship in derma363
Dermatology oncology tologic oncology. There is no specific board certification for dermatologic oncology. Dermatologic oncologists are taught to diagnose skin cancers and to perform simple treatments in the office setting or on an outpatient basis as well as more complex treatments. They usually receive training in working with other allied health professionals such as medical and surgical oncologists to deal with metastasized skin cancers. They are often trained to conduct clinical research. Services and procedures performed: Dermatologic oncologists provide a wide variety of diagnostic and treatment procedures. They usually begin with a visual inspection of the area believed to be cancerous. This checkup may be occasioned by concern expressed by a patient or because of a referral from a primary physician. If the dermatologic oncologist believes cancer is a possbility, the area will be biopsied. Biopsies generally fall into two categories, excisional and incisional. Excisional biopsies remove the entire lesion suspected of being cancerous as well as a small amount of healthy skin surrounding the lesion. The incisional biopsy is most frequently used when a lesion is very large and removal of the entire lesion is impractical. Biopsies are usually performed in the office or on an outpatient basis. The samples gathered are treated and examined under a microscope, often in the office by the dermatologic oncologist. However, the sample may be sent out to a dermapathologist if the diagnosis is not clear or the doctor lacks the necessary facilities. Once the lesion has been diagnosed as cancerous, dermatologic oncologists create a plan of treatment. They start by determining how deep the cancer has spread and if it has spread beyond the skin. If it has spread to the lymph nodes or other parts of the body, the dermatologic oncologist will work closely with other oncology professionals to provide treatment. If the cancer is diagnosed early and has not spread, it can usually be treated through surgery. An incision is made around the lesion, and the lesion is removed. For basal cell carcinoma and squamous cell carcinoma that are still small, this is often all that is needed. Malignant melanoma may be removed in this way, but noncancerous skin around the lesion is usually removed as well to ensure that all the cancer has been removed. Small lesions can be removed using cryosurgery, a technique in which the lesion is frozen off with liquid nitrogen, or electrodesiccation and curettage, during which the lesion is burned off with an electrified needle. Another treatment option, often used for larger lesions, is Mohs micrographic surgery. The dermatologic oncol364
Salem Health: Cancer ogist slowly removes small layers of tissue. The tissue is quickly examined to determine if it is cancerous, and if it is, another small layer of tissue is removed. This continues until a noncancerous layer of tissue has been removed. Related specialties and subspecialties: Many different health professionals may work with dermatologic oncologists. Assistants may help prepare patients, perform simple procedures, and do basic laboratory work. These assistants may also play a key role in helping patients understand their diagnosis and communicating information about preoperative and postoperative care. Dermatologic oncologists may send biopsies to a dermapathologist, a dermatologist who has received additional training in the diagnosis of dermatologic diseases and conditions. A dermapathologist will perform laboratory analysis on a submitted sample to determine if cancer is present, and if so, what type of cancer it is. If cancer is diagnosed and is believed or found to have spread to lymph nodes or other areas of the body, many health professionals will join the dermatologic oncologist in helping develop and carry out a plan of treatment for the patient. The health care team will include specialists in the area to which which the cancer has spread and will often involve a surgical or a medical oncologist, a radiologist, a chemotherapist, oncology nurses, and various other oncology experts. If the treatment for the cancer, or the cancer itself, is significantly disfiguring, a plastic surgeon may be involved. Helen Davidson, B.A. u
For Further Information Egan, Tracie. Skin Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Frankel, David H., ed. Field Guide to Clinical Dermatology. Philadelphia: Lippincott Williams & Wilkins, 2006. Harmey, Judith H., ed. VEGF and Cancer. New York: Kluwer Academic/Plenum, 2004. Kaufman, Howard L. The Melanoma Book: A Complete Guide to Prevention and Treatment. New York: Gotham Books, 2005. McClay, Edward F. One Hundred Questions and Answers About Melanoma and Other Skin Cancers. Sudbury, Mass.: Jones and Bartlett, 2004.
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Organizations and Professional Societies
American Academy of Dermatology http://www.aad.org P.O. Box 4014 Schaumburg, IL 60618-4014
Salem Health: Cancer American Board of Dermatology http://www.abderm.org Henry Ford Health System 1 Ford Place Detroit, Michigan 48202-3450 u
Other Resources
American Cancer Society http://www.cancer.org Skin Cancer Foundation http://www.skincancer.org See also Basal cell carcinomas; Bowen disease; Choriocarcinomas; Eyelid cancer; Hand-foot syndrome (HFS); Kaposi sarcoma; Keratosis; Lip cancers; Melanomas; Merkel cell carcinomas (MCC); Moles; Skin cancers; Squamous cell carcinomas; Sunlamps; Ultraviolet radiation and related exposures; Xeroderma pigmentosa.
u Desmoid tumors Category: Diseases, symptoms, and conditions Also known as: Aggressive fibromatosis Related conditions: Familial adenomatous polyposis (FAP), Gardner syndrome Definition: Desmoid tumors are tumors of the tissue surrounding muscle that may develop anywhere in the body, but often in the abdomen. Risk factors: Familial adenomatous polyposis (FAP), an inherited syndrome in which thousands of polyps are found in the colon, is a risk factor as well as surgical trauma, pregnancy and childbirth, and exposure to high levels of hormones. Etiology and the disease process: In many cases the cause of desmoid tumors is not known; however, they may be related to trauma (especially surgical trauma) or to hormones. There is a known genetic association between desmoid tumors and familial adenomatous polyposis. Incidence: Desmoid tumors are uncommon, with an approximate annual incidence of 2 to 4 cases per 1 million people. Desmoid tumors are more frequent in women than in men. The tumors are usually found in individuals between the ages of ten and forty. Individuals with familial adenomatous polyposis have a 4 to 20 percent chance of developing a desmoid tumor.
Desmoplastic small round cell tumor (DSRCT) Symptoms: A desmoid tumor is usually a painless mass; it may be felt as a lump. Pain may develop if nerves, muscles, or organs are affected by the growing tumor. Tumors in the abdomen can cause abdominal pain, a change in bowel habits, or rectal bleeding. Screening and diagnosis: Ultrasound imaging is used initially to examine soft-tissue tumors. A computed tomography (CT) scan or magnetic resonance imaging (MRI) may be used subsequently. The diagnosis of desmoid tumor is made by biopsy. Treatment and therapy: Surgery to remove the tumor is the best treatment, but radiation or drug therapy may also be used either alone (if the tumor is inoperable) or in combination with surgery. Drug therapy may range from aspirin or COX-2 inhibitors (including celecoxib) to hormonal therapy (such as tamoxifen, toremifene, raloxifene, or progesterone). Low-dose chemotherapy for one year or highdose chemotherapy for a shorter period may be used when other therapies have failed or when the tumor is fast growing or causes symptoms. If there are no symptoms, watchful waiting (observation without treatment) could be appropriate. Prognosis, prevention, and outcomes: Desmoid tumors are benign and very rarely spread from the site of the original tumor. However, they are locally aggressive and local recurrence rates can be as high as 70 percent. Recurrence is monitored by repeat MRI. Individuals with desmoid tumors should be tested for mutations of the APC gene. Vicki Miskovsky, B.S., R.D. See also Fibrosarcomas, soft-tissue; Gardner syndrome; Hereditary polyposis syndromes.
u Desmoplastic small round cell
tumor (DSRCT) Category: Diseases, symptoms, and conditions Also known as: Desmoplastic sarcoma, desmoplastic cancer Related conditions: Solid tumor, testicular cancer, ovarian cancer Definition: A desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive tumor usually appearing in the abdomen and surrounding lymph nodes. Risk factors: There are no known risk factors that have been identified as specific for the DSRCT. 365
Developing nations and cancer Etiology and the disease process: The tumors in DSCRT appear to arise from early developmental cells in childhood. The cell of origin for this tumor is unknown. The tumor shows characteristics of epithelial, mesenchymal, and neural differentiation. The tumor can metastasize through lymph nodes or the bloodstream primarily into areas of the abdomen including the spleen, diaphragm, liver, and intestines. Other sites include the lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain. Incidence: DSCRT is extremely rare, usually occurring in men in their twenties. Symptoms: The most common symptoms include abdominal pain, abdominal mass, and gastrointestinal obstruction. Screening and diagnosis: Patients are often misdiagnosed at onset of symptoms, and the rapid growth of the tumor cells can lead to an advanced stage (in which the cancer has spread to lymph nodes and other organs) before being diagnosed. Confirmation of DSCRT is usually done by biopsy. Identification of a genetic abnormality in chromosomes 11 and 22 has been useful in confirming the diagnosis of the tumor. Treatment and therapy: Because the tumors involve a large portion of the abdomen, surgery is rarely an option. Patients have some success with high doses of chemotherapy and radiation therapy. Prognosis, prevention, and outcomes: The prognosis of patients diagnosed with desmoplastic round cell tumors is very poor, with fewer than 20 percent surviving more than two to three years. Research has shown that a genetic abnormality called translocation is apparent in chromosomes 11 and 22, and scientists continue to study the pathogenesis of this tumor and various chemical agents to find which are most effective against the tumor. Robert J. Amato, D.O. u
For Further Information Johanson, Paula. Frequently Asked Questions About Testicular Cancer. New York: Rosen, 2008. Kurth, Karl H., Gerald H. Mickisch, and Fritz H. Schröder. Renal, Bladder, Prostate, and Testicular Cancer: An Update. New York: Parthenon, 2001. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Testicular Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health Publications, 2002. See also Fibrosarcomas, soft-tissue. 366
Salem Health: Cancer
u Developing nations and cancer Category: Social and personal issues Definitions: Cancer describes a group of more than one hundred diseases that are a result of abnormal cells that grow unchecked in the body. These cells can spread, or metastasize, to other sites of the body when the cancer is aggressive or goes untreated. Metastases are the major cause of cancer death. Least developed or developing countries—sometimes referred to as Third World countries—are those countries with low incomes and significant poverty, few industries, minimal health care, and poor living conditions for the population. In these countries, cancer treatment, which requires sophisticated drugs and equipment, is rarely available, as resources are instead directed to survival, sanitation, nutrition, and other basic needs. Impact of cancer: The United Nations has created a human development index that measures the gross domestic product of a country, life expectancy, per capita income, literacy levels and other factors, and also allows each government to categorize itself as least developed, a failed state, developing, newly industrialized, emerging, or developed. Most African, some Central and South American, and some Asian countries are considered to be developing or least developed. Newly industrialized countries, such as South Africa, China, and India, are facing cancer care issues similar to those in developing countries, but they have growing resources to address the health needs of their populations. Because cancer is a disease that affects not only the patients but also their families and communities, the economic burden is significant and includes the cost of care as well as the impact of lost earnings. Other issues are the lack of government regulation of public health and industrial issues that increase the risk for cancer among the population. Incidence, death, and survival statistics: According to the World Health Organization, 12 million cases of cancer are diagnosed annually worldwide, with almost 8 million people dying of the disease. Of all deaths in the world, 12 percent are due to cancer, more than twice the number of deaths from acquired immunodeficiency syndrome (AIDS). Of the cancer deaths that occur each year, almost three out of four were in low- and middle-income countries. Mortality from cancer is generally due to lung, stomach, liver, colon, and breast cancers, which account for almost 5 million of the 8 million deaths annually. As cancer prevention, screening, and treatment im-
Salem Health: Cancer prove in developed countries, these countries are likely to experience a decline in cancer incidence, while incidence rates in developing nations are likely to continue to grow. In addition, because cancer is a disease of the aging, as the populations of developing countries live longer, experts predict that the incidence rates of cancer will increase in these countries. A study by the American Cancer Society reported that China has 20 percent of the world’s cancer cases, followed by the United States at about 15 percent. Globally, the cancers with the highest mortality rates for men (from highest to lowest) are lung, stomach, liver, colorectal, and prostate. For women, the leading causes of cancer death in descending order are breast, lung, stomach, colorectal, and cervical cancer. In least developed or developing countries, the survival rates for cancer are dismal. Cancer patients are usually diagnosed at a late stage of disease with complications that make cures almost impossible. Up to 90 percent of patients in less developed or developing countries have advanced cancer and incurable clinical complications when diagnosed. Risk factors: Tobacco use is the most important risk factor related to cancer development. Use of all forms of tobacco—cigarettes, cigars, pipes, and smokeless tobacco—contributes to lung, larynx, esophageal, stomach, bladder, mouth, and other cancers. As per capita income grows, the use of commercial tobacco products often increases with it. Other behavioral risk factors include excessive alcohol use, which contributes to breast, esophageal, liver, and other cancers according to the World Health Organization; nutritional deficiencies, such as a lack of fruits and vegetables in the diet; obesity; and unprotected exposure to ultraviolet (UV) light from the sun. Infectious agent and viruses, sometimes the result of unsafe sex practices, contribute to the development of cancer. Cervical cancer, caused by human papillomaviruses (HPV), and Kaposi sarcoma, caused by the human immunodeficiency virus (HIV), are prevalent in Africa. Air pollution and food contaminated with chemicals and mycotoxins are environmental factors that can contribute to the development of cancer. Agriculture is a common field of employment in developing countries, and the chemicals used can raise the workers’ risk of cancer. Mining and other nonregulated industries may also expose workers to risks. Because of fewer government regulations, chemicals banned as hazardous in developed countries are often used in developing countries. Reducing the global cancer burden: Up to 40 percent of cancers can be prevented by controlling risk factors and
Developing nations and cancer promoting a healthy lifestyle, while recognizing the economic constraints of the population. The single most important factor in reducing the global cancer burden is to stop tobacco use. Education that takes into consideration economic issues and culture is the key to cancer control. The World Health Organization and the United Nations outlined recommendations for cancer control programs worldwide, identifying the critical parts of any program to be prevention, early detection, prompt treatment, and appropriate care. For patients diagnosed with advanced cancers, appropriate care should be provided when there is a chance of cure or prolonged survival with an acceptable quality of life. For advanced cancers with no chance of cure, pain relief and palliative care for patients, along with support for families, are important as part of any program. The problem with any cancer control plan is that it requires a level of health care knowledge and sophistication to implement. However, when developing countries are struggling to provide sanitary living conditions and sufficient food for their populations, their priorities may not include cancer control. Infant mortality, communicable diseases, tuberculosis, HIV/AIDS, and malaria compete for scarce health care resources. Improving global cancer care: Public and private donations to organizations dealing with health problems in developing countries are at an all-time high. Governments, individuals, and humanitarian groups are raising billions of dollars to improve health care in developing countries. The International Finance Corporation of the World Bank has a public-private partnership initiative aimed at developing countries to enlist health care entrepreneurs to provide health-related services such as hospitals, dialysis centers, and cancer centers. Both the World Health Organization and the United Nations are involved in health care efforts worldwide. However, the minimal infrastructure to support the money that is being spent is often lacking. Most developing countries have few, if any, hospitals; not enough doctors, nurses, and other health care workers; and little government support and regulation to support a sustained health care effort. The most important step in improving global cancer care is to develop a strategy to use available money to develop a health care infrastructure that allows ongoing diagnosis, treatment, and care of disease. The focus for cancer programs should be education and lifestyle change, because 40 percent of cancers can be prevented. Early detection of cancer with appropriate treatment in developing countries would lead to reduced mortality worldwide. Immunizations, use of the HPV vaccine, and resources such as radiation therapy and chemotherapy 367
Di(2-ethylhexyl) phthalate (DEHP) need to be made available. Pain control and symptom management should be a priority. Cancer is a complex disease, but there is hope that survival and improved quality of life can occur if an effort is made to improve existing resources in developing countries. Patricia Stanfill Edens, R.N., Ph.D., FACHE u For Further Information MacDonald, T. H. Third World Health: Hostage to First World Health. Abingdon, England: Radcliffe, 2005. Ramanakumar, A. V. “Need for Epidemiological Evidence from the Developing World to Know the CancerRelated Risk Factors.” Journal of Cancer Research and Therapeutics 3 (2007): 29-33. Stewart, B. W., and P. Kleihues, eds. World Cancer Report. Geneva: World Health Organization, International Agency for Research on Cancer, 2003. u
Other Resources
International Union Against Cancer http://www.uicc.org United Nations http://www.un.org World Health Organization Cancer http://www.who.int/topics/cancer/en/ See also Africans and cancer; Air pollution; Financial issues; Fruits; Geography and cancer; HIV/AIDS-related cancers; Human papillomavirus (HPV); Nutrition and cancer prevention; Poverty and cancer; Risks for cancer; Statistics of cancer; Survival rates; Vaccines, preventive; Vaccines, therapeutic; Virus-related cancers.
u Di(2-ethylhexyl) phthalate
(DEHP) Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1983; under review for removal from the Twelfth Report on Carcinogens (RoC) Also known as: Diethylhexyl phthalate, bis(2-ethylhexyl) phthalate Related cancers: DEHP does not seem to cause cancer in humans. The mechanism by which cancers are induced in experimental animals by prolonged high doses of DEHP is not relevant to humans. 368
Salem Health: Cancer Definition: DEHP is a water-insoluble organic compound, a widely used phthalate with the molecular formula of C 24H38P4. It is used as a plasticizer mainly in the plastic polyvinyl chloride (PVC) for flexibility and softness of the final product. Exposure routes: Inhalation, ingestion, dermal contact, and medical procedures such as intravenous (IV) drug administation and blood transfusion Where found: DEHP is mainly used in plastic products such as children’s toys, vinyl upholstery, raincoats, and food packaging. Because DEHP is not chemically attached to the plastic, it can leach out. DEHP release is found in IV bags, blood bags, dialysis bags, medical tubing products, atmosphere, soil, and water. Some manufacturers have begun not to use DEHP in their products. At risk: DEHP may cause toxicity in humans. Because of its minimum exposure to humans, however, it does not present a general risk to human health. Newborns and infants are particularly at risk for toxicity in the hospital setting. Thus, the risk of developmental and reproductive abnormalities is greater among this subpopulation. Etiology and symptoms of associated cancers: The hepatocarcinogenicity (potential to cause liver cancer) of DEHP in rats has been proven. DEHP-induced peroxisome proliferation in rats is a phenomenon in which peroxisomes in hepatocytes (liver cells) are increased in number. Peroxisomes, also called microbodies, are intracellular respiratory organelles like mitochondria. Peroxisome proliferation protects the cell from increased oxidation. Failure to do so results in carcinogenesis—cell replication and tumor formation. No such peroxisomal route of carcinogenesis and thus no form of cancer due to DEHP have been demonstrated in humans. It may be because there are fundamental differences in metabolism between rats and humans; also, prolonged exposure of higher doses of DEHP in humans is unlikely. History: Plasticized PVC was invented in 1926. DEHP was implicated in animal hepatocarcinogesis in 1982, which was followed by classification of DEHP as an anticipated human carcinogen. DEHP’s possible removal from the twelfth Report on Carcinogens is based on the experts’ conclusion that the chemical cannot be reasonably anticipated to cause cancer in humans. It is important to note, however, that human carcinogenicity data remain incomplete. Arun S. Dabholkar, Ph.D. See also Plasticizers.
Salem Health: Cancer
u Diarrhea Category: Diseases, symptoms, and conditions Also known as: Dysentery, intestinal flu Related conditions: Colorectal cancer, gastrointestinal disease Definition: Diarrhea is the passage of frequent loose or liquid stools. Diarrhea is usually characterized by the passage of loose stools more than three to four times in one day. Risk factors: Diarrhea may occur as a result of cancer treatment, such as chemotherapy or other cancer medications; radiation therapy to the pelvis, rectum, or abdomen; or surgery. Diarrhea may be the result of an underlying condition, including central nervous system disorders, bowel obstruction, diverticulitis (outpouchings of the colon), and hernia. Diarrhea may be a sign of gastric cancer, colon cancer, rectal cancer, bowel cancer, and other cancers, and it also may occur on the growth or spread of these types of cancer. Lactose intolerance and certain medications, such as antibiotics, can increase the risk of diarrhea. Anxiety about cancer or cancer treatment also can contribute to the development of diarrhea. Etiology and the disease process: Chemotherapy and radiation therapy can cause changes in the function of the intestines, including increased or decreased peristalsis (the wavelike contraction of the muscles to propel the contents of the intestines through the digestive tract). An increase in peristalsis can cause stool to move faster through the intestines, leading to diarrhea or cramping. Chemotherapy also can change the normal bacteria in the intestines, causing diarrhea. Dehydration is a concern for patients who have diarrhea. Dehydration occurs when more fluid is lost than is taken in, and the body does not have enough water and other fluids to carry out its normal functions. Signs of mild dehydration include dry mouth, weakness, dizziness, and fatigue. Signs of severe dehydration require immediate medical attention and include extreme thirst; irritability and confusion; very dry mouth, skin, and mucous membranes; decreased urination; low blood pressure; rapid heartbeat; and fever. Incidence: Diarrhea is very common among patients undergoing cancer treatments, particularly those receiving certain chemotherapy drugs as well as radiation to the stomach or abdomen. The National Cancer Institute reports that 25 percent of patients experience severe diarrhea.
Diarrhea Symptoms: Symptoms of diarrhea include the passage of frequent loose or liquid stools more than three times in one day. Other symptoms that accompany diarrhea include urgency to have a bowel movement, bloating, and nausea. Symptoms range from moderate to severe, and vary among patients. Symptoms can impede cancer treatment, resulting in a delay, dose reduction, or discontinuation of therapy. Changes in stool frequency, consistency, volume, or the presence of blood, mucus, or pus in the stool may indicate an underlying disease. If diarrhea occurs more than six times a day, or does not resolve within twenty-four hours after taking prescribed antidiarrheal medications, the patient should call the prescribing physician. Screening and diagnosis: A thorough review of the patient’s medical history and a physical exam are performed, and stool tests can be performed to identify blood and bacterial, fungal, parasitic, or viral pathogens. Diagnostic tests may include upper endoscopy, upper gastrointestinal series (barium swallow), abdominal X rays, sigmoidoscopy, and colonoscopy. Treatment and therapy: Symptom management is critical to avoid an interruption in the delivery of cancer treatment. Aregistered dietitian can provide nutritional therapy to help the patient develop an eating plan that meets dietary requirements while reducing side effects, helping to make treatment more tolerable. In some cases, antidiarrheal medications are prescribed. First-line treatment includes loperamide and diphenoxylate/atropine. Secondline treatment for persistent, chronic diarrhea includes octreotide subcutaneous injections. It is important for patients to ask their physician first before self-treating diarrhea and related symptoms, as some over-the-counter remedies could interfere with cancer treatment. Conservative techniques to manage diarrhea include the following: • Increasing fluid intake to prevent dehydration • Eating bland foods in small amounts • Following a clear liquid diet of juices and broth until symptoms subside • Avoiding spicy, high-fat, and sugary foods • Eating small, frequent meals • Eating slowly and chewing food completely before swallowing • Taking medication with food, unless advised otherwise • Avoiding high-fiber foods and dairy products • Avoiding caffeine and alcoholic beverages • Including high-potassium foods, as advised by the doctor 369
Dietary supplements In addition to these recommendations, relaxation techniques such as deep breathing and guided imagery may help. Patients should follow their physician’s specific guidelines for managing treatment side effects and should call the doctor when symptoms are severe or persist for more than twenty-four hours. When necessary, nutritional supplements also may be recommended to ensure sufficient caloric and nutrient intake. Prognosis, prevention, and outcomes: Diarrhea can be effectively managed with conservative treatments and medications and is generally relieved when cancer treatments are completed. There usually are no long-term effects of gastrointestinal symptoms that are properly managed, according to the American Cancer Society. Hospitalization is recommended for patients with severe dehydration or diarrhea that results in the inability to maintain adequate hydration or nutrition and for patients with chronic diarrhea that does not resolve within twentyfour hours after taking prescribed antidiarrheal medications. Left untreated, chronic diarrhea can cause significant morbidity and mortality because of nutritional deficiencies, and fluid and electrolyte imbalances may lead to potentially life-threatening dehydration or impaired kidney function. Although cancer treatments can result in diarrhea that may be temporarily unpleasant to the patient, the potential side effects, if adequately managed under a physician’s care, should be measured against the cancer-fighting benefits of a particular treatment. Angela M. Costello, B.S. u For Further Information Field, Michael, ed. Diarrheal Diseases. New York: Elsevier, 1991. Kogut, Valerie, and Sandra Luthringer. Nutritional Issues in Cancer Care. Philadelphia: Oncology Nursing Society, 2005. Scott-Brown, Martin, Roy A. J. Spence, and Patrick G. Johnston, eds. Emergencies in Oncology. New York: Oxford University Press, 2007. u
Other Resources
American Cancer Society http://www.cancer.org American College of Gastroenterology http://acg.gi.org National Cancer Institute http://www.cancer.gov 370
Salem Health: Cancer National Institute of Diabetes and Digestive and Kidney Diseases National Digestive Diseases Clearinghouse http://digestive.niddk.nih.gov/index.htm See also Adrenal gland cancers; Angiogenesis inhibitors; Anthraquinones; Antidiarrheal agents; Antinausea medications; Chemotherapy; Crohn disease; Diverticulosis and diverticulitis; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Inflammatory bowel disease; Laxatives; Rectal cancer; Side effects; Symptoms and cancer; Weight loss.
u Dietary supplements Category: Complementary and alternative therapies; lifestyle and prevention Definition: Dietary supplements are a broad category of materials that are defined by the U.S. Food and Drug Administration (FDA) as substances consumed in addition to a person’s normal diet. Subclasses of this group are vitamins, minerals, botanicals, amino acids, enzymes, and certain animal-derived products. Cancers treated or prevented: Dietary supplements are often taken, in an adjuvant mode, to help fight many types of cancer, although their effectiveness is rarely proven. Perhaps even more often, supplements are taken for cancer prevention or to boost the immune system. Delivery routes: Oral in the form of tablets, caplets, capsules, powders, and liquids such as extracts and teas. How these agents work: In the United States in 2007, dietary supplements were estimated to be a $22 billion industry. Supplements range from familiar multivitamin tablets to unusual substances such as snake venom. Some dietary supplements (such as vitamins and minerals) have accepted roles in conventional medicine as well as complementary and alternative uses. Other dietary supplements, including most botanicals, are used almost exclusively in complementary and alternative medicine. Complementary medicine supplements traditional Western medical care, while alternative medicine seeks to replace traditional Western medical care. Some dietary supplements, especially vitamins and minerals, are embraced by traditional Western medicine and play an important role in maintaining health, especially among individuals with cancer or other diseases that affect the body’s metabolism. Thirteen different vitamins are essential to human health. The body cannot make these
Salem Health: Cancer
Dietary supplements
compounds; they must be obtained either from food or In relation to cancer, people generally take dietary supfrom dietary supplements. The fat-soluble vitamins are plements for four reasons: to prevent a particular type of vitamins A, D, E, and K. The water-soluble vitamins are cancer; to meet the needs for a particular substance that vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 they cannot acquire from diet because of their cancer (vita(pantothenic acid), B6 (pyridoxine), B7 (biotin or vitamin min supplements); to boost the immune system and help it H), B9 (folate or folic acid), B12 (cobalamin), and vitamin fight their cancer (ginseng); and to reduce specific sympC. Vitamins are generally safe when taken in amounts less toms associated with their cancer (ginger for nausea). The than the upper safe limit set by the U.S. Institute of MediAmerican Cancer Society cautions individuals with cancine. Megadosing, or taking large quantities of vitamins, cer to choose dietary supplements with care and with the can cause serious health complications, especially with the knowledge and advice of their physician. Much misinforfat-soluble vitamins, which build up in the body. Minerals mation and many unproved anecdotal claims about dietary are inorganic compounds found in the earth that are necessupplements and cancer exist on the Internet and in some sary in small amounts for human health. Like vitamins, fad medicine books. many minerals are safe and effective unless taken in Although millions of Americans use dietary supplemegadoses. ments daily, the safety and effectiveness of these products Botanicals (herbs) are dietary supplements derived varies depending on the type of supplement, the purity of from plants. Botanicals have been used for centuries in trathe manufacturing process, the dosage, the health of the inditional Chinese medicine, Ayurvedic or traditional Individual, and the way in which the supplement interacts dian medicine, pre-nineteenth century Western medicine, with other supplements and drugs. In the United States, diand homeopathy. The National Center for Complemenetary supplements are regulated under the 1994 Dietary tary and Alternative Medicine (NCCAM) conducts rigorSupplement Health and Education Act (DSHEA). This act ous investigations and clinical trials of many botanicals. regulates supplements as foods rather than as pharmaceuCommon botanicals that are claimed to treat cancer or tical drugs. Under the act, dietary supplement manufacturcancer symptoms include apricot pit, foxglove, ginseng, ers do not need to prove that their products are either safe green tea, and reishi mushroom. These claims have not or effective before they are marketed. This contrasts with been proved to the satisfaction of Western medicine. both over-the-counter and prescription drugs, which canAmino acids are molecules that are the building blocks not be sold until extensive testing (clinical trials) proves of proteins. Humans require twenty amino acids, twelve them to be both safe and effective in treating specific conof which the body can produce for itself. The rest must be ditions. obtained through diet or supplementation. Enzymes are proteins made in the body that regulate metabolic reactions. Prescription enzymes and amino acids are used in Western medicine when they replace compounds that the body is unable to make because of genetic defects. These substances are also sold as dietary supplements, some of which claim to treat cancer. Most traditional physicians do not accept these claims. Animal-based supplements include products such as fish oil, bee pollen, and bear bile. Many of these products are used in alternative medicine and claim to prevent or treat disease. Practitioners of Western medicine generally acknowledge the benefits of some dietary supplements, such as vitamins, Although millions of Americans use dietary supplements daily, such as these made from minerals, and fish oils, but question freeze-dried grape seeds, the safety and effectiveness of these products varies. (AP/ extreme claims. Wide World Photos) 371
Dietary supplements DSHEA limits the health claims that can be made for dietary supplements. Supplements cannot legally claim to treat or cure a particular disease. They are, however, allowed to make general claims, such as “helps build strong bones” or “helps lower cholesterol.” Any structure or function claims made for dietary supplements must have on the label the exact words, “This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.” The packaging does not have to contain any warnings about potential side effects. Additional FDA regulations have been added since the original 1994 law. By the end of 2007, all supplement manufacturers were required to report consumer complaints, including complaints of adverse reactions, ineffectiveness, and contaminated products, to the FDA. Before 2007, there was no requirement to inform the FDA of any problems reported by consumers. In addition, in June, 2007, new FDA regulations established stronger good manufacturing practices for dietary supplements that required manufacturers to test for the identity, purity, strength, and composition of their products. These regulations were intended to help consumers determine exactly what is in the supplement and to certify that it is free from contamination by bacteria, fungi, glass, pesticides, heavy metals, and nonapproved additives. The new manufacturing regulations resulted from findings by independent laboratories and the FDA of many contaminated supplements, as well as those that contained material other that what was listed on the label or that contained less or none of the labeled ingredients. These regulations were scheduled to be phased in gradually and to apply to all supplements sold in the United States by 2010. Manufacturers are still not required to make any statements on the packaging about potential side effects, nor are they required to prove that a supplement is safe or effective. Side effects: The side effects of many dietary supplements have not been studied and are unknown. Megadosing with supplements that are generally safe at lower doses, however, may cause the supplement (if fat-soluble) to build up in the body and interfere with the absorption or metabolism of other supplements or pharmaceutical drugs. Botanicals may also change the way in which other drugs or supplements act in the body by speeding up or inhibiting their actions. In addition, many natural plant substances (such as foxglove, hemlock, or ephedra) can be dangerous or lifethreatening. According to the American Association of Poison Control Centers, twenty-seven U.S. deaths were 372
Salem Health: Cancer caused by dietary supplements in 2005, although some experts believe that the unreported number may be much higher. Finally, dependence on dietary supplements to treat cancer or any serious disease may deprive the individual of effective traditional drugs and medical care that can save or prolong life. Individuals interested in taking dietary supplements as part of their cancer treatment regimen should research information carefully and discuss their findings with their oncologist before beginning a supplement. Martiscia Davidson, A.M. u
For Further Information Alschuler, Lise, and Karolyn A. Gazella. Alternative Medicine Magazine’s Definitive Guide to Cancer: An Integrated Approach to Prevention, Treatment, and Healing. Berkeley, Calif.: Celestial Arts, 2007. Davis, W. Martin. Consumer’s Guide to Dietary Supplements and Alternative Medicines. Binghamton, N.Y.: Pharmaceutical Products Press, 2006. Micozzi, Marc S., ed. Complementary and Integrative Medicine in Cancer Care and Prevention: Foundation and Evidence-Based Interventions. New York: Springer, 2007. Quillin, Patrick. Beating Cancer with Nutrition. 4th ed. Tulsa, Okla.: Nutrition Times Press, 2005.
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Other Resources
American Cancer Society How to Know What Is Safe: Choosing and Using Dietary Supplements http://www.cancer.org/docroot/ETO/content/ ETO_5_3x_How_to_Know_What_Is_Safe_ Choosing_and_Using_Dietary_Supplements.asp MedlinePlus Dietary Supplements http://www.nlm.nih.gov/medlineplus/ dietarysupplements.html National Cancer Institute Office of Cancer Complementary and Alternative Medicine http://www.cancer.gov/cam/ National Institutes of Health Office of Dietary Supplements Dietary Supplements: Background Information http://dietary-supplements.info.nih.gov/factsheets/ dietarysupplements
Salem Health: Cancer U.S. Food and Drug Administration Dietary Supplements Overview http://www.cfsan.fda.gov/~dms/supplmnt.html See also Antioxidants; Artificial sweeteners; Beta-carotene; Bioflavonoids; Caffeine; Calcium; Carotenoids; Cartilage supplements; Chemoprevention; Chewing tobacco; Coenzyme Q10; Cruciferous vegetables; Fiber; Folic acid; Fruits; Garlic and allicin; Ginseng, panax; Glutamine; Green tea; Herbs as antioxidants; Indoles; Isoflavones; Lutein; Lycopene; Macrobiotic diet; Nutrition and cancer prevention; Nutrition and cancer treatment; Omega-3 fatty acids; PC-SPES; Phytoestrogens; Resveratrol; Saw palmetto; Soy foods; Sun’s soup; Wine and cancer.
u Diethanolamine (DEA) Category: Carcinogens and suspected carcinogens Also known as: Diethylolamine, 2,2 dihydroxydiethylamine, diolamine, bis-2hydroxyethylamine, iminodiethanol Related cancers: Liver and kidney cancer in mice Definition: Diethanolamine (DEA) is a secondary amine in a class of organic compounds known as ethanolamines, which combine the properties of amines and alcohols. A high-production chemical, DEA is a component of metalworking fluids, pesticides, antifreeze, pharmaceuticals, and personal care products. Its fatty acid derivatives, including cocamide DEA, lauramide DEA, and oleamide DEA, are emulsifiers or foaming agents. Exposure routes: Principally through dermal contact, inhalation of vapor and aerosols, ingestion Where found: Intermediates in agricultural and photographic chemicals, personal care products (such as lotions, creams, shampoos, and hair dyes), textile processing, pharmaceuticals, metalworking fluids, industrial gas treatments At risk: Workers in diethanolamine manufacturing facilities, metal industry workers exposed to lubricating liquids, consumers of personal care products and of some tobacco products Etiology and symptoms of associated cancers: Diethanolamine increases the risk of liver cancers (hepatocellular adenoma or carcinoma) and kidney cancers (renal tubule adenoma) in mice. The cancer risk to humans has not been firmly established by adequate epidemiological studies. DEA does not damage the genetic material; rather,
Diethylstilbestrol (DES) it perturbs cellular processes by causing a deficiency of choline, an essential nutrient in mammals. Choline depletion is known to induce changes in deoxyribonucleic acid (DNA) methylation, stimulate DNA synthesis, generate free radicals, and enhance susceptibility to oxidative damage—all events linked to tumorigenesis. Because rodents are more sensitive to choline deficiency than are humans, the relevance of the mouse tumor findings to humans is unclear. DEA’s potential carcinogenicity may stem from its ability to interact with nitrites. As contaminants or preservatives in commercial formulations, nitrites react with DEA to form nitrosodiethanolamine (NDELA), a carcinogen that induces tumors of the liver, nasal cavity, and kidney in laboratory animals. The National Toxicology Program has listed nitrosodiethanolamine as reasonably anticipated to be a human carcinogen. History: The industrial synthesis of ethanolamines depends on the wide-scale production of the primary reactant, ethylene oxide, discovered in 1859 by the French chemist Charles Adolphe Wurtz. In 1999 at the completion of a two-year carcinogenesis study, the National Toxicology Program reported that dermal applications of DEA or cocamide DEA induced liver and kidney cancers in mice. As early as 1979 the U.S. Food and Drug Administration urged the cosmetics industry to remove DEAderived nitrosamines from its products, but it has not strictly enforced the policy. In contrast, the European Union has enacted legislation to reduce DEA and nitrosodiethanolamine from cosmetics and toiletries. Anna Binda, Ph.D. See also 4-Aminobiphenyl; Antiperspirants and breast cancer; Carcinogens, reasonably anticipated.
u Diethylstilbestrol (DES) Category: Carcinogens and suspected carcinogens; chemotherapy and other drugs RoC status: Known human carcinogen since 1980 Also known as: Stilbestrol Related cancers: Breast, cervical, prostate, and vaginal cancers Definition: Diethylstilbestrol (DES) is a synthetic form of the hormone estrogen. Exposure routes: Patients are exposed to DES when it is used in medical therapies and in clinical trials for the treatment of prostate and breast cancer. It is typically adminis373
Digital rectal exam (DRE)
Salem Health: Cancer
tered orally or intravenously. Potential exposure by inhalation can occur to workers who are involved in the formulation and manufacturing of diethylstilbestrol. Where found: DES is found at sites where it is manufactured, packaged, and supplied. It can be found at medical facilities where it is prepared and administered during cancer clinical trials and treatments. During the 1970’s, it was found in cattle and sheep that were injected with diethylstilbestrol to promote their growth. At risk: Patients who are treated with DES for prostate and breast cancers are at high risk. Workers at locations where diethylstilbestrol is manufactured, packaged, and supplied for cancer clinical trials are at risk for contamination. Health care professionals who prepare and administer DES for cancer therapy risk contamination, as do workers in labs where diethylstilbestrol is used in biochemical research. Etiology and symptoms of associated cancers: DES behaves as a hormonal therapy. By acting as a chemical messenger in the body, it helps control the activity of cells and organs. When administered to pregnant women to help prevent miscarriages or premature deliveries, DES can cause clear-cell adenocarcinoma (CCA) of the vagina and cervix in the mother and in daughters exposed before birth. In sons exposed before birth, DES can increase the risk of testicular cancer. Since DES reduces the level of testosterone in the body, it helps slow down the growth of prostate cancer cells. Side effects of diethylstilbestrol chemotherapy include breast tenderness, lowering of sex drive, tiredness, nausea, and weight gain. History: DES was first synthesized in 1938 at the University of Oxford. It was the first synthetic estrogen. In 1941 diethylstilbestrol was found to be effective in the treatment of gonorrheal vaginitis, menopausal symptoms, and metastatic prostate cancer. Between the 1940’s and the 1980’s, it was used as estrogen-replacement therapy in estrogendeficient women. After epidemiological studies of women linked DES to vaginal and cervical cancers, the U.S. Food and Drug Administration (FDA) advised in 1971 that it no longer be given to pregnant women. To a large extent, tamoxifen has replaced the use of DES in breast cancer treatments, as has leuprolide in the treatment of prostate cancer. Alvin K. Benson, Ph.D. 374
See also Bisphenol A (BPA); Cervical cancer; Colposcopy; Gynecologic cancers; PC-SPES; Pregnancy and cancer; Testicular cancer; Vaginal cancer.
u Digital rectal exam (DRE) Category: Procedures Also known as: Rectal exam, prostate exam Definition: In this procedure, a gloved, lubricated finger is inserted into the rectum to check for abnormalities in the rectal wall. For men, the size and shape of the prostate gland can also be checked for any abnormalities. Cancers diagnosed: Prostate cancer, rectal cancer, colon cancer Why performed: A digital rectal exam (DRE) is a simple procedure used to screen for rectal, prostate, and colon cancers. This procedure allows the physician to check for any abnormal thickness or lumps in the rectal wall. For men, the physician can also check the prostate gland for any unusual characteristics, such as an increase in size or nodules and lumps, since it is located next to the rectum. The benefit of the DRE as a screening tool for prostate cancer is that it can reach a part of the prostate gland where most cancers generally begin. The American Cancer Society recommends that men over age fifty get a DRE annually. High-risk men, defined as those with a
A gloved hand palpates the prostate gland. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Salem Health: Cancer family history of prostate cancer or African Americans, should receive DREs yearly beginning at age forty-five. For women, this procedure is usually performed as part of an annual exam. Patient preparation: No special preparation is needed for this procedure. Steps of the procedure: A gloved, lubricated finger is inserted into the rectum. There may be slight discomfort during the exam, but this is a quick procedure that generally takes only a few minutes. A stool sample called a fecal occult blood test may also be taken to check for the presence of blood. This test is done to screen for colon cancer. After the procedure: There are no special instructions, and patients can return to normal activities after the procedure is completed. Risks: No risks are associated with this exam. Results: If abnormalities are detected during the procedure, then the physician will recommend additional screening tests, such as a colonoscopy or sigmoidoscopy, which are used to screen for colon cancer. If a problem is suspected with the prostate gland, then a prostate-specific antigen (PSA) blood test, an ultrasound, or possibly a biopsy of the prostate gland may be suggested to screen for prostate cancer. Vonne Sieve, M.A. See also Anal cancer; Anoscopy; Benign prostatic hyperplasia (BPH); Carcinomatosis; Colonoscopy; Diverticulosis and diverticulitis; Endorectal ultrasound; Prostate cancer; Prostate-specific antigen (PSA) test; Screening for cancer; Sigmoidoscopy; Urologic oncology.
u Dilation and curettage (D&C) Category: Procedures Also known as: Uterine scraping Definition: Dilation and curettage (D&C) is used to surgically remove sections of the lining of the uterus and suspicious growths in the uterus in an examination for cancer cells. The lining of the uterus is called the endometrium. “Dilation” refers to manually opening the cervix to access the uterus. “Curettage” refers to using a curette, a surgical instrument, to gently scrape sections of the endometrium away from the uterus. Cancers diagnosed: Uterine cancer (uterine sarcoma), endometrial cancer (endometrial carcinoma), precancer-
Dilation and curettage (D&C) ous cellular changes that can lead to cancer (endometrial hyperplasia), precancerous growths that can change to cancer (endometrial polyps) Why performed: D&C is performed to diagnose uterine cancer, endometrial cancer, or precancerous cells in the uterus. A D&C obtains tissue specimens for analysis by a pathologist. A D&C may be used if cancer is suspected or if a biopsy is suggestive of cancer but not conclusive. A small tissue sample is obtained in a biopsy, and a larger representation of the uterine tissues is collected with a D&C. Additionally, the tissue specimens may be tested for estrogen and progesterine receptor cells. Increases in these hormones are associated with an increased risk of uterine and endometrial cancer. Patient preparation: A D&C is a short outpatient procedure performed at a hospital’s surgery department or an outpatient surgical center. General anesthesia is usually used, so the patient is not awake. Patients should not eat or drink past midnight prior to the day of the procedure or for seven hours before the D&C. In some cases, spinal or epideral blocks may be used instead of general anesthesia. On the day of the procedure, the patient provides a urine sample and dons an examination gown. Steps of the procedure: The patient lies on her back on a surgical table. The patient’s knees are spread and her feet are placed in stirrups. The patient’s vital signs are monitored, and anesthesia is administered. The vaginal area and urethra are cleansed. A catheter tube may be inserted into the urethra to collect urine during the procedure. A speculum is inserted into the vagina to separate the vaginal walls. The cervix and vagina are cleansed. Metal devices are used to dilate the cervical opening to allow the doctor to access the uterus. A curette is an instrument used to remove the lining of the uterus in sections. It has a long narrow handle with a metal loop at the end. The curette is inserted through the vagina and cervix and into the uterus. The doctor uses the curette to gently scrape the lining of the uterus. The tissue specimens are prepared and sent to a pathologist for examination for cancer cells. When the D&C is complete, the dilating device, speculum, and catheter are removed. The patient is monitored in a postsurgical recovery area until she is alert and is provided with a sanitary napkin to protect her clothing from blood. The patient should not drive and needs to receive a ride home from another person. After the procedure: Patients may experience menstruallike cramps or backache and are prescribed pain medication. Bleeding and the passing of small blood clots may oc375
Dioxins cur for a few days following the procedure. Light vaginal bleeding or staining may continue for several weeks. Patients should wear sanitary napkins but should not use tampons. Patients are encouraged to rest for a few days following the surgery and should not participate in sexual intercourse during this time. Risks: A D&C is considered a low-risk procedure. The risks include those of general anesthesia as well as uterine perforation, cervical laceration, and endometrium scarring. Patients should contact their doctors if they experience heavy bleeding, increased pain, problems breathing, or fever and other signs of infection. Results: A pathologist examines the tissue specimens for cancerous or precancerous cells. The pathologist’s report is conveyed to the doctor. Mary Car-Blanchard, O.T.D., B.S.O.T. u For Further Information Engelsen, I. B., et al. “Pathologic Expression of p53 or p16 in Preoperative Curettage Specimens Identifies HighRisk Endometrial Carcinomas.” American Journal of Obstetrics and Gynecology 195, no. 4 (October, 2006): 979-986. Larson, D. M., et al. “Comparison of D&C and Office Endometrial Biopsy in Predicting Final Histopathologic Grade in Endometrial Cancer.” Obstetrics and Gynecology 86, no. 1 (July, 1995): 38-42. Merisio, C., et al. “Endometrial Cancer in Patients with Preoperative Diagnosis of Atypical Endometrial Hyperplasia.” European Journal of Obstetrics & Gynecology and Reproductive Biology 122, no. 1 (September 1, 2005): 107-111. Papaefthimiou, M., et al. “The Role of Liquid-Based Cytology Associated with Curettage in the Investigation of Endometrial Lesions from Postmenopausal Women.” Cytopathology 16, no. 1 (February, 2005): 32-39. Saygili, H. “Histopathologic Correlation of Dilatation and Curettage and Hysterectomy Specimens in Patients with Postmenopausal Bleeding.” European Journal of Gynaecological Oncology 27, no. 2 (2006): 182-184. Wang, X., et al. “Comparison of D&C and Hysterectomy Pathologic Findings in Endometrial Cancer Patients.” Archives of Gynecology and Obstetrics 272, no. 2 (July, 2005): 136-141.
See also Colposcopy; Conization; Cryoablation; Endometrial cancer; Gestational trophoblastic tumors (GTTs); Giant cell tumors (GCTs); Gynecologic cancers; Hysterectomy; Pap test; Uterine cancer. 376
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u Dioxins Category: Carcinogens and suspected carcinogens RoC status: Under the heading “2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD),” known human carcinogen since 2001 Also known as: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); polychlorinated dibenzo-p-dioxin (PCDD) Related cancers: All cancers, including lung cancer and non-Hodgkin lymphoma Definition: Dioxins are polychlorinated dibenzo-p-dioxins (two benzene rings bridged with two atoms of oxygen). The one in which carbons 2, 3, 7, and 8 are chlorinated is called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is the deadliest synthetic chemical—so much so that its toxicity is used as a benchmark by which to rate the toxicity of other chemicals through a value called a “toxic equivalency factor” (TEF). Exposure routes: All species are exposed to dioxins through inhalation or ingestion via air, water, and food. In humans, the major source of TCDD is diet. Out of an average 120 picograms per day in food, 38 are from meat, 24 from dairy foods, 18 from milk, 13 from chicken and pork each, 8 from fish, 4 from eggs, and 2 from air. Where found: TCDD and other dioxins are not commercial products but are formed as by-products during both organochlorine manufacturing and waste combustion and incineration operations. Dioxins contaminate the atmosphere through incineration and waste disposal; the land through manufacturing, agricultural herbicides, and incineration; and the water through effluent discharges, especially from pulp and paper plants. Residues of TCDD, because of its thermo- and bio-stability, are widely distributed in the air, soil, water, sediments, biota (flora and fauna of a region), and human food. Because it has very low solubility in water and a very high partition coefficient, it accumulates in fat, becomes concentrated in aquatic biota, and is ecomagnified through the food chain. Freshwater biota hold the highest amount of TCDD, which may also be bound to organics in sediments. At risk: People at greatest risk for exposure to TCDD and other dioxins are those living near contaminated sites or eating contaminated foods, such as waste-incineration workers, firefighters, workers in chemical research facilities, those working in the production and use of pentachlorophenol and other chlorinated compounds, and those associated with chlorophenoxy herbicide production, use, and disposal.
Salem Health: Cancer
Dioxins
Etiology and symptoms of associated cancers: TCDD has extreme potency for chronic biological effects. There is a general commonality among animal species in some of the effects of TCDD, while other effects are speciesspecific. For example, birth defects and lowering of male sex hormones (testicular atrophy) have been reported in several bird and mammalian species. Chronic toxicity of TCDD increases with the duration of exposure. TCDD is regarded a both a teratogen (an agent of developmental malformations) and carcinogen (an agent of malignancy). It affects both the reproductive system (causing low sperm counts, lowering of testosterone, and testicular atrophy, among other effects) and developmental stages (leading to malformations in newborns). In humans, birth defects, termination of pregnancy, decreased fertility (lower sperm count and testosterone and testicular atrophy), endometriosis, diabetes, learning disorders, skin and lung effects, and cancer are commonly recognized. The half-life of TCDD in humans varies from thirty days to ten years. Men cannot degrade TCDD, while women can transfer it to a fetus via the placenta and to a newborn via breast milk. TCDD causes neurobehavioral deficits and lowering of testosterone in neonates due to their exposure in utero. The U.S. federal government, for example, has had to issue warnings about the consumption of TCDD-tainted Lake Michigan fish by women who are pregnant or want to become pregnant and by children and young adults. The carcinogenic effects of TCDD are evident in the increased rate of both benign and malignant tumors seen in those who experience significant exposures to the chemical. By binding to the “Ah receptor”—a protein ubiquitous in human and other vertebrate animal tissues that plays a major role in gene transcription—TCDD activates biological responses that can lead to carcinogenic activity. Because the chemical accumulates in fat over long periods of exposure, this carcinogenic activity increases with time, even with low chronic exposures.
to an overall increased risk for all cancers combined, an increased risk for lung cancer, and an increased risk for nonHodgkin lymphoma. The U.S. government has therefore classified TCDD as a known human carcinogen since 2001. TCDD was present in herbicides widely used in the 1960’s and 1970’s, including Agent Orange, used during the Vietnam War. Although TCDD no longer is used in these agents, it continues to occur as a by-product of paper and pulp bleaching (which is why some people, for example, prefer to use unbleached coffee filters and paper towels); in the incineration of municipal and hospital waste; in the production of metals; and in the combustion of both wood and fossil fuels. M. A. Q. Khan, M.D., Ph.D.
History: First listed as a reasonably anticipated carcinogen in the National Toxicology Program’s Second Annual Report on Carcinogens (1981), from the U.S. Department of Health and Human Services, TCDD underwent several subsequent studies. Some of these considered cancers in human populations occupationally exposed to TCDD, while others examined what took place at the molecular and cellular levels in human and animal tissue exposed to TCDD. The data from studies conducted through 1996 were evaluated by the International Agency for Research on Cancer (IARC), whose results were published in 1997. The IARC concluded that exposure to TCDD was linked
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For Further Information Colborn, T., D. Dumanoski, and J. P. Myers. Our Stolen Future. New York: Dutton Press, 1995. Committee on EPA’s Exposure and Human Health Reassessment of TCDD and Related Compounds. Board on Environmental Studies and Toxicology. Division on Earth and Life Studies. National Research Council of the National Academies. Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment. Washington, D.C.: National Academies Press, 2006. Khan, M. A. Q., and R. H. Stanton. Toxicology of Halogenated Hydrocarbons. New York: Pergamon Press, 1980. U.S. Department of Health and Human Services. Public Health Service. National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. U.S. Environmental Protection Agency. Office of Research and Development. Office of Health and Environmental Assessment. Health Assessment Document for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Related Compounds. Washington, D.C.: Author, 1994. Other Resources
National Academy of Sciences http://www.nasonline.org National Cancer Institute http://www.cancer.gov National Toxicology Program http://ntp.niehs.nih.gov See also Agent Orange; Bile duct cancer; Curcumin; Organochlorines (OCs); Pesticides and the food chain; Sarcomas, soft-tissue; Vinyl chloride. 377
Disseminated intravascular coagulation (DIC)
u Disseminated intravascular
coagulation (DIC) Category: Diseases, symptoms, and conditions Also known as: Consumptive coagulopathy Related conditions: Bleeding, thrombosis Definition: Disseminated intravascular coagulation (DIC) is a condition that prevents the body from regulating blood clotting. Small blood clots develop throughout the body, and substances needed for clotting become depleted. This systemic coagulation and resulting inability to form clots can lead to organ failure and hemorrhage (excessive bleeding). DIC can be chronic and develop over time, or arise acutely and require emergency intervention. Risk factors: The clotting cascade associated with DIC can be brought on by a number of health problems: infection, severe trauma, cancer, complications during pregnancy and childbirth, and some types of snakebite. Patients with solid tumor cancers and acute leukemias have an increased risk. Chronic DIC may be induced or aggravated by various stimuli, including radiation therapy and chemotherapy. Acute DIC is usually associated with infections. Etiology and the disease process: DIC occurs when an overabundance of clotting factors are released into the bloodstream in response to tissue damage. Widespread clotting occurs within the microvasculature throughout the body. The excessive clotting can damage organs and, paradoxically, “uses up” clotting factors and platelets (clotting cells) such that the blood can no longer clot normally. Incidence: Some 10 to 15 percent of patients with metastatic cancer show evidence of DIC, and it is present in approximately 15 percent of patients with acute leukemia. Symptoms: Acute DIC symptoms include bleeding, sudden bruising, shortness of breath, and low urine output from kidney damage. Chronic DIC may produce no symptoms at all or only minimal bleeding or clotting. Screening and diagnosis: No single test is used to diagnose DIC. Blood tests include a D-dimer test (test for a certain breakdown product of blood clots), prothrombin time (measure of blood-clotting tendency), fibrinogen level (level of a protein needed for blood to clot), and complete blood count. The physician will look at the patient’s clinical symptoms (bleeding, bruising, and so on) along with available blood tests to make a diagnosis. 378
Salem Health: Cancer Treatment and therapy: Treatment for DIC involves treatment for the underlying cause. Supportive care with platelets and clotting factors will be used to stop excessive bleeding. Transfusions of blood cells may be necessary to replace blood that has been lost. In some cases, heparin (a blood thinner) may be used to stop the cascade of clotting events. Prognosis, prevention, and outcomes: Prognosis will be primarily determined by the underlying condition that led to DIC and the severity of the DIC itself. For patients with sepsis and severe trauma, the presence of DIC may increase the risk of death by 1.5 to 2 times. Melanie Hawkins, B.S.N., R.N., O.C.N. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Leukemias; Mesothelioma; Paraneoplastic syndromes.
u Diverticulosis and
diverticulitis Category: Diseases, symptoms, and conditions Also known as: Diverticular disease Related conditions: Perforated bowel, bowel obstruction, chronic constipation, peritonitis, gastrointestinal bleeding, colon cancer Definition: Diverticulosis is a condition in which an outpouching occurs in an area of the colon. This area of outpouching is known as a diverticulum. Occasionally a diverticulum becomes infected or inflamed, leading to a condition known as diverticulitis. Risk factors: Risk factors include a low intake of dietary fiber and chronic constipation. Etiology and the disease process: Inadequate intake of dietary fiber is thought to contribute to the development of diverticulitis. When fiber is lacking in the diet, there is less residue in the fecal matter. Reduced residue narrows the bowel lumen, increasing intraluminal pressure during defecation. A diverticulum results when high intraluminal pressure is exerted on an area of weakness in the gastrointestinal wall, where blood vessels enter. High pressure causes layers of the wall in the area of weakness to herniate through the muscular wall, forming a diverticulum. Fecal material, undigested food, and bacteria collect in the diverticulum, forming a hard mass that diminishes blood flow to the diverticulum. The diverticulum becomes
Salem Health: Cancer
Diverticulosis and diverticulitis
Colon
Diverticuli
Diverticulitis, a condition in which outpouchings on the colon wall become inflamed, is a risk factor for cancer.
inflamed and infected, causing fever and lower abdominal pain. If this condition is left untreated, an abscess may develop and the intestinal wall may perforate. Incidence: According to the National Institutes of Health, diverticular disease affects about 2.5 million people in the United States. Of those individuals, more than 600,000 require hospitalization annually for treatment of the disease. About 20 percent of those diagnosed with diverticulosis will develop diverticulitis at some point in their lives. Symptoms: Diverticulosis typically produces no symptoms. Symptoms occur when a diverticulum becomes inflamed or infected and diverticulitis develops. When diverticulitis is mild, symptoms include moderate pain in the left lower abdomen and low-grade fever. The inflammation may also cause irritability and spasticity of the adjoining abdominal wall, producing diarrhea. In acute diverticulitis, severe cramping pain suddenly occurs in the
left lower abdomen. Anorexia, nausea, constipation, fever, weakness, and abdominal distension may also occur. When an abscess occurs and the bowel perforates, abdominal pain becomes severe and abdominal rigidity develops. High fever, chills, low blood pressure, increased heart rate, decreased level of consciousness, diarrhea, and diminished urine output also occur. Without immediate treatment, death may occur. Screening and diagnosis: Because diverticulosis does not produce symptoms, it is commonly discovered during testing for another disorder. It is also commonly found during colonoscopy for routine colon cancer screening. When symptoms prompt a visit to a health care provider, diverticulitis is diagnosed through physical examination and diagnostic testing. The health care provider will begin by taking a medical history, asking questions about the onset and severity of symptoms, bowel habits, dietary intake, and medications. The health care provider may also perform a digital rectal examination to check for a mass or blockage. A small stool sample may be obtained to check for occult blood (blood that is not visible to the eye). The health care provider may also order a blood test, known as a complete blood count, to check for signs of infection and bleeding. Blood cultures may be ordered to determine whether the infection has spread to the blood. An abdominal computed tomography scan, commonly referred to as an abdominal CT scan, may be performed to detect diverticulitis and can reveal an abscess. A barium enema may also be performed. An abdominal X ray may show free air under the diaphragm, indicating that perforation has occurred. When acute diverticulitis subsides, the health care provider may order a colonoscopy to determine the extent of disease and to rule out other disorders. Diverticulitis may be a risk factor for contracting certain types of cancer, and it can make cancers of the colon more difficult to properly diagnose. Treatment and therapy: Treatment for diverticular disease depends on the severity of disease. Diverticulosis is commonly treated with a high-fiber diet. Increasing fiber in the diet softens stools and decreases the pressure within the colon so that fecal material moves through freely. Twenty to thirty-five grams of fiber should be consumed each day. A psyllium dietary fiber supplement may also be recommended. Fluid intake should also be increased to two liters per day, if other medical conditions allow. Exercise also helps increase the rate of stool passage. Mild diverticulitis may be treated with a liquid diet to rest the bowel until symptoms subside, followed by a highfiber diet. Antibiotics such as metronidazole, ciprofloxacin, levofloxacin, or co-trimoxazole may be prescribed 379
Do-not-resuscitate (DNR) order for seven to ten days. A mild analgesic such as acetaminophen may also be recommended. If discomfort is caused by spasm, an antispasmodic such as oxyphencyclimine may be prescribed. Severe diverticulitis may require hospitalization for administration of intravenous antibiotics and fluids. If the infection does not subside with antibiotic therapy, surgical intervention may be necessary. Emergency surgery may also be necessary if a fistula or perforation occurs. Surgery involves removing a portion of the colon and clearing the abdominal cavity. Because infection is present, the colon cannot be reconnected until the infection is cleared. Therefore the surgeon must create a temporary colostomy. A second surgery is required to reconnect the colon after the infection is gone. Prognosis, prevention, and outcomes: With early recognition and treatment, prognosis is good. According to the National Institutes of Health, approximately 3,300 deaths occurred as a result of diverticular disease in 2002. Collette Bishop Hendler, R.N., M.S. u For Further Information Black, P. and C. Hyde. Diverticular Disease. Hoboken, N.J.: John Wiley & Sons, 2005. Kruis, W., et al. Diverticular Disease: Emerging Evidence in a Common Condition. Norwell, Mass.: Springer and Falk Foundation, 2006. Munden, Julie, et al. Pathophysiology Made Incredibly Easy! 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2008. u
Other Resources
MedlinePlus Diverticulosis http://www.nlm.nih.gov/medlineplus/tutorials/ diverticulosis/htm/index.htm National Digestive Diseases Information Clearinghouse Diverticulosis and Diverticulitis http://digestive.niddk.nih.gov/ddiseases/pubs/ diverticulosis/ See also Antidiarrheal agents; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Crohn disease; Cruciferous vegetables; Diarrhea; Enterostomal therapy; Fecal occult blood test (FOBT); Fiber; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Hemorrhoids; Immunochemical fecal occult blood test (iFOBT); Inflammatory bowel disease; Laxatives; Nuclear medicine scan; Nutrition and cancer 380
Salem Health: Cancer prevention; Obesity-associated cancers; Pancolitis; Sigmoidoscopy; Small intestine cancer; Upper gastrointestinal (GI) series.
u Do-not-resuscitate (DNR)
order Category: Social and personal issues Also known as: AND (allow natural death), no code Definition: A do-not-resuscitate (DNR) order permits natural death for a patient who has an irreversible, terminal condition, such as advanced cancer, and receives care by health professionals at home or in a medical facility. Purpose: The purpose of the order is to allow a cancer patient to experience a natural death while under the care of medical personnel. The order is enacted only when the patient stops breathing or the heart stops beating because of the terminal illness. Even with a DNR, a natural death may not be allowed if heart or respiratory failure is caused by an unrelated event such as a car accident. Health care professionals providing care to patients without DNR orders, regardless of the severity of disease, are legally required to provide cardiopulmonary resuscitation (CPR) and perform medical interventions at the time of death. These efforts must not only be initiated but also be continued until they are deemed futile by the physician or a designated professional. The extraordinary measures performed by health care professionals in the event of respiratory or heart failure include CPR and placing the patient on life support. These procedures are invasive and often considered painful. Appropriately performed CPR can cause broken bones and punctured organs even in generally healthy individuals, such as accident victims. Such injuries are more likely to occur in frail individuals who are near death. Life support may consist of intravenous (IV) drugs that cause the heart to continue to beat. Without the medications, the heart will stop and death will be irreversible in a few minutes, even with aggressive treatment. Mechanical ventilation (a breathing machine) is another form of life support. A tube is inserted into the patient’s throat and is attached to a mechanical ventilator. If the patient needs the ventilator for a long period of time, a tracheostomy (a surgical opening in the neck) will be created to attach to the machine. The ventilator causes artificial breathing. Without the machine, the patient would be unable to breathe, and life would not be sustained. Life support requires that an individual has continuous care, often in a medical facility.
Salem Health: Cancer
Down syndrome and leukemia
Procedure: In the United States, an adult who receives health care services and wants to be allowed to die a natural death must consult with a physician before a DNR order is written. The majority of individuals with DNR orders have a terminal illness such as advanced or aggressive cancer. Electing to die a natural death allows the individual to have some control in the death process. Most individuals report they would prefer to die in their own home rather than in a hospital or nursing home. Terminally ill patients may be able to stay at home if nursing or other care is provided. If they want to die naturally at home, a DNR is needed. These patients may be transferred to the hospital if a higher level of care is needed. The DNR order must be provided to ambulance personnel transporting the patient to prevent unnecessary interventions in the event of respiratory or cardiac failure on the way to the hospital. The first step in obtaining a DNR order is for cancer patients to discuss the issue with their medical provider. The best time to discuss these issues is before death is imminent. This allows for a less emotional and more rational discussion of the situation. Any adult who is mentally competent and his or her physician can determine if a DNR order is appropriate. If the patient is not competent to discuss the issue, family members may approach the physician. If the patient (or family if the patient is not competent) and physician are in agreement, the physician can write the DNR order. If the patient disagrees with the physician’s recommendations, he or she may select another health care provider or the physician may ask for a medical ethics consultation. The consultation is provided by a professional in medical ethics who is not involved in the direct care of the patient.
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Medical care: Many cancer patients and their families are afraid of having a DNR order. There is concern that inadequate medical care may be provided to those who have a DNR order. However, these orders do not interfere with routine medical care. Care of the patient changes only in its focus, not in its provision. Pain management, comfort, and end-of-life issues become the priority rather than disease management. The patient may have extensive health care needs, such as personal grooming, bathing, and feeding. These activities are continued. A DNR order prohibits only extraordinary measures that would prevent death or prolong life unnecessarily. For the DNR order to be active, a copy of the order must be submitted when entering home health care, hospice, or any other medical facility. If the order is not present and respiratory or cardiac failure occurs, cardiopulmonary resuscitation is medically obligated. A DNR order can be revoked by a patient at any time. Amy Bull, D.S.N., A.P.N.
Related conditions: Transient leukemia (TL), transient myeloproliferative disorder, transient abnormal myelopoiesis
For Further Information Gott, Peter H. Live Longer, Live Better: Taking Care of Your Health After Fifty. Sanger, Calif.: Quill Driver Books, 2004. Kiernan, Stephen P. Last Rights: Rescuing the End of Life from the Medical System. New York: St. Martin’s Press, 2006. Mayo Clinic. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003.
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Other Resources
American Cancer Society Advance Directives http://www.cancer.org/docroot/MIT/mit_3_1_1.asp National Cancer Institute End-of-Life Decisions http://www.cancer.gov/cancertopics/pdq/ supportivecare/transitionalcare/HealthProfessional/ page9 See also Advance directives; Counseling for cancer patients and survivors; Elderly and cancer; End-of-life care; Grief and bereavement; Hospice care; Informed consent; Living will; Palliative treatment; Relationships; Stress management; Survivorship issues; Transitional care.
u Down syndrome and leukemia Category: Diseases, symptoms, and conditions Also known as: Trisomy 21 and cancer of white blood cells
Definition: In Down syndrome the individual has three copies of chromosome 21 instead of two. Those with Down syndrome have a significant risk of developing certain forms of leukemia. Leukemia is a blood cancer in which cancerous changes take place in marrow cells that form lyphocytes (white blood cells). Risk factors: Children with Down syndrome have a ten to twenty times greater risk of developing leukemia. They develop acute lympholastic leukemia and two types of megakaryoblastic leukemia: transient leukemia (TL) and acute megakaryoblastic leukemia (AMKL). Down children have a five hundred times greater risk of developing AMKL than other children. Some 10 percent of newborns with Down syndrome develop TL. 381
DPC4 gene testing Etiology and the disease process: In TL and AMKL, blasts (immature blood cells) accumulate in blood and bone marrow, and white blood cell differentiation is abnormal. TL in the newborn goes into remission within a few months. Of those who had TL, 20 to 30 percent will develop AMKL later in life. Although the relationship between Down syndrome and increased risk for leukemia is not understood, it has been observed that as well as having trisomy for chromosome 21, children who develop TL have mutations in the transcription factor GATA1, which plays an important role in the normal development of red blood cells, megakaryocytic, and basophilic cell lines. The GATA1 gene (also known as a hematopoietic growth factor) is on the X chromosome. It is thought that additional mutations must occur for AMKL to develop. Incidence: The incidence of Down syndrome is 1 in 800, and 1 in 95 Down syndrome children will develop leukemia, compared with 1 in 2,000 children in general. Symptoms: As with other leukemias, the symptoms associated with Down syndrome leukemias include fatigue, skin pallor, bruising, bleeding, difficulty in wound healing, enlarged lymph nodes, and joint pain. Screening and diagnosis: Analysis of the blood is done in children with Down syndrome to test for signs of leukemia. In TL in Down syndrome, analysis of blood and bone marrow shows variable numbers of blasts. The acute leukemia cell produces nonfunctional leukemia cells that crowd out normal cells. Treatment and therapy: Children with Down syndrome and leukemia are typically treated with chemotherapy. Blasts of Down syndrome TL are sensitive to low doses of cytosine arabinoside. Children with Down syndrome and leukemia are more sensitive than other children to some drugs used in chemotherapy, such as methotrexate, so Down syndrome children must be carefully monitored for drug toxicity. Prognosis, prevention, and outcomes: Down syndrome TL neonates have a 15 percent risk of developing a potentially fatal liver disease and an increased risk of developing cardiopulmonary failure and spleen necrosis. Though Down syndrome children are at an increased risk of developing leukemias, they have a reduced risk of developing solid tumors. Susan J. Karcher, Ph.D. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Blood cancers; Childhood cancers; Cytogenetics; Genetic testing; Myelodysplastic syndromes; Ultrasound tests. 382
Salem Health: Cancer
u DPC4 gene testing Category: Procedures Also known as: SMAD4, MADH4 Definition: The DPC4 gene product maintains normal cell growth rates. Mutations in DPC4 lead to uncontrolled cell growth and, ultimately, to many cancers, especially those of the gastrointestinal tract and pancreas. Inherited mutations in DPC4 are one cause of juvenile polyposis syndrome (JPS), an inherited condition that results in a predisposition to colorectal cancer. Cancers diagnosed: Juvenile polyposis syndrome, familial colon cancer Why performed: Approximately 20 percent of individuals afflicted with JPS, a condition in which numerous polyps form in the colon, bear mutations in the DPC4 gene. Other cases may be caused by mutations in BMPR1A or other genes. Although polyps resulting from JPS are initially benign, a small proportion may develop into carcinomas. Genetic testing is performed to confirm a diagnosis of patients exhibiting symptoms of JPS and to characterize the DPC4 mutation causing the disease. Because JPS is an inherited disorder, genetic testing is also often done in previously undiagnosed relatives of JPS patients to determine whether prophylactic treatment is required. Testing is performed at or before age fifteen, the time at which routine screening by colonoscopy is recommended. Patient preparation: Patients considering genetic testing may meet with a genetic counselor to discuss the benefits and risks of the test and the significance of negative, positive, and inconclusive tests. Material required for genetic testing is obtained from a blood sample or from cheek cells obtained by mouthwash. No special preparation is required. Steps of the procedure: Samples are sent to a clinical laboratory that offers DPC4 screening. Deoxyribonucleic acid (DNA) is isolated from the blood sample, and the DNA that encodes DPC4 is amplified by polymerase chain reaction (PCR) and sequenced using standard methods. After the procedure: The patient will consult with a physician and/or genetic counselor to discuss the implications of the test results. Risks: Complications from drawing blood are rare but may include excessive bleeding, hematoma, or infection. Because the information obtained from DPC4 screening
Salem Health: Cancer may have significant psychological effects, it is important that patients be offered genetic counseling. Results: Sequence analysis allows clinicians to identify the specific DNA mutation(s) present in a JPS patient. Once this mutation has been identified, close relatives can be screened to determine if they share the mutation that causes JPS. Routine colonoscopy and polypectomy, beginning at age fifteen, is recommended for those bearing mutations in DPC4. Kyle J. McQuade, Ph.D. See also Colorectal cancer; Colorectal cancer screening; Family history and risk assessment; Genetic counseling; Genetic testing; Hereditary cancer syndromes; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Juvenile polyposis syndrome.
u Drug resistance and
multidrug resistance (MDR) Category: Chemotherapy and other drugs Definition: Drug resistance is the loss of effectiveness of a drug used to kill or weaken cancer cells. It may be intrinsic (active in the cancer cell before treatment) or acquired (developed after treatment). Multidrug resistance (MDR) is the adaptation of cancer cells to withstand a large number of structurally and functionally unrelated drugs designed to kill cancer cells. Development of resistance: Drug resistance and MDR are major causes of treatment failure in cancer patients. When exposed to chemotherapeutic drugs, the cancer cell activates processes or synthesizes molecules that can inactivate or eliminate the drugs. Cancer cells have many alternative pathways at their disposal to overcome the toxic effects of chemotherapeutic drugs. Most of these mechanisms have origins in the normal cell. The oncologist recognizes the phenomenon of MDR and has developed treatment programs to delay its onset. Chemotherapy can consist of treatment with single drugs or multiple drugs. Chemotherapy is commonly combined with radiation or surgery. Research is ongoing to develop drugs that specifically target MDR when it develops. Anticancer drugs have to overcome many challenges before they can accomplish their mission. Tumors are rapidly growing and have a poorly developed vascular system. The cancer cells have difficulty in receiving adequate oxygen and nutrients and therefore adapt to a hypoxic (lowoxygen) environment. This hypoxic environment can cause
Drug resistance and multidrug resistance (MDR) cancer cells to become resistant to drugs. Drugs have difficulty navigating the poor tumor vascular system to reach the cells. The drugs must be able to pass the cell membrane, navigate the cytoplasm, and reach the nucleus, where most drugs exert their effects. They must accumulate in high concentrations in their active form and must sustain these concentrations long enough to kill the cancer cell. Drugs against MDR proteins: A major research focus is to develop drugs that counteract MDR proteins. The MDR proteins, known as drug efflux pumps, transport drugs out of cancer cells. These proteins belong to a family of proteins called the adenosine triphosphate (ATP) binding cassette proteins (ABCs). The ABC proteins are overexpressed (increase greatly) when exposed to chemotherapeutic drugs. These proteins reside in the cell membrane and consist of an embedded portion that forms a pore for transport of drugs and an internal portion that binds to the ATP molecule. When the ATP molecule is broken down, energy is released to drive the process. P-glycoprotein is the main MDR protein that has been studied, and it remains of primary interest. Intensive research has developed first-, second-, and third-generation inhibitors to this protein, with each generation improving on the previous generation. Researchers have begun development of inhibitors that act by binding to the ABC protein and inhibiting its activity. The drugs have diverse chemical structures and origins. Multidrug resistance-associated protein (MRP1) is also a major target of drug research. Six additional MRP proteins with structural similarities to MRP1 have been identified. Several other MDR proteins have been identified as well, including breast cancer resistant protein, mitoxantrone resistant protein, and others less well characterized. Cellular changes associated with MDR: MDR is commonly associated with changes in the intracellular distribution of the chemotherapeutic drug. Most cancer therapies target deoxyribonucleic acid (DNA) or nuclear enzymes. When MDR develops, there is a redistribution of drug from the nucleus into cellular vesicles such as the Golgi apparatus, endosomes, and lysosomes. The drugs are then transported toward the plasma membrane and excreted from the cell by the process of exocytosis. This process of elimination is considered passive and is different from the MDR efflux pumps, which require energy input to proceed. The expression of MDR pumps is also associated with altered drug distribution within cancer cells. Most chemotherapeutic drugs are mildly alkaline and have no charge. MDR cells have a more acidic pH inside subcellular vesicles than that of drug-sensitive cells. When drugs diffuse into the vesicles of MDR cells, they become 383
Drug resistance and multidrug resistance (MDR) protonated and take on a charge. The drugs are then trapped in the vesicles and cannot reach the nucleus to exert their effect. They can then be excreted from the cell by the process of exocytosis. Glutathione and its associated enzyme, glutathiononeS-transferase (GST), are commonly found in the body and serve as a natural detoxification mechanism. GST can increase in the presence of a chemotherapeutic drug in the cancer cell. GST then catalyzes the binding of glutathione to the drug. The drug then becomes more water soluble, less toxic to the cell, and more readily excreted. Research is under way to develop drugs that inhibit GST and thus restore the cancer cell’s sensitivity to the drug. Drugs that inhibit topoisomerase enzymes: The topoisomerase enzymes control the process of unwinding the DNA double helix during transcription or replication of the DNA molecule. This process is essential during cell division. Because cancer cells are rapidly dividing, topoisomerase inhibitor drugs are attractive treatments against a variety of cancers. To function, the drug must form a three-way complex with DNAand the enzyme. Conditions in the cell that interfere with this formation will lead to resistance. Mutations in the topoisomerase enzymes also cause resistance. Most topoisomerase inhibitors that have been the subject of clinical trials are derivatives of the plant extract camptothecin, although a semisynthetic derivative has also been developed. Drugs that inhibit DNA synthesis: Rapidly dividing cancer cells have a great need for DNA synthesis, so anticancer drugs such as methotrexate and 5-fluorouracil have been used to block pathways to its synthesis. Methotrexate inhibits the enzyme dihydrofolate reductase, while 5-fluorouracil blocks the enzyme thymidylate synthase. Both of these enzymes are required for the synthesis of nucleotides, the building blocks of DNA. Methotrexate was introduced in the mid-twentieth century for the treatment of acute lymphoblastic anemia, but resistance occurs rapidly. Resistance to the drugs can be due to increased production of the target enzymes, defective transport of the drugs, or increased excretion by efflux pumps. A number of chloroethyl- and methyl-nitrosourea therapeutic drugs attack the guanine unit of DNA in cancer cells to exert their toxic effect. The cancer cell acquires resistance to the drug by activating the enzyme O6-alkylguanine DNA alkyltransferase (AGT) to repair the damage. O6-benzylguanine inhibits the action of AGT and is used in the clinic in combination with nitrosourea drugs to reverse the resistance. Toxicity problems can occur when these drugs are used at levels needed to attain maximum effectiveness. 384
Salem Health: Cancer Protein kinase C is an enzyme that occupies a key role in the transfer of growth factor signals that result in DNA synthesis and cell division. This enzyme directly affects the expression of several proteins involved in drug resistance. These activities make protein kinase C an attractive target for therapeutic drugs. Drugs that stimulate apoptosis: Most cancer drugs act by stimulating the process of apoptosis (programmed cell death). The susceptibility of a cancer cell to apoptosis depends on the balance between pro- and antiapoptotic proteins in the cell. When the TP53 protein (the primary proapoptotic protein) discovers genetic damage to the DNA molecule, it summons other proteins to halt cell division, and if necessary, to initiate apoptosis. Most cancers show mutations in the TP53 gene, so that instead of helping to destroy cancer cells, they can even promote cancer. Antiapoptotic proteins, particularly the Bcl-2 family, become more active during chemotherapy, leading to resistance to apoptosis. Drugs that stimulate ceramide synthesis: Ceramide is the basic unit of sphingomyelin, a lipid structural element of cell membranes. Various stress stimuli, including radiation and chemotherapy, result in the formation of ceramide through the breakdown of sphingomyelin, or through synthesis from other molecules. Ceramide then acts as a second messenger relaying a signal to initiate apoptosis or other biological processes. MDR can result in a reduction in ceramide concentration through conversion to an inactive molecule. This reduces the effectiveness of chemotherapy, since many chemotherapeutic drugs exert their effect through apoptosis. Drugs are under development that increase ceramide levels in tumor cells by promoting ceramide synthesis or by blocking the conversion of ceramide to inactive compounds. Side effects: Depending on the chemotherapeutic drug administered, a variety of side effects can occur. These can include nausea and vomiting, diarrhea and vomiting, anemia, malnutrition, memory loss, depression of the immune system, and toxicity to certain body organs. David A. Olle, M.S. u
For Further Information Bredel, Markus. “Anticancer Drug Resistance in Primary Human Brain Tumors.” Brain Research Reviews 35 (2001): 161-204. Liscovitch, Mordechai, and Yaakov Lavie. “Cancer Multidrug Resistance: A Review of Recent Drug Discovery Research.” I Drugs 5, no. 4 (April, 2002): 349-355. Simon, Sanford M., and Melvin Schindler. “Cell Biologi-
Salem Health: Cancer cal Mechanisms of Multidrug Resistance in Tumors.” Proceedings of the National Academy of Sciences 91 (1994): 3497-3504. u
Other Resources
Chemocare.com http://www.chemocare.com National Cancer Institute Helping Yourself During Chemotherapy http://www.cancer.gov/cancertopics/helpingyourself-during-chemotherapy See also Alkylating agents in chemotherapy; Androgen drugs; Angiogenesis inhibitors; Antiandrogens; Antiestrogens; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Biological therapy; Chemotherapy; Immunotherapy; Matrix metalloproteinase inhibitors; Plant alkaloids and terpenoids in chemotherapy; Proteasome inhibitors; Topoisomerase inhibitors; Tyrosine kinase inhibitors.
u Dry mouth Category: Diseases, symptoms, and conditions Also known as: Xerostomia, Sjögren syndrome, cotton mouth (slang), oral dryness, aptyalism, asialia, stomatitis sicca, Zagari disease
Dry mouth systemic lupus erythematosus (SLE), increased progesterone levels, and decreased estrogen levels. Other factors that amplify dry mouth include smoking tobacco or marijuana, hormone imbalances, mouth breathing, dry air environment, drinking strong citrus juices, vitamin or mineral deficiencies, anxiety and stress, alcohol consumption, high fevers, stones or tumors in the salivary ducts, hyperventilation, nasal obstruction, vomiting or diarrhea, and excessive sweating. Etiology and the disease process: Saliva contains enzymes that help break down and rinse away food particles and liquids. It also neutralizes acids and sugars in the mouth. Inadequate lubrication causes a dry mouth environment. When a person loses the ability to produce the normal amount of saliva, plaque and bacteria build up and adhere to the teeth, causing rapid, extensive decay and serious oral infections. Oral infections have the potential to interfere with planned cancer treatment therapies. Incidence: In general, dry mouth issues are more frequent in men; however, they also are more common in women during menopause and postmenopause. Dry mouth syndrome increases with the number of medications taken by an individual. Dry mouth can also be caused by an autoimmune disease called Sjögren syndrome. Approximately 4 million people are diagnosed each year with Sjögren syndrome. Approximately one-third to one-half of all cancer patients develop dry mouth complications because of radiation therapy, chemotherapy, and medication treatments.
Related conditions: Tooth decay, canker sores and mouth sores, geographic tongue, gum sensitivity, gingivitis, halitosis (bad breath), dysphagia (difficulty swallowing), dry eyes, nasal dryness, nosebleeds Definition: Dry mouth is an insufficient amount of saliva and moisture that would otherwise naturally lubricate and rinse the oral cavity. Risk factors: Many medications (prescription and over the counter) can cause dry mouth: antihistamines, antidepressants, antianxiety drugs, antihypertensive drugs, decongestants, sinus medications, pain medications, asthma and allergy medications, diuretics, and Parkinson’s medications. Chemotherapy or radiation treatments (particularly radiation therapy to the head and neck regions) also can cause this condition. Diseases and disorders that increase the risk of dry mouth include Parkinson’s disease, thyroid disorders, cancer, diabetes, human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), Sjögren syndrome, stroke,
Dry mouth in Sjögren syndrome. (Custom Medical Stock Photo)
385
Duct ectasia Symptoms: Symptoms include a dry or fissured tongue, a dry oral cavity, chapped or cracked lips, difficulty swallowing, increased risk of tooth decay, increased chance of mouth sores, bad breath (halitosis), increased gum sensitivity, gingivitis, bleeding gums, a burning sensation in the mouth, a dry throat, dry eyes, and increased oral infections. Screening and diagnosis: The patient is the first to notice symptoms. Friends and relatives often hear the lack of saliva within the patient’s speech and notice an unpleasant mouth odor. Dentists often note the dryness during dental exams and discover an increase in the number of cavities. Treatment and therapy: Patients should drink plenty of liquids during meals and sip on water between meals to help rinse away food particles, make it easier to swallow, and neutralize any oral debris. Sipping on soda all day or sucking on sugary hard candies in an effort to alleviate dry mouth should be avoided. Instead, patients may eat sugarfree candy or chew sugarless gum to help stimulate their natural salivary secretions. They should also eat healthy foods including those with natural oils such as peanuts, peanut butter, and fish. Patients should avoid coffee and tea that have sugar or creamers added. They should stop smoking, avoid all tobacco products, and stop drinking alcohol. Patients should brush twice daily, floss after snacks and meals, and use alcohol-free fluoride mouth rinses. Some patients may need hormone replacement therapy (HRT) or vitamin supplements. They may also use artificial saliva substitutes or fluoride gels such as PreviDent, Biotene, or PerioGard. Prognosis, prevention, and outcomes: Dry mouth can be a temporary or permanent situation depending on its cause. Radiation therapy can permanently damage salivary glands, and chemotherapy can cause saliva to become thick. Patients may reduce dry mouth symptoms by changing their medications; however, they should check with their doctor before changing or discontinuing any medications. Using water rinses, saliva substitutes, and fluoride rinses without alcohol will help alleviate dry mouth symptoms, strengthen teeth, and fight future tooth decay. Serious oral infections and extensive decay may result in loss of teeth and difficulty wearing dentures. Maintaining excellent oral hygiene is a challenge with dry mouth issues. More frequent dental exams and cleanings are necessary to check for decay. By avoiding the triggers that provoke dry mouth and using the recommended treatments, dry mouth may be manageable. Suzette Buhr, R.T.R., C.D.A. 386
Salem Health: Cancer u
For Further Information American Dental Association. ADA Guide to Dental Therapeutics. 4th ed. Chicago: Author, 2006. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperResource, 2003. National Institutes of Health. Dry Mouth. NIH Publication 99-3179. Bethesda, Md.: Author, 1999. Shafer, William G., Maynard K. Hine, and Barnet M. Levy. A Textbook of Oral Pathology. 4th ed. Philadelphia: W. B. Saunders, 1983. Waal, Isaac van der. Diseases of the Salivary Glands Including Dry Mouth and Sjögren’s Syndrome: Diagnosis and Treatment. New York: Springer-Verlag, 1997. u
Other Resources
American Cancer Society http://www.cancer.org American Dental Association http://www.ada.org National Institutes of Health National Institute of Dental and Craniofacial Research http://www.nidcr.nih.gov/HealthInformation/ DiseasesAndConditions/DryMouthXerostomia/ DryMouth.htm What Causes Dry Mouth? http://www.drymouth.info/consumer/ whatcausesDM.asp See also Aids and devices for cancer patients; Antidiarrheal agents; Antinausea medications; Appetite loss; Diarrhea; End-of-life care; Endoscopic retrograde cholangiopancreatography (ERCP); Graft-versus-host disease (GVHD); Hysterectomy; Lambert-Eaton myasthenic syndrome (LEMS); Mucositis; Opioids; Radiation therapies; Sjögren syndrome; Smoking cessation; Taste alteration; Weight loss.
u Duct ectasia Category: Diseases, symptoms, and conditions Also known as: Plasma cell mastitis, mastitis obliterans, comedomastitis, secretory disease of the breast Related conditions: Periductal mastitis Definition: Duct ectasia is a benign condition in which the mammary milk ducts (small tubes that carry breast milk to the nipple) fill with fluid and become plugged and inflamed.
Salem Health: Cancer Risk factors: Duct ectasia is more common in women with a history of periductal mastitis (infection of the breast ducts), cigarette smoking, an inverted nipple, and more than one pregnancy. The hormonal changes that occur with aging increase a woman’s risk of developing duct ectasia, as does a lack of vitamin A. Etiology and the disease process: Duct ectasia appears to start with an inflammatory process (the body’s response to irritation or injury), similar to an infection. A duct fills with fluid from the blood plasma, the lymph system, and the circulatory system. Lipids (fatty substances) and dead cells block the fluid from draining and lead to a buildup of the fluid in the duct. This causes the duct to dilate and become hardened. Incidence: Duct ectasia typically develops in women who are in their forties or fifties and are in perimenopause or menopause. Symptoms: Duct ectasia may appear as a lump in the breast or as an infection, marked by redness, swelling, pain, hardness, and fever. There may be a nipple discharge that is tan, white, greenish, or black. Sometimes, the nipple is inverted. Screening and diagnosis: Duct ectasia is diagnosed by physician examination of the nipple discharge, breast selfexamination, mammography, or breast ultrasound. Although the symptoms usually provide the necessary information for diagnosing duct ectasia, in some instances it may be necessary to biopsy the affected area of the breast. Treatment and therapy: The treatment for duct ectasia usually involves medication. The patient is given an antibiotic based on the culture and sensitivity of the nipple discharge. Warm, moist compresses are applied to the affected breast area three to four times a day for ten to fifteen minutes. The patient should wear a supportive bra and sleep on the unaffected side. In rare instances, it is necessary to incise (surgically open) and drain the infected duct. Prognosis, prevention, and outcomes: There is no method for preventing duct ectasia. Because duct ectasia is a benign problem, recovery is generally complete. Some women do have multiple incidences of duct ectasia. This condition does not increase a woman’s risk of developing breast cancer. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Breast cancer in pregnant women; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Lumps; Nipple discharge; Ultrasound tests.
Ductal carcinoma in situ (DCIS)
u Ductal carcinoma in situ
(DCIS) Category: Diseases, symptoms, and conditions Also known as: Stage 0 breast cancer Related conditions: Breast cancer, Paget disease of the nipple Definition: Ductal carcinoma in situ (DCIS) is a noninvasive form of breast cancer occurring in the ducts that are responsible for secreting milk. It is the most common type of noninvasive breast cancer, and because it is nonmetastatic, most patients survive their disease. Risk factors: Reproductive risk factors include women who never had a full-term pregnancy, had their first pregnancy after age thirty, started menstruation early, or had a late menopause. The use of oral contraceptives and postmenopausal estrogen-progestin replacement therapy (more than five years) has been shown to increase the risk of breast cancer. Having a family history of early-onset or bilateral disease and carrying the breast cancer susceptibility gene BRCA1 or BRCA2 increase the risks as well. Breast cancer risk increases with age, with most cases occurring in women over the age of sixty. The following are factors that reduce the risk of breast cancer: physical activity (exercise), multiple pregnancies, breast-feeding, and early removal of both ovaries. Etiology and the disease process: Not all DCIS lesions become invasive breast cancer, but most invasive lesions are preceded by DCIS. Most of the genetic changes present in invasive breast cancer are already present in DCIS, suggesting that if left untreated, these tumors would indeed become invasive. Incidence: The National Cancer Institute estimates that 12.7 percent of women born today will be diagnosed with breast cancer at some time in their lives. DCIS is the most common type of breast cancer, representing 21 percent of all newly diagnosed cases and as many as 30 to 50 percent of new breast cancers diagnosed by mammography. In 2005, there were estimated to be more than 60,000 new cases of DCIS in the United States. The use of mammography has greatly increased the detection and diagnosis of DCIS, leading to an increased rate of survival for those women whose lesions are detected early. Symptoms: Most breast cancers do not cause any pain, making them hard to detect. However, any change in the size or shape of the breast, change in the look or feel of the breast or nipple, or any lump or thickening in or near the 387
Ductal carcinoma in situ (DCIS) breast or underarm area may be a symptom of breast cancer. Other more obvious changes include nipple discharge, tenderness, an inverted nipple, and ridges in or pitting of the breast (when the skin looks like that of an orange). Screening and diagnosis: Because this disease can remain symptomless, monthly self-examination of the breasts after the age of twenty, yearly checkups, and regular mammographies after the age of forty are crucial to early detection. Most of the new cases of DCIS detected by mammography are not detectable by examination alone. Once DCIS is detected, tissue is sampled using fine needle aspiration (FNA) biopsy or core needle biopsy. According to the standard staging system, DCIS is a Stage 0 breast cancer. Pathologic analysis will determine the classification of the tumor, its size and margins, and if the tumor is hormone dependent. These criteria are then further classified as follows: • Grade I (low grade): Non-high grade without necrosis (the tumor cells look similar to normal cells, and the tumor may be solid, cribiform, or papillary) • Grade II (medium grade): Non-high grade with necrosis • Grade III (high grade): Very quickly growing tumor with the cells in the center of the duct becoming starved from the blood supply; described as “comedo” Treatment and therapy: Treatment will vary from case to case depending on the size and grade of the tumor and whether there is a family history of breast cancer. Typically, once diagnosis is confirmed, a lumpectomy is performed to remove the entire area of the DCIS and a marginal area of normal breast tissue around it. This is followed by radiation to the whole breast to kill cancer cells outside the surgical margin and to reduce the risk of the cancer coming back. In some cases a mastectomy, in which the entire breast is removed, may be recommended if the DCIS covers a very large area or multiple areas of the breast, or if the patient has a family history of breast cancer or a known gene abnormality (BRCA1 or BRCA2). Because this type of cancer has not invaded into the normal tissue, chemotherapy is not needed for DCIS. If the tumor tests positive for hormone receptors, hormonal therapy (tamoxifen and aromatase inhibitors) can be used to lower the risk of recurrence. Prognosis, prevention, and outcomes: Because DCIS is a precancerous or preinvasive lesion, the prognosis is very good. Less than 1 percent will die from this disease. It is possible that an invasive focus not found at the time of diagnosis will later develop into metastatic disease, but the likelihood is small. About 40 to 50 percent of local recur388
Salem Health: Cancer rences are invasive and 10 to 20 percent of patients will develop metastases and die from their disease. The more aggressive the therapy, the lower the rate of mortality. Additional treatment, including surgery, radiation therapy, antiestrogen therapy, or a combination of these, will reduce the chances of recurrence of the disease. Terry J. Shackleford, Ph.D. u
For Further Information Hunt, Kelly K., Geoffrey L. Robb, Eric A. Strom, and Naoto T. Ueno. Breast Cancer. M. D. Anderson Cancer Care Series. New York: Springer, 2001. Link, John. Breast Cancer Survival Manual: A Step-byStep Guide for the Woman with Newly Diagnosed Breast Cancer. 4th ed. New York: Holt, 2007. “The Picture Problem: Mammography, Air Power, and the Limits of Looking.” The New Yorker, December 13, 2004. http://www.gladwell.com/2004/2004_12_13_a_ picture.html. Roses, Daniel F. Breast Cancer. Philadelphia: Elsevier, 2005. Shockney, Lille D. Navigating Breast Cancer: A Guide for the Newly Diagnosed. Sudbury, Mass.: Jones & Bartlett, 2006.
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Other Resources
American Cancer Society http://www.cancer.org Breastcancer.org http://www.breastcancer.org National Cancer Institute Breast Cancer http://www.cancer.gov/cancertopics/types/breast Susan G. Komen for the Cure http://www.komen.org University of Texas, M. D. Anderson Cancer Center Breast Cancer http://www.mdanderson.org/diseases/breastcancer/ See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Comedo carcinomas; Ductal lavage; Ductogram; Invasive ductal carcinomas; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Mucinous carcinomas; Progesterone receptor assay; Tubular carcinomas.
Salem Health: Cancer
u Ductal lavage Category: Procedures Definition: Ductal lavage is a minimally invasive method used to detect gradual changes in breast cells that could indicate a precancerous or cancerous condition. It has been dubbed the “breast Pap smear.” The idea dates back to the 1950’s, when Dr. George Papanicolaou (1883-1962), the inventor of the Pap smear to detect cervical cancer, first theorized that nipple fluid could be analyzed for precancerous changes.
Ductogram recommend that the procedure be done along with clinical breast examination and an imaging study, such as mammography. Kelli Miller Stacy, ELS See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Ductogram; Invasive ductal carcinomas; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Microcalcifications; Mucinous carcinomas; Progesterone receptor assay; Tubular carcinomas.
Cancers diagnosed: Ductal carcinoma in situ (DCIS) Why performed: According to the American Cancer Society, more than 95 percent of breast cancers originate in the cells lining the milk ducts. Ductal lavage can identify atypical or abnormal changes in breast cells that may fuel cancer development in the future. The test is used to assess women at high risk of breast cancer. It is not intended as a screening tool for breast cancer, nor is it a replacement for mammography. Patient preparation: No preparation is needed. Steps of the procedure: A numbing cream is applied to the nipple area. The woman is asked to massage the breast area gently with both hands to help move fluid toward the nipple. A suction device placed over the nipple siphons tiny amounts of fluid from the milk ducts, which helps detect the natural duct openings. Once they are identified, a slender, hollow tube called a catheter is inserted into each duct that produced fluid. Saline flows through the catheter, rinsing out the duct and washing out cells. (Lavage is a French word that means “wash” or “rinse.”) The fluid containing the cells is then analyzed under a microscope. After the procedure: The procedure does not usually cause any discomfort. Some women may have a temporary feeling of pressure, tingling, or fullness afterward. No special follow-up care is needed. Risks: The risks of ductal lavage are rare but may include damage to a milk duct and infection at the site of the catheter insertion. Signs of infection include breast redness, warmth, severe tenderness, and/or persistent fever. Results: A normal result means that no abnormal cells were detected. In some cases, analysis of the milk duct cells may reveal atypical changes but cannot pinpoint their exact origin in the breast. Not every woman with atypical breast cell changes will develop breast cancer. Experts
u Ductogram Category: Procedures Also known as: Mammary ductogram, galactogram, galactography, ductogalactography Definition: A ductogram is an imaging procedure that uses a radio-opaque contrast dye to enhance mammography pictures. A ductogram is used to help identify if cancer is present in the duct of the nipple, which transport breast milk in lactating women. Cancers diagnosed: Breast cancer, ductal carcinoma in situ (DCIS) Why performed: A ductogram is used to help determine the source of abnormal nipple discharge and the location of possible cancer. Cancer may cause abnormal nipple discharge. DCIS begins as cancer in the cells that line the ducts. The cancer may remain contained in the nipple or may spread to other parts of the breast. Standard mammography may show small areas of microcalcifications, calcium collections that can be a sign of DCIS. A ductogram creates even better pictures of the suspicious area. Patient preparation: The patient should not use deodorant or powder on the day of the ductogram. The patient should not express discharge from the nipple before the procedure but should let her doctor know if she does not experience nipple discharge on the day of the procedure. In such cases, the ductogram may need to be rescheduled. The patient should inform her doctor if she is pregnant so that a protective drape will be placed over the abdomen during the procedure. A ductogram is performed at the radiology department of a hospital or an outpatient radiology center. It is an outpatient procedure that lasts from thirty minutes to an hour. The patient disrobes from the waist up and wears an examination gown for the procedure. 389
Duke Comprehensive Cancer Center
Salem Health: Cancer
A doctor injects a contrast medium into the breast of a female patient. (©BSIP/Phototake—All rights reserved)
Steps of the procedure: The breast and nipple are cleansed before the procedure. The nipple is sterilized with alcohol. The radiologist identifies which duct is producing abnormal discharge by applying pressure to the nipple to elicit discharge. Local anesthesia may be applied before a blunt-tipped cannula, a small needlelike device, is inserted into the duct. A syringe attached to the cannula delivers the radiopaque contrast dye. The cannula is removed, and mammography images are taken. After the procedure: A bandage is placed over the nipple. Patients should drink plenty of fluids to help eliminate the dye from the body. Risks: A ductogram is a low-risk procedure, but pain, infection, or bleeding may occur. Results: A healthy nipple does not reveal abnormalities. Any abnormalities, such as possible cancer, are highlighted on ductogram images. Mary Car-Blanchard, O.T.D., B.S.O.T. See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Comedo 390
carcinomas; Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Nipple discharge.
u Duke Comprehensive Cancer
Center Category: Organizations Definition: The Duke Comprehensive Cancer Center in Durham, North Carolina, is one of thirty-nine cancer centers that have been designated as comprehensive cancer centers by the National Cancer Institute. U.S. News & World Report has ranked the center in the top ten cancer hospitals in the United States and named it the top cancer facility in the South. The center serves patients not only from North Carolina but also from throughout the nation and the world. More than 25,000 new patients are seen every year at the center.
Salem Health: Cancer Facilities: Established in 1972, the Duke Comprehensive Cancer Center is a part of a large teaching hospital. Many of the physicians and nursing staff are well known for their research and expertise. In 2006, the hospital treated 9,000 inpatients and 175,000 outpatients. Programs and areas of strength include breast and ovarian oncology, the Preston Robert Tisch Brain Tumor Center at Duke, stem cell transplantation, esophageal and lung cancer, melanoma, the Cancer Patient Support Program, and the Oncology Recreation Therapy Program. The center treats children and young adults through the Division of Pediatric Hematology-Oncology at Duke University Medical Center, and the center’s Hereditary Cancer Clinic focuses on genetic cancers. Specializations: The Duke Comprehensive Cancer Center treats a large variety of both primary and metastatic cancers, including head and neck cancers, digestive cancers, respiratory cancers, bone and soft tissue cancers, melanoma and other skin cancers, breast cancer, genitourinary cancers (both male and female), brain and central nervous system cancers, endocrine cancers, lymphomas, myeloma, and leukemia. Oncology services are linked with hematology, surgery, neurology, orthopedics, and women’s health clinics. The center serves cancer patients from diagnosis to treatment and through survivorship. It also provides patients and their families with numerous resources, including a large network of oncologists. Oncologists are located not only on the Duke Hospital campus but also throughout the network, which extends up into Virginia and as far south as Florida. On the main campus, patients are seen in various specialty clinics: a hematology oncology clinic, a surgical oncology clinic, a brain tumor center, and an adult bone marrow clinic. The patients visit the clinics from the beginning of diagnosis well into remission. Also on the main campus is the Oncology Treatment Room, which serves outpatient chemotherapy patients and has a pheresis division. The center’s cutting-edge radiation oncology department provides the latest and best equipment for cancer patients. The center has three inpatient units that care for patients who are not able to receive their therapy on an outpatient basis. The Duke Center for Fertility provides an invaluable resource in addressing fertility issues surrounding cancer treatment. With improved therapies, cancer patients are surviving longer, and some wish to have children after treatment. The Center for Integrative Medicine offers support of the cancer patient as a whole person. Integrative medicine
Duke Comprehensive Cancer Center takes into consideration not only a patient’s diagnosis and treatment but also the individual’s diet, exercise, and mental well-being. The patient’s well-being is, in fact, an important aspect of all care provided by the center. It offers support groups and special programs to guide patients through their treatment and help them adjust to survivorship. Programs include chemotherapy classes, wig and turban programs, and the Look Good, Feel Good program. Duke also provides a cancer treatment library to help patients and family learn more about the disease. Research: The center conducts research on a regular basis, including small and large clinical trials. All oncology departments are involved with some aspect of cancer research, which covers areas such as vaccines, immunotherapies, chemotherapies, and stem cell research. The center also participates in the Duke Tumor Registry, a statewide program to improve the detection and treatment of cancer. The registry gathers information relating to cancer prevention, diagnosis, and treatment. Katrina Green, R.N., B.S.N., O.C.N. u
For Further Information Laszlo, John, and Francis A. Neelson. The Doctor’s Doctor: A Biography of Eugene A. Stead, Jr., MD. Durham, N.C.: Carolina Academic Press, 2006. National Cancer Institute, Division of Cancer Research Resources and Centers. The Cancer Centers Program. Washington, D.C.: U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health, 1974.
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Other Resources
Duke Comprehensive Cancer Center http://www.cancer.duke.edu Duke Health System http://www.dukehealth.com National Comprehensive Cancer Network Duke Comprehensive Cancer Center http://www.nccn.org/members/profiles/duke.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic 391
Dukes’ classification
Salem Health: Cancer
Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Dukes’ classification Category: Procedures Definition: Dr. Cuthbert E. Dukes (1890-1977) was a pathologist who developed the classification for operable colon or rectal cancer. He began his studies at St. Mark’s Hospital in 1922 and published the Dukes’ classification in 1932. Through many years of examining the various clinical stages and prognoses of patients diagnosed with rectal cancer, he was able to develop a pathological classification system that reflected the prognosis based on three categories: A, B, and C. Dukes’ classification has been modified to include B1 and B2 as well as C1 and C2. Dr. Vernon Astler and Dr. Fredrick Coller later modified Dukes’ classification to include a fourth stage, D.
Dukes’ Stages Stage
Description
A B1 B2 C1 C2 D
Confined to the lining of the colon Into the thin muscle right below the lining Through the thin muscle right below the lining Limited to bowel wall, with lymph nodes affected Through the bowel wall, with lymph nodes affected Distant spread of cancer or inoperable cancer
Steps of the procedure: The patient will be positioned for comfort. If in the operating room, then the patient will be given general anesthesia. If a sample is to be taken by CTguided biopsy or colonoscopy, then the patient may be given medications to cause sleepiness and block any pain. Once the patient is positioned and medication is given, the entrance site for the biopsy is cleansed with an appropriate solution. The physician will obtain the biopsy and then place the sample either in a vial with a preservative or on a slide for viewing. The samples will then be sent to the pathologist so that diagnosis and classification can be done. After the procedure: The patient will be monitored after the procedure for signs of bleeding or pain for a couple of hours. A patient who has completely awakened from the medication-induced sleep and is able to tolerate fluids is able to be driven home by a friend or Five-Year family member.
Survival Rate (%)
Cancers diagnosed: Colorectal cancers Why performed: Patients diagnosed with cancer of the colon or rectum will have treatment and therapy guided by the Dukes’ classification system. Patients who have been classified as Stage A may receive more aggressive treatment; those patients classified as Stage D may receive only palliative treatment. Patient preparation: Dukes’ classification is used for a patient who has had a biopsy of the tumor. The biopsy may be obtained surgically or through colonoscopy or a CTguided biopsy. The patient will have nothing to eat or drink for at least eight hours before any of these proce392
dures. If the cancer is in the lower gastrointestinal (GI) tract, then the patient will have to complete a bowel prep, which includes drinking a liquid to cause the stool in the GI tract to be evacuated. If the biopsy will be taken surgically, then the patient may have the skin shaved at the incision site.
97 80 80 65 35 5
Risks: Infections, pain, and bleeding are all risks of obtaining a biopsy for Dukes’ classification.
Results: Dukes’ classification is based on the pathology of the cancer. A patient will have a biopsy of the disease site and the pathologist will be able to stage the disease based on the defined classification stage. A better prognosis, or five-year survival rate, is directly related to the stage of the disease of the patient. Stage A indicates minimal disease and a high five-year survival rate. Stages B and C indicate that the disease has progressed into the surrounding tissue and the survival rate is decreased. Stage D indicates that the disease has spread, or metastasized, to another site. Stage D is directly related to a poor prognosis or poor chance of fiveyear survival rate. Katrina Green, R.N., B.S.N., O.C.N. See also ABCD; Breslow’s staging; Carcinomas; Gleason grading system; Grading of tumors; Staging of cancer; TNM staging.
Salem Health: Cancer
u Duodenal carcinomas Category: Diseases, symptoms, and conditions Also known as: Small intestine cancer Related conditions: Crohn disease, celiac disease, colon polyps Definition: Duodenal carcinoma is a cancer of the duodenum, the first (upper) part of the small intestine. Risk factors: Risk factors include Crohn disease, celiac disease, familial adenomatous polyposis (FAP), exposure to radiation, smoking, alcohol consumption, and a diet high in fats or high in salted, pickled, or smoked foods. Etiology and the disease process: Genetic disposition, environmental exposures, and lifestyle are all potential root causes of duodenal carcinoma. The duodenum is the first part of the small bowel that is exposed to ingested
Duodenal carcinomas chemicals that may be carcinogenic and to pancreatic biliary juices that may also be carcinogens. There are five types of small intestine cancers (adenocarcinoma, sarcoma, carcinoid tumors, gastrointestinal stromal tumors, and lymphoma). The most common type of duoendal carcinoma is adenocarcinoma. Incidence: Duodenal carcinoma is a relatively rare cancer that makes up less than 1 percent of gastrointestinal cancers. Symptoms: The symptoms of duodenal carcinoma may include abdominal pain, weight loss, bloating, cramping, blood in stools, and less commonly anemia and jaundice. Screening and diagnosis: There may be a considerable amount of time between the identification of nonspecific symptoms (such as abdominal pain and bloating) and the diagnosis of duodenal carcinoma. A physical exam, medical history, X rays of the abdomen, abdominal ultrasound, a barium contrast study, and an upper gastrointestinal series may be used in the diagnosis. Small intestine adenocarcinomas are staged beginning with adenocarcinoma in situ, Stage I (the cancer has invaded the connective tissue or muscular layer of the bowel), Stage II, Stage III (the cancer has spread to regional lymph nodes), and Stage IV (the cancer has spread to distant organs). Treatment and therapy: Surgery is the usual treatment, but surgical removal of a duodenal tumor can be difficult because of the area in which it is located. Surgery to bypass the area of the tumor (connecting the stomach to an area of the intestine beyond the mass) is sometimes necessary. Chemotherapy and radiation therapy are sometimes used to try to shrink the cancer or if the cancer has spread. Prognosis, prevention, and outcomes: Individuals with duodenal carcinoma should be monitored after treatment for signs and symptoms of recurrence and should have abdominal computed tomography (CT) scans every six months. Vicki Miskovsky, B.S., R.D. See also Cholecystectomy; Gallbladder cancer; Gastric polyps; Gastrinomas; Gastrointestinal cancers; Gastrointestinal oncology; Multiple endocrine neoplasia type 1 (MEN 1); Pancreatitis; Percutaneous transhepatic cholangiography (PTHC); Small intestine cancer; Upper gastrointestinal (GI) endoscopy; Upper gastrointestinal (GI) series; Zollinger-Ellison syndrome.
A tumor on the wall of the duodenum. (©MedicalRF.com/Corbis)
393
Dysplastic nevus syndrome
u Dysplastic nevus syndrome Category: Diseases, symptoms, and conditions Also known as: Atypical mole syndrome, dysplastic mole, Clark’s nevus Related conditions: Malignant melanoma, familial atypical mole and melanoma (FAMM) syndrome Definition: Dysplastic nevus syndrome is a skin condition characterized by the presence of numerous atypical nevi, or moles. Risk factors: White men and women with light-colored hair and freckled skin are believed to be at high risk for dysplastic nevi, especially with excessive sun exposure. Dysplastic nevi are strongly linked to melanoma: The presence of the former may signify an increased risk for developing the latter. Individuals with a family history of dysplastic nevi, with numerous dysplastic nevi on their bodies, and with at least two family members diagnosed with melanoma, are almost certain to develop melanoma. This is called familial atypical mole and melanoma (FAMM) syndrome. Etiology and the disease process: Dysplastic nevi are abnormally growing moles. Whether ultraviolet exposure plays a significant role in their development is still a subject for debate. Dysplastic nevi are, however, associated with frequent and severe sunburns, a family history of dysplastic nevi, and weakened immunity (for example, due to cancer chemotherapy). Incidence: In the United States, dysplastic nevi are present in 2 to 5 percent of the white population. In other countries, such as Australia, New Zealand, Germany, and Sweden, dysplastic nevi are clinically diagnosed in as much as
394
Salem Health: Cancer 18 percent of the adult white population. This condition rarely occurs in individuals of Middle Eastern, black, or Asian descent. No gender predilection exists; the condition may start manifesting as early as childhood. Symptoms: Unlike common moles, atypical nevi are asymmetrical; have uneven shades of tan, brown, red, or pink; have irregular borders; and are greater than 5 millimeters in diameter. Atypical moles are frequently found on the back, chest, abdomen, scalp, arms, or legs, but they can sometimes arise on unexposed areas such as the breasts or buttocks. Screening and diagnosis: A thorough examination of the patient’s skin surface and a detailed family history are important in screening for dysplastic nevi. An excisional biopsy and histological analysis of the tissue sample will differentiate between dysplastic nevi and malignant melanoma. Treatment and therapy: There is no definitive treatment for dysplastic nevi. Surgical removal of dysplastic moles does not guarantee against the development of melanoma. Prognosis, prevention, and outcomes: Individuals with dysplastic nevi syndrome should avoid prolonged sun exposure without sunscreen protection. Regular skin examinations will help monitor for any suspicious changes in dysplastic nevi. Ophelia Panganiban, B.S. See also Carney complex; Choriocarcinomas; Craniosynostosis; Gestational trophoblastic tumors (GTTs); Hereditary cancer syndromes; Human chorionic gonadotropin (HCG); Hydatidiform mole; Melanomas; Moles; Sjögren syndrome; Skin cancers.
Salem Health: Cancer
u Edema Category: Diseases, symptoms, and conditions Also known as: Lymphedema, fluid retention Related conditions: Cancers of the breast, colon, ovary, uterus, and testicles Definition: Edema, known as fluid retention, results from the accumulation of fluid in certain tissues, leading to swelling. In lymphedema, lymph (a fluid containing a high amount of lymphocytes, or white blood cells) accumulates in tissues because the excess fluid and proteins cannot be returned into the circulation. Edema can result in decreased mobility of the affected limb, as well as pain, risk of infection, and poorer quality of life. Risk factors: The main risk factor for edema is surgery for breast and other cancers in which removal of the primary tumor may lead to removal of nearby lymph nodes. Etiology and the disease process: Cancer-related edema either is caused directly by the cancer or is a result of treatment. In some cases, cancer cells may build up in the neighboring lymph nodes, blocking the flow of the lymphatic fluid. Cancer patients may also have poor nutritional intake, in part because of loss of appetite and metabolic disorders, and their bodies may not have sufficient amounts of protein to function normally. If the kidneys are impaired, they will not be able to properly rid the body of salt through the urine. This leads to an increased amount of salt in the body, causing water to be retained and leading to edema. Edema can also be the result of the drugs that cancer patients receive. Chemotherapy drugs associated with an increased risk of edema include cyclosporine, docetaxel, gemcitabine, imatinib, and thalidomide. Additional anticancer agents known to cause edema include corticosteroids, anabolic steroids, progestins, and nonsteroidal anti-inflammatory agents. In addition, some treatments may directly affect the lymphatic system. For example, in breast cancer patients, the neighboring axillary lymph nodes may be affected either by targeted radiation therapy or surgical removal (known as node dissection). Disrupting the lymphatic system is a cause of lymphedema. Incidence: Edema in the arm is a common side effect in breast cancer patients, especially if they have received radiation therapy or had a lymph node removed. The reported incidence depends on the type of breast cancer therapy administered and the time since treatment. Based on an analysis of multiple studies in which women received a variety of surgical procedures and adjuvant therapies, it is
Edema estimated that approximately 1 in 4 women may develop arm edema after treatment for breast cancer. Moreover, the frequency of lymphedema rises over time since treatment. Symptoms: The symptom of edema is swelling of the limbs. Screening and diagnosis: Edema may be diagnosed by measuring limbs; a difference of more than 2 centimeters between the circumference of the normal and affected limbs would indicate edema. Bioelectrical impedance (to quantify the fluid accumulation) and lymphoscintigraphy (to visualize the lymphatic system) may also be used. Treatment and therapy: Treatment for edema can be broken down into three categories: diet, supportive therapy, and pharmacological therapy. Reducing the amount of dietary salt consumed may help to manage edema. Patients should avoid foods that are high in salt or sodium, including canned soups, canned or processed meats, prepared mixes and foods (including frozen dinners and fast foods), snack foods (pretzels, potato chips, olives, cheeses, pickles), and high-salt seasonings (bouillon cubes, seasoned salts, soy sauce, Worcestershire sauce, and premixed spice packets). Supportive therapies are also important in treating edema. Elevating affected limbs above the heart may help reduce swelling. Other strategies include wearing elastic compression stockings or sleeves, which help to return the excess fluid into the circulation. Massage, compression pumps, and specialized physical therapy and exercise regimens may also be effective. Less frequently used methods include electrically stimulated lymphatic drainage (such as uniform or sequential compression with either pneumatic or hydrostatic pressure devices) and surgery (such as surgical excision of the affected area, insertion of a lymphatic-venous shunt, or liposuction). Diuretics are a commonly prescribed medication to reduce edema, since they inhibit the ability of the kidneys to reabsorb and retain salt, leading to the elimination of more salt and water in the urine. Loop diuretics, named because they target the loop of Henle within the kidney tubules, include furosemide (Lasix), torsemide (Demedex), and butethamide (Bumex). Thiazide diuretics may also be used, but they may cause potassium to be excreted in the urine. Potassium-sparing diuretics include spironolactone (Aldactone), triamterene (Dyrenium), and amiloride (Midamor). Elizabeth A. Manning, Ph.D. 395
Elderly and cancer u For Further Information Bourgeois, P., O. Leduc, and A. Leduc. “Imaging Techniques in the Management and Prevention of Posttherapeutic Upper Limb Edemas.” Cancer 83 (December 15, 1998): 2805-2813. Cohen, S. R., D. K. Payne, and R. S. Tunkel. “Lymphedema: Strategies for Management.” Cancer 92 (August 15, 2001): 980-987. Erickson, V. S., et al. “Arm Edema in Breast Cancer Patients.” Journal of the National Cancer Institute 93, no. 2 (January 17, 2001): 96-111. Mortimer, P. S. “The Pathophysiology of Lymphedema.” Cancer 83 (1998): 2798-2802. Petrek, J. A., P. I. Pressman, and R. A. Smith. “Lymphedema: Current Issues in Research and Management.” CA: A Cancer Journal for Clinicians 50, no. 5 (September/October, 2000): 292-307. u
Other Resources
Huntsman Cancer Institute Edema http://www.hci.utah.edu/patientdocs/hci/ drug_side_effects/edema.html MedicineNet.com Edema http://www.medicinenet.com/edema/article.htm National Cancer Institute Lymphedema http://www.cancer.gov/cancertopics/pdq/ supportivecare/lymphedema/healthprofessional See also Beckwith-Wiedemann syndrome (BWS); Lymphangiosarcomas; Lymphedema; Magnetic resonance imaging (MRI); Mastectomy; Nephroblastomas; Rhabdomyosarcomas.
u Elderly and cancer Category: Social and personal issues Definition: The risk of cancer increases with age. The National Cancer Institute (NCI) reports that 60 percent of new cases of cancer are diagnosed in those over the age of sixty-five. No definitive answer is found among the various theories for the increased risk. Possible connections include a reduced ability of the immune system to fight disease, increased vulnerability to toxic substances that alter deoxyribonucleic acid (DNA), and the cumulative effect of exposure to carcinogens over time. Managing can396
Salem Health: Cancer cer as a chronic disease, with attention to long-term survivor needs, helps this age group maintain a good quality of life. The physical, psychological, emotional, spiritual, social, and financial aspects of living with cancer require multiple tools and resources for individuals and caregivers coping with a malignant condition. Description of the population: In 2005, there were 36.8 million people aged sixty-five or older, representing 12.4 percent of the United States population. This was an increase of 3.2 million, or 9.4 percent, from 1995. The population under the age of sixty-five increased 13.3 percent during this same time period. However, the group aged forty-five to sixty-four increased by 40 percent, illustrating the exponential growth of the elderly population that will continue. There were 21.4 million older women compared with 15.4 million older men in 2005, a ratio of 139 women for every 100 men. This ratio increases with age because women live longer than men. The population as a whole is living longer. The group of people age eighty-five and up was forty-two times larger in 2005 than that same age group in 1900. According to the U.S. Census Bureau, the elderly population is expected to more than double by 2050, representing 1 out of every 5 people in the United States. Numbers will continue to grow as life expectancy improves and as advances in science are made that lead to improved treatments for cancer and higher survival rates. The elderly population is vulnerable to depression and a cancer diagnosis may worsen it. The loss of a spouse and deaths of friends create feelings of isolation and despair. They may face pressure to leave a long established residence or need to enter an assisted living facility or nursing home. Financial burdens from living on a fixed income and dwindling resources is another stressor. Visual and auditory deficits strain communication and may necessitate giving up hallmarks of independence such as driving. Coping skills are taxed with advancing age, especially when a person is faced with a new diagnosis of cancer or a recurrence after a period of remission. Medicare reimbursement for cancer treatments and supportive medications is driven by policy changes and may become insufficient over time. Homelessness among the elderly is not uncommon and may prevent early diagnosis of cancer from lack of health care access. Incidence, death, and survival statistics: The probability of developing an invasive cancer at the age of seventy or older is 1 out of 3 for men and 1 out of 4 for women. From ages sixty to sixty-nine, it is 1 in 6 for men and 1 in 9 for women. The elderly are ten times more likely to get cancer and fifteen times more likely to die from cancer than people under the age of sixty-five, according to the
Salem Health: Cancer
Elderly and cancer
Cancer is more common among those aged sixty-five and over, possibly because of a weaker immune system, increased vulnerability to substances that alter DNA, free-radical cell damage with time, and the cumulative effect of carcinogen exposure. (Digital Stock)
NCI. Some 70 percent of deaths from cancer occur in this age group. Reasons for increased mortality may be affected by less aggressive treatment, a delay in diagnosis and start of treatment, a personal choice to decline treatment, and the impact of other health problems on the cancer. Cancers linked to aging and common in the elderly include bladder, breast, colon, lung, pancreas, prostate, rectal, stomach, and acute myelogenous leukemia (AML), a cancer of the blood. Approximately one-third of nonHodgkin lymphomas are diagnosed in individuals over seventy years old. The average age for developing colorectal cancer is seventy-one according to the NCI. Risk and prevention: People aged fifty-five and older account for approximately 75 percent of cancer diagnoses. The majority of breast cancers occur after age fifty, with the highest incidence in those between the ages of seventyfive and seventy-nine. For women with ovarian cancer, survival is twice as likely in those under the age of sixty-
five as in those sixty-five and older. The majority of people with lung cancer are at least seventy years old at diagnosis. Older patients diagnosed with AML are less likely to achieve remission after treatment than younger ones. When elderly people think that their symptoms are related to aging, they may ignore the signs and delay consultation with a physician. The prevention of cancer in the elderly is much the same as in people of any age. Eating a low-fat, high-fiber diet; exercising; avoiding excessive use of alcohol; and limiting exposure to chemicals and radiation are ways to help reduce the risk of cancer. Cancer screening should continue throughout the life span, although there is disagreement among experts about screening frequency and situations in which it is reasonable to discontinue screening for certain cancers. Treatment considerations: Age is not the only factor used to decide whether aggressive treatment should be pursued. The functional status of older patients indicates 397
Elderly and cancer their ability to tolerate and respond to therapy. Treatment options may be limited by existing health problems such as hypertension and heart disease, which reduce tolerance to therapies. Drugs and chemotherapy agents may interact with medications taken for other conditions. Cognitive impairment caused by dementia or slowing mental processes compounds the side effects of medications such as opioids for pain, which cause somnolence. The normal effects of aging may alter or slow the way the body metabolizes drugs, increasing toxicities from treatment or reducing efficacy. Bias and stereotypes regarding the elderly may impede full recovery after treatment. For example, sexuality does not necessarily diminish in the elderly, but because many assume the loss of libido, subsequent problems with intimacy after treatment may not be adequately assessed. Another assumption is that a cancer diagnosis is less devastating for an older person than for someone younger because the older person is closer to the end of life. However, the majority of older adults are active and independent, with the potential to enjoy years of life despite cancer. Autonomy is preserved when the elderly learn everything possible about their diagnosis and prognosis, use providers trained in geriatrics, and obtain second opinions before choosing among treatments that include chemotherapy, radiation, immunotherapy, investigational agents, watchful waiting, palliative care, and hospice care. Perspective and prospects: Scientific data are used to determine appropriate treatment for a particular cancer and are based on the stage of the cancer, its potential for growth, and the order of administration when more than one therapy or regimen is employed. More clinical trials, with a design that accommodates participation of older people, are needed to enhance knowledge about cancer in the elderly and identify the best interventions for this age group. Cancer survivors benefit from a comprehensive plan that facilitates a return to a functional state after treatment. The education and training of health care providers in the specialty of geriatrics promotes the well-being and longevity of this population. Individuals of advanced age who live with cancer understand the unique challenges better than anyone and, as proponents of change, accelerate the gains in cancer management and treatment. Selfadvocacy by the elderly is made easier by availability of cancer resources in communities and on the Internet. For example, online cancer support groups provide an alternative for those who are homebound, and pharmaceutical companies have programs that furnish medication at no cost or at a discount. Linda August Vrooman, R.N., B.S.N., O.C.N. 398
Salem Health: Cancer u
For Further Information Beers, Mark H., and Robert Berkow. Merck Manual of Geriatrics. Rahway, N.J.: Merck Sharp & Dohme Research Laboratories, 2000. Hunter, Carrie P., Karen A. Johnson, and Hyman B. Muss. Cancer in the Elderly. New York: Marcel Dekker, 2000. Lichtman, M., et al. “International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients—An Analysis of the Medical Literature.” Journal of Clinical Oncology 25, no. 14 (May 10, 2007): 1832-1843.
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Other Resources
Administration on Aging Statistics on the Aging Population http://www.aoa.gov/prof/Statistics/statistics.asp Association of Cancer Online Resources http://www.acor.org Cancer Survival Toolbox Pain and the Elderly http://www.canceradvocacy.org/resources/ treatment-issues/pain/elderly.html Caring Connections http://www.caringinfo.org Federal and State Agencies for Seniors http://www.usa.gov/Topics/Seniors/ FederalState.shtml Foundation for Health in Aging http://www.healthinaging.org/public_education/ eldercare Gerontological Society of America http://www.geron.org National Institute on Aging http://www.nia.nih.gov See also Aging and cancer; Counseling for cancer patients and survivors; End-of-life care; Free radicals; Genetics of cancer; Home health services; Hospice care; Living with cancer; Long-distance caregiving; Medicare and cancer; Nutrition and cancer prevention; Occupational therapy; Overtreatment; Pain management medications; Palliative treatment; Psycho-oncology; Self-image and body image; Side effects; Social Security Disability Insurance (SSDI); Stress management; Support groups; Survival rates; Symptoms and cancer; Watchful waiting.
Salem Health: Cancer
Electromagnetic radiation
u Electrolarynx
u Electromagnetic radiation
Category: Social and personal issues Also known as: Artificial or mechanical larynx, AE or EL, throat back
Category: Carcinogens and suspected carcinogens RoC status: Solar radiation, exposure to sunlamps or sunbeds, known human carcinogens since 2000; broad-spectrum ultraviolet radiation (UVR), known human carcinogen since 2002; ultraviolet A, B, and C (UVA, UVB, UVC), reasonably anticipated human carcinogens since 2002; X radiation, gamma radiation, known human carcinogens since 2004 Also known as: EM radiation, EMR
Definition: The electrolarynx is an electronic device that allows a person with laryngeal cancer to communicate after having the larynx or voice box surgically removed. Communication after a laryngectomy: Laryngeal cancer can affect various places in the voice box, or larynx. One treatment is partial or total surgical removal of the larynx (laryngectomy). This leaves the patient without the capacity for speech and voice communication. Written communication is effective but may prove frustrating for patients. One option available for these patients is the electrolarynx, an electromechanical medical device used to make vibration to produce sound that the patient can form into words with the tongue, lips, teeth, and cheeks. Types of electrolarynx devices: Basically two devices for speech are available after loss of the voice to cancer. One is the battery-powered machine that is placed against the patient’s throat. The patient pushes a button and the device transmits vibrations that can be formed into words. In the second type, a small tube in the mouth receives vibrations directly into the mouth, with words made in a similar way. Charges for an electrolarynx can vary from $200 to $800, depending on the brand, model, and accessories. Both private insurance and Medicare may cover all or part of the costs. Some states provide these free of charge; these states include California, Georgia, Massachusetts, Kansas, North Carolina, South Carolina, and Texas. Enhancing communication: The patient using an electrolarynx can make communication easier by controlling the environment. When the patient talks to someone, it helps for both people to look at each other and remain in the same room or area, as part of successful communication is visual. Choosing an area without distracting background noise such as a television also helps. The patient can also use nonverbal communication, such as nodding or shaking the head, and can exaggerate consonants and prolong vowels to produce intelligible speech. Carrying a pen and paper as a backup may ease frustration. Marylane Wade Koch, M.S.N., R.N. See also Cordectomy; Esophageal speech; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy; Throat cancer; Tracheostomy.
Related cancers: Skin cancers, especially melanoma; leukemia Definition: Electromagnetic radiation is a form of energy, composed of individual oscillating photons. The amount of energy carried by each photon is proportional to its frequency. The collection of all possible frequencies of electromagnetic radiation is called the electromagnetic spectrum; this is subdivided (from highest to lowest frequency) into gamma rays, X rays, ultraviolet (UV) light, visible light, infrared light, microwaves, and radio waves. Alternatively, electromagnetic radiation can be divided into ionizing and nonionizing frequencies based on its ability to disrupt electrons. Exposure routes: Unshielded incident radiation Where found: Electromagnetic radiation is pervasive, and life would not be possible without it. Sunlight is the most important source of ultraviolet and visible light. Many devices also emit electromagnetic radiation. At risk: Individuals with occupational or volitional exposure to ionizing electromagnetic radiation Etiology and symptoms of associated cancers: When electromagnetic radiation interacts with matter, some of the photons’ energy alters the structure or increases the kinetic energy of atoms. Structural alterations include ionization (loss of electrons) and breakage of covalent bonds. Deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins are all susceptible to damage by radiation. The skin is the primary carcinogenic target, and UVcaused skin cancers occur mostly on sun-exposed areas. Shorter wavelength electromagnetic radiation such as X rays and gamma rays penetrate the skin and can cause leukemia, lung cancer, and bone cancer. The interaction of electromagnetic radiation with DNA results in abnormal dimerization of adjacent pyrimidine bases, damage to individual bases, strand breakage, and cross-linkages between DNA and adjacent proteins. Such DNA damage contributes to cancer formation through the release of cy399
Electroporation therapy
Salem Health: Cancer
In this experiment, rats are exposed to electromagnetic fields to determine if they cause cancer. (Mauro Fermariello/Photo Researchers, Inc.)
tokines, induction of latent viruses, or mutations that cause functional changes in encoded protein molecules. History: The biological effects of electromagnetic radiation in the form of sunlight have been known since antiquity. The understanding of visible light as part of a continuous spectrum was advanced with the discovery of radio waves in 1887 by Heinrich Hertz and of X rays in 1895 by Wilhelm Conrad Röntgen. One of the first publications on the carcinogenicity of sunlight appeared in 1907, and a causal relationship was demonstrated by study in a 1928 publication that involved induction of skin cancer in mice by exposure to ultraviolet light. Cancers were linked to penetrating electromagnetic radiation (X rays and gamma rays) shortly after the isolation and characterization of radioactive isotopes in the 1800’s. John B. Welsh, M.D., Ph.D. See also Cell phones; Occupational exposures and cancer; Risks for cancer; Skin cancers; Sunlamps; Sunscreens; Ultraviolet radiation and related exposures; X-ray tests. 400
u Electroporation therapy Category: Procedures; complementary and alternative therapies Also known as: EPT Definition: Electroporation therapy is a process that uses high-intensity electrical currents that increase the permeability of cell membranes and enhance the ability of cytotoxic drugs, vaccines, and genes to enter into tumor cells. Cancers treated: Squamous cell carcinoma, basal cell carcinoma, melanoma, head and neck cancers, cutaneous and subcutaneous tumors, Kaposi sarcoma Delivery routes: Electrical pulses are delivered directly into tumors using special devices called electroporators or applicators. Description: Many potentially effective anticancer drugs are limited by their ability to permeate the cell membranes and gain entry into tumor cells. The lipid bilayers of cell
Salem Health: Cancer membranes possess unique physical and biochemical properties that prevent easy entry of exogenous materials. The principle of electroporation therapy is to increase permeability of the cell membranes by pulses of intense electric current, leading to formation of transient pores in the cell membrane. Pores aid in easy uptake of cytotoxic drugs and increase the intracellular drug concentration, thereby increasing their chances of direct action on tumor cells. An electroporator consists of a circular array of six electrode needles (as three pairs) that deliver pulses directly inside tumors and create an electric field through potential differences generated between these electrodes. Effective electroporation depends on strength and duration of the applied electric field. Optimization is required for each type of tissue and the kind of molecule being delivered (for example drug vs. deoxyribonucleic acid, or DNA). Application of short pulses of electric field results in the transient formation of pores on the cell membrane. Pores close shortly after the application of electric field is terminated, resulting in almost an entrapment of drugs or other molecules. Electroporation therapy results in enhanced killing of cancer cells and early necrosis of tumors. Clinical trials on squamous cell carcinoma patients that incorporated a treatment regimen with the drug bleomycin (a cytotoxic drug derived from the bacterium Streptomyces verticillus) followed by electroporation, demonstrated complete remission in a significant proportion of patients and partial remission in others. Combination therapy with bleomycin and electroporation was more effective than either treatment alone. Bleomycin in combination with electroporation dramatically enhanced the percentage of cells killed. Among the multitudes of drugs tested in combination with electroporation, bleomycin has been proven to be the most effective. Combined therapy also increases the duration of drug retention and decreases the dose of drug needed for effective treatment. Side effects: Minimal side effects have been observed with electroporation therapy. Some electric shocks can be experienced after administration of electric pulses. Geetha Yadav, Ph.D. See also Basal cell carcinomas; Electrosurgery; Kaposi sarcoma; Melanomas; Skin cancers; Squamous cell carcinomas.
Electrosurgery
u Electrosurgery Category: Procedures Also known as: Electrofulguration, fulguration, medical diathermy, surgical diathermy Definition: Electrosurgery is the use of electric current to cut, kill tumor cells, or cauterize. Cancers treated: A variety of cancers, especially those of the skin and mouth Why performed: Surgeons have many options for removing cancerous growths or tumors. The most traditional method is to use a sharp metal scalpel to cut around the tumor and remove it. This is frequently the method in which surgeons were originally trained and with which they have the most experience. It also is often the most cost effective. There is often significant bleeding during and after this type of procedure, however, and research scientists are always trying to identify new ways to better serve patients. One way that has been developed involves the use of a laser, while another is electrosurgery. Electrosurgery uses an instrument that gives off high-frequency alternating electrical current that heats up cells and allows surgeons to cut with a reduced amount of bleeding. The same equipment can also be used for electrocautery to stop bleeding. Patient preparation: The required patient preparation depends on the type of electrosurgery being done, as well as on the extent of the procedure. In many cases, the patient will be instructed to prepare in a way similar to preparations for other types of surgeries. This can include avoiding food and liquids for a specified period of time and may involve taking antibiotics to help prevent infection. Patients will generally be specially screened to ensure that they are good candidates for electrosurgery. Individuals with pacemakers or other devices may not be appropriate candidates because of the use of electrical current that flows through the patient’s body during the procedure. Steps of the procedure: Electrosurgery is performed by a surgeon who has had extensive specialized training in using electrosurgical equipment and performing related procedures. The procedure is done using a special generator that takes regular electric current and converts it to electrical current that alternates at a frequency slightly lower than that of AM radio stations. This is done because the electrical current in normal use would result in damage to the patient, including possible nerve or muscle damage and even electrocution. Electrical current of the frequency 401
Embolization used by electrosurgical devices is usually considered safe for most individuals, except for those with pacemakers or other implanted devices. The surgeon uses a special instrument through which the electrical current flows. The surgeon has a number of choices of voltage and frequency, which can be used to achieve various effects, and will usually start with the lowest possible power and increase it until the desired effect is achieved. The tip of the surgical instrument remains cool, but the energy is transferred to the surrounding cells. At low levels, this can cause water to leave the cells and the cells to dehydrate and shrivel. At higher levels, the water inside the cells actually heats enough to boil, but so quickly that it does not have time to escape the cell and the cell actually ruptures. The surgeon can use this instrument to make very thin and precise cuts, to heat tumors to destroy them, or to cauterize cells to stop bleeding, depending on the goal of the procedure. After the procedure: After electrosurgery, the patient will generally be taken to a recovery room if the procedure was performed under general anesthesia. If there is a wound at an incision site, then it will need to be cleaned and cared for regularly until healing is complete. In many cases, electrosurgery is not the only cancer treatment option being used in a patient’s comprehensive cancer care plan. If electrosurgery is used to remove a cancerous growth, then radiation therapy or chemotherapy may still be necessary to kill any cancer cells that remain after the majority are removed surgically. Risks: Many of the risks associated with electrosurgery are the same or similar to those associated with traditional surgical methods. There is a risk of significant blood loss, pain, swelling, and infection. With electrosurgery, there is also some risk of damage to healthy tissues surrounding the cancerous tissue. Because electrosurgery is usually performed under general anesthesia, there are also the risks associated with anesthesia, such as negative cardiovascular events or allergic reaction. There is some risk of severe burning at a site other than the site of the electrosurgery. Often, smoke is produced during electrosurgery that can be a risk not only to the patient but also to the surgery team if the room is not effectively ventilated. Results: Results from electrosurgery can vary greatly depending on the type of procedure performed, the area on which the procedure was performed, and other factors. In general, it is believed that electrosurgery can be an effective method for removing tumors or for destroying cancerous growths with less blood loss than traditional surgical methods. For some applications, however, there is concern 402
Salem Health: Cancer that electrosurgical techniques may lead to a higher rate of recurrence than other available techniques. Helen Davidson, B.A. u
For Further Information Dietel, M., ed. Targeted Therapies in Cancer. New York: Springer, 2007. Egan, Tracie. Skin Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen Publishing Group, 2006. Lyons, Lyman. Diagnosis and Treatment of Cancer. New York: Chelsea House, 2007. Nathan, David G. The Cancer Treatment Revolution: How Smart Drugs and Other New Therapies Are Renewing Our Hope and Changing the Face of Medicine. Hoboken, N.J.: John Wiley & Sons, 2007. See also Electroporation therapy; Skin cancers; Urinary system cancers.
u Embolization Category: Procedures Also known as: Vascular embolotherapy; transcatheter embolization; vascular occlusion Definition: Embolization introduces an agent into the bloodstream to occlude or block a blood vessel that supplies a tumor or organ. This procedure is minimally invasive and can be an alternative to surgery. Cancers treated: Hepatic (liver) cancer and hepatic metastases; colorectal, pancreatic, and renal (kidney) cancers Why performed: The purpose of embolization is to shrink a tumor or slow its growth, to redirect blood flow, or to control bleeding. For example, preoperative embolization can reduce blood loss in a subsequent operation, such as liver resection (surgical removal of part of the liver) or nephrectomy (removal of a kidney). Occlusion of blood vessels of the liver to shrink hepatic metastases (cancer that has spread from other parts of the body) is an alternative to surgery when an existing condition, such as cirrhosis, precludes resection. Embolization can be combined with chemotherapy in a procedure called chemoembolization. It involves introducing a chemotherapeutic drug at the tumor site to enhance local concentration of the drug, thereby avoiding systemic side effects. The blood vessel supplying the tumor is then occluded with an embolic agent. In addition, embolization is an alternative to fibroidectomy (removal of uterine fibroids).
Salem Health: Cancer Patient preparation: A physician may order diagnostic images based on ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), or X rays to assess the involved organ or site and size of a tumor. In addition, diagnostic tests may be ordered to evaluate the patient’s blood and liver and kidney function. Prior to the embolization procedure, the patient is asked about the use of drugs and herbal supplements and about any allergies, such as to contrast media used in imaging. The night before the procedure, the patient may need to abstain from food and liquid for several hours. Steps of the procedure: A radiologist or other specially trained physician performs the procedure in an interventional suite or, perhaps, in an operating room. A nurse or anesthesiologist sedates the patient and, in some cases, administers general anesthesia. A small incision is made to insert a catheter through the skin into a blood vessel, such as the femoral artery of the leg. The physician threads the catheter through the blood vessel toward the organ or tumor site. A contrast medium or dye is injected into the blood so that angiographic images of the blood vessels can guide the radiologist’s progressive threading of the catheter. Sometimes the doctor replaces the initial catheter with a smaller one to move into smaller, branching blood vessels. When the site is reached, the physician introduces or injects an embolic agent via the catheter and then observes the resulting obstruction of blood flow on a video monitor. Embolic agents can be temporary or permanent. They include metallic coils, gelatin sponge particles or foam, polyvinyl alcohol foam granules, acrylic polymer microspheres, and liquid adhesive (glue). If additional blood vessels need to be embolized, then the physician repeats the process. Embolization can take about thirty minutes to complete, but it may take several hours. At the end of the procedure, the catheter is withdrawn and pressure is applied to the initial incision. After the procedure: The patient rests horizontally for several hours and usually stays one or more nights in the hospital, mainly for pain control. Some patients experience postembolization syndrome (pain, fever, nausea, vomiting, and fatigue) for a few days or weeks. These symptoms are more likely after embolization of a solid tumor. Many patients resume normal activity within a week. The physician may order follow-up imaging studies to assess the effects of embolization. Sometimes the patient undergoes an operation after the procedure. Risks: The risks associated with embolization are small when compared to surgery. A few patients, however, may be allergic to the contrast material used for angiography
Embryonal cell cancer during the procedure. In general, the use of catheters can bruise or damage blood vessels and can introduce infection. If the embolus (plug) occludes the wrong blood vessel, then an unintended interruption of blood flow can damage normal tissue. Results: Successful embolization alleviates the patient’s symptoms and may extend survival time. In some cases, diverting blood deliberately causes hypertrophy (increase in size) of part of the liver, thereby enabling surgery on what was previously an unresectable liver. If embolization is meant to reduce the size of a bulky tumor, then the associated pain becomes more manageable. Tanja Bekhuis, Ph.D. u
For Further Information Cahill, Bridget A. “Management of Patients Who Have Undergone Hepatic Artery Chemoembolization.” Clinical Journal of Oncology Nursing 9, no. 1 (2005): 69-75. “Interventional Radiology for the Cancer Patient.” In Cancer Medicine, edited by Donald W. Kufe et al. 6th ed. Hamilton, Ont.: BC Decker, 2003. Also available online at http://www.ncbi.nlm.nih.gov/books.
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Other Resources
RadiologyInfo http://www.radiologyinfo.org Society of Interventional Radiology Http://www.sirweb.org Web MD Embolization: Vascular Lesions http://www.emedicine.com See also Arterial embolization; Carcinoid tumors and carcinoid syndrome; Chemoembolization; Hemoptysis; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Leiomyomas; Liver cancers; Urinary system cancers; Virus-related cancers.
u Embryonal cell cancer Category: Diseases, symptoms, and conditions Also known as: Embryonal cancer Related conditions: Testicular cancer, germ-cell tumor Definition: Embryonal cell cancer is a malignant germcell tumor that occurs most often in the testes and accounts 403
End-of-life care for about 40 percent of testicular tumors. Under the microscope, these tumors may resemble tissues of early embryos. This type of tumor can grow rapidly and spread outside the testicle. Risk factors: Birth defects such as male infants with undescended testis (chryptorchidism) can lead to embryonal cancer. Etiology and the disease process: Embryonic cells grow in the embryo, and some develop into germ cells that make up the reproductive system in men and women. These embryonic germ cells follow a midline path through the body after development and descend into the pelvis as ovarian cells or into the scrotal sac as testicular cells. Embryonal cell cancer results when the reproductive germ cell develops abnormally into cancerous cells. Differing from the other types of testicular cancers, embryonal carcinoma can have several of the properties of an abnormally developed fetus. Incidence: Embryonal cell cancer is very rare, accounting for approximately 40 percent of all testicular tumors, which occur in less than 1 percent of the male population. Embryonal carcinomas are usually seen in men age twentyfive to thirty-five but have also affected youths in their late teens. The chances of an embryonal carcinoma spreading from one testicle to the other are less than 1 percent. Embryonal carcinoma in the ovaries of females is extremely rare and usually occurs before the age of thirty. Symptoms: Patients with embryonal cell cancer usually have a tumor, swelling, or mass that can be felt or seen, or an abnormal shape, or irregularity in, testicular size. Screening and diagnosis: Diagnostic procedures for embryonal cell cancer may include biopsy of the tumor; blood tests, including testing for tumor markers and a complete blood count (CBC) to determine the size, number, and maturity of different blood cells within the blood; and multiple imaging studies such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and X ray. Treatment and therapy: Specific treatment for germ-cell tumors is determined by the patient’s age, overall health, medical history, and the extent of the disease. Surgery is generally performed to remove the malignant cells, and patients may undergo chemotherapy or radiation to reduce the risk of recurrence of cancerous cells. Prognosis, prevention, and outcomes: With all testicular cancers, strategies employing surgery, chemotherapy, or radiation therapy (either alone or in combination) have 404
Salem Health: Cancer created cure rates approaching 100 percent for low-stage or early disease and more than 85 percent for more advanced tumors. Early detection by performing monthly testicular self-exams can greatly improve the chances of curing the cancer. Robert J. Amato, D.O. See also Beckwith-Wiedemann syndrome (BWS); Cryptorchidism; Germ-cell tumors; Kidney cancer; Rhabdomyosarcomas; Teratocarcinomas; Testicular cancer; Testicular self-examination; Yolk sac carcinomas.
u End-of-life care Category: Social and personal issues Also known as: Palliative care, supportive care, hospice care Definition: End-of-life care is palliative or supportive care given to terminally ill patients whose treatment goals have switched from curing cancer or extending life to achieving the best possible quality of life. Goals: Palliative care is patient- and family-centered care focused on achieving quality of life through the management of pain and other distressing symptoms. It also addresses intellectual, emotional, social, spiritual, and existential needs of patients and their families, while facilitating patient autonomy and control over care. Many cancer centers are integrating palliative care with lifeprolonging treatments as a part of comprehensive cancer care. Over the course of treatment for a potentially fatal illness such as cancer, goals are constantly evaluated based on the response of the disease. When a disease progresses despite treatment and no further treatment is available or if a person decides that the burden of treatment outweighs the benefit, palliative care becomes the main focus of care. The goals of end-of-life palliative care are set by patients in consultation with their families and health care providers. The treatment plan is based on the goals and is shaped by the patient’s definition of quality of life, treatment preferences concerning the type of care and the care setting, and physical and emotional condition. Aspects of care: An end-of-life palliative care plan is developed with the health care provider in consultation with family or in some cases a palliative care consultant. Symptom management and patient function are constantly assessed so that appropriate interventions can be made. When deciding on a course of treatment, care can be cate-
Salem Health: Cancer gorized as that which should be given, care that is optional, and care that should not be given because the patient or medical proxy refuses, it is not aligned with the patient’s goals, or it presents a burden of treatment that outweighs the benefits. There are many physical symptoms that are the focus of end-of-life palliative care: pain, fatigue, difficulty breathing, loss of appetite and weight, dry mouth, bedsores, depression, confusion or delirium, and vomiting, constipation, or diarrhea. Of these symptoms, pain, fatigue, and difficulty breathing are among the most common and distressing in people dying of cancer. Pain, as a direct result of the cancer or treatments, is treated with opioid and other pain medications, given orally or through a skin patch, rectal suppositories, injections, or patient-controlled analgesic devices in which a pump injects medication intravenously, subcutaneously, or into the spine. Around-the-clock dosing is recommended for chronic pain, while intermittent pain is treated as needed. Pain is often inadequately treated because of poor communication between patients and health care providers, fears of adverse side effects and addiction, and the health care provider’s lack of knowledge or experience in managing pain. Fatigue that cannot be relieved by rest is caused by the disease, treatment, medications, psychiatric comorbidities, difficulty breathing, infection, nutritional or chemical imbalances, sleep disturbances, or uncontrolled pain. It profoundly affects a person’s quality of life. Treatment of fatigue primarily involves addressing the cause, some drug therapies, and having the patient engage in exercise. Difficulty breathing, or dyspnea, can be caused by heart and lung conditions or infections, anemia, anxiety, malnutrition, or urinary retention or constipation. Treatment involves medical intervention when appropriate and focusing on comfort, which can include the provision of oxygen, having the patient sit up, moving the air around a room, relaxation techniques, and discontinuation of intravenous fluids to reduce the amount of fluid in the lungs. Some patients in the later stages of dying elect to use a ventilator or to take opioid pain medications or sedatives to ease the distress. In addition to management of physical symptoms, endof-life care provides psychological and psychiatric care to patients and families to provide support, to assist in making difficult decisions, and to help with depression, grief, life completion, or life closure issues. Education concerning the prognosis and the dying process provides autonomy over care and helps prepare patients and families. Information is often provided concerning patients’ legal rights to receive relief from pain and suffering, to make
End-of-life care their own health care choices, to document those choices through advance directives, and to have those choices enforced by a medical proxy if their decision-making capacity becomes impaired. Financial planning may also be provided with respect to facilitating insurance coverage of services or accessing community resources to provide or pay for services. Patients’ religious, spiritual, and cultural needs are assessed so that care can be delivered in the most respectful and effective manner possible. End-of-life care can be provided in the home, hospital on an inpatient or outpatient basis, nursing homes, or longterm care facilities. Since the 1970’s, the most developed and available form of end-of-life palliative care has been hospice care, provided in freestanding hospice centers or off-site in the community. People are typically eligible for hospice care if their doctors estimate they have six months or less to live and they have refused or exhausted all treatment options. Imminent death: Special end-of-life care provisions are made when a person is actively dying or death is imminent. These provisions include focus on comfort care;
End-of-life care focuses on achieving comfort for the patient through the management of pain and other symptoms. (Digital Stock)
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Endocrine cancers discontinuation of diagnostic tests or monitoring, especially unnecessary needle sticks; ensuring access to pain medications if the oral route is not available; relieving dry mouth and lips; repositioning for comfort; ensuring patient privacy; and facilitating the family’s desire for round-the-clock presence and uninterrupted time together. Education of patients and family members on the signs and symptoms of the stages of death will help ease their anxieties and fear and assist in decision making. Patients and families also often benefit from psychological or religious support. Patients or families may be faced with difficult decisions, which ideally should be discussed ahead of time. These include withdrawing or withholding medical interventions such as nonoral feeding, artificial hydration, mechanical ventilation, medications other than those for pain, dialysis, and cardiopulmonary resuscitation (CPR). Patients and families may also have to decide if termination sedation is appropriate. Sedation is indicated when a patient is removed from a ventilator and is expected to die shortly thereafter or for control of refractory symptoms that cannot be controlled despite aggressive efforts. Legal and ethical considerations: The federal Patient Self-Determination Act of 1990 gives patients the rights to participate in and direct their own health care. State law protects these rights through advance directives, which legally document a patient’s health care choices and designate a medical proxy who is authorized to make decisions if the patient loses decision-making capacity or is deemed incompetent by a court of law. Decision-making capacity is determined by physicians based on a patient’s ability to receive and evaluate information; communicate wishes; understand the risks, benefits, and alternatives to treatment; and make consistent and logical decisions, regardless of whether the person agrees with the physicians. If there are no advance directives and the patient loses decision-making capacity and has not designated a medical proxy, the health care provider must make the medical decisions. The intent of treatment dictates whether it is ethical. If the intent of treatment is desirable and helpful to a patient, then adverse effects, such as dying, are acceptable in endof-life palliative care; however, it is unethical to take measures solely to hasten death. There is no ethical or legal mandate to continue medical interventions if it is against the wishes of a patient with decision-making capacity or of a legally designated medical proxy or if the health care provider determines the burden of medical intervention outweighs the benefits. The decision to withdraw or withhold medical intervention is not euthanasia or assisted sui406
Salem Health: Cancer cide. Medical interventions are distinguished from pain relief and from ordinary care that can be given by a layperson, which should be given to ensure quality of life. Amanda McQuade, Ph.D. u
For Further Information Lynn, Joanne, and Joan Harrold. Handbook for Mortals: Guidance for People Facing Serious Illness. New York: Oxford University Press, 1999. Shannon, Joyce Brennfleck, ed. Death and Dying Sourcebook: Basic Consumer Health Information for the Layperson About End-of-Life Care and Related Ethical and Legal Issues. 2d ed. Detroit: Omnigraphics, 2006. Young, Carolyn, Cyndie Koopsen, and Daniel Farb. End of Life Care Issues Guidebook: A Guide for Healthcare Providers and the Public on the Care of the Dying. Los Angeles: University of Health Care, 2005. u
Other Resources
End of Life/Palliative Education Resource Center http://www.eperc.mcw.edu National Comprehensive Cancer Network http://www.nccn.org National Hospice and Palliative Care Organization http://www.nhpco.org Promoting Excellence in End-of-Life Care http://www.promotingexcellence.org See also Advance directives; Brompton cocktail; Do-notresuscitate (DNR) order; Elderly and cancer; Grief and bereavement; Home health services; Hospice care; Living will; Medicare and cancer; Pain management medications; Palliative treatment; Support groups.
u Endocrine cancers Category: Diseases, symptoms, and conditions Related conditions: Prolactinoma, acromegaly, gigantism, pituitary adenoma, thyroid cancer (papillary, medullary, follicular, C-cell, anaplastic), parathyroid adenoma, parathyroid carcinoma, pheochromocytoma, insulinoma, glucagonoma, somatostatinoma, multiple endocrine neoplasia (MEN) type 1 (Wermer syndrome), MEN type 2A (Sipple syndrome), MEN type 2B, carcinoid tumor, islet cell tumor, Cushing disease Definition: Endocrine cancers are a group of benign and malignant growths that originate from the tissues of the endocrine glands. The endocrine glands are responsible
Salem Health: Cancer for regulating a number of bodily functions, including cellular metabolism, growth, development of male and female primary and secondary sex characteristics, the menstrual cycle, water and sodium balance, calcium distribution, and blood pressure. A number of functions also relate to reactions to stressors, which include the fight-orflight response and immune system modulation. The endocrine system is related functionally to the nervous system in that it maintains the long-term equilibrium of vital organ systems. Complex feedback loops at the pituitary (secondary) or hypothalamic (tertiary) level as well as physiologic demands normally regulate hormone secretion. The hypothalamus-anterior pituitary axis regulates several glands, including the adrenal cortex, thyroid gland, and reproductive system. The hypothalamus-posterior pituitary axis directly regulates physiologic functions such as breast milk ejection and uterine contraction, and stimulates water retention in the kidneys. The autonomic axis regulates body functions in response to stress and injury and includes the adrenal medulla, the juxtoglomerular apparatus in the kidney, and the alpha and beta islet cells in the pancreas. The parathyroid gland does not belong to any axis. Endocrine cancers can alter this equilibrium, leading to potentially life-threatening conditions in extremis. Risk factors: The risk factors for developing an endocrine cancer depend on the cellular origin of the cancer and the stimulus that promotes cancer cell proliferation, and they can generally be classified as environmental or hereditary. Environmental risk factors may include exposure to radiation as in the case of thyroid cancers. Although spontaneous cases do arise, such as in cases of parathyroid adenomas and insulinomas, other endocrine cancers arise as part of a distinct clinical syndrome with multiple endocrine gland involvement. The most prominent risk factor for the development of hereditary endocrine tumors is a genetic predisposition. The MEN syndromes are autosomal dominant, with a 50 percent probability of offspring inheriting the disease. Etiology and the disease process: The transformation of a normal endocrine cell into a cancerous cell is often caused by a single or a number of additive unrepaired gene alterations that prevent uncontrolled cellular division and programmed cell death. These cancer cell transformations do not differ much from the transformation of cells in other organs and have common etiologic agents such as the tumor-suppressor gene TP53. However, specific tumorsuppressor gene mutations are responsible for the genesis of certain endocrine cancers. MEN 1 originates from either a mutation within the embryonic crest cell or inactivation of the tumor-suppressor gene MEN1, located on the
Endocrine cancers long arm of chromosome 11 (11q13). MEN 2A, 2B, and familial medullary thyroid carcinoma originate from a mutation in the RET proto-oncogene, located on the long arm of chromosome 10 (10q11.2). MEN1 tumor-suppressor gene mutations, along with changes in the RET protooncogene, have also been implicated in sporadic medullary thyroid carcinoma cases. Papillary thyroid cancer genesis has been attributed to mutations in the PTC and TRK-A genes, in conjunction with the RET proto-oncogene and RAS oncogene, respectively. Endocrine cancers may be functional or nonfunctional. Functional endocrine cancers are so named because the hormone secretions from the cancer cells have the same effect on the same target organs as do hormones from normal endocrine cells. These cancer cell hormones may be structurally identical or slightly altered. Functional endocrine cancers do not respond in a normal fashion to the inhibitory feedback mechanisms in normal endocrine cells. Although some cancers lack receptors that decrease or halt hormone secretion, other cancers may be stimulated by their own secretions in a way that resembles the inhibitory mechanisms of some endocrine glands. Nonfunctional endocrine cancers do not secrete hormones or hormonelike molecules. They may be derived from hormonesecreting cells but are more often derived from stromal tissue (tissue surrounding supporting tissue). They may nonetheless interfere with normal gland function by compressing or infiltrating surrounding tissue. Incidence: According to the American Cancer Society, about 25,520 new cases of endocrine cancer were reported in 2004, or less than 1 in 10,000 people. By affected organ, thyroid cancers are the most common of all endocrine cancers, followed by pituitary gland cancers. Specific data regarding the rarer cancers are sparse. Some endocrine cancers such as thyroid cancer tend to appear in individuals older than fifty years. Symptoms: Symptoms of endocrine cancer are generally related to both the indirect effects of malignancy—such as fever, malaise, anorexia, weight loss, or paraneoplastic syndrome—and the direct and gland-specific effects of the tumor. The specific symptoms of endocrine cancers are classically related to the endocrine gland axis from which they originate, wherein serum measurements of the hormones causing symptoms directly or indirectly follows. For example, a tumor in the thyroid gland causing symptoms of increased cellular metabolism (sweating, irritability, palpitations, irregular heartbeats, heat intolerance) may be confirmed by measurements of both thyroidstimulating hormone (TSH) and thyroid hormone. Alternately, a TSH tumor would be suspected in a patient who 407
Endocrine cancers
Salem Health: Cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Thyroid Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 59 34 5 3
99.7 96.9 56.0 89.3
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
exhibits hyperthyroid symptoms but has a normal thyroid gland, being mindful of the loss of the inhibitory feedback mechanism in these tumors. Other endocrine cancers may require a combination of laboratory tests relating to their functional status in addition to hormone levels. For example, a simple parathyroid gland tumor secreting parathyroid hormone-like substances may manifest in a patient with recurrent kidney stones and heart rhythm disturbances from a high serum calcium with a correspondingly low phosphorus level because of bone demineralization. Symptom overlap is more often present because of the different possible locations of a tumor along the hypothalamic-pituitary-target organ axis, requiring an exhaustive diagnostic workup. For instance, an anterior pituitary tumor such as a prolactinoma may have the symptoms of milk production and cessation of menses in a nonpregnant woman. Similarly, a gonadotropic hormone-secreting tumor or gonadotropin-releasing hormone (GnRH) tumor in the hypothalamus may also halt the menstrual cycle. Endocrine cancers can also manifest by compressing or infiltrating adjacent tissue and structures, altering their function. An example is anterior pituitary tumors, which may initially manifest as a partial blindness termed bilateral hemianopsia (involving the right and left visual fields of the right and left eyes, respectively) in which right and left optic nerve fibers are compressed as they cross below the anterior pituitary. The specific pituitary cells may be nonfunctional or secrete excess hormones that can affect the axis accordingly. Posterior pituitary tumors may also manifest in this fashion. Other cancers may remain undetected or grow to large sizes (as with ovarian cancers). 408
The hereditary multiple endocrine neoplasia (MEN) syndromes consist of two main variants, MEN 1 and MEN 2. MEN 1 has pituitary, parathyroid, and pancreas involvement. MEN 2A manifests as medullary thyroid cancer (MTC), pheochromocytoma, an adrenal medulla tumor, and parathyroid hyperplasia (overproliferation). MEN 2B is essentially type 2A without parathyroid involvement and with the addition of mucosal neuromas and gut ganglioneuromas (nerve cell tumors) with a Marfanoid body habitus (long limbs and fingers, flexible joints, lens dislodgement, and mitral valve prolapse). Isolated MTC may also be familial and is less aggressive compared with MEN-associated MTC. Screening and diagnosis: As clinical symptoms and signs of endocrine cancers can vary widely from textbookstyle presentations, diagnosis is generally oriented toward confirming clinical suspicions through routine laboratory tests and tests measuring hormone levels. Although interpretation of some tests—such as thyroid function tests and a twenty-four-hour urine collection for catecholamine metabolites of epinephrine and norepinephrine (metanephrine, vanillylmandelic acid, or VMA) for a suspected pheochromocytoma—may be straightforward, other tests approach diagnosis by process of elimination. Tests that require such multiple steps include the dexamethasone suppression test and the progesterone challenge test. The dexamethasone suppression test involves a screening of a twenty-four-hour urine collection for cortisol as well as evaluation of the anterior pituitary (Cushing syndrome) and adrenal cortex hormone levels in response to low and high doses of dexamethasone. The progesterone challenge is similar in that it assesses the onset of bleeding with administration of suppressing doses of estrogen and progesterone to assess the presence of an androgen-secreting tumor, among other, nontumor-related diseases. These tests may also be used to assess baseline glandular functioning. Tumor markers such as cancer antigen 125 (CA 125) for ovarian cancer are rarely used alone to confirm diagnoses, although they can be used to monitor for disease recurrence. Visualization of a suspected cancer is carried out as much as possible. Imaging studies provide information for determining whether surgery is possible. If surgery is a plausible option, imaging studies provide surgeons with a means by which to plan their approach. Conventional imaging studies include computed tomography (CT) and magnetic resonance imaging (MRI). Organ-specific studies such as thyroid scans or OctreoScans for islet cell tumors rely on tumor uptake of radiolabeled substances to disclose their location. Thyroid scans also help determine
Salem Health: Cancer the presence of hormone activity, which is absent in most thyroid cancers. Occasionally, local or distal spread of tumors may occur, in which case more comprehensive imaging studies of probable areas of spread, such as the chest, abdomen, pelvis, or head, are conducted. A biopsy of tumors with high-yield procedures such as fine needle aspiration of thyroid nodules or masses can greatly aid in planning future treatment. Occasionally, this may be done during an operation through frozen section, in which a tumor specimen is frozen and thinly sliced for microscopic evaluation by a pathologist. Formal, regular screening is not usually done because of the rareness of these cancers but may be conducted when patients have a family history of multiple endocrine gland involvement. Although tumors that are hereditary have a clear genetic etiology, routine genetic testing such as that for RET is reserved for patients with medullary thyroid cancer. Treatment and therapy: Treatment of endocrine cancers generally consists of surgical removal of the lesions alongside chemotherapy or radiotherapy. Medical therapies are often limited but nonetheless essential in reducing complications. These include ensuring the control of other diseases and correcting blood pressure and fluid and electrolyte derangements, particularly in patients in whom the thyroid, parathyroid, pancreatic islet cells, and adrenal glands are involved. The surgical approach for endocrine cancers usually conforms to the relevant local anatomy while achieving optimal visualization even if the surgical field may be quite limited. For instance, a transsphenoidal approach to the pituitary gland involves making a surgical “window” through the posterior aspect of the mouth, as opposed to thyroid surgery at the base of the neck. Spread to neighboring structures may entail lymph node sampling conforming to the lymph drainage within the area of the tumors in addition to removal of secondary sites of spread wherever possible. Chemotherapy and radiotherapy are instituted for most endocrine cancers to eliminate remaining tumor cells not removed by surgery and thus decrease the chance for recurrence. Prognosis, prevention, and outcomes: The 2004 ratio of deaths to incidence in the United States from endocrine cancers irrespective of cause was estimated at 9.6 percent. Total deaths from endocrine cancers from the same year were estimated at 2,440. Most endocrine cancers have high five-year survival rates approaching 95 percent or more. Thyroid cancers in particular have high five-year survival rates, around 96 percent if detected early. As with all other cancers, this may drop to 5 percent in advanced disease involving more malignant variants (medullary,
Endocrinology oncology follicular, anaplastic). Cancers that are detected late, such as ovarian or adrenal cancers, have correspondingly lower survival rates of 50 percent and 40 percent, respectively. Complications from surgery include bleeding, marked reduction or total loss of endocrine gland function, or interruption of hypothalamic-pituitary axis equilibrium. Hormone replacement therapy may eventually be lifelong, particularly in thyroid and pituitary gland cancers. Preventive measures include proper radiation shielding of neck and genital areas. Aldo C. Dumlao, M.D. u
For Further Information Braverman, Lewis E. Diseases of the Thyroid. 2d ed. Totowa, N.J.: Humana Press, 2003. Clark, Orlo H. Endocrine Tumors. Hamilton, Ont.: BC Decker, 2003. Kelloff, Gary, Ernest T. Hawk, and Caroline C. Sigman. Cancer Chemoprevention. Totowa, N.J.: Humana Press, 2005.
u
Other Resources
American Cancer Society http://www.cancer.org Cancer Index Endocrine Malignancies http://www.cancerindex.org/clinks2e.htm Stanford Cancer Center Endocrine Cancers http://cancer.stanford.edu/endocrine/ See also Adrenal gland cancers; Adrenocortical cancer; Endocrinology oncology; Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Human growth factors and tumor growth; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Pancreatic cancers; Parathyroid cancer; Pituitary tumors; Thyroid cancer.
u Endocrinology oncology Category: Medical specialties Also known as: Endocrine oncology Definition: Endocrinology oncology is the treatment of cancers affecting the endocrine organs, which are organs that produce hormones. Endocrine organs include the thyroid, adrenal glands, endocrine pancreas, and pituitary gland. 409
Endocrinology oncology Cancers treated: Thyroid tumors (including papillary, follicular, medullary, anaplastic, and mixed papillary/ follicular tumors); parathyroid tumors; adrenal tumors (including pheochromocytoma and incidentally discovered adrenal masses); tumors of the endocrine pancreas (for example, insulinoma, gastrinoma, glucagonoma); tumors of the pituitary gland Training and certification: Most doctors who treat patients with endocrine cancers are not specifically trained through endocrinology oncology residencies and fellowships. Instead, they may have completed surgical residencies, either in general surgery or in oncology or endocrine surgery. The average length of a surgical residency is five years. They may also be trained in internal medicine (a
Glands of the Endocrine System
Salem Health: Cancer three-year residency), followed by specialized residency training in oncology or endocrinology (hormone and metabolic diseases), which usually takes another three years. In addition to postgraduate clinical training, residents and fellows may elect to participate in endocrine research. Research grants are available from organizations such as the American Association of Endocrine Surgery and the American Thyroid Association to support research in the areas of diagnosis, prevention, and treatment of endocrine disease, as well as in the underlying molecular, cellular, and physiologic disease mechanisms. These residency and fellowship programs are accredited by the Accreditation Council for Graduate Medical Education. In addition, physicians are usually certified by an American Board of Medical Specialties (ABMS) Member Board, and they continually receive accredited education to update their knowledge and skills and maintain their certification. There are relatively few endocrine specialists, compared with specialists in other fields. For example, a study conducted by the American Association of Endocrine Surgeons discovered that a small number of high-volume endocrine surgeons perform 24 percent of all endocrine surgeries. The number of specialized endocrine surgeons is projected to increase in the coming years, based on the growing number of endocrine cases and the increasing number of endocrine fellowships. Services and procedures performed: The major endocrine tumors treated are those of the thyroid, parathyroid, and adrenal glands. Thyroid cancers usually grow from nodules within the thyroid. Less than 1 percent of thyroid nodules are cancerous. The oncology team, led by an endocrinologist/oncologist/surgeon, is involved in biopsying, staging, and treating endocrine tumors. Thyroid tumors are usually diagnosed by needle biopsy of a thyroid nodule (this can be guided by ultrasound) or by biopsy of the excised nodule. The biopsy sample is examined under the microscope and, based on its cellular appearance, classified as papillary, follicular, medullary, anaplastic, or a mixed type. The next step is staging, based on the
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Salem Health: Cancer characteristics of the primary tumor and the degree of metastasis. The primary tumor is examined for size and extent of invasion of surrounding tissues. The presence, number, and location of metastases in the lymph nodes and in other organs are determined. Tumors may be well differentiated or poorly differentiated, similar to tumors affecting other organs. In general, thyroid tumors that are poorly differentiated are associated with a worse prognosis. However, this is not always the case, because a patient’s prognosis also depends on other factors, such as age and health status. Anaplastic tumors, making up 1 to 2 percent of thyroid tumors, are the most aggressive type of thyroid tumor. They are poorly differentiated and are almost always fatal within twelve months of a diagnosis. Some thyroid tumors can be treated by surgical removal of the affected parts of the thyroid; this procedure is called a hemithyroidectomy and is mainly used for lowrisk papillary thyroid tumors that are localized in one lobe of the thyroid gland (the degree of risk is calculated based on several factors known to affect prognosis). Sometimes almost the whole thyroid is removed (near-total thyroidectomy) to decrease the risk of cancer spread to the recurrent laryngeal nerve or parathyroid glands. If the primary tumor is more than 1 centimeter in diameter or if metastases are present, the entire thyroid needs to be removed (total thyroidectomy). Surgeons have started to use minimally invasive endoscopic thyroidectomy techniques with smaller neck incisions for patients with low-risk, welldifferentiated tumors. Although these techniques are gaining popularity, some controversy persists about the selection of patient candidates for this treatment. Surgical removal of the tumor is often followed by treatment with radioactive iodine. Most thyroid cancer cells retain their ability to absorb iodine; radioactive iodine is taken up by any remaining cancer cells, specifically destroying them. Other cells in the body lack the ability to absorb iodine and remain unharmed. After radioactive iodine treatment, patients are given thyroid hormone pills to replenish thyroid hormone levels. For the diagnosis of adrenal tumors, computed tomography (CT) and magnetic resonance imaging (MRI) techniques are frequently employed. Some adrenal tumors require angiography (study of the tumor blood supply) to determine if the tumor is affecting the blood supply to surrounding organs. Pheochromocytomas are rare tumors (annual incidence in the United States is 800) arising from cells in the adrenal medulla. These tumors secrete catecholamines that can cause hypertension, and raised levels of free catecholamines in the urine form the basis of the diagnostic test for pheochromocytoma. The typical treat-
Endocrinology oncology ment is surgical resection of tumors. Unresectable, recurrent, or metastatic pheochromocytoma has a five-year survival rate of less than 50 percent. Parathyroid tumors occur in the parathyroid glands, which produce parathyroid hormones. These tumors are most commonly adenomas and rarely carcinomas. Surgery is the typical treatment. Endocrine pancreatic tumors occur in the endocrine pancreas, which constitutes less than 5 percent of the pancreas and consists of pancreatic islet cells that produce hormones such as insulin, glucagon, and somatostatin. Surgical resection is the standard treatment for endocrine pancreatic tumors. Related specialties and subspecialties: The team that cares for endocrine oncology patients typically consists of the endocrinologist/oncologist/surgeon, radiologists, and oncology nurses. Radiologists specialize in techniques that are used to image tumors, including X ray, computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI). The radiologists work closely with the other members of the team, using various techniques to diagnose tumors in endocrine organs. Once a tumor is found, radiologists help design and execute treatment plans, including highprecision external-beam radiation therapy for pituitary tumors and postsurgical treatment of thyroid and parathyroid tumors with radioactive iodine. Oncology nurses are involved in administering therapies to the patient, monitoring their progress, and managing any adverse effects the patient may experience while on therapy. Oncology nurses also help manage patients’ expectations of treatment efficacy and adverse effects, starting at treatment initiation, to ensure a high level of adherence to the therapy. Oncology nurses are typically registered nurses (RNs) who have undergone additional training, such as acquiring a master’s degree in nursing, and have attained certification in oncology. These certifications include oncology certified nurse (OCN), certified pediatric oncology nurse (CPON), advanced oncology certified clinical nurse (AOCN), advanced oncology certified clinical nurse specialist (AOCNS), and advanced oncology certified nurse practitioner (AOCNP) credentials. Oncology nurses maintain their certifications by periodically participating in continuing nursing education in their specialized field. Nurses are certified through nurses associations in the state where they work; these associations are accredited by the American Nurses Credentialing Center arm of the American Nurses Association. Ing-Wei Khor, Ph.D. 411
Endometrial cancer u For Further Information Brunt, L. M. “Endoscopic Parathyroid and Thyroid Surgery.” In Current Review of Minimally Invasive Surgery, edited by D. C. Brooks. Philadelphia: Current Medicine, 1998. Patel, K. N., and A. R. Shaha. “Poorly Differentiated and Anaplastic Thyroid Cancer.” Cancer Control 13, no. 2 (2006): 119-128. Sosa, J. A., et al. “The Maturation of a Specialty: Workforce Projections for Endocrine Surgery.” Surgery 142 (2007): 876-883. u
Organizations and Professional Societies
American Association of Clinical Endocrinologists http://www.aace.com 245 Riverside Avenue, Suite 200 Jacksonville, FL 32202 American Board of Medical Specialties http://www.abms.org 1007 Church Street, Suite 404 Evanston, IL 60201 American Association of Endocrine Surgeons http://www.endocrinesurgery.org 3550 Terrace Street Pittsburgh, PA 15261 The Endocrine Society http://www.endo-society.org 8401 Connecticut Ave, Suite 900 Chevy Chase, MD 20815 u
Other Resources
American Thyroid Association http://www.thyroid.org/index.html National Cancer Institute Pheochromocytoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ pheochromocytoma/healthprofessional See also Adrenal gland cancers; Adrenocortical cancer; Endocrine cancers; Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Human growth factors and tumor growth; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Pancreatic cancers; Parathyroid cancer; Pituitary tumors; Thyroid cancer. 412
Salem Health: Cancer
u Endometrial cancer Category: Diseases, symptoms, and conditions Also known as: Uterine corpus cancer, uterine cancer Related conditions: Obesity, hypertension, polycystic ovary syndrome, endometrial hyperplasia Definition: Endometrial cancer is cancer of the endometrial cells that line the uterus, which is the female organ in which the fetus develops. Estrogen, a female hormone, is a primary growth signal for the endometrium (lining of the uterus). When endometrial cells are exposed to increased levels of estrogen for long periods of time and when they acquire certain genetic mutations, they can become cancerous. Risk factors: Certain demographic characteristics—being over the age of fifty, being white, and never having been pregnant—can contribute to the risk of endometrial cancer. Long-term exposure to estrogen may also affect the incidence of endometrial cancer. Estrogen exposure can be in the form of hormone replacement therapy (commonly used to control menopause-related symptoms) or tamoxifen (an estrogen-like drug used to prevent or treat breast cancer). Increased exposure to estrogen can also occur in women who began menstruation early (before the age of twelve) or reached menopause late (after the age of fifty). Because estrogen can be produced in fatty tissue, being overweight can increase the risk of endometrial cancer. Furthermore, obesity-related conditions, such as type 2 diabetes and high blood pressure, may increase the risk. Finally, many diseases may also be associated with an elevated risk of endometrial cancer, including endometrial hyperplasia (a noncancerous condition characterized by overgrowth of the endometrium), a history of breast or ovarian cancer, and hereditary nonpolyposis colorectal cancer (a disease caused by mutations in deoxyribonucleic acid, or DNA, repair genes). Etiology and the disease process: Within the female reproductive system, the ovaries are responsible for producing the hormones estrogen and progesterone. The levels of these hormones fluctuate each month, allowing the endometrium to thicken (because of endometrial cell growth) at the beginning of the monthly menstruation cycle in preparation for an egg to be fertilized and implanted within the uterus. At the end of the monthly cycle, the endometrium is shed if pregnancy does not occur. Because estrogen is responsible for stimulating the growth of endometrial cells, too much estrogen may lead to too much cell growth. Genetic changes may also contribute to the transformation of normal cells into cancerous cells. Endometrial can-
Salem Health: Cancer cer can be divided into type 1 and type 2 carcinomas based on their relationship with estrogen and how the cells look under a microscope. Type 1 carcinoma, which accounts for 70 to 80 percent of all endometrial cancer cases, is estrogen dependent and associated with the inactivation of PTEN (a tumor-suppressor gene) and mutations in DNA repair genes, KRAS (a gene that encodes a proto-oncogene), and beta-catenin (a protein). In the less prevalent (but more aggressive) type 2 carcinoma, which follows an estrogenindependent pathway, major genetic changes within endometrial cells include mutations in TP53 (another tumorsuppressor gene) and overexpression of human epidermal growth factor receptor 2/neu (HER2/neu). When cells have tumor-suppressor genes and DNA repair genes that are not functional, they lose the ability to regulate growth and cell division, as well as the ability to fix additional mutations that may arise. Expressing excess growth factor receptors also means that cells may grow and divide more quickly and may not respond when cellular signals try to stop proliferation. Incidence: In women, endometrial cancer is the fourth most common cancer (after breast, lung, and colon cancers). Some 95 percent of uterine cancers are endometrial; the other 5 percent are due to cancerous muscle or myometrial cells within the uterus. The American Cancer Society estimated that in 2007 more than 39,000 new cases would arise and about 7,400 people would die from endometrial cancer in the United States. Symptoms: The most common symptoms in endometrial cancer are pelvic pain and vaginal bleeding between menstrual periods or after menopause. Screening and diagnosis: Screening tests such as a pelvic exam, a Pap smear (to check for cervical cancer), and a transvaginal ultrasound (to determine if the endometrium is too thick) may be performed. Blood tests can look for lower red blood cell counts (possibly indicating loss of blood from the uterus) and for raised levels of cancer antigen 125 (CA 125, a protein that is associated with tumors of the endometrium and ovaries). To make a diagnosis, a tissue sample from the uterine lining should be removed and analyzed under the microscope. Tissue samples can be obtained either by a biopsy or by dilation and curettage (D&C). AD&C is a more invasive procedure for obtaining endometrial tissue and may be done if the biopsy did not obtain a large enough sample or if the biopsy was positive for cancer and a confirmation is needed. Endometrial cancer is staged using the International
Endometrial cancer Federation of Gynecology and Obstetrics (FIGO) cancer staging system, as follows: • Stage I: The tumor is only in the uterus. • Stage II: The cancer has spread from the body of the uterus to the cervix. • Stage III: The cancer has spread outside the uterus but not outside the pelvis (and not to the bladder or rectum). Lymph nodes in the pelvis may contain cancer cells. • Stage IV: The cancer has spread into the bladder or rectum, or it has spread beyond the pelvis to other parts of the body. Treatment and therapy: Women with endometrial cancer may undergo surgical removal of the uterus, in a procedure known as a hysterectomy. Often, the uterus is removed along with the Fallopian tubes and ovaries as well as neighboring lymph nodes to ensure that all of the cancerous cells have been removed. Although this is the standard treatment for women already in menopause and no longer fertile, women of childbearing age need to consider the outcome of this surgery as they will lose the ability to have a child. For Stage I endometrial cancer, surgery to remove the uterus has been shown to be 90 percent effective. Radiation therapy, where high-dose X rays are used to kill cancer cells, may be used after surgery to prevent the formation of or treat existing cancer cells outside the uterus. Radiation may also be used in place of surgery if women refuse a hysterectomy or if a tumor is growing rapidly, associated closely with muscle cells in the uterus, or is highly vascularized (with lots of blood vessels infiltrat-
Age at Death for Uterine Cancer, 2001-2005 Age Group
Percentage Diagnosed
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
0.0 0.4 2.2 8.1 18.4 26.4 28.7 15.9
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of death from 2001 to 2005 was seventy-three, with an age-adjusted death rate of 4.1 per 100,000 women per year.
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Endometrial hyperplasia ing the tumor). Radiation therapy can be delivered either conventionally (the standard external X ray) or as brachytherapy (internal radiation to target only the inner lining of the uterus). Although brachytherapy has fewer side effects than conventional radiation therapy, its effects are only local, so it cannot be used if the cancer has spread outside the uterus. Hormone therapy is often used when cancer has spread outside the uterus. Synthetic progestin, which is a form of progesterone, is used to inhibit the growth of cancerous endometrial cells. Although this therapy may be associated with higher risks of recurrence than surgical removal of the uterus, this option is attractive to women who still want to have children or who were diagnosed in a very early stage. Chemotherapy may also be used to kill cancer cells that have spread beyond the uterus. Prognosis, prevention, and outcomes: To prevent endometrial cancer (both initial and recurrent cases), taking hormones with progesterone may help slow or inhibit the growth of endometrial cells. Women may undergo hormone therapy with progestin or take birth control pills. Women who take birth control pills have a reduced risk of endometrial cancer for up to ten years after discontinuing oral contraceptives. As with other cancers, living a healthy lifestyle is important in reducing the risk of cancer. This includes maintaining a healthy weight (as obesity is a risk factor for developing endometrial cancer) and exercising regularly. For endometrial cancer, the five-year survival rates for women receiving the proper treatment are approximately 75 to 95 percent for women diagnosed at Stage I, 50 percent for Stage II, 30 percent for Stage III, and less than 5 percent for Stage IV. In a study analyzing recurrence rates across sixteen studies, the overall risk of recurrence was 13 percent, and this was even less in low-risk patients who were diagnosed with Stage I or II cancers or who did not have associated diseases known to increase the risk of endometrial cancer. This study also showed that about 70 percent of recurrences were accompanied by symptoms, and 68 to 100 percent of these recurrences occurred within about a threeyear span after the follow-up visit. Elizabeth A. Manning, Ph.D.
Salem Health: Cancer view.” Gynecologic Oncology 101, no. 3 (June, 2006): 520-529. Liu, F. S. “Molecular Carcinogenesis of Endometrial Cancer.” Taiwanese Journal of Obstetrics and Gynecology 46, no. 1 (March, 2007): 26-32. Robertson G. “Screening for Endometrial Cancer.” Medical Journal of Australia 178, no. 12 (June 16, 2003): 657-659. Sherman, M. E. “Theories of Endometrial Carcinogenesis: A Multidisciplinary Approach.” Modern Pathology 13, no. 3 (March, 2000): 295-308. u
Other Resources
MayoClinic.com Endometrial Cancer http://www.mayoclinic.com/health/endometrialcancer/DS00306/DSECTION=1 National Cancer Institute Endometrial Cancer http://www.cancer.gov/cancertopics/types/ endometrial See also Antiestrogens; 1,4-Butanediol dimethanesulfonate; CA 125 test; Chemoprevention; Colposcopy; Computed tomography (CT) scan; Conization; Dilation and curettage (D&C); Endometrial hyperplasia; Endoscopy; Family history and risk assessment; Geography and cancer; Ginseng, panax; Gynecologic cancers; Herbs as antioxidants; Hormonal therapies; Hormone replacement therapy (HRT); Hysterectomy; Hysterography; Hysterooophorectomy; Hysteroscopy; Isoflavones; Leiomyomas; Leiomyosarcomas; Mitochondrial DNA mutations; MLH1 gene; MSH genes; Nutrition and cancer prevention; Obesity-associated cancers; Pap test; Transvaginal ultrasound; Uterine cancer.
u Endometrial hyperplasia Category: Diseases, symptoms, and conditions Also known as: EH, endometrial neoplasia, endometrial intraepithelial neoplasia Related conditions: Endometrial cancer
u
For Further Information Canavan, T. P., and N. R. Doshi. “Endometrial Cancer.” American Family Physician 59, no. 11 (June, 1999): 3069-3077. Fung-Kee-Fung, M., et al. “Follow-Up After Primary Therapy for Endometrial Cancer: A Systematic Re414
Definition: Endometrial hyperplasia is the abnormal proliferation of the cells that comprise the inner cell lining of the uterus (endometrium). The endometrium is the tissue layer in which a fertilized ovum implants itself and divides. It consists of glands and surrounding supportive tissue (stroma) and is rich in blood, from which the develop-
Salem Health: Cancer ing embryo derives oxygen and nutrients through the placenta. Risk factors: Risk factors for endometrial hyperplasia are related to lifetime exposure to excess estrogen and include estrogen therapy without progesterone, tamoxifen therapy, late menopause, no history of childbirth, infertility or failure to ovulate, obesity, and obesity-related diseases (diabetes, hypertension). A known hereditary nonpolyposis colon cancer (HNPCC) genetic mutation carrier or a woman with a strong family history of colon cancer is at high risk not only for hyperplasia but for cancer as well. Etiology and the disease process: Endometrial hyperplasia is primarily caused by estrogen stimulation of the endometrial glands. These glands then proceed to multiply and enlarge. Abnormal endometrial hyperplasia may eventually arise from normal cyclic estrogen stimulation. However, there may be sources of excess estrogen independent of the menstrual cycle involved in abnormal endometrial proliferation, such as granulosa cell tumors, polycystic ovary syndrome (PCOS), tamoxifen therapy, or use of estrogen-containing birth control pills. Estrogen stimulation alone results in an unstable endometrial bed, which is prone to breakdown and bleeding. Over time, excessive endometrial stimulation and rapid cell division increase the chance of cell mutations that ultimately predispose the woman to cancer. Incidence: In women with documented abnormal uterine bleeding, 20 percent was caused by endometrial hyperplasia. The incidence may be as high as 25 percent in postmenopausal women on estrogen hormone replacement therapy (HRT); 36 to 49 percent in nonmenstruating, nonovulating women whose condition is the result of PCOS or other undetermined cause; and close to 50 percent in hypertensives and diabetics, although concomitant obesity as a source of excess estrogen formation may account for this according to other studies. Symptoms: Abnormal uterine bleeding is the main symptom associated with endometrial hyperplasia. The bleeding, compared with the woman’s normal menstrual cycle, may be characterized as excessive in amount, duration, frequency, or a combination of these. Painless spotting or bleeding from the vagina in a postmenopausal woman is the most common symptom reported in endometrial cancer. In premenopausal women, heavy menstrual bleeding can be confused with physiologic hyperplasia that occurs during the menstrual cycle. Bleeding between periods may also raise the suspicion of endometrial hyperplasia, although extrauterine masses producing excess estrogen or intrauterine masses such as polyps or fibroids bleeding
Endometrial hyperplasia into the uterine cavity must also be considered. Symptoms accompanying long-standing significant blood loss include fatigue due to anemia. On examination of the pelvis, an enlarged uterus in a nonpregnant or postmenopausal woman may also suggest hyperplasia. This may or may not be accompanied by abnormal findings in the ovaries, Fallopian tubes, and supporting ligaments. Screening and diagnosis: The American Cancer Society currently has no screening recommendations for endometrial hyperplasia. Further testing is carried out in patients who exhibit a high clinical suspicion for endometrial cancer, particularly postmenopausal women over forty years of age. These tests include an endometrial biopsy and an optional pelvic ultrasound when a mass is detected on physical examination. An adequate endometrial biopsy is the standard by which the endometrium is evaluated for cellular characteristics suggestive of precancer. Diagnosis of endometrial hyperplasia and type are dependent on microscopic examination of the biopsy sample. The biopsy sample, containing glands and tissue surrounding these glands (stroma), is examined and classified according to the proportion of glands to stroma, morphology of the glands, and cellular characteristics suggestive of precancer (cellular atypia). Simple, enlarged glands seen within a larger proportion of stroma pose about a 1 percent risk of progression to endometrial cancer. More complex glands possessing more cellular outpouchings than the previous type and a paucity of stroma pose a 3 to 5 percent risk. Simple and complex type glands with atypical cell characteristics (darkstaining cells with large nuclei and little cytoplasm) pose an 8 to 10 percent and 25 to 30 percent risk, respectively. Treatment and therapy: The type of treatment depends on the classification of the hyperplasia irrespective of atypia and, in premenopausal women, the desire to bear children after treatment. Cyclic progestin therapy is used for premenopausal women with no atypical cell findings on biopsy or for those with atypical findings who still wish to bear children. Treatment takes place over three to six months using progesterone contraceptives that can be taken by mouth, such as megestrol acetate and medroxyprogesterone acetate. Intramuscular medroxyprogesterone acetate and levonorgestrel via an intrauterine device (IUD) may also be used for three months and five years, respectively. Follow-up with endometrial biopsies is done every six months to check for recurrence. Discontinuation of progestin depends on the absence of symptoms and a normal biopsy. A total hysterectomy is the recommended course of action in premenopausal women who no longer desire to 415
Endorectal ultrasound bear children or are no longer of childbearing age, and in postmenopausal women with findings of atypia on endometrial biopsy. Prognosis, prevention, and outcomes: A substantial number of patients diagnosed with endometrial hyperplasia with and without atypical cells found on biopsy spontaneously regress (50 percent and 80 percent, respectively). However, treatment as described above should be strongly considered. Aldo C. Dumlao, M.D. u
For Further Information Boston Women’s Health Book Collective. Our Bodies, Ourselves: Menopause. New York: Simon & Schuster, 2006. Goodwin, Scott C., Michael S. Broder, and David Drum. What Your Doctor May Not Tell You About Fibroids: New Techniques and Therapies—Including Breakthrough Alternatives to Hysterectomy. New York: Warner Books, 2003. Rosenthal, Sara M. The Gynecological Sourcebook. 4th ed. New York: McGraw-Hill, 2003. u
Other Resources
American College of Obstetricians and Gynecolgists Endometrial Hyperplasia http://www.medem.com/MedLB/ article_detaillb.cfm?article_ID= ZZZ7Z2GWQMC&sub_cat=9 National Cancer Institute What You Need to Know About Cancer of the Uterus http://www.nci.nih.gov/cancertopics/wyntk/uterus/ page3
Salem Health: Cancer ities (such as fiber-optic or electronic and two- or threedimensional), and configuration (that is, the ultrasound transducer is either mounted on or passed through an endoscope). Cancers diagnosed: Rectal cancer Why performed: ERUS may be performed either as a diagnostic procedure to determine tumor boundaries and to assess spread into lymph nodes and pelvic organs or as a surveillance procedure to detect local recurrence. Patient preparation: A few days before the procedure, the patient may need to stop certain medications, such as aspirin products and blood thinners. The day before the procedure, the patient cleans the rectum, as with an enema. Steps of the procedure: ERUS is scheduled in a physician’s office or other outpatient setting. The patient wears a gown and lies on the side. The patient is awake; if needed, sedation or local anesthetic can be given. First, the physician performs a digital rectal exam. Then, the ultrasound transducer is inserted through the anus into the rectum, and a latex balloon (or alternative for a latex-sensitive patient) covering the ultrasound transducer is inflated. The ultrasound transducer is turned on, sending pulses of sound waves through the balloon into the rectal wall and adjacent tissues. As each pulse of sound waves hits different tissues, some sound waves bounce back and become a gray-scale image on a video monitor. The physician views the images as the ultrasound transducer is moved through the rectum. Tumor dimensions and lymph node sizes are measured. Abnormal tissues are sampled (biopsied) with a fine needle; all tissue samples are taken to the laboratory for cytologic evaluation.
See also Dilation and curettage (D&C); Endometrial cancer; Granulosa cell tumors.
After the procedure: The patient leaves and resumes normal activities, unless sedation or local anesthetic was needed. In the latter case, the patient will need to be driven home by a friend or family member.
u Endorectal ultrasound
Risks: ERUS is relatively safe, with a small risk of these side effects: perforation, bleeding, and infection.
Category: Procedures Also known as: Endorectal echoscopy, endorectal ultrasonography, rectal endosonography, transrectal ultrasound Definition: Endorectal ultrasound (ERUS) is the insertion of an ultrasound transducer through the anus to construct detailed images of the rectal wall and adjacent tissues. ERUS instruments vary in insertion tube design (such as size, flexibility, and view), ultrasound technology (such as frequency, orientation, and scanning), imaging capabil416
Results: ERUS images are interpreted with criteria developed by Ulrich Hildebrandt and Gernot Feifel in 1985. Boundaries of the tumor in the rectal wall are accurately determined from the thickness and continuity of each layer of the rectal wall. Lymph nodes and pelvic organs are assessed for size, shape, and irregularities. Because cancerous and inflamed tissues look similar in ERUS images, however, cytologic evaluation must verify that abnormalities in lymph nodes or pelvic organs are cancerous. Patricia Boone, Ph.D.
Salem Health: Cancer See also Anal cancer; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Prostate cancer; Prostate-specific antigen (PSA) test; Rectal cancer; Sigmoidoscopy; Transrectal ultrasound.
u Endoscopic retrograde
cholangiopancreatography (ERCP) Category: Procedures Definition: Endoscopic retrograde cholangiopancreatography (ERCP) is the X-ray study of the bile and pancreatic ducts using contrast dye injected in the ducts from a tube with a tiny camera at the end (endoscope) inserted down the patient’s throat and through the stomach to the duodenum.
Endoscopy complications, the patient may be allowed to return home. Some patients report a sore throat for several days and should eat a soft diet for the next twenty-four hours. Risks: The risk of complications for ERCP is minor (less than 5 percent) and includes pancreatitis, bleeding, and perforation of the esophagus, stomach, or small intestine. Pain, fever, and chills may indicate an infection. Patients may react to the anesthetic or dye with nausea, hives, blurred vision, dry mouth, retention of urine, or a burning or flushed feeling. Results: Normal findings show the biliary and pancreatic ducts are of normal size with no obstructions. Abnormal results include narrowing or inflammation of the ducts. Marcia Pinneau, R.N. See also Bile duct cancer; Endoscopy; Gallbladder cancer; Hepatomegaly; Pancreatic cancers.
Cancers diagnosed: Pancreatic cancer, bile duct cancer, gallbladder cancer
u Endoscopy
Why performed: ERCP permits a doctor to check for swelling or tumors in the ducts that pass digestive fluids from the gallbladder and pancreas to the stomach, to perform a biopsy, and to remove minor obstructions in the ducts. It may be recommended for patients with a familial history of pancreatic cancer, but it is not used as a routine screening tool for those with an average risk for cancer.
Category: Procedures Also known as: Brochoscopy, capsule endoscopy, colonoscopy, colposcopy, cystoscopy, cystourethroscopy, endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), enteroscopy, esophagogastroduodenoscopy (EGD), flexible bronchoscopy, flexible sigmoidoscopy, gastroscopy, hysteroscopy, laparoscopy, laryngoscopy, lower endoscopy, mediastinoscopy, panendoscopy, peritoneal endoscopy, pleuroscopy, proctosigmoidscopy, sigmoidoscopy, thorascopy, upper endoscopy, virtual endoscopy
Patient preparation: This procedure is done in an X-ray room. Patients must take nothing by mouth for eight hours prior to the procedure. The doctor may restrict medications such as aspirin, which may increase the risk of bleeding. Patients should report any allergy or sensitivity to anesthetics, dyes, or other medications. Steps of the procedure: The patient receives a sedative for relaxation and a local anesthetic in the throat to suppress the gag reflex. The doctor helps the patient swallow the endoscope and threads it through the esophagus and stomach into the duodenum, where the common bile duct enters the small intestine. The tube is narrow and flexible and does not interfere with breathing. With the end at the common bile duct, the doctor injects a radiopaque dye and takes an X ray. After removing a biopsy specimen, the doctor removes the tube. The procedure usually takes less than an hour. After the procedure: To prevent choking, the patient is not given anything to eat or drink until the anesthetic has worn off. After several hours of observation to rule out any
Definition: Endoscopy is a procedure that involves inserting a thin tube with a viewing instrument inside the body to examine the internal anatomy. There are many types of endoscopes, depending on the purpose of the procedure and the part of the body being examined. Endoscopes may be equipped with lights, fiber optics, ultrasound, lasers, or surgical instruments. Endoscopes may be inserted into the body through small incisions or through natural openings, such as the mouth, vagina, anus, or urethra. Common types of endoscopes include bronchoscopes, colonoscopes, colposcopes, cystoscopes, esophagogastroduodenoscopes, hysteroscopes, laparoscopes, laryngoscopes, mediastinoscopes, sigmoidoscopes, and thoracoscopes. Cancers diagnosed or treated: Anal cancer, bile duct cancer, bladder cancer, cancer of unknown origin, carcinoid 417
Endoscopy
Salem Health: Cancer Endoscopy and Its Uses
cancer, cervical cancer, colon cancer, colorectal cancer, endometrial cancer, esophageal cancer, gallbladder cancer, laryngeal and hypolaryngeal cancer, liver cancer, lung cancer, cancer of the nasal cavity and parasinuses, metastasized cancer, oral cavity and oropharynngeal cancer, ovarian cancer, pancreatic cancer, prostate cancer, small intestine cancer, stomach cancer, vaginal cancer, uterine cancer 418
Why performed: Endoscopies are medical procedures used to screen, diagnose, biopsy, stage, treat, and palliatively treat cancer. Endoscopy is used to screen for certain cancers, allowing early detection and treatment. It is used to provide more detailed information about suspicious tissues seen on imaging scans, which then can be biopsied or removed. Endoscopy is used to determine how far cancer has spread to help in staging. In advanced
Salem Health: Cancer cancer, surgical endoscopy is used for palliative care. Endoscopes are used in minimally invasive or “keyhole” surgeries. Capsule endoscopy is a newer technology in which a miniature camera and light source are contained in a capsule, which is swallowed. The capsule creates images of the intestine that cannot be reached with standard endoscopy. Virtual endoscopy is another newer technology that uses endoscopy and computed tomography (CT) scans to create three-dimensional images. Patient preparation: Preparation depends on the type of endoscopy that is being performed. Generally, upper endoscopies use sedation and local or general anesthesia and require fasting. Lower endoscopies use sedation and local or general anesthesia and require fasting, a liquid diet, laxative use, or an enema. Laparoscopic procedures require fasting and general anesthesia. Some endoscopic procedures may use local anesthesia and may not require fasting. Patients receive specific instructions prior to the procedures. Many types of endoscopies are performed as outpatient procedures at hospitals or surgical centers. Some procedures may require a short stay in the hospital. Steps of the procedure: The steps of the procedure depend on the type of endoscopy being performed. An upper endoscopy involves the use of a plastic mouthpiece to keep the mouth open. The well-lubricated endoscope is placed in the mouth and swallowed by the patient. The doctor gently guides the endoscope through the esophagus, stomach, and small intestine by viewing images on a monitor. A lower endoscopy involves placing a well-lubricated endoscope through the anus and into the rectum and/or colon. The procedure is guided by visual images on a screen. Laparoscopic endoscopy involves inserting the endoscope through a small incision. Air may be inserted to expand the body cavity to create a better view. Surgery may be performed with endoscopy. Surgical instruments may be used to take a biopsy. Lasers or surgical instruments may be used to remove small cancerous or precancerous growths. After the procedure: The patient is observed in the recovery area until alert. Patients receiving outpatient procedures may need another person to drive them home. Some procedures may require a short inpatient stay. Depending on the type of endoscopy, patients may experience discomfort and minimal bleeding. They will receive specific care instructions related to their procedures. Risks: The risks of endoscopy include pain, bleeding, infection, organ or tissue perforation, and those associated with general anesthesia.
Endoscopy Results: Healthy tissues are free of atypical or abnormal growths. Suspicious tissues may be biopsied during the endoscopy or with a separate procedure. Biopsied tissues or suspicious growths that are removed are tested for the presence of cancerous and precancerous cells. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Ersoy, O., B. Sivri, and Y. Bayraktar. “How Helpful Is Capsule Endoscopy to Surgeons?” World Journal of Gastroenterology 13, no. 27 (July 21, 2007): 36713676. Faigel, Douglas O., and David R. Cave, eds. Capsule Endoscopy. Philadelphia: Saunders Elsevier, 2008. Ginsberg, Gregory, et al. Clinical Gastrointestinal Endoscopy. Philadelphia: Elsevier Saunders, 2005. Hara, A. K., et al. “Imaging of Small Bowel Disease: Comparison of Capsule Endoscopy, Standard Endoscopy, Barium Examination, and CT.” Radiographics 25, no. 3 (May/June, 2005): 697-711. Hartmann, D., et al. “Capsule Endoscopy: Technical Impact, Benefits, and Limitations.” Langenbecks Archives of Surgery 389, no. 3 (June, 2004): 225-233. Pennazio, M. “Capsule Endoscopy: Where Are We After Six Years of Clinical Use?” Digestive and Liver Disease 38, no. 12 (December, 2006): 867-878. Sterman, Daniel, et al. Thoracic Endoscopy: Advances in Interventional Pulmonology. Malden, Mass.: Blackwell, 2006. Wilcox, C. Mel, Miguel Muñoz-Navas, and Joseph J. Y. Sung. Atlas of Clinical Gastrointestinal Endoscopy. 2d ed. Philadelphia: Saunders Elsevier, 2007.
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Other Resources
American Cancer Society http://www.cancer.org American Society for Gastrointestinal Endoscopy http://www.asge.org Society of International Gastroenterological Nurses and Endoscopy Associates http://www.signea.org See also Anoscopy; Bronchoscopy; Colonoscopy and virtual colonoscopy; Colposcopy; Culdoscopy; Cystoscopy; Endoscopic retrograde cholangiopancreatography (ERCP); Gonioscopy; Hysteroscopy; Laparoscopy and laparoscopic surgery; Laryngoscopy; Mediastinoscopy; Sigmoidoscopy; Thoracoscopy; Upper gastrointestinal (GI) endoscopy. 419
Endotheliomas
u Endotheliomas Category: Diseases, symptoms, and conditions Also known as: Hemangioendotheliomas, hemangiosarcomas, angiosarcomas, hemangiomas, meningiomas Related conditions: Soft-tissue sarcoma, benign tumors Definition: Endothelioma is a general term used to describe malignant or benign neoplasms of endothelial tissue (the cells that line blood vessels or lymphatic channels). These tumors can arise in any part of the body and often are referred to by terms specific to their location. For example, meningioma or dural endothelioma is a type of benign brain tumor, hepatic angiosarcoma or hemangioendothelioma is a type of liver cancer, and hemangioma is a tumor that often develops on or just under the skin. All fall under the somewhat broader heading of soft-tissue sarcomas. Risk factors: There are no readily identifiable risk factors particular to malignant endothelioma (angiosarcoma), although several risk factors associated with soft-tissue sarcomas in general have been identified. These include exposure to chlorophenols in wood preservatives and phenoxyacetic acid in herbicides, exposure to ionizing radiation, and very rare genetic predispositions in some families. Infantile hemangiomas do not appear to have a hereditary origin, and no known food, medication, or activity during pregnancy has been identified as a risk factor. Etiology and the disease process: The etiology of malignant endothelioma is obscure, although tumors have been known to develop as complications from a preexisting condition. Lymphedema resulting from radical mastectomy may trigger the development of angiosarcoma, and radiation-induced angiosarcomas have developed many years following successful radiotherapy for visceral carcinomas and Hodgkin disease. Environmental carcinogens such as vinyl chloride and thorium dioxide have been shown to induce hepatic hemangioendothelioma. Once initiated in the lining of the blood vessels, the tumor spreads rapidly and builds its own blood vessel network. The causes of infant and neonatal benign hemangioma are also unknown, although some studies have implicated the process of estrogen signaling in hemangioma proliferation. Other studies suggest that an interaction between fetal skin and the maternal placenta may trigger the tumor formation. Incidence: Less than 1 percent of newly diagnosed cancers are soft-tissue sarcomas. Of these, only about 2 percent are classified as hemangiosarcomas or angiosarco420
Salem Health: Cancer mas. The annual incidence of soft-tissue sarcomas in the United States is approximately 2 to 3 cases per 1 million people. Hemangiomas, on the other hand, are the most common benign childhood tumors, occurring in approximately 4 to 10 percent of white children (although they are much less prevalent in children of other races). They are common in twin pregnancies, and the incidence may be as high as 25 percent in premature infants weighing less than 1,000 grams. Female children are three to five times more likely to be affected than male children. Symptoms: Symptoms vary greatly depending on tumor location. Soft-tissue sarcomas of the extremities usually present as painless swellings that grow at a moderately rapid pace. Abdominal and thoracic endotheliomas may grow to large masses before detection. Neurologic symptoms may result from the compression of lumbar or pelvic nerves, and in the case of liver, heart, or bowel tumors, organ function may be compromised as the tumors grow. Up to one-third of patients may present with anemia or other evidence of recent hemorrhage, including gastrointestinal bleeding, hemothorax, or persistent hematoma. Infantile hemangiomas present a more predictable growth pattern. Although occasionally present at birth, most arise during the first few weeks after birth and grow rapidly over the next several months. This is followed by a gradual shrinking, which may occur over a period of one to seven years. Regression appears to be complete in 50 percent of children by the age of five and in essentially all children by the age of twelve. Screening and diagnosis: Diagnosis of malignant endothelioma in most cases is based on surgical biopsy and direct histological examination of tumor tissue. The characteristic network of blood vessels usually provides an unambiguous identification. Screening tests for industrial workers exposed to vinyl chloride are available, but screening programs for people exposed to other environmental carcinogens are not generally available because of the rarity of this type of cancer. Staging of these tumors generally follows the guidelines established by the American Joint Committee on Cancer. These stages are based on the size of the tumor (T), the degree of spread to regional lymph nodes (N), and spread to distant lymph nodes and organs (metastasis, M) as well as its grade. Treatment and therapy: Treatment of malignant endothelioma varies considerably depending on tumor location, although surgical removal with wide margins (2 centimeters, or cm) is recommended whenever possible. However, surgery may be inadvisable for a massive tumor or one extending into vital structures. In these cases and some-
Salem Health: Cancer
Enteritis
times following successful surgery, chemotherapy, radiation therapy, or both are often recommended. Most infantile hemangiomas disappear without treatment, often leaving no visible marks or scars. Occasionally in the case of large affected areas, cosmetic surgery may be indicated. Oral corticosteroids may be prescribed, and small raised lesions may be treated by the direct injection of corticosteroids. In cases of incomplete resolution or for flat, superficial lesions in cosmetically significant areas, pulsed dye laser therapy can be useful.
u Enteritis
Prognosis, prevention, and outcomes: Malignant endotheliomas, like most soft-tissue sarcomas, are clinically aggressive, often difficult to treat, and have a high rate of local recurrence and metastasis. The prognosis is poor, with reported five-year survival rates generally less than 20 percent. Jeffrey A. Knight, Ph.D.
Risk factors: In cancer patients, enteritis is caused by radiation therapy to the abdomen, pelvic area, or rectum. Radiation therapy is given either to treat an inoperable tumor or as an adjunct to surgery or chemotherapy. The likelihood of developing radiation enteritis depends on multiple factors, including: • where the radiation was targeted • strength and frequency of radiation treatment • tumor size • amount of bowel (large or small intestine) exposed to radiation • whether radiation therapy is given at the same time as chemotherapy • presence of radioactive implants to target tumors • patient health and nutritional status Generally, the higher the dose and frequency of radiation and the larger the amount of intestine exposed, the more likely the individual is to develop radiation enteritis. Patients who have diabetes, high blood pressure, poor nutritional status, or conditions that interfere with blood flow to the intestines are more likely to develop radiation enteritis.
u For Further Information DeVita, Vincent T., Jr., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, 2007. Weiss, Sharon W., and John R. Goldblum. Enzinger and Weiss Soft-Tissue Tumors. 4th ed. St. Louis: Mosby, 2001. u
Other Resources
Angiosarcoma Support Organization http://www.angiosarcoma.org/ Liddy Shriver Sarcoma Initiative http://liddyshriversarcomainitiative.org MayoClinic.com Angiosarcoma http://www.mayoclinic.com/health/angiosarcoma/ AN00841 National Cancer Institute Soft Tissue Sarcoma http://www.cancer.gov/cancertopics/types/ soft-tissue-sarcoma/ See also Angiosarcomas; Ewing sarcoma; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Meningiomas; Sarcomas, soft-tissue; TNM staging.
Category: Diseases, symptoms, and conditions Also known as: Radiation enteritis Related conditions: Crohn disease, irritable bowel syndrome Definition: Enteritis is an inflammation of the small or large intestine or both. Enteritis can be acute (short term) or chronic (long lasting).
Etiology and the disease process: Enteritis is an inflammation of the bowel. In noncancer patients, acute enteritis most often occurs because the individual has consumed food or water contaminated with bacteria or viruses that irritate the intestine. Chronic enteritis occurs from gastrointestinal disorders such as Crohn disease. Radiation enteritis is a specific type of enteritis that occurs as the result of radiation therapy during cancer treatment. Radiation is used to kill rapidly dividing cancer cells. However, it also kills normal cells, especially those that divide frequently. The cells lining both the large and small intestine tend to divide often and can be substantially damaged by exposure to radiation necessary to treat cancer occurring in the abdomen and pelvis. As the cells lining the wall of the intestine are damaged, the digestive function is disrupted, and water and nutrients are no longer efficiently absorbed. In acute radiation enteritis, the changes to the cells are reversible and the con421
Enterostomal therapy dition usually clears up a month or two after radiation therapy stops. In chronic radiation enteritis, the cellular damage continues. Symptoms usually improve for a time, but recur between six and eighteen months after radiation therapy has been completed. Damage to the intestinal lining in chronic radiation enteritis is permanent, and symptoms are difficult to control. Incidence: There is controversy over how many people develop radiation enteritis. Some studies have found that almost all patients exposed to abdominal radiation develop some acute symptoms, while other studies have recorded rates of about 35 percent. This variation is probably due to different techniques and doses used at different cancer centers. Of those people who develop acute symptoms, between 5 and 15 percent develop chronic problems. Symptoms: Many symptoms of acute and chronic radiation enteritis are similar. They include crampy abdominal pain, nausea, vomiting, watery or bloody diarrhea, mucous discharge, and bleeding from the rectum. Individuals with chronic enteritis also lose weight, have vitamin deficiencies, and pass loose, fatty or greasy stools. Occasionally with chronic enteritis, the intestine may become obstructed or a perforation (hole) may develop. Screening and diagnosis: For acute radiation enteritis, diagnosis is made on the basis of symptoms appearing shortly after radiation therapy has begun. For chronic radiation enteritis, observation of symptoms and a patient history are used for diagnosis. In chronic enteritis, tests are done to rule out a return of the tumor or other conditions that could cause similar symptoms. Treatment and therapy: Radiation enteritis is treated by managing the symptoms. Dietary changes include avoiding spicy, fatty, and high-fiber foods, alcohol, and milk products, because the intestine often loses the ability to make the enzyme lactase, which is needed to digest milk. Diarrhea is treated with antidiarrheal medicines such as bismuth subsalicylate (Kaopectate), diphenoxylate and atropine (Lomotil), anhydrous morphine (Paregoric), or loperamide (Imodium). Fluid intake is increased to compensate for fluids lost with diarrhea. Antispasmodics may also be given to slow contractions in the bowel. Nutritional counseling is important, especially in chronic enteritis, because the bowel loses the ability to absorb nutrients. Nutritional supplements and digestive aids are often given. Surgery to remove the damaged portion of the bowel in chronic enteritis is controversial. Prognosis, prevention, and outcomes: Symptoms of acute radiation enteritis usually continue two to three 422
Salem Health: Cancer weeks after radiation therapy has finished. Within a few months, symptoms usually disappear completely, and the cells lining the intestine return to normal. In chronic radiation enteritis, the cells lining the intestinal wall are permanently damaged, and symptoms continue indefinitely, although treatment may help to control them. Nutritional counseling and modified diet can help reduce some symptoms of the disorder. Martiscia Davidson, A.M. u
For Further Information Dodd, Marilyn J. Managing the Side Effects of Chemotherapy and Radiation. 2d ed. San Francisco: Regents University of California School of Nursing, 2001. Keane, Maureen, and Daniella Chace. What to Eat if You Have Cancer. 2d ed. New York: McGraw-Hill, 2007. Smith, Tom. Coping with Bowel Cancer. London: Sheldon Press, 2006. Staritz, M., et al., eds. Side Effects of Cancer Chemotherapy on the Gastrointestinal Tract. Boston: Kluwer Academic, 2003.
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Other Resources
MedlinePlus Radiation Enteritis http://www.nlm.nih.gov/medlineplus/ency/article/ 000300.htm National Cancer Institute Gastrointestinal Complications http://www.cancer.gov/cancertopics/pdq/ supportivecare/gastrointestinalcomplications/patient See also Colorectal cancer; Crohn disease; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Inflammatory bowel disease; Small intestine cancer.
u Enterostomal therapy Category: Procedures Also known as: Stomal therapy, stoma care, ostomy care Definition: Enterostomal therapy is the acute care and rehabilitative treatment of patients who have had an ostomy procedure. Cancers treated: Colorectal cancer, familial adenomatous polyposis, bladder cancer Why performed: Enterostomal therapy teaches patients how to care for abdominal stomas (surgically constructed
Salem Health: Cancer connections between the intestines and the skin). It also includes care for urinary or fecal incontinence and treatment of chronic wounds or pressure ulcers. A colostomy is a surgically created opening of the colon (large intestine) to divert stool, and an ileostomy is a surgically created opening of the ileum (end of the small intestine) to divert stool. Bypassing or removing part of the intestine or rectum may be necessary in the treatment of colorectal cancer, diverticulitis, or inflammatory bowel disease, especially when there is a blockage. The remaining end of the intestine is brought through the abdominal wall where wastes are excreted through a stoma and collected outside the body in an external pouching system adhered to the skin. The location of the stoma on the abdomen is dependent on where the ostomy was created. In some ileostomy procedures, an internal pouch (called an ileoanal reservoir, ileoanal anastomosis, or “J” pouch), is constructed from the remaining end of the small intestine and connected to the anus to allow normal stool passage via the anal sphincter muscles. Sometimes, a colostomy or ileostomy is temporary, allowing the newly constructed gastrointestinal system to heal when part of these organs have been removed or resected. A urostomy is a surgical procedure that diverts urine away from the bladder. The ileum or cecum (beginning of the large intestine) is surgically removed and reconstructed into a conduit created for the passage of urine from the kidneys through a stoma in the abdominal wall. The urine is collected outside the body in an external pouching system. A urostomy may be necessary in the treatment of bladder cancer. In some cases when the urinary sphincter muscle does not need to be removed, a “replacement bladder,” called an orthotopic neobladder, can be constructed from a section of the intestines and connected to the urethra to allow normal urination. Patient preparation: Tests performed before ostomy surgery may include X rays, ultrasound, colonoscopy or sigmoidoscopy, blood tests, urine tests, and an electrocardiogram (ECG). Complete bowel cleansing is required beforehand, and the patient will receive specific bowel preparation guidelines. The patient will also receive medication and dietary guidelines, which include following a clear fluid diet. Depending on the type of procedure to be performed, additional tests or patient preparations may be required. Steps of the procedure: The steps required for enterostomal therapy vary greatly, depending on the type of ostomy that the patient has had. In general, steps include gathering supplies; examining the stoma and condition of
Enterostomal therapy the surrounding skin daily and reporting abnormalities to the health care team; cleansing the skin; irrigating the stoma with water either daily or every other day; applying barriers, borders, or pastes to the skin around the stoma and applying the pouch; emptying the pouch when it is one-third full; and changing the pouch as prescribed (every one to three days). After the procedure: Patients who have had an ostomy wear an external pouching system to collect stool or urine because they cannot control the passage of stool, gas, or urine through the stoma. The pouching system also protects the skin around the stoma. There are a wide variety of pouching systems, and an enterostomal therapy nurse will work with the patient to select a system that meets the patient’s preferences and lifestyle. The stoma is usually swollen and large, but it will reduce in size once it has fully healed, within six to eight weeks after surgery. A nurse will teach the patient how to care for the stoma and skin around the stoma, change the ostomy bag, perform the irrigation procedure, and manage problems or emergencies. The patient will be required to demonstrate these activities independently before being discharged from the hospital. The patient will also receive resources for purchasing ostomy supplies. The patient does not have feeling in the stoma, but abdominal pain, cramping, bloating, and discomfort are common for a few weeks after the procedure. Pain medication is prescribed as needed. The patient is usually discharged in three to five days after the procedure, depending on the rate of recovery. Home care enterostomal therapy nursing services will be offered to aid recovery. Regular activities can usually be resumed within six to eight weeks. After surgery, patients often have concerns about resuming regular activities, returning to work, and engaging in sexual activity. The nurse will discuss these concerns with the patient and can provide referrals to community support resources and other medical specialists as needed. Risks: As with all surgeries, there are risks associated with ostomy procedures. Complications are rare but may include bleeding, need for further surgery, infection, or scarring. The health care team will discuss the potential risks of the procedure with the patient and his or her family or caregiver. Results: An ostomy can be a lifesaving surgery, improving symptoms and allowing a patient to enjoy a full range of activities. Angela M. Costello, B.S. 423
Eosinophilic leukemia
Salem Health: Cancer
u For Further Information Aronovitch, Sharon. “Changing a Bowel Diversion Ostomy Appliance: Pouching a Stoma.” In Delmar’s Fundamental and Advanced Nursing Skills. 2d ed. New York: Delmar Learning, 2004.
cell lineage. The abnormality generally begins in the early blast (immature) cell stage and results in an uncontrolled proliferation of the cells. Eosinophilic leukemias involve the specific white cell known as an eosinophil, a bilobed white cell that stains with the dye eosin.
u
Incidence: Eosinophilic leukemia is considered a subcategory of chronic myelogenous leukemias, a group of diseases with an annual incidence of 1 to 2 cases per 100,000 people. The specific number categorized as hypereosinophilic syndrome is not determined, due to its rarity.
Other Resources
Canadian Association for Enterostomal Therapy A Guide to Living with a Colostomy http://www.caet.ca/booklet_colostomy1.htm. International Ostomy Association http://www.ostomyinternational.org National Association for Continence http://www.nafc.org United Ostomy Association, Inc. http://www.uoa.org United Ostomy Associations of America http://www.uoaa.org Wound, Ostomy and Continence Nurses Society http://www.wocn.org/patients See also Abdominoperineal resection (APR); Colectomy; Coloanal anastomosis; Colorectal cancer; Colostomy; Diverticulosis and diverticulitis; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Ileostomy; Urostomy.
u Eosinophilic leukemia Category: Diseases, symptoms, and conditions Also known as: Primary eosinophilia, hypereosinophilic syndrome (HES) Related conditions: Myelogenous leukemias Definition: Eosinophilic leukemia is a malignancy of blood-forming cells in which eosinophils (a type of white blood cell) are the prominent neoplastic leukocytes. Risk factors: Some forms have a genetic basis originating with chromosomal abnormalities (FIP1L1-PDGFRA fusion gene). However, most cases are idiopathic (of unknown origin). Etiology and the disease process: Leukemias are neoplastic lymphoproliferative diseases that involve bone marrow cells. The specific type of leukemia depends on which particular cell, usually in the leukocyte/white blood 424
Symptoms: Symptoms are often general, categorized as “flulike” symptoms. These include an unexplained fever, swollen lymph nodes, and unexplained fatigue. Screening and diagnosis: Screening is generally not carried out for leukemias. The extent of chromosomal abnormalities is occasionally used to determine prognosis. Diagnosis is based on the microscopic observation of immature or abnormal leukocytes, in particular, early-stage eosinophils, using either blood samples or bone marrow biopsies. Treatment and therapy: Treatment is based on the extent or stage of the disease and may involve a variety of procedures. The treatment of choice begins with chemotherapy involving the use of antiproliferative drugs such as vincristine or cyclophosphamide either orally or intravenously. Most chemotherapeutic drugs produce side effects such as nausea or a lowering of the blood count. Steroids are sometimes included with treatment as a means to reduce such effects. Other methods of treatment include surgery—removal of the spleen, a site of neoplastic cell production or accumulation—and radiation therapy. Radiation therapy has proven most useful as a palliative treatment rather than one that effects a “cure.” Biological therapy, the use of interferon-alpha, as a means to stimulate an immune response against the neoplasm may also be included in treatment. Prognosis, prevention, and outcomes: Since the genetic basis for eosinophilic leukemia is unknown, there is no known means of prevention. Prognosis depends on the effectiveness of treatment, the maturation stage of precursor cells, and the extent of neoplastic cell infiltration into other organs. Survival may be measured in months, or in some cases remission may last for decades. Richard Adler, Ph.D. See also Leukemias; Myeloproliferative disorders.
Salem Health: Cancer
u Ependymomas Category: Diseases, symptoms, and conditions Related conditions: Glial tumors and gliomas Definition: An ependymoma is a central nervous system cancer that arises from the ependymal cells that line the fluid-containing ventricles and central canal of the brain and spinal cord, respectively. Ependymomas are a type of glial cell tumor and are collectively derived from the cells that provide support and nourishment to neural cells. Ependymomas account for 3 percent of all glial cell tumors and 6 to 9 percent of all primary central nervous system tumors. Risk factors: The most salient risk factor relates to a genetically mediated transformation of normal ependymal cells into tumor cells. A history of neurofibromatosis type 2 is associated with the development of spinal ependymomas. Neurofibromatosis type 2, an autosomal dominant syndrome, is caused by a mutation in the NF2 gene manifesting with skin lesions (café-au-lait spots) and bilateral hearing loss from acoustic nerve tumor growth. Familial occurrences of isolated ependymomas have also been documented. Etiology and the disease process: Ependymomas originate from the transformation of an ependymal cell. Although no single aberration has been implicated, involvement of chromosome 22 has been most commonly implicated, the same chromosome that bears the NF2 tumor-suppressor gene (22q12). Changes seen in genetic studies include translocation (removal and subsequent reattachment of a chromosomal segment to another chromosome), deletion of the long arm (22q), or monosomy (absence of one half of a chromosome pair). One family study has narrowed down this region (22pter-22q11.2), suggesting that a tumor-suppressor gene may be responsible. Other aberrations in several other chromosomes were noted in other studies. Incidence: Ependymomas have two incidence peaks: in early childhood and in adulthood. The mean age of ependymoma occurrence in childhood is at five years, peaking again during adulthood at a mean age of thirty-four. However, a substantial number of ependymomas in children, 30 percent of all childhood cases, manifest before age three. By location, ependymomas in the brain are seen more commonly in children (90 percent of cases), while spinal (intramedullary) tumors are more commonly seen in adults (60 percent of cases).
Ependymomas Symptoms: Obstruction of the flow of cerebrospinal fluid (CSF) within the fourth ventricle, with resulting pressure buildup and tissue compression, usually occurs. Brain stem involvement may be seen as irritability or lethargy. Cerebellar symptoms denoting involvement may be seen as frequent loss of balance and dizziness. Occasional cerebrum involvement may manifest as personality and behavioral changes or one-sided body weakness or paralysis. Symptoms of increased pressure include nausea, vomiting, morning headache, and vision changes. Physical examination findings may include papilledema (swelling of both optic nerves), limb incoordination with voluntary movements, cranial nerve VI to X compression signs such as eye movement (nystagmus, lateral gaze weakness or paralysis), facial movement, speech and swallowing abnormalities, and increase in head circumference in babies less than two years of age. Spinal cord manifestations roughly correspond with the affected nerve root level, ranging from pain to sensory deficits, weakness, paralysis, loss of reflexes, and muscle wasting. Screening and diagnosis: There are no routine screening tests available for ependymomas. Clinical history, physical examination, and neuroimaging tests such as magnetic resonance imaging (MRI) or computed tomography (CT) can suggest an ependymoma. These tumors are seen as intraventricular or intramedullary masses that closely match or are darker in contrast to surrounding tissue. Clues that may aid in distinguishing a tumor from normal tissue include cystic formations, calcifications, hemorrhage, or necrosis. The final diagnosis of the type of ependymoma is mainly pathological, when a tissue sample is examined microscopically and classified according to the World Health Organization classification for ependymal tumors. Grade I includes subependymomas and myxopapillary ependymomas; grade II includes cellular, papillary, and clear-cell ependymomas, and grade III ependymomas are of the anaplastic (malignant) variety. Treatment and therapy: Treatment of ependymomas includes surgical removal, radiation therapy, and chemotherapy. The most important factor in a good prognosis is surgical removal, in which a gross total resection is done irrespective of tumor location, removing the entire primary tumor. Postoperative radiotherapy and chemotherapy—a regimen of cisplatin, etoposide, carboplatin, vincristine, and mechlorethamine or of ifosfamide, carboplatin, and etoposide (ICE)—are carried out to prevent recurrence. Radiotherapy is preferred over chemotherapy except in malignant cases. Restoration of normal cerebrospinal fluid circulation through the ventricles and central canal is a secondary objective if assessment of cerebrospinal fluid 425
Epidemiology of cancer shows poor outflow postoperatively. This may be achieved with the addition of a device diverting excess cerebrospinal fluid to the abdominal cavity (ventriculoperitoneal shunt). Prognosis, prevention, and outcomes: The overall fiveyear survival rate for all ependymoma patients is 50 percent. Children have a much lower five-year survival rate (14 percent) when compared with adults (76 percent) because of where children’s tumors are typically located. Prognosis depends on several predictors, the most significant being the extent of tumor resection. Five-year survival rates approach 70 percent in gross total resection as opposed to 30 to 40 percent in partial resection irrespective of tumor grade. Other factors include amount of remaining tumor, tumor grade, age, infratentorial location, local spread to the brain stem, metastases, and rate of recovery. Complications associated with surgery in posterior fossa (cerebellar) resections include cerebellar mutism (speech deficits or absence with cerebellar deficits) and long-term neurologic deficits. Aldo C. Dumlao, M.D. u For Further Information Dempsey, Sharon. My Brain Tumour Adventures: The Story of a Little Boy Coping with a Brain Tumour. London: Jessica Kingsley, 2003. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Adult Brain Tumors: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. _______. The Official Patient’s Sourcebook on Childhood Ependymoma: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. u
Other Resources
Cancer Backup Ependymoma http://www.cancerbackup.org.uk/Cancertype/Brain/ Typesofbraintumour/Ependymoma National Cancer Institute Childhood Ependymoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ childependymoma/patient/ See also Brain and central nervous system cancers; Carcinomatous meningitis; Craniotomy; Gliomas; Simian virus 40; Spinal axis tumors. 426
Salem Health: Cancer
u Epidemiology of cancer Category: Cancer biology Definition: Cancer epidemiology is the study of the distribution, determinants, and frequency of malignant disease in specific populations. Three broad objectives related to the use and importance of epidemiologic cancer research are to identify factors related to the etiology of specific cancers; to use cancer-risk data to formulate theories regarding cancer prevention and control; and to educate a diverse public regarding the prevention and control of cancer. These strategies attempt to match educational and dissemination methods to population needs with attention to cancer risk, literacy, trust of medical professionals, and palatability of information, factors known to vary widely across population subgroups. Three types of epidemiologic research apply to the field of cancer. Descriptive epidemiology focuses on the trends and frequency of cancer in specific populations. Analytic epidemiology identifies causes and predisposing risk factors associated with the development of specific cancers. Clinical epidemiology delineates screening programs and evaluates outcomes for the range of prevention strategies implemented. Descriptive epidemiology: In 1995 the American Cancer Society estimated 1,252,000 new cancer cases and 547,000 cancer deaths in the United States. Cancer incidence and mortality rates are higher among men than women. Furthermore, African Americans have a higher cancer mortality rate than whites, which has been a source of discussion and controversy. Some argue that inherent genetic factors account for the discrepancy, whereas others attribute the difference to an overrepresentation of poverty among African Americans and superior health care received by affluent versus impoverished groups. The leading cancers in the United States are lung, breast, prostate, colorectal, and ovary, accounting for about 61 percent of cancer diagnoses. Americans over the age of sixty-five have a tenfold greater risk of developing cancer than do younger Americans. Despite an increase in overall cancer mortality rate between 1950 and 1990, mortality rates for all cancers combined have declined substantially for individuals under age forty-five. They have increased in people over age fifty-five, with that increase primarily related to lung cancer deaths. Many reports identify a decline in cancer mortality of about 14 percent since 1950, although these reports exclude deaths from lung cancer. These data seem biased and problematic, as smoking is the primary etiologic factor in lung cancer diagnoses and a leading public health issue. Excluding lung cancer from
Salem Health: Cancer cancer death statistics implies that if lifestyle issues and behaviors relate to etiology, science is not responsible or interested in research to develop effective prevention and treatment strategies. This denies the role of social, political, and economic factors in promoting increasingly prevalent maladaptive behaviors among vulnerable members of society and is an area worthy of aggressive debate and action in terms of research funding. U.S. Cancer Statistics: 2004 Incidence and Mortality marks the sixth time that the Centers for Disease Control (CDC), the National Program of Cancer Registries (NPCR), and the National Cancer Institute’s (NCI’s) Surveillance, Epidemiology, and End Results (SEER) Program have combined their data sources to produce a collaborative set of federal cancer incidence statistics (newly diagnosed cases) for a single year. Mortality statistics from the CDC’s National Vital Statistics System are also included and report 2003 cancer deaths both nationally and by state. The report was produced in collaboration with the North American Association of Central Cancer Registries. Analytic epidemiology: The goal of analytic cancer epidemiology is to identify the factors that predispose individuals to a cancer diagnosis and to quantify risk. Cancer risk factors include environmental exposures, genetic susceptibility, and immunosuppressive state and may be secondary to a history of malignancy, viral infection, or medical therapy. These risk factors can account for various aspects of carcinogenesis and assume varied degrees of causal primacy. Clinical epidemiology: Epidemiologic research plays an important role in the development of cancer-screening modalities and prevention strategies. Cancer prevention focuses on decreasing incidence by lowering risk through changes in lifestyle patterns and behavior. Primary prevention attempts to stop the development of cancer. Secondary prevention aims to improve cure rates by cancer screening and early diagnosis and treatment. Cancer screening involves testing to detect early-stage cancer in asymptomatic individuals. Ideally, screening tests should be easy to administer, noninvasive, and inexpensive. To be beneficial, early detection should alter prognosis and improve survival. Emerging data and discovery: New data are rapidly emerging that are changing cancer screening and prevention practices. Although these changes are quite positive, the proliferation of data can create confusion among health consumers and avenues to receive reliable information are needed.
Epidemiology of cancer For example, the human papillomavirus (HPV), types 16 and 18, has been causally related to cervical intraepithelial neoplasia. A history of genital warts is linked to human papillomavirus types 6 and 11 and may explain the increased risk associated with multiple sexual partners. Other sexually transmitted viruses, such as herpes simplex virus 2, may interact as etiologic factors. The vaccine Gardasil protects against four HPV types, which together cause 70 percent of cervical cancers and 90 percent of genital warts. Ideally, girls and young women should get the vaccine before they are sexually active because the vaccine is most effective in those who have not yet acquired any of the four HPV types covered by the vaccine. Girls and women who have not been infected with any of those four HPV types will get the full benefits of the vaccine; those who are sexually active may also benefit from the vaccine, although they may get less benefit from the vaccine if they may have already acquired one or more of the HPV types covered. One would assume that the worldwide annual rate of 300,000 deaths from cervical cancer could easily be reduced by application of the vaccine—but this new technology raises questions and obstacles to care, along with offering care: First, there is no test available to tell if a woman has had any or all of these four HPV types. Second, the need to vaccinate women before they become sexually active raises ethical issues, particularly among populations that fear the vaccine will send a message condoning teenage sexual activity. Other issues revolve around who should advertise and promote the vaccine, how it should be promoted in developing nations, and whether parents who resist vaccination should be held liable for their children’s sexual health. These and a host of other issues demonstrate how medical advances complicate cancer epidemiology as well as offering hope. Sociocultural issues: A sensitive issue regarding cancer screening relates to the fact that cancer prevention and control efforts center on the development of strategies to benefit the general population rather than individual lives. As new knowledge and technologies have proliferated at unprecedented rates, many ethical questions—such as fair and equitable allocation of health resources across diverse populations, the priority of individual needs versus those of the social aggregate, and the unfair distribution of resources to privileged groups—have come under considerable scrutiny. Some of these issues have become especially poignant as genetic technologies have identified specific ethnic factors to enhance the risk for certain cancers. The incidence increases fiftyfold in whites and thirtyfold in African Americans between the ages of fifty and 427
Epidemiology of cancer eighty-five. African Americans have the highest incidence of prostate cancer in the world, whereas Japanese have one of the lowest rates. Japanese who migrate to Hawaii develop a risk for prostate cancer higher than that of Japanese who remain in their home country, but only half that of American whites. African American men tend to have metastatic disease at diagnosis—indeed, 40 percent more often than whites do. The overall survival rate for African American men is 10 percent lower than that for white men, even when they are diagnosed at the same stage of disease. Endometrial carcinoma is the most common gynecologic malignancy. Its incidence is highest among white women, whereas its mortality rates are higher among African American women. For the past two decades, the incidence rates have been declining, except among African American women over fifty years old. Cultural, psychosocial, and demographic factors may discourage the use of genetic testing services among individuals who could benefit from them or, conversely, may promote use when testing has the potential to create more harm than benefit. To develop effective cancer detection and prevention programs, therefore, it is essential to consider cultural, demographic, and psychosocial issues that may foster or hinder utilization. Consumer lead advocacy groups have taken a grassroots approach to soliciting research dollars to fund basic and clinical research programs. That fact alone may skew inquiry toward those cultural, ethnic, and socioeconomic subgroups who value and can interpret results of medical research and who have sufficient personal resources to advocate on their own behalf. Lack of interest in genetic testing has been associated with less education, minority status, lower socioeconomic status, and less performance of other health-promoting behaviors. Culture plays a central role in determining health beliefs, attitudes, and behavior, but few health care providers realize that health is a cultural concept defined differently across cultures. Many are unaware that the health care system is culturally designed and administered largely according to mainstream values. In genetics, cultural consideration is particularly important. Although knowledge that certain diseases run in families spans all societies, beliefs about causation of familial diseases vary considerably. Cultural attitudes toward disease also differ among ethnic populations. Moreover, culture comes into play in providerclient interaction and communication, which are both key components of genetic counseling. People from cultures that expect authority figures to be directive may find nondirective genetic counseling confusing and bewildering. Between 1970 and 1990, the minority population grew at a rate about three times that of the total population. The U.S. Census Bureau projects that minorities will ac428
Salem Health: Cancer count for about one-third of the U.S. population by the year 2010. Given these trends, attention to ethnocultural barriers is paramount in achieving universal access to genetic services. Although cultural competency is not a licensing requirement for health professionals, it is vital in view of the sensitive nature of the issues to be discussed and the need for privacy and confidentiality of information exchanged. The professional genetics community includes few minorities, despite demographic trends—further limiting the access of minorities to culturally sensitive and relevant genetic services. This lack of input from minority communities also limits the shaping of public policy and planning of genetic research and counseling in ways meaningful to ethnic minorities. For individuals to benefit from genetic services, those services must be available, culturally appropriate, accessible, and affordable. Unless such issues are addressed, any attempt to broaden access to genetic services will be limited and perhaps even hazardous to a less informed population. Few primary care providers are ready to take on these new tasks. They need education in understanding not only the scientific advances in genetics but also their ethical, legal, cultural, and psychosocial implications. Inadequate appropriations to develop the needed service infrastructure have resulted in an inadequate number of genetic specialists, primary care providers, and public health providers prepared to incorporate genetics into practice. Among primary care providers, inadequate preparation in genetics is compounded by the severe time constraints imposed on virtually all service providers and by a lack of reimbursement for cognitive services. Most consumers also have low scientific literacy and know little about basic genetics or genetic testing. Without a degree of genetics literacy and an understanding of the limitations and risks involved including insurance and employment discrimination, psychological trauma, intrafamilial conflict, and social stigmatization, people cannot make truly informed decisions. Chemoprevention: A relatively new approach to cancer prevention is through chemoprevention (as opposed to chemotherapy, or drug treatment, following a cancer diagnosis). Cancer chemoprevention is defined as the reversal of carcinogenesis in the premalignant phase. The observation that retinoids, acting as modulators of cell differentiation, are effective in suppressing oral carcinogenesis and, therefore, in preventing second primary tumors in squamous cell carcinoma of the head and neck has led to the evaluation of these agents as chemopreventive therapy for tumors of the upper aerodigestive tract in high-risk
Salem Health: Cancer populations. Studies of adjuvant hormonal therapy with tamoxifen for breast cancer have shown a 50 percent reduction of contralateral disease, which led to a national tamoxifen chemoprevention trial to evaluate risk reduction for primary breast cancer in women at high risk. With the development of new molecular techniques, chemoprevention trials will be aided by the identification of markers for premalignant lesions. Prognosis for cancer epidemiology: Decision making regarding genetic susceptibility testing, health surveillance, chemoprevention and preventative surgery are being quickly added to the realm of health care options without adequate knowledge among professionals and the public regarding the meaning and practical relevance of this information. Psychosocial, cultural, and economic factors may affect the study, dissemination, and utilization of genetic discoveries to create service barriers and widen the gap between the haves and have nots among health care consumers. Genetic information is received against a backdrop of deeply held personal beliefs. The influence of culture on health beliefs and actions is enormous, and the role that culture, ethnicity, and religion play in formulating an individual’s motivation toward health-seeking behaviors must be addressed in all educational and clinical activities. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u
For Further Information Centers for Disease Control. U.S. Cancer Statistics: 2004 Incidence and Mortality. Washington, D.C.: Author, 2004. Dennis, Leslie K., and Deborah Dawson. “Meta-analysis of Measures of Sexual Activity and Prostate Cancer.” Epidemiology 13, no. 1 (January, 2002): 72-79. Gandini, S., H. Merzenich, C. Robertson, and P. Boyle. “Meta-analysis of Studies on Breast Cancer Risk and Diet: The Role of Fruit and Vegetable Consumption and the Intake of Associated Micronutrients.” European Journal of Cancer 36 (March, 1990). Green, Lawrence W., and Marshall W. Kreuter. Health Promotion Planning: An Educational and Ecological Approach. 3d ed. Mountain View, Calif.: Mayfield, 1999. Little, Jullian. Epidemiology of Childhood Cancer. IARC Scientific Publications 149. Lyon, France: International Agency for Research on Cancer, 1999. Moolgavkar, S., et al., eds. Quantitative Estimation and Prediction of Human Cancer Risks. IARC Scientific Publications 131. Lyon, France: International Agency for Research on Cancer.
Epidermoid cancers of mucous membranes u
Other Resources
Centers for Disease Control and Prevention National Program of Cancer Registries http://www.cdc.gov/cancer/npcr National Cancer Institute Cancer Clusters http://www.cancer.gov/cancertopics/factsheet/risk/ clusters North American Association of Central Cancer Registries http://www.naaccr.org See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Childhood cancers; Elderly and cancer; Ethnicity and cancer; Family history and risk assessment; Geography and cancer; Latinos/Hispanics and cancer; Native North Americans and cancer; Occupational exposures and cancer; Poverty and cancer; Singlehood and cancer; Statistics of cancer; Survival rates; Young adult cancers.
u Epidermoid cancers of
mucous membranes Category: Diseases, symptoms, and conditions Related conditions: Squamous cell carcinoma, skin cancers, head and neck cancers, nasopharyngeal cancer, laryngeal cancer, nasal cavity and paranasal sinus cancers, oral and oropharyngeal cancers, gastrointestinal cancers, urinary system cancers Definition: Epidermoid cancers of mucous membranes are squamous cell malignancies in tissues in which glands produce mucosal fluids to protect epithelial cells and assist various physiological functions. These membranes line the interiors of body cavities, organs, and structures that connect either directly or indirectly to external skin openings. Some references to epidermoid cancers of mucous membranes limit them to head and neck cancers. Since the mid-nineteenth century, medical literature has mentioned epidermoid cancers in other mucous membranes, which are extensive throughout the torso, including respiratory, gastrointestinal, and genitourinary tracts. Risk factors: Nicotine exposure increases people’s risk for developing epidermoid malignancies in mucous membranes in the mouth, larynx, and pharynx. Alcohol consumption exacerbates epidermoid cancer risks. Oncology 429
Epidermoid cancers of mucous membranes experts have associated epidermoid cancers of mucous membranes with such carcinogens as asbestos and industrial by-products, including sawdust. Medical professionals have connected these cancers to diets containing large amounts of salt and preservatives, which can damage mucous membranes. They have also tied these cancers to periodontitis and the Epstein-Barr virus. Some researchers hypothesize that the human papillomavirus (HPV) might cause epidermoid cancer in mucous membranes. Investigators have studied how pemphigoid, an autoimmune condition causing blistering of mucous membranes, possibly affects patients’ vulnerability to cancer. Etiology and the disease process: Epidermoid carcinomas form in squamous cells both in external skin tissues and internal membrane tissues in organs and cavities. Squamous cell carcinomas develop in the outer epithelial layer of membranes when routine cell division and replacement and sometimes epithelial cell production of keratin proteins deviate and extra abnormal cells and keratin accumulate. Malignant squamous cells typically first appear as lesions known as erythroplasia if they are red or brown and leukoplakia if they are white. Tumors grow and spread into other epithelial layers. For example, epidermoid tumors in lungs begin in respiratory passage membranes, then extend to adjacent organs or lymph nodes. Incidence: Squamous cell carcinomas associated with external skin cancers, with an estimated 400,000 diagnoses in the United States yearly, occur more frequently than they develop in mucous membranes. Statistics for each type of mucous membrane affected by epidermoid cancers vary. More than 90 percent of various head and neck cancers consist of squamous cell carcinomas. Some 30 percent of non-small-cell lung cancer cases diagnosed involve squamous cell carcinomas. Men are more susceptible than women to developing epidermoid cancers in mucous membranes. These malignancies tend to occur after the age of fifty. Symptoms: Many patients locate lumps in their neck or detect lesions on their lips or inside their mouth. These oral sores as well as others in mucous membrane tissues do not undergo the normal healing processes. Epidermoid cancers in mucous membranes may cause sore throats and affect how people chew, swallow, and speak. Swollen or numb sinus, jaw, or neck areas; impaired hearing; respiration difficulties; and altered sensory abilities are other symptoms. Some patients experience problems with how dentures fit. 430
Salem Health: Cancer Screening and diagnosis: Health professionals, including dentists, screen patients for potential membrane cancers and collect tissue or fluid samples for laboratory testing. Diagnostic procedures include computerized imaging and scanning, endosonography, and other tests. Physicians differentiate epidermoid carcinomas in mucous membranes from keratin cysts and mucosal melanomas. Oncologists stage most epidermoid cancers of mucous membranes with the TNM (tumor/lymph node/metastasis) system, devising designations that expand the four basic stages to describe lymph node impact more precisely in terms of tumor size, extent of metastasis, and location relative to nodes. Various types of mucous membrane epidermoid cancers have specific staging criteria, such as which vocal cord is affected. Treatment and therapy: Many physicians use radiation, chemotherapy, and surgical treatment to remove tumors, lymph nodes, or affected organs. Radiation and chemotherapy without surgery enables patient to continue normal activities and capabilities by retaining such body parts as their larynx, which is essential for speech. Some oncologists deliver chemoradiation intravenously to tumors. Researchers have tested the potential for using herpes simplex virus type 1 to treat tumors in mucous membranes. Speech and physical therapists, nutritionists, prosthodontists, plastic surgeons, and other specialists enhance treatment of epidermoid cancers in mucous membranes. Psychologists offer emotional support because an estimated 40 percent of mucous membrane cancer patients suffer intense depression. Prognosis, prevention, and outcomes: Patients with epidermoid cancers in mucous membranes are most likely to survive if their malignancies are detected at an early stage, with an estimated 90 percent survival rate. Medical professionals estimate that more than 50 percent of cases, however, remain undiagnosed until tumor growth has expanded to later stages, increasing fatalities within five years of diagnosis, compared with other cancers. Elizabeth D. Schafer, Ph.D. u
For Further Information Egan, Conleth A., et al. “Anti-Epiligrin Cicatricial Pemphigoid and Relative Risk for Cancer.” The Lancet 357, no. 9271 (June 9, 2001): 1850. Gallegos-Hernández, José-Francisco, et al. “The Number of Sentinel Nodes Identified as Prognostic Factor in Oral Epidermoid Cancer.” Oral Oncology 41, no. 9 (October, 2005): 947-952. Sonis, Stephen T., Douglas E. Peterson, Deborah B. Mc-
Salem Health: Cancer Guire, and David A. Williams, eds. “Mucosal Injury in Cancer Patients: New Strategies for Research and Treatment.” Journal of the National Cancer Institute Monographs 29 (2001): 1-54. u
Other Resources
American Cancer Society Detailed Guide: Oral and Oropharyngeal Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=60 National Cancer Institute Head and Neck Cancer: Treatment http://www.cancer.gov/cancertopics/treatment/ head-and-neck See also Gastrointestinal cancers; Head and neck cancers; Laryngeal cancer; Lung cancers; Mucinous carcinomas; Nasal cavity and paranasal sinus cancers; Oral and oropharyngeal cancers; Salivary gland cancer; Skin cancers; Squamous cell carcinomas; Throat cancer; Urinary system cancers.
u Epstein-Barr virus Category: Carcinogens and suspected carcinogens Also known as: EBV, human herpesvirus 4 (HHV-4) Related cancers: Burkitt lymphoma, a type of non-Hodgkin lymphoma (NHL), nasopharyngeal carcinoma Definition: Epstein-Barr virus is one of the eight known types of human herpesviruses and is a member of the gamma subtype of this group. Like many herpesvirus species, Epstein-Barr virus appears to establish a lifelong presence in the human body, remaining quiescent for long periods of time and then inexplicably becoming active. Causally related to mononucleosis, it is also associated with a variety of human cancers, such as Burkitt lymphoma and nasopharyngeal carcinoma, and is therefore considered to be a carcinogenic virus. Exposure routes: Humans are the only known reservoir of Epstein-Barr virus, which is present in oropharyngeal secretions and is most commonly transmitted through saliva; transmission of the virus requires intimate contact with the saliva (found in the mouth) of an infected person. Transmission through the air or blood does not usually occur. Epstein-Barr virus is causally related to infectious mononucleosis (IM), a disease characterized by the proliferation of single-nucleus white blood cells, resulting in fever, sore
Epstein-Barr virus throat, and sometimes hepatitis. Infectious mononucleosis may be contagious for a period of weeks. However, isolation measures are not practical, since Epstein-Barr virus is frequently present in the saliva of healthy persons, who may carry and spread the virus intermittently for life. Transmission of Epstein-Barr virus is therefore practically impossible to prevent. Where found: The Centers for Disease Control and Prevention (CDC) estimates that 95 percent of adult Americans between the ages of thirty-five and forty have been infected by Epstein-Barr virus, but it is less prevalent in children and teenagers, a pattern observed in the developed world but not in developing regions such as Africa and Asia. In Africa, for example, most children have been infected by the virus by the age of three. Epstein-Barr virus has also been associated with nasopharyngeal cancers in Asia (especially China) and Burkitt lymphoma in equatorial Africa and Papua New Guinea. In tropical regions, Burkitt lymphoma has been shown to coexist with malaria. In the United States, Epstein-Barr virus has also been associated with nasopharyngeal cancers in immigrants from Asia. The incidence of Burkitt lymphoma has been increasing. Non-Hodgkin lymphomas are found in people whose immune systems have been compromised by drug therapy and disease. At risk: Epstein-Barr virus has been shown to take advantage of those with weakened immune systems; Burkitt lymphoma, a non-Hodgkin lymphoma (NHL), is found in organ transplant patients undergoing immunosuppression therapy, as well as those living with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrom (AIDS) who are immunocompromised by their disease. Because Burkitt lymphoma typically occurs in tropical climes where malaria is endemic, it is believed that the immune systems of those with malaria are altered, resulting in tumor production. Epstein-Barr virus is also associated with nasopharyngeal carcinoma, which is prevalent in those of Chinese ancestry; both genetic and environmental factors such as a diet high in nitrosamines may also contribute to cancer development. Environmental/ occupational exposure to pesticides and solvents shows no significant pattern of positive association with EpsteinBarr virus and related cancers. Etiology and symptoms of associated cancers: Occurring in nearly all regions of the world, Epstein-Barr virus is among the most ubiquitous of viruses, and most people will become infected with Epstein-Barr virus sometime during their lifetimes. In the United States, as soon as maternal antibodies disappear, infants become vulnerable 431
Epstein-Barr virus
Salem Health: Cancer
Oral hairy leukoplakia caused by Epstein-Barr virus in an immunosuppressed HIV-positive patient. (Sol Silverman, Jr., D.D.S./Centers for Disease Control)
to Epstein-Barr virus infection. In adolescents, infection with the Epstein-Barr virus results in infectious mononucleosis in 35 to 50 percent of cases. Although the symptoms of infectious mononucleosis usually dissipate within several months, the Epstein-Barr virus lies dormant in a few cells in the throat and blood for the remainder of the person’s life. From time to time, the virus may reactivate and is often present in the saliva, suppressing the immune system by causing repeated mutations in B cells, which may then proliferate unabated, resulting in tumors. Epstein-Barr virus establishes a lifelong latent infection in the body’s immune system that may later result in the emergence of Burkitt lymphoma and nasopharyngeal carcinoma. The initial symptoms of Burkitt lymphoma may include a swollen lymph node in the upper body or abdomen. If the tumor is found in the chest, breathing difficulties may ensue. In others, itching, weight loss, fever, and fatigue may be present. Commonly, Burkitt lymphoma results in formation of a large tumor mass in the jawbone. Adults with AIDS often develop tumors in various parts of the body. Symptoms of nasopharyngeal can432
cer may include a lump in the neck or nose, numbness on the side of the face, headaches, ear pain, and difficulty speaking and breathing. History: In the latter part of the nineteenth century and in the early part of the twentieth century, the medical community in the United States and in Europe began to report on a novel syndrome of fever, sore throat, and swollen glands that was later termed mononucleosis and later found to be causally related to Epstein-Barr virus. EpsteinBarr virus was discovered in the 1960’s from a biopsy of a tumor associated with Burkitt lymphoma and was the first virus to be directly linked to human cancer; in 1964 Michael Epstein and Yvonne Barr isolated virus particles from cell lines derived from Burkitt lymphoma, hence the name, Epstein-Barr virus. Subsequently, Epstein-Barr virus was found to be the main viral cause of cancer in humans, having an etiological role in Burkitt lymphoma and other B-cell lymphomas as well as nasopharyngeal carcinoma. Cynthia Racer, M.A., M.P.H.
Salem Health: Cancer u For Further Information Robertson, E. S. Epstein-Barr Virus. Portand, Oreg.: Caister Academic Press, 2005. Tselis, A., and H. B. Jenson. Epstein-Barr Virus. New York: Taylor & Francis, 2006. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Young, L. S., and A. B. Rickinson. “Epstein-Barr Virus: Forty Years On.” Nature Reviews: Cancer 4, no. 10 (2004): 757-768.
See also Blood cancers; Burkitt lymphoma; Carcinoma of unknown primary origin (CUP); Epidermoid cancers of mucous membranes; Head and neck cancers; Hodgkin disease; Immune response to cancer; Infectious cancers; Leiomyosarcomas; Leukoplakia; Lymphomas; NonHodgkin lymphoma; Oncogenic viruses; Proto-oncogenes and carcinogenesis; Risks for cancer; Throat cancer; Viral oncology; Virus-related cancers.
u Erionite
Erythroplakia catalysts, desiccants, oil and gas absorbents, pesticides, purification of water, and the cleanup of wastewater. Etiology and symptoms of associated cancers: Through inhalation of erionite dust, erionite fibers can lodge in lung and mesothelial tissue. Due to the shape of the fibers, their surface reactivity, their ability to selectivity adsorb molecules from air and liquids, and their resistance to dissolution in fluids within the lung, erionite is extremely irritating and toxic to the lungs and mesothelium, producing malignant tumors in the lungs and in the thoracic and abdominal cavities. History: Mineral ores containing erionite have been mined commercially in the United States since the early 1960’s. During the 1960’s and the 1970’s, it was one of four commercially important zeolites. Erionite is found in many different rock types and geological settings but is rarely found in pure form. Until the late 1980’s, erionite was used as a catalyst in a hydrocarbon-cracking process. During the 1980’s, erionite was linked with the development of mesothelioma and lung cancer in some villages in Turkey where residents experienced chronic exposure to erionite. The use of erionite was banned in the United States by the Environmental Protection Agency in 1991. Alvin K. Benson, Ph.D.
Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1994 Also known as: Erionit, erionita
See also Asbestos; Silica, crystalline.
Related cancers: Mesothelioma, lung cancer
u Erythroplakia
Definition: Erionite is a colorless or white crystalline solid that forms woollike fibers and belongs to a group of minerals known as zeolites.
Category: Diseases, symptoms, and conditions Also known as: Oral cancer
Exposure routes: Inhalation Where found: Erionite is found in rock deposits in Arizona, California, Nevada, Oregon, South Dakota, and Utah in the United States and in the Faroe Islands. It is found with associated minerals that include calcite, opal, pyrite, halite, and other zeolites. Before the late 1980’s, a few homes were built in the western United States with blocks that contain erionite. At risk: Workers involved in the production and mining of erionite and its related minerals known as zeolites are at risk for contamination. As erionite occurs naturally as a mineral in outcrops of Earth’s crust, residents or tourists in areas where it is found can be exposed to it. The general public is at risk for contamination from erionite that is contained within zeolites that are used in a variety of applications that include animal feed, pet litter, soil conditioners,
Related conditions: Leukoplakia Definition: Erythroplakia is a precancerous soft, reddened patch found on the floor of the mouth, the tongue, or the soft palate. Risk factors: Smoking and alcohol consumption, especially in combination, are known risk factors for erythroplakia; use of smokeless tobacco and smoking marijuana also are considered potential risk factors. Etiology and the disease process: A history of smoking and use of alcohol may be an underlying cause of erythroplakia, but sometimes there is not an identifiable cause. This type of oral lesion has a high rate of developing cancer. Incidence: Oral cancers usually appear in older adults (over sixty years) and represent approximately 3 percent of all malignancies in men and approximately 2 percent of all malignancies in women. 433
Esophageal cancer Symptoms: There may be no early symptoms other than the reddened patch; some lesions may be mixed with white patches (this is called erythroleukoplakia). Later symptoms may include bleeding, loose teeth, and a change in the fit of dentures. Screening and diagnosis: Early detection is important, and screening exams should be performed by primary care physicians and dentists. When a suspicious reddened patch is found in the mouth, a biopsy is taken; this can be done by the primary care physician or by a head and neck specialist. Oral tumors are staged using the TNM system that describes the size of the primary tumor (T), the involvement of the regional lymph nodes (N), and whether the cancer has spread (metastasis, M). A numerical rating is assigned to each letter, and a stage grouping of 0-IV is assigned based on the ratings for the three categories. Treatment and therapy: Excision of the oral cancer is usually the necessary treatment; radiation therapy may be used alone or in combination with surgical treatment. The treatment team is multidisciplinary and may include a head and neck surgeon, an oral and maxillofacial pathologist, a general pathologist, a radiation oncologist, a neuroradiologist, a reconstructive surgeon, a medical oncologist, a general dentist, an oral and maxillofacial surgeon, a maxillofacial prosthodontist, a dental hygienist, a nurse specialist, a speech pathologist, a nutritionist, and a tobacco cessation counselor. Prognosis, prevention, and outcomes: The prognosis of oral cancers depends on the pathology findings and the extent of the lesion. A complete head and neck evaluation should be done to look for other cancers. As tobacco and alcohol use are known risk factors, avoiding or ceasing use will help prevent erythroplakia. Vicki Miskovsky, B.S., R.D. See also Alcohol, alcoholism, and cancer; Chewing tobacco; Leukoplakia; Oral and oropharyngeal cancers.
u Esophageal cancer Category: Diseases, symptoms, and conditions Also known as: Cancer of the esophagus Related conditions: Barrett esophagus Definition: Esophageal cancer is a disease caused by a malignant tumor that forms in the tissues of the esophagus. The two main types are adenocarcinoma and squamous cell carcinoma. 434
Salem Health: Cancer Risk factors: Gastroesophageal reflux disease (heartburn) causes about one-third of all esophageal cancers, particularly adenocarcinoma. Tobacco use of any form and heavy alcohol consumption are major risk factors for squamous cell carcinoma. Individuals who both smoke and drink excessively have a synergistic (greater than additive) risk of developing esophageal cancer. People with a diet low in fruits and vegetables have a higher incidence of esophageal cancer, and there is evidence that a high intake of refined cereals and red and processed meats can be detrimental as well. Obese people have a greater risk for adenocarcinoma, primarily through an increased incidence of acid reflux disease. Etiology and the disease process: The esophageal wall has several layers. The inner lining is called the mucosa and has two parts: the epithelium and lamina propria. The epithelium consists of thin, flat squamous cells. The submucosa lies under the mucosa, followed by two layers of muscle. The esophageal wall is connected to various lymph nodes. Esophageal tumors begin in the epithelial layer. Risk factors such as tobacco use and heavy alcohol consumption may case squamous cell carcinoma. This cancer tends to spread linearly across the submucosal layer. Adenocarcinoma occurs largely because of chronic acid reflux and develops mainly in the lower esophagus. Acid reflux occurs when the lower esophageal sphincter between the stomach and esophagus malfunctions and allows gastric contents to reflux back into the esophagus. Acid reflux can cause inflammation and erosion of the epithelium. When the healing process takes place, the squamous cells can be replaced by glandular cells that look like the cells that line the stomach. This abnormal epithelium is termed Barrett esophagus. Although this abnormal epithelium is more resistant to acid reflux, a person with the condition is at higher risk to develop adenocarcinoma. When adenocarcinoma develops, it spreads by penetration through the full thickness of the esophageal wall. Both types of esophageal cancer can spread via the lymph nodes and eventually throughout the body. Incidence: Each year about 13,200 people in the United States are diagnosed with esophageal cancer, and 12,500 die of the disease. The risk of developing esophageal cancer increases with age, with the highest incidence between ages fifty-five and seventy. Men are two to four times more likely to contract the disease than women are. Blacks are six times more likely than whites to acquire squamous cell carcinoma, while adenocarcinoma is four times more frequent in whites than in blacks. Adenocarcinoma has increased more than fourfold in the United States over the
Salem Health: Cancer last thirty years. People with Barrett esophagus have a highly increased risk for developing adenocarcinoma, estimated between thirty and one hundred times normal. Certain regions of the world have a very high incidence of squamous cell carcinoma, such as northern Iran and northern China. Symptoms: The most common symptom of esophageal cancer is dysphagia (difficulty in swallowing). Dysphagia primarily involves solid foods and can progress rapidly in severity (over a period of weeks to months). This symptom does not usually appear until at least half of the esophagus is blocked by a tumor. Weight loss can occur because of reduced food intake or muscle wasting from cancer-caused changes in metabolism. Other symptoms such as hoarseness, pain in the chest or throat, or vomiting of blood can be caused by tumor spread. Screening and diagnosis: When a patient complains of symptoms to the physician, many diagnostic tests are available. A barium swallow begins with a patient drinking a barium solution that coats the normally smooth surface of the esophageal lining. Subsequent X rays can reveal early cancers that appear as small, round bumps or flat, raised areas. Advanced cancers reveal larger irregular areas and a narrowing of the esophagus. Upper endoscopy or esophagoscopy is a procedure involving the use of a flexible viewing tube called an endoscope. The doctor can view suspicious growths and abnormalities in the esophagus and take biopsies for laboratory examination. Endoscopic ultrasound involves attaching a small ultrasound probe to the endoscope. The probe sends very sensitive sound waves that penetrate deep into tissues. This technique can determine how far the tumor has spread into the tissues. Computed tomography (CT) is used to determine the extent (stage) of the cancer, rather than an initial diagnosis. The CT scan takes many X-ray images as it rotates around the body. A computer then translates this information into thin sections of the body. The scans can show tumors in the esophagus, lymph nodes, and other organs where the cancer may have spread. A positron emission tomography (PET) scan involves injecting a small amount of radioactive glucose tracer into the patient’s vein. The tumors show up brighter on the resultant scan. The PET scan indicates the presence or absence of malignancy based on the increased metabolic activity of tumors. PET scans can detect cancer before the anatomic and structural changes shown by tumors have time to develop. This test is valuable in detecting cancer spread to distant lymph nodes or throughout the body.
Esophageal cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Esophageal Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 24 30 30 16
33.7 16.9 2.9 10.8
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
The progression of esophageal cancer is described by staging classification systems. The National Cancer Institute uses the following staging system: • Stage 0: The cancer is confined to the epithelial layer. It is also called carcinoma in situ, meaning “in place.” • Stage I: Cancer has spread to the submucosal layer. • Stage IIA: Cancer has spread to the muscle layer or to the outer wall of the esophagus. • Stage IIB: Cancer may have spread to any of the first three layers of the esophagus and to nearby lymph nodes. • Stage III: Cancer has spread to the outer walls of the esophagus and may have spread to tissues or lymph nodes near the esophagus. • Stage IVA: Cancer has spread to nearby or distant lymph nodes. • Stage IVB: Cancer has spread to distant lymph nodes or organs in other parts of the body. Treatment and therapy: Surgery is the most common treatment for esophageal cancer; however, there are many risks involved. The surgeon removes the cancerous part of the esophagus and may remove lymph nodes and part of the stomach if the cancer is advanced. Surgery is mainly useful for Stages 0 to I, when it is most likely to be curative. If surgery is contemplated for Stages III and IV, it is usually done in combination with other therapies such as chemotherapy and radiation. Surgery is not feasible for cancers that have spread beyond the esophagus. Radiation is most effective when used with other therapies. Radiation is used to relieve symptoms of dysphagia, or in combination with chemotherapy to shrink tumors before surgery. Radiation used alone is rarely curative. 435
Esophageal speech Chemotherapy helps to sensitize cancer cells to radiation, so chemotherapeutic agents are often used in combination, with or without surgery. The most effective agent is cisplatin. Fluorouracil has synergistic activity with cisplatin so is often used in combination. Other chemotherapeutic agents showing promise include paclitaxel, irinotecan, and oxaliplatin. Chemotherapy alone is rarely curative. Photodynamic therapy can be used to treat very early cancers that are on or just under the epithelial lining. It is also used for palliative therapy to alleviate dysphagia. A nontoxic chemical is injected into the blood and allowed to accumulate in the tumor. A special laser light is focused on the tumor through an endoscope. The light converts the chemical to a toxic form that kills tumor cells. Prognosis, prevention, and outcomes: Esophageal cancer is a very deadly cancer with an overall curative success of less than 10 percent. By the time symptoms appear, the disease is incurable in half the cases. The benefit of a screening program to detect esophageal cancer at an earlier stage has not been demonstrated. Even monitoring patients with gastrointestinal reflux disease for the presence of Barrett esophagus has not been shown to improve survival rate. The best preventive measures are to minimize the risk factors. David A. Olle, M.S. u For Further Information Koshy, Mary, et al. “Multiple Management Modalities in Esophageal Cancer.” The Oncologist 9 (2004): 137159. Rankin, Sheila C., ed. Carcinoma of the Esophagus. New York: Cambridge University Press, 2008. Sharma, Prateek, and Richard Sampliner, eds. Barrett’s Esophagus and Esophageal Adenocarcinoma. 2d ed. Malden, Mass.: Blackwell, 2006. u
Other Resources
American Cancer Society http://www.cancer.org MayoClinic.com Esophageal Cancer http://www.mayoclinic.com/health/ esophageal-cancer/DS00500 National Cancer Institute Esophageal Cancer http://www.cancer.gov/cancertopics/types/ esophageal/ 436
Salem Health: Cancer See also Alcohol, alcoholism, and cancer; Bacteria as causes of cancer; Barium swallow; Barrett esophagus; Cardiomyopathy in cancer patients; Cigarettes and cigars; Endoscopy; Esophagectomy; Esophagitis; Fanconi anemia; Gastrointestinal cancers; Gastrointestinal oncology; Oral and oropharyngeal cancers; Stent therapy; Thoracotomy; Upper gastrointestinal (GI) endoscopy.
u Esophageal speech Category: Lifestyle and prevention; social and personal issues Definition: Esophageal speech, also called esophageal voice, is speech produced by swallowing air and forcing it out again through the esophagus. Patients who have had their larynx, or voice box, removed because of cancer have to practice esophageal speech to communicate verbally. Anatomy and physiology: The larynx (voice box) is a 2inch (5-centimeter, or cm), tube-shaped organ in the neck toward the front of the body between the pharynx (throat) and the trachea (windpipe). The larynx is part of the body’s respiratory (breathing) system. One of its main functions is to protect the airway to the lungs from food or drink “going down the wrong tube.” The pharynx is a hollow tube about 5 inches (12 cm) long that starts behind the nose and ends at the top of the trachea and esophagus. The trachea, also part of the respiratory system, connects the larynx to the lungs. The esophagus is a muscular tube that connects the mouth and pharynx to the stomach. It lies between the trachea and the spine. The esophagus is part of the digestive system. When food is chewed and swallowed, the esophagus contracts to push the food down into the stomach, where digestion takes place. Briefly, the human speech process begins when air streams from the lungs and passes over the vocal folds (vocal cords) in the larynx. The steady airstream causes the vocal folds to vibrate, which produces sound waves. The sound waves are then shaped and modified by the pharynx, tongue, lips, palate, and teeth to produce intelligible speech sounds. Throat cancer: Throat cancer—also called vocal cord cancer, laryngeal cancer, and cancer of the glottis—strikes the vocal folds, larynx, or other areas of the throat. It appears as a malignant tumor in almost any part of the throat. Although a person’s genes may contribute to the development of throat cancer, the most common cause is smoking. Excessive alcohol use also increases the risk of developing throat cancer. Throat cancer occurs most often in adults
Salem Health: Cancer
Esophageal speech
older than the age of fifty and in men ten times more often than in women. In the early stages, doctors can successfully treat throat cancer with radiation therapy or chemotherapy or a combination of the two. Following such treatments, most patients are able to keep their larynx and speak more or less normally. In the later stages of the disease, the most common treatment is surgery to remove the larynx along with the cancerous tumor. When a patient needs surgery, the type of operation depends on the size and exact location of the tumor. Surgeons may remove part of the larynx (partial laryngectomy) or the entire larynx (total laryngectomy). Speaking after a laryngectomy: Patients without a voice box must learn to speak all over again. Several methods and a number of medical devices are available to help patients recover their ability to speak. One of the most common techniques is esophageal speech. With esophageal speech, the patient learns to take air into the mouth and swallow it or force it into the esophagus and then trap the air by locking the tongue to the roof of the mouth. The air is now in the digestive system, not in the respiratory system as normal. The patient then forces the air through the esophagus and back up into the mouth, much like a controlled belch. This causes the air to vibrate, along with the walls of the esophagus and the throat, and produce a low-pitched sound that becomes the patient’s voice. The patient then shapes the voiced sound into recognizable words, as normal speakers do, with the tongue, lips, palate, and teeth. The esophageal voice emits a low-pitched guttural, croaking, sometimes soft and barely audible sound that many listeners find difficult to understand. Because they must learn to train parts of their body for a new purpose, many patients find esophageal speech more difficult than speech they might produce with special medical devices. On the plus side, esophageal speech costs patients less than some other techniques because it does not require special equipment. Living without a larynx: People who have had their larynx removed are known as laryngectomees. They must contend with more than learning to speak a new way. When the larynx is taken out, it leaves an opening in the neck called a tracheostoma, or stoma, for short. Patients cough, sneeze, and breathe through the stoma. They be-
come neck breathers. The trachea is exposed through the stoma, so they need to take special care of the stoma. They have to keep it clean and moist. They have to cover it when showering and shaving. They usually have to avoid activities such as swimming or water skiing. They have to watch for a buildup of dried mucus, a substance that lubricates and moistens the esophagus. They must be especially careful of coughing and sneezing, which can expel large amounts of phlegm, a mucus of the respiratory system. They must eat much more slowly. They also must cope with the changes in their physical appearance. Wendell Anderson, B.A. u
For Further Information Lazaroff, M. The Complete Idiot’s Guide to Anatomy and Physiology. Indianapolis, Ind.: Alpha Books, 2004. Prosek, R., and L. Vreeland. “The Intelligibility of TimeDomain-Edited Esophageal Speech.” Journal of Speech, Language, and Hearing Research 44, no. 3 (2001): 525-534. Thomas, J., and R. Keith. Looking Forward: The Speech and Swallowing Guidebook for People with Cancer of the Larynx or Tongue. New York: Thieme, 2005.
u
Other Resources
American Cancer Society Speech After Laryngectomy http://www.cancer.org/docroot/MBC/content/ MBC_3_2X_Speech_After_Laryngectomy .asp?sitearea=MBC
A tumor on the wall of an esophagus. (CNRI/Photo Researchers, Inc.)
437
Esophagectomy WebWhispers http://www.webwhispers.org See also Cordectomy; Electrolarynx; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy; Laryngoscopy; Parathyroid cancer; Throat cancer; Tracheostomy; Upper gastrointestinal (GI) series.
u Esophagectomy Category: Procedures Also known as: Transhiatal esophagectomy, transthoracic esophagectomy, esophagogastrectomy Definition: Esophagectomy is the surgical removal of part of the esophagus for the treatment of cancer or the relief of cancer symptoms. How much of the esophagus is removed is variable, depending on the location of the malignancy or obstruction. The top part of the stomach may also be removed (a procedure referred to as esophagogastrectomy). After removal of the cancer or obstruction, the stomach is connected to the remaining part of the esophagus, which is restructured into a tube to form a new esophagus. Cancers diagnosed and treated: Esophageal cancer; highgrade dysplasia with Barrett esophagus; end-stage benign diseases including achalasia, hiatal hernia, and gastroesophageal reflux disease (GERD) Why performed: An esophagectomy may be recommended as a treatment option for patients with cancer of the esophagus or high-grade dysplasia that occurs with Barrett esophagus. It also may be performed to provide relief of symptoms associated with benign conditions that affect swallowing, such as achalasia, hiatal hernia, and gastroesophageal reflux disease. Esophagectomy is the only surgical treatment currently available for the treatment of esophageal cancer, and it is most successful when performed for patients with early-stage disease. Because of the complexity of the procedure, an esophagectomy should be performed by an experienced thoracic surgeon at a medical center that specializes in the care of patients with esophageal diseases. Research has shown that patients who undergo an esophagectomy at hospitals with thoracic surgeons who perform large numbers of procedures have improved clinical outcomes and lower mortality rates than do patients who have an esophagectomy at lower-volume hospitals. Patient preparation: Tests performed before the procedure include a complete cardiac evaluation, esophageal manometry, esophagoscopy with biopsy, endoscopic ul438
Salem Health: Cancer trasound, computed tomography (CT) scan, positron emission tomography (PET) scan, and blood tests. Chemotherapy or radiation therapy may be performed to reduce the size of the tumor before surgery. One week before the procedure, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician. Steps of the procedure: General anesthesia is administered. The surgical technique and type of incisions vary, depending on the location and extent of the cancer, the patient’s pulmonary function, and the surgeon’s recommendations. Surgical techniques include the following: • transhiatal esophagectomy, in which incisions are made in the abdomen and left side of the neck, but not in the chest • transthoracic esophagectomy (Ivor-Lewis procedure), in which incisions are made in the chest wall (thoracotomy) and upper abdomen • triincisional esophagectomy (McKeown esophagectomy), in which incisions are made in the right chest, abdomen, and left side of the neck • minimally invasive esophagectomy, in which several 1-inch incisions are made between the ribs, a thoracoscope (small video-scope) is used to view the surgical area, and surgical instruments are inserted through the other incisions; this procedure minimizes trauma, decreases postoperative pain, and promotes a shorter hospital stay and a quicker recovery The esophagus, the tumor or obstruction, and affected lymph nodes are removed. The gastrointestinal system is reconstructed: The stomach is connected to the remaining part of the esophagus. Surgery may last from four to seven hours. After the procedure: The patient recovers in an intensive care unit (ICU) for twenty-four to forty-eight hours. The patient is intubated to aid breathing and has a chest tube to drain fluid and air. Medications are given to manage pain. A feeding tube is placed in the small intestine (jejunostomy or J-tube) to provide adequate nutrition during the early postoperative period when the patient is unable to eat by mouth. The patient performs deep breathing and coughing exercises to remove lung secretions. Recovery in the hospital takes about seven days, and full recovery usually occurs within six to eight weeks. The patient is able to advance gradually from clear liquids to soft foods during recovery at home. The J-tube is removed after the esophagus has healed, usually within four weeks after the procedure. The patient’s swallowing mechanism is usually restored, as well as the ability to taste food. In
Salem Health: Cancer some cases, surgical treatment with an esophagectomy may be followed by chemotherapy or radiation therapy. Risks: The risks of this procedure include leaks from the internal suture line, pneumonia, pulmonary edema, respiratory distress, bleeding, infection, abnormal heart rhythms, pneumothorax (collapsed lung), and persistent pain. The risk of heart attack is rare. Strictures or narrowed areas may occur at the site where the esophagus and stomach were reconstructed, causing difficulty swallowing in 10 to 15 percent of patients. The mortality rate (rate of death) associated with esophagectomy ranges from 3 to 8 percent. Results: Despite the risks, surgical advancements have improved the long-term success of the procedure. Twoyear survival rates for patients who undergo an esophagectomy for the treatment of esophageal cancer range from 35 to 42 percent, and five-year survival rates range from 15 to 24 percent, with higher survival rates in patients with early-stage cancers. Surgery performed for the relief of dysphagia (difficulty swallowing) improves symptoms in 80 percent of patients, according to the American Cancer Society. Angela M. Costello, B.S. u For Further Information Ercan, S., et al. “Does Esophagogastric Anastomic Technique Influence the Outcome of Patients with Esophageal Cancer?” Journal of Thoracic and Cardiovascular Surgery 129 (2005): 623-631. Ma, J. Y., et al. “Clinicopathologic Characteristics of Esophagectomy for Esophageal Carcinoma in Elderly Patients.” World Journal of Gastroenterology 12, no. 8 (2006): 1296-1299. MacKenzie, D. J., et al. “Care of Patients After Esophagectomy.” Critical Care Nurse 24, no. 1 (February, 2004): 16-31. Van Lanshott, J. J., et al. “Hospital Volume and Hospital Mortality for Esophagectomy.” Cancer 91 (2001): 1574. u
Other Resources
American Cancer Society http://cancer.org American College of Chest Physicians http://www.chestnet.org National Cancer Institute http://www.cancer.gov Society of Thoracic Surgeons—Patient Section http://www.sts.org/sections/patientinformation/
Esophagitis See also Alcohol, alcoholism, and cancer; Bacteria as causes of cancer; Barium swallow; Barrett esophagus; Candidiasis; Cardiomyopathy in cancer patients; Cigarettes and cigars; Endoscopy; Esophageal cancer; Esophagitis; Fanconi anemia; Gastrointestinal cancers; Gastrointestinal oncology; Hematemesis; Oral and oropharyngeal cancers; Premalignancies; Stent therapy; Stomatitis; Thoracotomy; Upper gastrointestinal (GI) endoscopy.
u Esophagitis Category: Diseases, symptoms, and conditions Also known as: Inflammation of the esophagus Related conditions: Gastroesophageal reflux disease (GERD), Barrett esophagus, heartburn (pyrosis), difficulty swallowing (dysphagia), painful swallowing (odynophagia) Definition: Esophagitis is a general condition in which the esophagus, the muscular tube connecting the mouth to the stomach, is inflamed. Different medical conditions are associated with esophagitis, including GERD, a condition in which the stomach contents flow backward into the esophagus, and nonreflux esophagitis. Serious gastrointestinal complications of esophagitis include a narrowing of the esophagus (strictures), ulcers, and in rare cases a risk of esophageal cancer. Risk factors: Factors that may increase the risk of developing esophagitis include pregnancy, obesity, scleroderma, smoking, alcohol, caffeine, chocolate, fatty or spicy foods, spinal cord injury, and certain medications (such as nonsteroidal anti-inflammatory drugs, or NSAIDs, including aspirin and ibuprofen). Etiology and the disease process: The etiology of esophagitis differs depending on the cause of the inflammation. In GERD-associated esophagitis, a backflow (reflux) of acidic fluid from the stomach (containing gastric acid, pepsin, and sometimes bile) to the esophagus causes irritation of the epithelium (the cells lining the esophagus). In some instances, a premalignant condition called Barrett esophagus can develop, which can increase the risk of developing esophageal cancer. However, the risk of esophageal cancer in patients with Barrett esophagus is relatively small: less than 1 percent of Barrett esophagus patients a year. Nonreflux esophagitis may be caused by infection (viral, bacterial, fungal, or parasitic organisms), chemicals (ingestion of a caustic chemical or medication), radiation therapy (physically damaging the lining of the esophagus 439
Esophagitis leading to inflammation and ulceration), or in rare instances immune-mediated disorders (eosinophilic esophagitis). Incidence: Esophageal reflux symptoms are estimated to occur in 33 to 44 percent of the general population on a monthly basis with up to 7 to 10 percent of people having daily symptoms. Radiation esophagitis occurs in up to 80 percent of patients receiving radiation therapy to the esophagus. Symptoms: The most common symptom is heartburn (pyrosis). Other common symptoms of esophagitis include upper abdominal discomfort, nausea, bloating, and fullness. Less common symptoms of esophagitis include dysphagia, odynophagia, cough, hoarseness, wheezing, and vomiting of blood (hematemesis). Screening and diagnosis: A physician can establish a diagnosis of GERD based on patient history alone. However, if symptoms are severe or do not respond to treatment, the physician may order diagnostic tests designed to determine mucosal injury, amount of reflux, and pathophysiology, including barium X-ray series, endoscopy, an ambulatory acid (pH) probe test, and an esophageal impedance test. During a barium X-ray series, the patient drinks a barium solution that, through a series of X rays, provides a picture of the shape and condition of the esophagus, stomach, and upper intestine (duodenum). X rays can also reveal a hiatal hernia, an esophageal narrowing, or a growth. During an endoscopy, or an esophagogastroduodenoscopy (EGD), a flexible tube with a light and camera (endoscope) is inserted down the throat and can reveal inflammation of the esophagus or stomach. A biopsy may also be taken during an EGD to test for Barrett esophagus, esophageal cancer, or the presence of a bacterium that may cause peptic ulcers. An ambulatory acid (pH) probe test can identify when and for how long stomach acid flows back into the esophagus. A flexible tube (catheter) is inserted through the nose into the esophagus to position a probe in the esophagus just above the stomach. The other end of the catheter is attached to a small computer that records acid measurements. The probe remains in place for one or two days while measurements are recorded. The esophageal impedance test is similar to the ambulatory acid probe test except that it measures whether gas or liquids reflux back into the esophagus. Treatment and therapy: The goals of treatment are to provide symptom relief, heal ulcerations, and prevent complications. Reflux esophagitis is managed with over440
Salem Health: Cancer the-counter agents, such as H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine) and with lifestyle changes such as altering eating habits (for example, avoiding alcohol, caffeine, carbonated beverages, chocolate, fatty foods, or overly large meals), ceasing to smoke cigarettes, and sleeping with the head of the bed elevated by about 4 to 6 inches. Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole, esomeprazole, or rabeprazole) are frequently prescribed and appear effective at relieving symptoms and healing erosive esophagitis in up to 90 percent of patients. Infectious esophagitis is treated with antibiotics, whereas glucocorticoids are effective in patients with immune-mediated esophagitis. Radiation esophagitis treatment involves symptom management (similar to reflux esophagitis) and prevention (radioprotectors, varying treatment doses and schedules). For severe cases, a temporary feeding tube can be inserted into the stomach or surgery may be required to treat the injuries. To treat pain associated with esophagitis, a prescription analgesic can be gargled with and swallowed. Prognosis, prevention, and outcomes: Though the response to therapy may be different depending on the specific cause of the esophagitis, the disorders that cause esophagitis usually respond to treatment. Anita P. Kuan, Ph.D. u
For Further Information Icon Health. Esophagitis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Parkman, Henry, and Robert S. Fisher, eds. The Clinician’s Guide to Acid/Peptic Disorders and Motility Disorders of the Gastrointestinal Tract. Thorofare, N.J.: SLACK, 2006. Yamada, T., ed. Textbook of Gastroenterology. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Zoler, Mitchel L., and Robert Finn. “Drug Update: Gastroesophageal Reflux Disease.” Family Practice News 32, no. 9 (2002): 25.
u
Other Resources
Cleveland Clinic Health Information Center Esophagitis http://www.clevelandclinic.org/health/health-info/ docs/2800/2896.asp?index=10138 International Foundation for Functional Gastrointestinal Disorders http://aboutgimotility.org/
Salem Health: Cancer MayoClinic.com GERD http://www.mayoclinic.com/health/gerd/DS00967 MedlinePlus Esophagitis http://www.nlm.nih.gov/medlineplus/ency/article/ 001153.htm See also Alcohol, alcoholism, and cancer; Bacteria as causes of cancer; Barium swallow; Barrett esophagus; Candidiasis; Cardiomyopathy in cancer patients; Cigarettes and cigars; Endoscopy; Esophageal cancer; Esophagectomy; Fanconi anemia; Gastrointestinal cancers; Gastrointestinal oncology; Hematemesis; Oral and oropharyngeal cancers; Stent therapy; Stomatitis; Thoracotomy; Upper gastrointestinal (GI) endoscopy.
u Essiac Category: Complementary and alternative therapies Also known as: Flor-Essence, Herbal Essence, NAP Herbal Tea, Tea of Life, Vitalitea Definition: Essiac is an herbal mixture that was originally used by the Ojibwa tribe in Canada to cure cancerous tumors. The Ojibwa formula comprised four herbs: burdock root (Arctium lappa), slippery elm inner bark (Ulmus fulva), sheep sorrel (Rumex acetosella), and Indian rhubarb root (Rheum palmatum). Later formulas added watercress (Nasturtium officinale), blessed thistle (Cnicus benedictus), red clover (Trifolium pretense), and kelp (Laminaria digitata). Essiac was popularized in the early 1920’s by Rene Caisse (pronounced “reen kays”), a Canadian public health nurse. (Essiac is Caisse’s surname spelled backward.) For the next fifty years, despite government obstacles, she used Essiac to treat cancer in both Canada and the United States. Cancers treated or prevented: Essiac is very versatile. The Ojibwa used the herbal mixture to treat various tumors, including breast and stomach cancer. The herbs have also been used to treat leukemias and melanoma in addition to cancer of the bone, colon, esophagus, lung, and prostate. Delivery routes: Essiac is available in dry (capsules) and liquid (tea or extract) formulas. It is sold as a dietary supplement and therefore is not regulated as a drug. How this substance works: Each of the four basic herbs in Essiac has been reported to possess antioxidant and
Estrogen receptor downregulator (ERD) anticancer activity. The original claim was that Essiac softened, shrank, and discharged tumors from the body, thereby changing tumors into normal tissue. While there is no scientific evidence to support these claims, ongoing studies of Essiac continue both to refute and to confirm Essiac’s benefits. Essiac was found to be ineffective in controlling tumors in both older and recent studies by the Memorial SloanKettering Cancer Center and the U.S. National Cancer Institute (the 1950’s to 1980’s), the University of British Columbia (2005), and the University of Michigan (2006). A 2006 study by the National Institute for Occupational Safety and Health, however, determined that Essiac tea possesses potent antioxidant and DNA-protective activity, properties that are common to natural anticancer agents. A Canadian study in 2005 confirmed that Essiac was beneficial to a man with prostate cancer. Despite these controversial findings, Essiac continues to be a popular herbal remedy used as an adjunct to treat breast cancer, prevent secondary problems, improve quality of life, and control negative side effects of conventional breast cancer treatment. Side effects: Serious side effects, such as liver and kidney damage, are uncommon. Other side effects may include headache, nausea and vomiting, diarrhea or constipation, and low blood sugar. Renée Euchner, R.N. See also Anthraquinones.
u Estrogen receptor
downregulator (ERD) Category: Chemotherapy and other drugs; cancer biology ATC code: 102BA03 Definition: Estrogen receptor downregulator (ERD) is a compound that prevents the action of estrogen by attenuation of estrogen-receptor-mediated transcription and suppression of estrogen-dependent gene expression. The only known ERD is fulvestrant (Faslodex), which is described as “pure” ER antagonist, as it lacks the agonistic effects exhibited by other estrogen receptor modulators. Subclasses of this drug group are antiestrogens and selective estrogen receptor modulators (SERMs), the latter of which also downregulate the estrogen receptor but are selective in their antagonistic action. Cancers treated or prevented: Breast cancer 441
Estrogen-receptor-sensitive breast cancer Delivery routes: Intraperitoneal injection How this drug works: Estrogen is the female hormone that is mainly secreted in the ovaries and acts on female organs such as the breasts and uterus. Estrogen is responsible for activating the endothelial cells of the uterus during menstrual cycles. It performs its function by binding with specific receptors, called estrogen receptors (ER), that are present in various parts of the body. This binding is critical in inducing conformational changes of the ER protein, resulting in induction of expression in associated genes, ultimately leading to proliferation of endothelial cells. In cancer patients, proliferation of cancerous cells is triggered by estrogen binding to ER. Preventing estrogen from binding to its receptor is therefore a viable pharmacological strategy in cancer research. The estrogen receptor downregulator fulvestrant is a steroidal analog of the hormone 17β-estradiol. Fulvestrant was approved by the Food and Drug Administration (FDA) in 2002 for treating cancer. It binds to estrogen receptors and blocks downstream processes such as receptor dimerization, leading to blockade of induction of gene expression. Fulvestrant also expedites degradation of ER protein, resulting in drastic downregulation of ER levels. Estrogen cannot exert its proliferative action in the absence of ER, and thus the progression and spread of cancer can be controlled by fulvestrant treatment. Fulvestrant is administered to postmenopausal women whose cancer has metastasized and does not respond to traditional medications, such as the classic antiestrogen tamoxifen. Fulvestrant has about a hundredfold higher affinity for ER than tamoxifen and, unlike tamoxifen, does not have any agonistic effects on ER. Tamoxifen prevents proliferation of cells in the breast but acts like estrogen and exerts agonistic effects in the uterus. Clinical trials using fulvestrant have shown decelerated cancer growth and delayed recurrence rates. Using fulvestrant in combination therapy for cancer is now considered a treatment option. Side effects: The side effects of fulvestrant are nausea, vomiting, constipation, diarrhea, abdominal pain and hot flashes. Geetha Yadav, Ph.D. See also Antiestrogens; Breast cancers; Estrogen-receptorsensitive breast cancer; Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Phytoestrogens; Progesterone receptor assay; Receptor analysis.
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u Estrogen-receptor-sensitive
breast cancer Category: Diseases, symptoms, and conditions Also known as: Estrogen-receptor-positive breast cancer, hormone-dependent breast cancer Related conditions: Breast cancer, fibroadenomas, breast cysts, fibrocystic breasts Definition: Estrogen-receptor-sensitive breast cancer is the diagnosis given for a breast cancer that is driven by estrogen stimulation. It is by far the most common type of breast cancer. Breast cancer cells are primarily epithelial. About 75 percent of breast cancers originate in the ducts of the breast, in which cells are larger than normal epithelial cells and exhibit a variety of patterns, and 15 percent originate in the lobules, in which cells are smaller, uniform, and appear in rows. Rare, invasive cancers compose the remaining 10 percent. Risk factors: Age and gender are the strongest risk factors, with about 75 percent of cases occurring in women over age fifty, although younger women tend to have more aggressive tumors. Early menstruation (before age twelve), late menopause (after age fifty-five), and reproductive history (late pregnancy) are associated with higher risk, possibly because of the longer lifetime exposure to growth-stimulating estrogen. Inherited mutations in the tumor-suppressor genes BRCA1 and BRCA2 and a family history of the disease can increase risk as well. Etiology and the disease process: Although the cause of estrogen-receptor-sensitive breast cancer is unknown, estrogen appears to be involved with the proliferation and progression of the disease. Estrogen is produced by the ovaries, adrenal glands, and some fat tissue. In normal breast cells, especially the milk glands, estrogen stimulates cell division both directly and through its influence on other hormones (such as progesterone) and growth factors. Researchers believe that higher than normal amounts of estrogen can increase the rate of cell division (and the risk for chance mutations) and trigger the proliferation of cells already harboring genetic mutations. Even after cancer has developed, estrogen-receptor-sensitive cells depend on estrogen stimulation for continued growth and possibly for survival. Incidence: Estrogen-receptor-sensitive breast cancer is the most common cancer in women in the United States (excluding nonmelanoma skin cancers). After steadily increasing during the previous two decades, breast cancer incidence began to decrease between 2001 and 2003 from
Salem Health: Cancer approximately 100 to 75 per 100,000 in the United States, with a couple hundred thousand cases diagnosed each year and a little over 1 million cases worldwide. Symptoms: The classic symptom for this type of cancer is a palpable lump in the breast. Other symptoms include a noticeable difference in breast size or shape, breast swelling, nipple discharge or inversion, dimpling of the skin, orange peel consistency of skin, and enlarged lymph nodes in the area of the armpit or collarbone.
Estrogen-receptor-sensitive breast cancer
Breast Cancer Stages Stage
Tumor Size
Node Involvement
Metastasis
I
Less than 2 centimeters
No
No
IIA, IIB
2-5 centimeters
Possible
No
IIIA, IIIB, IIIC
More than 5 centimeters; cancer may extend to chest wall
Possible for IIIA; most likely for IIIB and IIIC
No
IV
N/A
N/A
Yes
Screening and diagnosis: The breast self-exam in combination with the clinical exam and mammogram, during which X rays are taken of the breasts to detect masses too small to feel, are the best screening tools available. Newer options include ultrasound, which can differentiate between cysts and solid tumors and is useful in diagnosing younger women who typically have higher breast density; magnetic resonance imaging (MRI), used to visualize tumor size and locate additional tumors; and computer-aided detection (CAD), which scans a mammogram for undetected tumors. In the future, nuclear medicine studies may be utilized as additional screening and diagnostic tools. Biopsy is necessary to confirm cancer, and the type of biopsy selected depends on size, location, and number of masses, as well as the patient’s medical history. A fineneedle aspiration biopsy uses a very thin needle to draw out fluid from abnormal tissue, a core biopsy uses a larger needle to remove a tissue sample, a Mammotome (or vacuum-assisted) biopsy inserts a probe that suctions and slices several tissue samples, and surgical biopsy removes all or part of the abnormal tissue. Surgical biopsy may be ultimately necessary for confirmation of cancer. Tumors are described using the TNM (tumor/lymph node/metastasis) classification system, which corresponds with four main breast cancer stages. Treatment and therapy: Treatment options include a breast-conserving lumpectomy (removal of the tumor and part of the surrounding tissue) or a modified radical mastectomy (removal of the breast, lymph nodes, and fatty tissue associated with the breast and lining of the chest). Both surgeries are a drastic improvement over the disfiguring Halstead radical mastectomy that was used until the 1970’s. Postoperative radiation is recommended, followed with chemotherapy, which consists of a combination of cyclophosphamide (Cytoxan), methotrexate or doxorubicin
(Adriamycin), and 5-fluorouracil (5-FU). Because this type of breast cancer responds to hormone stimulation, hormone therapy that antagonizes the estrogen receptor (either tamoxifen or one of the newer aromatase inhibitors) is used in addition to chemotherapy. Prognosis, prevention, and outcomes: Due to increased screening and the advantages of hormone therapy, survival rates are greater than 80 percent for women with estrogen-receptor-sensitive breast cancer. Mortality has decreased since the 1980’s from 33 deaths per 100,000 to 25 deaths, although it remains the second leading cause of cancer deaths in women. (Lung cancer is the first.) Because the cause is unknown, preventive measures are difficult to outline. Researchers are investigating possible links between estrogen-receptor-sensitive breast cancer and oral contraceptives, environmental factors, silicone implants, obesity, hormone replacement therapy, smoking, alcohol, and lack of exercise. Amber L. Fields, M.S. u
For Further Information DeGregorio, Michael W., and Valerie J. Wiebe. Tamoxifen and Breast Cancer. New Haven, Conn.: Yale University Press. 1996. Hartmann, Lynn C., and Charles L. Loprinzi. Mayo Clinic Guide to Women’s Cancers. New York: Kensington, 2005. Ricks, Delthia. Breast Cancer Basics and Beyond. Alameda, Calif.: Hunter House Books, 2005.
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Other Resources
American Cancer Society http://www.cancer.org BreastCancer.org http://www.breastcancer.org 443
Ethnicity and cancer National Cancer Institute http://www.cancer.gov See also Antiestrogens; Breast cancers; Estrogen receptor downregulator (ERD); Hormonal therapies; Hormone receptor tests; Hormone replacement therapy (HRT); Phytoestrogens; Progesterone receptor assay; Receptor analysis.
u Ethnicity and cancer Category: Social and personal issues Definition: For socioeconomic, dietary, lifestyle, environmental, and genetic reasons, cancer affects various population groups differently. This is quite apart from strictly individual causes that may also play out in the incidence and mortality rates of carcinomas. Ethnicity: An ethnic group is distinguished by common cultural and frequently racial or linguistic, social, or religious characteristics. When there is prolonged mingling of ethnic groups within a geographic area or when an ethnic group is exposed to a new environment, as in the case of immigrants to the United States, the distinguishing features of a particular ethnic group will become blurred. Even the group’s distinctive health profile will be modified by virtue of changes in not only environment but also income, educational level, and thus diet, lifestyle, and access to medical care—in short, socioeconomic status (SES). Although socioeconomic status, which varies among different ethnicities, has considerable bearing on the incidence of cancer, inherited predispositions also play an important role in determining which ethnic group is afflicted by what type of cancer. Therefore, some ethnic differences in health indicators, including cancer markers, appear to be independent of socioeconomic status. Making general statements about the importance of particular factors becomes harder when comparing different ethnic groups. Although some minority older adults, particularly blacks and generally American Indians and Alaska Natives, are considerably less healthy than older whites, others, particularly Hispanics and Asian Americans and Pacific Islanders (AAPIs), are often healthier. There are many inconsistencies, and correlations are difficult, to begin with because the terms race and ethnicity are variously defined. For example, not all cancer-related data distinguish between nonwhite Hispanics and Latinos and white Hispanics and Latinos. Despite these caveats, a few correlations can be hypothesized. 444
Salem Health: Cancer Some generalizations: According to the Centers for Disease Control and Prevention, the five leading causes of cancer death for American men in 2004, expressed as ageadjusted death rates per 100,000 people, were lung, 70.3; prostate, 25.4; colon and rectum, 21.6; pancreas, 12.3; and leukemias, 9.7. The five leading causes of cancer death for American women in 2004 were lung, 40.9; breast, 24.4; colon and rectum, 15.2; pancreas, 9.2; and ovary, 8.8. Although the cancers most likely to cause death remained largely the same among ethnic groups, their rankings differed. In men, lung and colorectal cancer retained their rankings (one and three) throughout the ethnic groups, but in Asian Americans and Pacific Islanders, liver cancer replaced prostate cancer as the number-two cause of mortality. Liver cancer also was the third cause of death in male American Indians and Alaska Natives and Hispanics. Stomach cancer was the fifth-ranked cause of cancer death among male blacks and Asian Americans and Pacific Islanders. In women, lung cancer was the number-one cause of mortality except for Hispanics, in whom the first- and second-ranked causes of death were reversed. Colorectal cancer was the third cause of death in all female ethnic groups. Liver cancer was the fourth cause of death among female American Indians and Alaska Natives. For all forms of cancer in 2004, the incidence and mortality rates per 100,000 population broken down by ethnic categories were as follows: whites, 455.4 and 184.1, respectively; blacks, 469.6 and 228.1; Hispanics, 356.5 and 122.8; Asian Americans and Pacific Islanders, 289.8 and 110.9, and American Indians and Alaska Natives, 261.3 and 127.9. Cancer and the role of ethnicity: Worldwide, there are regional variations in the incidence of specific types of cancer according to the ethnicities predominant in those areas. The stomach cancer common in Japan and Scandinavia is thought to be of dietary origin, while the liver cancer common in parts of Africa and Asia is believed to be a result of infection with the hepatitis B virus. However, when people from these areas immigrate to the United States, they often acquire the health profile of Americans through consuming more red meat and living a more sedentary lifestyle. For example, Chinese Americans, who no longer follow the fish, rice, and vegetable diet and active lifestyle of their ancestors, tend to have a higher rate of colorectal cancer as a result. Nature and nurture both appear to be relevant in explaining cancer trends among different ethnic groups. Factors in human geography can explain only part of the incidence of cancer; genetics also plays a role. For example, Ashkenazi women have a higher rate of breast and often
Salem Health: Cancer ovarian cancer than women in the population at large. Although rare in the general population, the A636P mutation is detected in up to 7 percent of Ashkenazi Jews with earlyage-of-onset colorectal cancer and may account for up to one-third of hereditary nonpolyposis colorectal cancer (HNPCC) in the Ashkenazi Jewish population. The difficulty of linking ethnicity to hereditary cancers stems from the fact that ethnicity and socioeconomic differences are intertwined. Failure to consider this may lead to inappropriate attribution of differences to ethnic—and thus genetic—factors rather than to socioeconomic status, which in turn may misdirect health care research and funding. The incidence of cancer falls as levels of education and income rise. Ethnic groups with a higher proportion of members with lower socioeconomic status, such as African Americans and Hispanics, tend to be less knowledgeable about health matters, have fewer financial resources to devote to them, and be more likely to be uninsured than groups with higher socioeconomic status. Some statistics: African Americans The incidence rates of the two most common forms of cancer—prostate for men and breast cancer for women— vary considerably by ethnicity. African Americans, with an incidence rate of 180.6 per 100,000 people, had the highest rate of prostate cancer, followed by whites, with a rate of 134.7 per 100,000. However, the incidence rate of breast cancer was higher in white women, with 113.0 per 100,000 versus 95.4 per 100,000 for black women. In 2004, in men the incidence of all invasive cancers combined per 100,000 people was 303.5 among African Americans, 224.8 among whites, 152.8 among Hispanics, 151.2 among American Indians and Alaska Natives, and 137.0 among Asian Americans and Pacific Islanders. In women, the incidence rates were 182.8 among African Americans, 156.4 for whites, 110.7 for American Indians and Alaska Natives, 101.9 for Hispanics, and 92.3 for Asian Americans and Pacific Islanders. African Americans experience disproportionately high age-adjusted cancer incidence and mortality rates, but few studies have separated the impact of lower socioeconomic status from that of genetics. In 2004, the cancer death rate for African Americans was 303.5 per 100,000 people versus 224.8 per 100,000 for white Americans. However, studies have shown that within comparable strata of education and income, African Americans aged twenty-five and over have a similar or lower incidence of all cancers combined when compared with white Americans. This implies that many of the disparities in cancer incidence associated with ethnicity may be caused by factors linked to poverty rather than to genetics. Lower socioeconomic
Ethnicity and cancer status limits educational attainment, reduces access to medical screening or care, and is often associated with greater exposure to tobacco use, heavy alcohol consumption, poor nutrition, physical inactivity, overweight and obesity, and other risk factors. Nevertheless, just why cancer incidence and death rates are higher in African American men remains somewhat baffling, although mortality rates may be influenced by the tendency for cancer to be diagnosed at a later stage among people with lower socioeconomic status, which results in poorer survival rates. Other ethnic groups: Besides African Americans, other ethnic groups in the United States have distinctive cancer patterns. Relative to whites, age-adjusted incidence and mortality rates among Mexican Americans are higher for gallbladder, stomach, and cervical cancer. American Indian men and women have lower incidence rates of most cancers other than those of the gallbladder, stomach, and cervix. Japanese Americans have higher rates of stomach and liver cancer. Chinese Americans have higher rates of nasopharyngeal, liver, and stomach cancer. Native Hawai-
Five-Year Relative Survival Rates Among Whites and African Americans, 1995-2000 Survival Rates (%) Site of Cancer
Whites African Americans
All sites Lung Breast Colon and rectum Prostate Bladder Uterus (corpus uteri) Non-Hodgkin lymphoma Oral cavity and pharynx Leukemia Melanoma of skin Pancreas Kidney Stomach Ovary Cervix uteri
65.5 15.4 88.9 64.1 100.0 82.7 86.1 60.3 60.9 47.8 90.7 4.2 63.9 21.5 44.0 74.0
55.2 13.2 75.2 54.6 96.0 61.9 63.1 50.5 39.0 38.6 74.0 3.8 63.5 24.2 37.9 65.7
Source: Data from U.S. Department of Commerce, Statistical Abstract of the United States: 2004-2005, 124th ed. (Washington, D.C.: U.S. Dept. of Commerce, Economics and Statistics Administration, Bureau of the Census, Data User Services Division, 2004)
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Ethnicity and cancer
Salem Health: Cancer
Incidence Rates per 100,000 People of Prostate Cancer (for men) and Breast Cancer (for women) by Ethnicity/Race, 1988-1992 Prostate (men) 180.6 46.1 52.5 46.0 69.8 57.2 88.3 24.2 40.0 134.7
Ethnicity/Race African American Alaska Native American Indian Chinese Filipino Hawaiian Japanese Korean Vietnamese White
Breast (women) 95.4 78.9 31.6 55.0 73.1 105.6 82.3 28.5 37.5 113.0
Source: Data from B. A. Miller et al., eds. Racial/Ethnic Patterns of Cancer in the United States, 1988-1992 (Bethesda, Md.: National Cancer Institute, 1996) Note: Incidence rates are age standardized to the U.S. population of 1970.
ians have higher death rates from esophagus, liver, pancreas, lung, breast, and cervical cancer. Filipinos have a lower risk of most cancers other than those of the stomach, liver, oral cavity, and esophagus. Again, many of these ethnic differences are believed to reflect differences in tobacco use, dietary habits, infectious exposures, or access to medical care. Some of these higher incidence rates, however, can be attributed to specific causes. For example, the high rate of stomach cancer among recent migrants from Latin America, Asia, and parts of Africa correlates with a higher prevalence of chronic helicobacterial infection in childhood and a greater consumption of salted and smoked foods but lower consumption of fresh fruits and vegetables. Similarly, ethnic groups with increased incidence of liver cancer usually have a higher prevalence of infection with the hepatitis B virus or less commonly hepatitis C virus. The incidence of cervical cancer may reflect exposure to human papillomavirus (HPV), especially when sexual activity begins early and with multiple partners, as is the case with some ethnic groups, whereas the survival rate from cervical cancer varies according to the use of Pap tests and early treatment. In some ethnicities, darker skin, with its increased pigmentation and melanosomal dispersion, helps protect people from skin tumors, but this may change with increased participation in outdoor activities and the depletion of the protective ozone layer in the stratosphere. 446
The future: Research into cancer has brought increased understanding of the major environmental determinants of cancer, such as infections, diet, tobacco, and exposure to ultraviolet (UV) rays and certain chemicals. Differential exposure to these risks explains to a considerable degree why ethnic groups have varying rates of cancer, especially as, because of socioeconomic status and culture, they differ in levels of early screening, diagnosis, and access to health care. However, it appears that, for many cancers, an important component of risk differentials among various ethnic groups is related to genetic susceptibility. The development of genotyping techniques opens prospects for additional investigations, so that research can focus on possible underlying genetic mechanisms to solve the enigmas still being posed by interethnic variations in cancer incidence and mortality rates. Peter B. Heller, Ph.D. u
For Further Information Aguirre-Molina, Marilyn, et al., eds. Health Issues in the Latino Community. San Francisco: Jossey-Bass, 2001. American Cancer Society. Cancer Facts and Figures for African Americans. Atlanta: American Cancer Society, 2007. Bulatao, Randy A., and Norman B. Anderson. Understanding Racial and Ethnic Differences in Health in Late Life: A Research Agenda. Washington, D.C.: National Academies Press, 2004. Johnson, Bernett L., Jr., et al. Ethnic Skin: Medical and Surgical. St. Louis: Mosby, 1998. Kedar-Barnes, I., and P. Rozen. “The Jewish People: Their Ethnic History, Genetic Disorders, and Specific Cancer Susceptibility.” Familial Cancer 3, nos. 3/4 (2004): 193-199. Lillie-Blanton, Marsha D., et al. Key Facts: Race, Ethnicity, and Medical Care. Menlo Park, Calif.: Henry J. Kaiser Family Foundation, 2003. Macbeth, Helen, and Prakash Shetty, eds. Health and Ethnicity. London: Taylor & Francis, 2001. Miller, Barry A., et al., eds. Racial/Ethnic Patterns of Cancer in the United States, 1988-1992. Bethesda, Md.: National Cancer Institute, 1996. Purnell, Larry D., and Betty J. Paulanka. Transcultural Health Care: A Culturally Competent Approach. 2d ed. Philadelphia: E. A. Davis, 2003. Vlahov, David, et al. Racial/Ethnic Differences in Screening for Colon Cancer. Atlanta: International Society on Hypertension in Blacks and New York Cancer Project, 2005.
Salem Health: Cancer u
Other Resouces
Centers for Disease Control and Prevention U.S. Cancer Statistics http://apps.nccd.cdc.gov/uscs M. D. Anderson Cancer Center Race, Ethnicity, and Cancer http://www.mdanderson.org/topics/ethnicity See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Family history and risk assessment; Geography and cancer; Latinos/Hispanics and cancer; Native North Americans and cancer; Poverty and cancer.
u Ethylene oxide Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: 1,2-epoxyethane, oxacyclopropane, dimethylene oxide, oxirane Related cancers: Leukemia, stomach, lymphatic, pancreatic, and brain cancers Definition: Ethylene oxide is a flammable, colorless gas at temperatures above 51.3 degrees Fahrenheit. It is a three-atom ring made of two carbon atoms and one oxygen atom. Each of the two carbon atoms is bonded to two hydrogen atoms.
Ewing sarcoma History: Ethylene oxide has been produced in large quantities in the United States since 1921. Annual production ranges between 2.6 million and 3.4 million metric tons. It is one of the top twenty-five chemicals in volume. Well over half of the production is consumed in the synthesis of the antifreeze, ethylene glycol. Five studies of workers exposed to ethylene oxide, beginning in the mid-1980’s, showed that exposure produces statistically significant excess tumor appearance. There are difficulties in the interpretation of each of these studies, but a causal relationship between the compound and tumor production is likely. Animal studies involving rats, mice, and hamsters clearly show its carcinogenicity. Federal regulations exist for the control of ethylene oxide. The Department of Transportation (DOT) lists the chemical as hazardous and requires special marking, labeling, and transporting precautions. The Environmental Protection Agency (EPA) requires that the manufacture of ethylene oxide meet provisions for the control of volatile organic compounds (VOCs). Also, under the Clean Air Act, the compound is listed as one of thirty-three hazardous air pollutants that present the greatest threat to public health, and the EPA requires that as little as ten pounds of the substance must be reported. The Occupational Safety and Health Administration (OSHA) has set the permissible exposure limit at one part per million. K. Thomas Finley, Ph.D. See also 1,3-Butadiene; Diethanolamine (DEA); Formaldehyde.
Exposure routes: Inhalation, ingestion, skin contact
u Ewing sarcoma
Where found: Fumigation of foodstuffs, sterilization of hospital instruments, and various synthetic chemical operations
Category: Diseases, symptoms, and conditions Also known as: Ewing’s sarcoma, Ewing sarcoma of the bone, extraosseus Ewing sarcoma, extraskeletal Ewing sarcoma, Ewing tumor, Ewing angioendothelioma, Ewing endothelial sarcoma, Ewing syndrome, malignant primary bone tumor, red bone marrow tumor, neural tumor
At risk: Workers in the detergent, fungicide, and synthetic chemical fields, especially those related to ethylene glycol manufacture Etiology and symptoms of associated cancers: The high reactivity of ethylene oxide is shown by ring opening and the introduction of new carbon groups at reactive sites in deoxyribonucleic acid (DNA). This type of reaction takes place largely at a nitrogen atom of guanosine. Such modified nucleic acid fragments have been observed in mice and are most prevalent in the liver, kidney, spleen, and testis. A variety of mutations and reverse mutations have also been found. Gene mutations and heritable translocations are common.
Related conditions: Primitive neuroectodermal tumor, peripheral primitive neuroectodermal tumor, Askin’s tumor, osteosarcoma Definition: Ewing sarcoma is a rare disease involving cancer cells found in bones and soft tissue. It usually occurs in the pelvis, ribs, arm bone (humerus), shoulder blade, or leg bone (femur). It gets its name from James Ewing, who in the 1920’s first described the disease as being separate from other known types of cancers such as lym447
Ewing sarcoma phoma or neuroblastoma. Ewing noticed that this type of cancer responded well to radiation. It belongs to a group of tumors sometimes called the Ewing family of tumors because of the close molecular relationship between these kinds of tumors. Risk factors: More than 90 percent of people who develop this disease have an unusual rearrangement between chromosomes: A piece of chromosome 11 and a piece of chromosome 22 have switched places (called a gene translocation). However, this translocation is not inherited or
Salem Health: Cancer passed on genetically, so family members of those affected with Ewing sarcoma have no more risk of developing the cancer than the general population does. Male teenagers are most often diagnosed with this disease. The cancer is thought to be linked somehow to the rapid growth that occurs during puberty. Whites are more likely to develop this disease than are Asians and African Americans. Very rarely, Ewing sarcoma can develop as a secondary tumor in patients who have had radiation therapy for another type of cancer. Etiology and the disease process: Because this cancer occurs most often during the teenage years, there may be a link between the onset of puberty and early stages of this disease. Ewing sarcoma usually starts in a bone, though it can start in soft tissue. The most common starting place for these tumors is in the pelvis or in the leg bones. The tumors may then spread to the chest cavity, other bones, bone marrow, lungs, kidneys, or heart when tumor cells enter the bloodstream and travel elsewhere in the body. This disease may also spread to the central nervous system or lymph nodes, but this is much less common. Incidence: This disease occurs most often in male children and teenagers, mostly between ten and twenty years old. However, female children and teenagers also develop this disease. In the United States, this cancer affects children less than three years of age at a rate of 0.3 per million and teenagers between the ages of fifteen and nineteen at a rate of 4.6 per million. People over the age of twenty-five rarely develop this type of cancer. Experts estimate that in the United States each year about 200 new cases of this cancer are diagnosed in children and about 20 in adults. These tumors make up about 30 percent of the bone cancers in children. Symptoms: Symptoms of Ewing sarcoma involve pain (which may be worse at night), swelling (especially when the tumor is located in the long bones of the arm or leg), redness, tenderness, stiffness, a mass that grows quickly and may feel warm, or a bone that breaks unexpectedly. Some patients have fever, fatigue, anemia, or weight loss. Numbness, tingling, or paralysis can also be symptoms if the tumor is located near nerves.
A fibula with Ewing sarcoma. (©Ism/Phototake—All rights reserved)
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Screening and diagnosis: Because this disease is so rare, no screening is recommended. When Ewing sarcoma is suspected, doctors generally use X rays to determine if there is a suspicious growth. A magnetic resonance imaging (MRI) scan or blood tests also may be helpful in making a diagnosis. If Ewing sarcoma is suspected, two addi-
Salem Health: Cancer tional tests are used to see if the disease has spread: a computed tomography (CT) scan, which usually includes the lungs to see if the disease has spread there, and a bone scan. Ewing sarcoma may initially be mistaken for a bone infection (osteomyelitis) or another type of bone cancer (osteosarcoma). A sample of the tumor (biopsy) is necessary to confirm the diagnosis of Ewing sarcoma. A biopsy may be performed with a fine needle, taking only a small sample of the tumor, or by surgery, where all or a large part of the tumor is removed. Sometimes, bone marrow also is biopsied to determine if the disease has spread there. There is no formal staging for Ewing sarcoma. Gauging the extent of this disease is done by simply determining whether the cancer has spread into other tissues. Treatment and therapy: Ewing sarcoma is usually a very aggressive disease. By the time of diagnosis, nearly all patients with Ewing sarcoma have some spreading of the disease throughout the body. Most patients are treated with chemotherapy, sometimes before and after surgery, to ensure treatment of any tumors throughout the body. Surgery or radiation may also be used at the local site of the main tumor if the tumor can be removed without damaging vital organs. Sometimes surgery involves removing bones, which can be replaced or rebuilt with artificial bones or bone grafts. With Ewing sarcoma, radiation therapy usually involves radiation that comes from a machine outside the body rather than from implanted radiation seeds. Radiation therapy can shrink large tumors to alleviate symptoms if the tumor cannot be removed with surgery. Other types of treatment may include rehabilitation, including occupational or physical therapy. Patients may also need supportive care to help with side effects of chemotherapy, radiation, or surgery. Some patients may benefit from a transplant of blood stem cells or bone marrow. Diagnosis of Ewing sarcoma usually occurs during the teenage years, sometimes an already turbulent period. Surgery may cause disfigurement during a period of life when looks are very important. Support groups in which teens meet other people with this condition may be especially helpful in dealing with the psychological trauma that this disease can cause. Generally, patients with Ewing sarcoma benefit from treatment at a children’s hospital or medical center with doctors who have experience treating pediatric cancers. Prognosis, prevention, and outcomes: The prognosis for patients with this disease depends on how far the disease has spread, the size and location of the main tumor, and how responsive the tumors are to chemotherapy. For pa-
Ewing sarcoma tients who at diagnosis show no signs of the spread of the disease and choose an aggressive course of treatment involving chemotherapy, surgery, and radiation, survival rates at five years are 70 to 75 percent. However, at diagnosis, at least 15 percent of these patients already have cancer throughout their bodies, generally because symptoms are so vague and nonspecific. These patients have a five-year survival rate of 30 percent. Children under the age of eleven, female children and teenagers, those with smaller tumors, and those who have tumors below the elbow or below the calf have the highest survival rates. People who have had Ewing sarcoma need continual follow-up care. Even if the cancer is treated and its spread stopped, it often develops again in the place where it first arose and tends to spread throughout the body. Health issues may spring up later that are caused by the type of treatment given. These issues may involve heart and lung problems, slowed or decreased growth and development, and problems with sexual development. It is important for a patient who has had this disease to be regularly monitored for these types of concerns. There is no known way to prevent Ewing sarcoma. However, not everyone with the gene translocation develops this disease. Scientists are investigating why the gene translocation causes the disease only in some people to see if there are ways to block this cancer from forming. Research is also under way to determine new and improved techniques for diagnosing this cancer earlier in the disease process. Marianne M. Madsen, M.S. u
For Further Information Icon Health. Ewing’s Sarcoma: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Pappo, Alberto S., ed. Pediatric Bone and Soft Tissue Sarcomas. New York: Springer, 2005. Theroux, Nicole. Ewing’s Sarcoma Family of Tumors: A Handbook for Families. Glenview, Ill.: Association of Pediatric Oncology Nurses, 1999. u
Other Resources
Cancer Index Ewing’s Sarcoma: Frequently Asked Questions http://www.cancerindex.org/ccw/faq/ewings.htm The Cure Our Children Foundation Ewing’s Sarcoma and Pediatric Cancer Support Group Resources Page http://www.cureourchildren.org 449
Exenteration Ewing’s Research Foundation http://www.letsbeatthis.org National Cancer Institute Ewing Family of Tumors Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ ewings/healthprofessional See also Amputation; Bone cancers; Limb salvage; Neuroectodermal tumors; Pediatric oncology and hematology; Spinal axis tumors; Tumor markers; Young adult cancers.
u Exenteration Category: Procedures Definition: Exenteration is a major surgical procedure in which the entire contents of a body cavity, such as the pelvis or the orbit (eye socket), are totally removed. Cancers treated: In female patients, cancer of the reproductive organs such as the uterus, cervix, and Fallopian tubes; in male patients, cancer of the prostate and certain ducts and glands; for both genders, cancer of the rectum and cancers of the eye and surrounding tissues Why performed: Exenteration of the pelvis in female patients is performed when less radical surgery, chemotherapy, and radiotherapy have failed in the management of advanced and/or invasive cases of vaginal, cervical, uterine, and rectal cancer. Most often, previously treated patients with recurrent cervical cancer undergo the procedure. Cancer that has spread or metastasized is rarely treatable with exenteration; because of characteristic distant metastasis, ovarian cancer does not lend itself to the procedure. In male patients, pelvic exenteration is indicated when prostate and/or rectal cancer is unresponsive to radiation and hormonal therapy and when biopsy demonstrates recurrent cancer and ultrasound shows rectal involvement. Orbital exenteration is indicated for large orbital tumors, or the extension of intraocular tumors, most commonly when squamous and basal cell carcinoma affecting the orbit and its contents are unmanageable by simple removal or irradiation. Patient preparation: For exenteration of the pelvis, along with laboratory tests, patients are evaluated with pelvic and rectal exams. Imaging procedures include rectal and liver ultrasound, computed tomography (CT) scans, chest X rays, bone scans, and magnetic resonance imaging (MRI) to determine the extent and/or spread of the cancer. 450
Salem Health: Cancer Biopsy may confirm a recurrence of cancer. Immediately preceding the operation, the patient is given a bowel prep and antibiotics to prevent postsurgical infection. In orbital exenteration, a physical exam, history, laboratory tests, and imaging methods such as ultrasound, CT scans, angiography (to examine the orbital blood vessels), and biopsy are employed. Patients may undergo preoperative radiation and/or chemotherapy. Steps of the procedure: Total pelvic exenteration is an ultraradical surgery comprising total resection (removal) of female reproductive organs (cervix, uterus, tubes, ovaries, and vagina), part of the lower urinary tract (urethra and bladder) and rectum, as well as the muscles that form the pelvic floor. The process commences with a generous midline (vertical) incision in the abdomen that allows for exploration; during the operation, biopsies may be taken to assess the presence of cancer. If a tumor cannot be found or if pathology shows that the cancer has spread to the pelvic sidewall or has metastasized to the lymph nodes, then the procedure should be discontinued. If a decision is made to continue, then pelvic blood vessels are clamped and the organs are removed. Before the incision is closed, a urostomy and a colostomy may be performed. A urostomy diverts urine to a small pouch created from the small intestine, which is then connected to the abdominal wall so that urine can pass through a stoma (small opening) for collection. A colostomy attaches the colon to the abdominal wall so that fecal waste may exit the body via a stoma for collection in a small bag. Variations of pelvic exenteration include anterior exenteration, in which the rectum is left intact, and posterior exenteration, in which the bladder and the urethra are spared. In male patients, removal of the bladder and prostate is called a cystoproctectomy. In orbital exenteration, the entire contents of the globe are removed, including the eyeball, surrounding tissues, and part of the bony orbit. In certain patients, the eyelids and conjunctiva may be spared. Less radical procedures include evisceration, which spares the extraocular muscles, and enucleation, in which the eye is removed while all other orbital structures are spared. After the procedure: With pelvic exenteration, a drainage tube is placed into the incision site; there is usually discharge, bleeding, and quite a bit of tenderness and pain for at least a few days. While side effects vary, they often include difficulty with urination, particularly if catheterization is involved. Before the patient is sent home, stitches are removed and a pain medication is prescribed. After orbital exenteration, the majority of patients ex-
Salem Health: Cancer perience headache for several days, which may dissipate with the use of pain medications. An ocular ointment containing antibiotics and steroids may also be prescribed. Risks: With pelvic exenteration, morbidity and mortality depend on the specific procedure and the condition of the patient; the elderly and those with comorbidities are most affected. There is a 30 to 44 percent chance of complications such as kidney failure, fistula formation, and bowel obstruction during the procedure, a mortality rate of 2 to 5 percent, and a five-year survival rate of 23 to 61 percent. The success with rectal anastomosis depends on the degree of resection and concurrent reconstructive procedures; complications such as leaks and fistulas may occur in 30 to 50 percent of cases. Overall, a poor prognosis is associated with recurrence of cancer, a tumor larger than 3 centimeters, involvement of the resection margin or pelvic sidewall, and nodal metastasis. With orbital exenteration, there may be ear pathology, sinusitis, chronic orbital pain that throbs, orbital cysts, and recurrence of cancer. A five-year survival rate of 64 percent has been observed. Results: While pelvic exenteration may often be a lifesaving measure, patients should be made aware of postoperative sequelae so as to attenuate the psychological distress related to lifestyle changes such as dealing with permanent catheterization, a colostomy and/or urostomy, and loss of sexual functions. The services of a psychologist and sex therapist may be required. In addition, a variety of postoperative reconstructive procedures are available to support the pelvis and even create a “neovagina” in female patients. Orbital exenteration will require that the patient adapt to a dramatic change in appearance and loss of eyesight in the affected eye. Wearing an eye patch is a popular option for many patients; after the site has healed, a temporary prosthesis such as a plastic eye may be used. Later, a permanent prosthesis may be attached. Cynthia Racer, M.A., M.P.H. u
For Further Information Ben Simon, G. J., R. M. Schwarcz, R. Douglas, et al. “Orbital Exenteration: One Size Does Not Fit All.” American Journal of Ophthalmology no. 139, no. 6 (2005): 7-11. Della Rocca, Robert, Edward H. Bedrossian, Jr., and Bryan Arthurs, eds. Ophthalmic Plastic Surgery: Decision Making and Techniques. New York: McGrawHill, 2002. Nemet, A. Y., P. Martin, R. Benger, et al. “Orbital Exenteration: A Fifteen-Year Study of Thirty-eight Cases.”
Exercise and cancer Ophthalmic Plastic & Reconstructive Surgery 23, no. 6 (November/December, 2007): 468-472. O’Donovan, Peter J., and Ellis G. R. Downes, eds. Advances in Gynaecological Surgery. San Francisco: GMM, 2002. Rock, John A., and Howard W. Jones III, eds. Te Linde’s Operative Gynecology. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Stolzenburg, J.-U., M. T. Gettman, and E. N. Liatsikis, eds. Endoscopic Extraperitoneal Radical Prostatectomy: Laparoscopic and Robot-Assisted Surgery, London: Springer, 2007. See also Lacrimal gland tumors; Nasal cavity and paranasal sinus cancers; Urinary system cancers; Vaginal cancer.
u Exercise and cancer Category: Lifestyle and prevention Definition: Regular exercise has been found to reduce cancer risk and mortality. The more time a person spends in occupational or leisure activities requiring physical exertion, the lower the risk of cancer. For those who have cancer, regular exercise has been shown to improve recovery and help manage the side effects of treatments. Protective effects of exercise: Many studies have found an inverse relationship between exercise and many types of cancer. Exactly how exercise protects individuals against various cancers is difficult to determine. A number of logical theories have been presented. Regular exercise has a positive effect on the blood by lowering glucose and insulin levels and improving white blood cell function. Hormonal changes include an increase in steroid hormones from the adrenal cortex and improvements in the insulin effects on cancer-fighting T cells. Exercise is also believed to improve vitamin C metabolism. All of these effects could protect the body from cancer. A more complex area where benefits are likely is cell division, which is rapid in cancers. Exercise increases anti-inflammatory cytokines, which decrease cell division. It also has beneficial effects in preventng the activation of cancer genetic material called oncogenes. Another effect is the promotion of interferon production, which decreases viral reproduction. By decreasing cell reproduction, exercise may slow cancer growth. Rehabilitation effects of exercise: The main goal of exercise for those who have cancer is to maintain or improve the physical capabilities of the body, resulting in an im451
Exercise and cancer
Salem Health: Cancer
proved quality of life during and after treatment. No obvious effects of exercise on the immune system of cancer patients have been identified at this time. Some of the immediate effects of exercise on the cancer patient are decreased nausea and lessened symptoms of fatigue. Part of the goal of exercise for cancer patients is to protect them from other health problems. Exercise helps them maintain healthy weights by decreasing fat but also de-
creasing the loss of muscle due to inactivity and treatments. Exercise increases blood flow throughout the body, reducing blood clot formation, particularly in the legs. Longer-term health risks such as osteoporosis (loss of bone) and cardiovascular disease are lowered by regular exercise. Psychological benefits can also be obtained by cancer patients who exercise. Decreased anxiety and depression and improved self-esteem have been found. The ability to be more independent and do normal daily activities can Physical Activity Recommendations contribute to this improved psychologfor Healthy Adults from the Centers for ical state. With all of these potential Disease Control and Prevention benefits, cancer patients are advised to participate in exercise programs with Aerobic or Cardio Activity individualized exercise prescriptions. Option 1: 30 minutes (minimum) of moderate-intensity exercise most days of the week
• • • • • • • • • • • • • •
Walking, moderate to brisk pace (3-4.5 mph) on level surface Bicycling 5-9 mph, level terrain Yoga Ballroom dancing Tennis, doubles Golf, wheeling clubs and walking Shooting baskets Swimming recreationally Horseback riding Gardening and yard work Moderate housework (scrubbing the floor on all fours, carrying out trash) Hand washing and waxing a car Walking, running, or climbing when playing with children Walking while pushing or pulling a child in a stroller
Option 2: 20 minutes (minimum) of vigorous-intensity exercise 3 days a week
• • • • • • • • • • • • • •
Jogging or running Walking briskly up a hill Roller skating or in-line skating briskly Bicycling more than 10 mph or on uphill terrain Karate, judo Jumping rope Stair climber machine at fast pace Professional or energetic ballroom dancing Tennis, singles Competitive sports such as football, basketball, soccer Ice skating quickly or speed skating Swimming laps Heavy yard work or gardening (felling trees, digging ditches) Racewalking or jogging while pushing a sports stroller
Strength Building Activity 2 days a week
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Weight lifting, 6 to 8 exercises, with 8 to 12 repetitions per exercise
Exercise prescription and cancer: Cancer patients must check with their physicians before beginning an exercise program. It is generally recommended that patients first complete a supervised exercise test to determine which types of exercise can be done safely. Exercise tests should not be conducted if the patient has dizziness, shortness of breath, fever, or nausea and vomiting. Exercise tests are usually conducted on a treadmill or stationary bicycle, paying close attention to symptoms and fatigue. This is not be a maximal test to exhaustion but rather a submax test. The information obtained from the exercise test is used to complete an exercise prescription. Mode, frequency, intensity, duration, and progression are considered. The type of exercise recommended includes activities that work the large muscle groups such as walking and cycling. It is recommended that cancer patients exercise three to five times per week. In cases in which patients have low levels of conditioning, shorter sessions are attempted every day. Cancer patients are advised to exercise at a lower intensity than the general population. For healthy people, the typical heart rate range considered desirable for exercise is 70 to 85 percent of maximum heart rate, and in cancer patients, it is 60 to 70 percent of maximum
Salem Health: Cancer heart rate. The recommended duration of the exercise session is twenty to thirty continuous minutes. However, many cancer patients may not be able to exercise that long. In these cases, the patients can space out the twenty to thirty minutes with periodic rest intervals. The goal is gradually to shorten the length and frequency of rest periods until the patient can complete the exercise session without stopping. In the healthy population, people progress by gradually increasing intensity, duration, or frequency. This may not be possible for cancer patients because of treatments that may cause regression. Therefore periodic modifications in the exercise program may need to be made. Several precautions are advised for cancer patients. Treatments frequently lower blood counts, resulting in increased risk for infections, anemia, and bleeding. Blood counts are monitored during treatment and used to determine appropriate exercise times. Patients are advised to stop exercise during periods of low blood counts. Sodium and potassium levels can decrease with excessive vomiting. This decrease can lead to other health complications, and exercise should be avoided during these times. Treatments also can cause severe fatigue. When patients are fatigued, less intense exercise, or a break in exercise, is appropriate. For cancer patients, lifting heavy weights and exercising on uneven floors that can affect balance are not advised. Conditions that warrant contacting a physician are swollen ankles; unexplained weight loss; shortness of breath with low-level activity; or exercise-induced nausea, vomiting, or unrelieved pain. Dizziness or blurred vision that does not go away with rest needs immediate attention from a physician. By paying attention to these safety measures, cancer patients can exercise safely and effectively. Exercise, cancer, and fatigue: Cancer treatments such as chemotherapy and radiation cause fatigue in most patients. Incorporating exercise into the treatment gives the expectation of greater fatigue and less willingness to participate. However, appropriate, low-level aerobic exercise can actually decrease fatigue. Strategies exist to improve exercise adherence during cancer treatments. One important factor is rest. Physical activity and rest must be balanced so there is no interference with nighttime sleep. This is best accomplished with a regular daily routine in which exercise takes place during times when the patient feels best. Reducing stress with regular relaxation techniques is helpful, along with a balanced diet that includes adequate protein. Getting plenty of fresh air, such as exercising outside, is beneficial.
Exercise and cancer
The more time people exert themselves physically, whether as part of work or leisure, the lower their risk of cancer. (PhotoDisc)
Perspective and prospects: Although much progress is being made in the fight against cancer, it will continue to be one of the major health problems. New drugs and other treatments to force cancer into remission will be developed, giving more hope to cancer patients. However, lifestyle interventions involving exercise, nutrition, and stress management can also be used to help treat and minimize treatment side effects. At the least, lifestyle interventions will improve the quality of life of cancer patients. The correlation between cancer prevention and exercise has not been investigated to the same extent as exercise and cardiovascular disease. The cardiovascular benefits of exercise were found many years ago, and many studies have been conducted to determine the best exercise practices. As more research is conducted, the mechanisms for decreasing cancer risk will become more evident and the specific types of exercises associated with both prevention and treatment of specific cancers will be identified. This will give health professionals more options for fighting cancer and improving the quality of life for cancer survivors. 453
External beam radiation therapy (EBRT) In the meantime, cancer patients can participate in appropriate exercise programs that include low-intensity aerobic activities. Health care professionals as well as exercise leaders and trainers need to be continually updated about cancer and the benefits of exercise as additional information is found. Cancer is a challenging disease and all strategies must be used to reduce risk and improve outcomes. Bradley R. A. Wilson, Ph.D. u For Further Information McTiernan, Anne. Cancer Prevention and Management Through Exercise and Weight Control. Boca Raton, Fla.: CRC Press, 2006. Schneider, Carole M., Carolyn A. Dennehy, and Susan D. Carter. Exercise and Cancer Recovery. Champaign, Ill.: Human Kinetics, 2003. Schwartz, Anna L. Cancer Fitness: Exercise Programs for Patients and Survivors. New York: Fireside, 2004. Stidwill, Howard. Exercise Therapy and the Cancer Patient: A Guide for Health Care Professionals and Their Patients. Belgium, Wis.: Champion Press, 2006. u
Other Resources
American Cancer Society Physical Activity and the Cancer Patient http://www.cancer.org/docroot/MIT/content/ MIT_2_3x_physical_activity_and_the_cancer_ patient.asp?sitearea=MIT National Cancer Institute Energy Balance: Weight and Obesity, Physical Activity, Diet http://www.cancer.gov/cancertopics/energybalance See also Aging and cancer; Anxiety; Chemoprevention; Dietary supplements; Fiber; Macrobiotic diet; Nutrition and cancer prevention; Prevention; Self-image and body image; Smoking cessation; Stress management.
u External beam radiation
therapy (EBRT)
Salem Health: Cancer Cancers treated: Most cancers, with approximately 60 percent of all cancer patients receiving radiation Why performed: EBRT is performed as a curative treatment alone or in combination with chemotherapy, surgery, and other treatments. EBRT may also be used to treat symptoms or side effects from cancer, such as spinal cord compression and metastases. Patient preparation: The patient will be referred to a radiation oncologist for a consult visit to determine if external beam radiation therapy is appropriate. Prior to receiving treatment, patients have a simulation using a computed tomography (CT) scanner or other device to visualize the area to be treated. A simulation may take one to two hours. Small marks may be applied to the skin to provide assistance in positioning the radiation beams. The simulation data are used to plan the radiation dose amounts to be given by the linear accelerator. Accurate tumor targeting is the key to protecting normal tissues while killing cancer cells. Steps of the procedure: The treatment plan will outline the patient position on the treatment table, define the number of treatments to be given, and prescribe the daily total dose to be given. The patient usually has four to six weeks of treatment, five days a week, with two days a week off for normal cells to rest and recover. The patient may need to change into a hospital gown. In the treatment room, the staff will position the patient carefully and then leave the room to program the linear accelerator with the required treatment data. The total time for positioning and radiation administration is about fifteen minutes. After the procedure: Treatments are generally done on an outpatient basis, and the patient may leave immediately after the daily treatment. Patients are not radioactive following treatments. Risks: External beam radiation therapy is a local treatment, so risks are generally associated with the site being treated. Skin reactions, similar to sunburn, may occur. Fatigue is often associated with EBRT, but the cause is unknown. There is a risk of a second cancer caused by the radiation. There is also a risk that the radiation will not kill all the cancer cells.
Category: Procedures Also known as: Radiotherapy
Results: Expected after external beam radiation therapy is expected to kill cancer cells and thus reduce tumor size. Patricia Stanfill Edens, R.N., Ph.D., FACHE
Definition: External beam radiation therapy (EBRT) uses a linear accelerator to generate high-energy radiation beams or a machine with a radioactive source, cobalt 60, to kill cancer cells by altering their genetic material.
See also Afterloading radiation therapy; Brachytherapy; Cervical cancer; Computed tomography (CT) scan; Medulloblastomas; Radiation oncology; Radiation therapies; Thyroid cancer.
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Eye cancers
u Eye cancers Category: Diseases, symptoms, and conditions Also known as: Intraocular cancers, uveal cancers Related conditions: Retinal detachment, angle-closure glaucoma Definition: Eye cancers are malignant tumors of the eye, which is made up of the globe, the orbit, and the adnexal structures. The globe (or eyeball) is filled with a fluid called vitreous humor and contains the retina and the uvea. The uvea consists of the iris (pigmented area surrounding the pupil), choroid (pigmented lining of the eyeball that brings blood to the retina and the front of the eye), and ciliary body (made up of the cells producing the aqueous humor and the muscles that control the shape of the lens). Cancers that develop in the globe (retina and uvea) are called intraocular cancers. The orbit is made up of the tissues surrounding the eyeball, including the muscles that control the directional movement of the globe and the nerves of the eye. Tumors in these tissues are called orbital cancers. The adnexal structures consist of the eyelids and the tear glands. Cancers that occur in these structures are called adnexal cancers. Risk factors: For intraocular melanoma, the risk factors include advanced age (the peak age is seventy), being white, and having light (blue or green) eye color, fair skin, and the ability to tan. For retinoblastoma in children, 10 percent of patients have retinoblastoma in their family history. If the disease is passed from parent to child, the child often has retinoblastoma in both eyes. Etiology and the disease process: The most common intraocular or uveal eye cancers are melanomas, although these are rare, with approximately 4.3 new cases per 1 million people. Most intraocular melanomas initially do not cause any symptoms, but as the tumor grows, symptoms may include distortion of the pupil, blurred vision, and decreased visual acuity caused by secondary retinal detachment. Extensive retinal detachment can be accompanied by secondary angle-closure glaucoma. Other tumors that can resemble intraocular melanomas in clinical presentation are metastatic carcinoma, posterior scleritis, and benign tumors such as nevi and heman-
giomas. This should be considered when making a diagnosis of intraocular melanoma. Approximately 90 percent of intraocular melanomas occur in the choroid and are called choroidal melanomas. Choroidal melanomas are primary intraocular cancers, that is, cancers that originate in the eye. They initiate from pigmented cells in the choroid and have the potential to become malignant (metastasize to other organs). The remaining intraocular melanomas are melanomas of the iris. These tumors often grow from pigmented spots in the iris that may be present for many years before developing into tumors. They are relatively slow growing and rarely metastasize, and therefore are associated with a better prognosis than choroidal melanomas. Another kind of intraocular cancer is intraocular lymphoma, which can be either Hodgkin disease or nonHodgkin lymphoma. These lymphomas typically originate in the lymph nodes but can also originate in the stomach, lungs, and eye. Primary intraocular lymphomas are rare and are always of the non-Hodgkin type. These cancers usually occur in elderly or immunosuppressed people. Adnexal tumors affecting the eyelid include basal cell carcinomas, which constitute 85 to 95 percent of all malignant eyelid tumors; squamous cell carcinoma; sebaceous cell carcinoma; and malignant melanoma. Basal cell carcinomas and squamous cell carcinomas are most common in elderly people with fair skin. Basal cell carcinomas commonly occur in the inner part of the lower eyelid and are often nodular, appearing as raised pearly bumps with tiny blood vessels. Sebaceous cell carcinomas originate in the
Malignant melanoma on the iris. (Sue Ford/Photo Researchers, Inc.)
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Eye cancers eyelid tear glands in elderly people and can be highly malignant, returning after removal and invading the eye socket and lymph nodes. Malignant melanomas are associated with unusual or changing pigmentation. Tumors of the conjunctiva can be squamous cell carcinoma, malignant melanoma, or lymphoma. Secondary intraocular cancers originate in other organs in the body and spread (metastasize) to the eye. Breast and lung cancers are most likely to metastasize to the eye, especially the uvea. Tumors can also metastasize from the prostate, kidneys, thyroid, and the gastrointestinal tract, though this occurs less frequently than metastasis from the breast and lung. Retinoblastoma is the most common form of eye cancer in children. It is most common in children younger than the age of five, and affects boys and girls in equal proportion. Approximately 75 percent of retinoblastoma cases are unilateral (affecting one eye). Some 90 percent of patients do not have a family history of retinoblastoma. Incidence: In 2008, about 2,390 adults were estimated to be diagnosed with cancer of the eye and orbit and 240 were estimated to die of the cancer. The incidence of intraocular melanomas, the most common form of intraocular cancer, is approximately 4.3 new cases per 1 million people. Retinoblastoma affects 1 in every 15,000 to 30,000 live babies per year, with 350 new cases annually. It affects all races with similar frequency. Symptoms: Symptoms of intraocular tumors may include distortion of the pupil, blurred vision, bulging eyes, watery eyes, pain in or around the eye (rare), and decreased visual acuity caused by secondary retinal detachment. Extensive retinal detachment may be accompanied by secondary angle-closure glaucoma. Other symptoms may include floaters, where spots, flashes, or wavy lines appear in the visual field; loss of peripheral vision, where objects to the side cannot be seen; and a pigmented spot on the iris that enlarges with time (this could be a sign of iris melanoma). Symptoms of retinoblastoma include a white pupil reflex (leukocoria or cat’s-eye reflex) instead of the normal black pupil or red reflex. Screening and diagnosis: Diagnosis of eye tumors can be performed by means of an eye examination with an ophthalmoscope or slit lamp. This is the single most important diagnostic test for eye tumors. For example, most choroidal melanomas can be diagnosed by visual examination of the pupil for the presence of tumors. Choroidal melanomas range in shape and pigmentation, from dark brown to unpigmented. However, most choroidal melanomas are 456
Salem Health: Cancer brown to gray-green in color and have a dome or nodular shape. Other tumors may need additional tests, which include echography or ultrasound, in which sound waves are directed at the eye from a small probe placed on the eye. The reflection patterns are then analyzed to determine if tumors are present. Another diagnostic technique is called fluorescein angiography and involves the introduction of eye drops that cause pupil dilation followed by the injection of a fluorescent dye into a vein in the arm. The dye passes through the blood vessels in the back of the eye and a camera takes a series of photographs, from which the physician can determine if a tumor is present. Echography and fluorescein angiography can also be used to distinguish between eye tumors and hemorrhages or macroaneurysms that may occur in the choroid or below the retinal epithelium. The most invasive diagnostic test that can be performed is the eye biopsy. This involves inserting a long narrowbored needle into the eye and extracting tissue for examination with a microscope. The risk of ocular mortality associated with an eye biopsy, however, is a serious drawback to this diagnostic test and influences many physicians to use alternative means of diagnosis. Staging of intraocular tumors involves determining the tumor thickness (apical height) and width (basal diameter). Tumor sizes are classified as small (apical height of 1 millimeter, or mm, to 3 mm, basal diameter equal to or greater than 5 mm), medium (apical height of 2 mm to 10 mm, basal diameter less than 16 mm), large (apical height greater than 10 mm, basal diameter equal to or greater than 16 mm), and diffuse (horizontal, flat growth pattern and tumor thickness 20 percent or less than the greatest basal dimension). Diffuse tumors are rare and have a poorer prognosis. Physicians also determine if the tumor has metastasized and, if so, to what extent. Metastasis of the tumor to preauricular, submandibular, or cervical lymph node regions indicates that subconjunctival extension has occurred. Systemic metastasis usually occurs first in the liver and may also occur in the lung, bone, and subcutaneous sites. Metastasis or spreading of the cancer to the optic nerve, eye socket, or meninges is very rare and is called extraocular extension. The American Joint Committee on Cancer has developed a method for intraocular cancer staging. Metastasis of retinoblastoma tumors is rare but when it occurs, tumors can spread to the brain, central nervous system, and bones. Treatment and therapy: One of the most commonly used methods of treating eye cancers is radiation therapy, which can shrink tumors but usually does not eliminate them en-
Salem Health: Cancer
Eye cancers
Stage at Diagnosis and Five-Year Survival Rates for Eye and Orbit Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 75 9 4 12
86.7 68.7 70.4 77.6
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
tirely. It can take two forms: plaque radiation therapy and external-beam, charged-particle radiation therapy. Plaque radiation therapy uses plaques with radioactive pellets on one side and gold coating on the other side. An incision is made in the conjunctiva, and plaques are sewn to the outside of the eye directly over the tumor with the side coated with radioactive pellets facing the tumor. Plaque radiation therapy has a five-year control rate of more than 90 percent but has the disadvantage of a high risk of secondary cataracts. External-beam, charged-particle radiation therapy involves irradiating tumors with precisely focused radiation from a cyclotron, a piece of equipment that is available only at specialized centers. This type of therapy specifically kills tumor tissue without damaging surrounding healthy eye tissue and appears to have a control rate similar to that of plaque radiation therapy. The drawbacks are the need for specialized equipment with limited availability, the need for patient cooperation during the procedure (the eye needs to be held still so that the radiation beam can be directed at the tumor), and the possibility of anteriorsegment complications. Other treatments include local tumor resection, which is used for ciliary body or anterior choroidal tumors that have smaller basal dimensions and greater thickness. The eye tumor can also be treated with chemotherapy, which is administered intravenously and delivered to the eye through the bloodstream. In cases in which treatment of the tumor is unsuccessful, surgery may be required to remove the eye (enucleation). The empty eye socket can then be filled with an eyeball implant made of synthetic material.
Newer treatments include photocoagulation with white light and laser radiation, transpupillary thermotherapy, and cryotherapy. Photocoagulation involves the destruction of small tumors by directing light through the pupil into the tumor. Newer photocoagulation techniques use a diopexy probe that directs the light through the wall of the eye instead of through the pupil. This method can be used alone or together with plaque radiation therapy and cryotherapy. Cryotherapy involves applying a penlike probe to the sclera just next to the tumor and freezing the tumor while the patient is under local or general anesthesia. This usually has to be repeated multiple times before the tumor is destroyed and can cause swelling of the eye and eyelids. Prognosis, prevention, and outcomes: The prognosis of intraocular cancers depends on several factors, including cell type, tumor size, location of the anterior margin, the extent of ciliary body involvement, extraocular extension, and tumor recurrence. Cell type is the most commonly used factor for predicting cancer prognosis. Intraocular melanomas usually consist of spindle cells and epithelioid cells. Spindle cells have less potential for metastasis than epithelioid cells, and a tumor that is mostly made up of spindle cells is considered to have a better prognosis than one that consists mostly of epithelioid cells. Recurrent melanoma always has a poor prognosis, regardless of cell type or stage. The treatment selected depends on the tumor size, age and health of the patient, site of recurrence, and previous treatment. The prognosis for retinoblastoma is usually very good, with most children (more than 95 percent) surviving to live normal lives. Ing-Wei Khor, Ph.D. u
For Further Information “Malignant Melanoma of the Uvea.” In AJCC Cancer Staging Manual, edited by Frederick L. Greene et al. 6th ed. New York: Springer-Verlag, 2002. Singh, A. D., L. Bergman, and S. Seregard. “Uveal Melanoma: Epidemiologic Aspects.” Ophthalmology Clinics of North America 18 (2005): 75-84. u
Other Resources
American Cancer Society What Is Eye Cancer? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1x_What_is_eye_cancer_74.asp?sitearea= Bascom Palmer Eye Institute Ocular Oncology http://www.eyecancermd.org/eye_cancers.html 457
Eyelid cancer Cancer Help UK Symptoms of Eye Cancer http://www.cancerhelp.org.uk/help/ default.asp?page=18546 Collaborative Ocular Melanoma Study About Choroidal Melanoma http://www.jhu.edu/wctb/coms/general/about-mm/ coms1.htm Eyecancernetwork http://www.eyecancer.com Memorial Sloan-Kettering Cancer Center Retinoblastoma http://www.mskcc.org/mskcc/html/2867.cfm National Cancer Institute Intraocular (Eye) Melanoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ intraocularmelanoma/healthprofessional See also Eyelid cancer; Gonioscopy; Lacrimal gland tumors; Neurofibromatosis type 1 (NF1); Ophthalmic oncology; Orbit tumors; Retinoblastomas; Rhabdomyosarcomas; Rothmund-Thomson syndrome; Sjögren syndrome.
u Eyelid cancer Category: Diseases, symptoms, and conditions Related conditions: Eye cancers Definition: Eyelid cancer can occur as one of a variety of types of cancer that begin on or around the eyelid. The most common types of eyelid cancer are slow to spread and can often be successfully be treated with surgery to remove the tumor followed by eyelid reconstruction. Risk factors: The main risk factors for eyelid cancer are light skin tone, skin that easily burns or freckles, and frequent exposure to the sun. Eyelid cancer is most common in people over the age of fifty. Men are affected slightly more often than women. Individuals who have skin around the eye that has been sunburned, burned, or that has been injured because of a disease or infection are believed to be at higher risk for eyelid cancer. A history of other skin cancers is also thought to increase the risk. Etiology and the disease process: There are four main types of eyelid cancers. Basal cell carcinoma and squamous cell carcinoma are usually slow growing and do not tend to spread to other areas of the body. Sebaceous gland carcinoma and malignant melanoma are more aggressive, 458
Salem Health: Cancer faster growing, and much more likely to spread. Basal cell carcinoma is a cancer that develops in the lower epidermis. Squamous cell carcinoma begins in the top layer of the epidermis. Sebaceous gland carcinoma arises in the glands of the eyelid. Melanoma begins in the very bottom layer of the epidermis in the cells called melanocytes. From these beginnings, eyelid cancer can spread to the lymph nodes, areas around the eyelid, and to other areas of the body. Incidence: Eyelid cancer is not a very common form of cancer. According to the American Society of Clinical Oncology, in the United States the annual rates of eyelid cancer are 19.6 cases for every 100,000 men, and 13.3 cases for every 100,000 women. The most common form of eyelid cancer is basal cell carcinoma, which makes up between 85 and 95 percent of reported cases of eyelid cancer. Sebaceous cell carcinoma makes up about 5 percent of reported cases, sebaceous gland carcinoma between 1 and 5 percent of cases, and malignant melanoma a little less than 1 percent of cases. Symptoms: The main symptom of eyelid cancer is usually an abnormality in the skin of the eyelid or the surrounding area. Often, the eyelid cancer presents as a small bump, sometimes with small red veins in it. The area may differ in color from the surrounding skin and may seem to change colors or grow in size. The eyelashes in the affected area may be missing. There may be a sore that is crusted over or will not heal, or a tear that does not seem to heal properly. Other possible symptoms include swelling or thickening of the eyelid, and an eyelid infection that will not go away or keeps returning. There is often no pain associated with the discolored or bumpy area. Screening and diagnosis: The ophthalmologist will determine if the suspicious bump or discoloration is cancerous. If cancer seems likely, a biopsy will be performed. During the biopsy some or all of the suspected lesion is removed. It is then sent to a lab, where a pathologist performs tests and examines it under a microscope to determine if cancer is present and, if so, the type and possible extent. Eyelid cancer is staged based on the size of the tumor, if the cancer has spread to the nearby lymph nodes, and whether it has spread to any other parts of the body. Treatment and therapy: For many cases of eyelid cancer, especially basal cell carcinomas, the biopsy procedure may actually be all the treatment required. If it is determined that the biopsy removed all the cancerous tissue, no other procedures may be necessary. Most eyelid cancers are treated primarily with surgery. Other procedures, such as cryosurgery, in which the cancerous cells are frozen off, may be necessary. If the cancer has spread to any other
Salem Health: Cancer parts of the body, appropriate treatment will be required. Radiation and chemotherapy are not usually required for eyelid cancers that have not spread. Because surgical removal of the cancerous tissue is usually the primary treatment option, reconstructive surgery is frequently required after the cancer has been removed. Prognosis, prevention, and outcomes: The prognosis for cases of eyelid cancer that are caught early is generally very good. According to the American Society of Clinical Oncology, estimates indicate a cure rate of up to 95 percent for basal cell carcinoma. The prognosis for each person depends on the stage at which the cancer was diagnosed and other factors. Sebaceous cell carcinoma is not always treatable with as much success as basal cell carcinoma, because it is more likely to have spread and has a higher incidence of recurrence. Malignant melanoma is most likely to not be treatable successfully because of its tendency to spread to other areas of the body quickly. The best way to prevent eyelid cancer is to take the precautions that are generally recommended to prevent any form of skin cancer, such as avoiding prolonged exposure to intense sun, wearing UV-protective sunglasses, and always wearing sunscreen. Helen Davidson, B.A.
Eyelid cancer u
For Further Information Albert, Daniel M., and Arthur Polans, eds. Ocular Oncology. New York: Marcel Dekker, 2003. Bospene, Edwin B., ed. Eye Cancer Research Progress. New York: Nova Science, 2007. Fekrat, Sharon, and Jennifer S. Weizer, eds. All About Your Eyes. Durham, N.C.: Duke University Press, 2006.
u
Other Resources
Eyecancernetwork Squamous Carcinoma of the Eyelid http://www.eyecancer.com/patient/ Condition.aspx?nID=54&Category=Eyelid+Tumors &Condition=Squamous+Carcinoma+of+the+Eyelid Vision Channel Skin Cancer of the Eyelids http://www.visionchannel.net/skincancer/index.shtml See also Eye cancers; Gonioscopy; Lacrimal gland tumors; Neurofibromatosis type 1 (NF1); Ophthalmic oncology; Orbit tumors; Retinoblastomas; Rothmund-Thomson syndrome; Sjögren syndrome.
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Fallopian tube cancer
u Fallopian tube cancer Category: Diseases, symptoms, and conditions Also known as: Fallopian tube adenocarcinoma, Fallopian tube sarcoma, Fallopian tube mixed mesodermal tumor, broad ligament tumor Related conditions: Cancer of the uterus, cancer of the ovary, peritoneal carcinomatosis Definition: Fallopian tube cancer is a rare cancer in one of the Fallopian tubes, which lie on both sides of the top of the uterus (womb). These tubes serve as the site of fertilization for oocytes (eggs) released from the ovary and sperm ascending from the vagina, and then as passageways by which the zygote (fertilized egg) returns to the uterus to implant and where the fetus grows and develops. Cancer of the Fallopian tube is primary (originating in the Fallopian tube) in 10 to 20 percent of cases; the majority of Fallopian tube cancers, however, are metastatic from the ovary, uterus, or gastrointestinal tract (stomach and intestines). Risk factors: The major risk factors for Fallopian tube cancers are thought to be chronic inflammation in the form of endometriosis or pelvic infections, although this has not been proven. Other possible risk factors include a history of infertility and low parity (fewer than two children). Fallopian tube cancer is a disease of older women, diagnosed at an average age of fifty-nine years, with those diagnosed ranging between ages twenty-six and eighty-five. Oral contraceptive use and pregnancy may reduce a woman’s risk of Fallopian tube cancer. Etiology and the disease process: Based on molecular studies, cancer of the Fallopian tube and ovary share abnormalities of the genes TP53 and ERBB-2, suggesting similar genetic risks and environmental factors. Incidence: Fallopian tube cancer is the rarest cancer involving the female genital tract, accounting for approximately 1 percent of all gynecologic malignancies. The incidence of Fallopian tube cancer in the United States is 3.6 cases per million women per year, with approximately 300 cases diagnosed in the United States each year. Any woman’s individual lifetime risk of Fallopian tube cancer is therefore small. Symptoms: For the most part, cancer of the Fallopian tube is a disease without specific symptoms. Symptoms that are associated with cancer of the Fallopian tube include an abnormal, watery vaginal discharge or excessive bleeding; such symptoms occur in approximately 50 percent of 460
Salem Health: Cancer those with Fallopian tube cancer. Pain and a palpable pelvic mass are infrequently associated with Fallopian tube cancer. Occasionally, the pain associated with Fallopian tube cancer mimics appendicitis. Screening and diagnosis: No routine screening exists or is recommended for Fallopian tube cancer. Most often, the diagnosis of Fallopian tube cancer is made at the time of exploratory surgery to evaluate the patient’s symptoms, such as pelvic pain or a mass. Aside from nonspecific symptoms and the triad of symptoms in postmenopausal women (pelvic pain, a pelvic mass, and vaginal bleeding or discharge), the diagnosis should be suspected when cancer cells show up on microscopic evaluation of vaginal discharge with a negative Pap smear and biopsy of the uterus. An abdominal mass can be further evaluated with a pelvic ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), or a laparoscopic examination of the pelvis (outpatient surgery performed through the belly button with a small, lighted instrument). Definitive diagnosis of primary Fallopian tube cancer, as opposed to metastatic cancer, requires that the tumor be contained within the cavity of the Fallopian tube (lumen), the lining of the Fallopian tube (mucosa) be involved with the tumor, and a transition be demonstrated between the portion of the tube involved and that not involved with cancer. Cancer of the Fallopian tube is based on International Federation of Gynecology and Obstetrics (FIGO) staging. Stage 0 is cancer limited to the lining of the Fallopian tube (mucosa). Stage I is cancer limited to one tube with extension into the muscular layer of the tube but not to the external surface of the tube. Stage II cancer involves one or both tubes with extension beyond the Fallopian tube. Stage III cancer involves one or both tubes with spread beyond the pelvic cavity. Stage IV cancer involves one or both Fallopian tubes with distant metastases (for example, the lungs). Unlike ovarian cancer, which is usually advanced at the time of diagnosis, approximately 50 percent of Fallopian tube cancers are Stage I or II at the time of diagnosis, and 50 percent are Stage III or IV. Treatment and therapy: Because Fallopian tube cancer is generally diagnosed during surgery, staging is performed at that time to determine the extent of disease so that optimal treatment can be offered. Treatment includes a hysterectomy (removal of the uterus), a bilateral salpingo-oophorectomy (removal of both Fallopian tubes and ovaries), inspection of the surfaces of the lining of the abdominal cavity (the peritoneum) for cancer cells, sampling of lymph nodes, and removal of the omentum (a fatty layer covering the intestines).
Salem Health: Cancer For Stage I disease, surgery alone is recommended unless the peritoneum is positive. In that case, postoperative radiation or chemotherapy is offered. For Stages II through IV, postoperative chemotherapy is the standard treatment. A second laparoscopy is often performed on completion of chemotherapy or radiation therapy to confirm control of the disease. A blood test, the cancer antigen 125 (CA 125), can be ordered to monitor disease recurrence. Prognosis, prevention, and outcomes: The five-year survival for all stages of Fallopian tube cancer is approximately 40 to 50 percent. Patients diagnosed with Stage I Fallopian tube cancer have five-year survival rates of 65 percent; those with Stage II, 50 to 60 percent; and those with Stages III and IV, 10 to 20 percent. D. Scott Cunningham, M.D., Ph.D. u For Further Information Ajithkumar, T. V., A. L. Minimole, M. M. John, and O. S. Ashokkumar. “Primary Fallopian Tube Carcinoma.” Obstetrics and Gynecological Survey 60 (2005): 247-252. Pectasides, D., and T. Economopoulos. “Fallopian Tube Carcinoma: AReview.” Oncologist 11 (2006): 902-912. u
Other Resources
Abramson Cancer Center of the University of Pennsylvania Fallopian Tube Cancer: The Basics Http://www.oncolink.com/types/article .cfm?c=6&s=49&ss=801&id=9502 Eyes on the Prize Gynecologic Cancer: Fallopian Tube Cancer http://www.eyesontheprize.org/FAQ/gynca/ fall_tube.html See also Adenomatoid tumors; BRCA1 and BRCA2 genes; Culdoscopy; Endometrial cancer; Endometrial hyperplasia; Exenteration; Family history and risk assessment; Fertility issues; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Hysterectomy; Hystero-oophorectomy; Leiomyomas; Oophorectomy; Ovarian cancers; Ovarian cysts; Pelvic examination; Salpingectomy and salpingooophorectomy; Uterine cancer.
Family history and risk assessment
u Family history and risk
assessment Category: Medical specialties; social and personal issues Also known as: Cancer genetics risk assessment, assessment of inheritance patterns Definition: Individuals who have a familial risk of developing cancer are those who also have with a strong family history of cancer, including affected relatives with unusual or multiple cancers or family members diagnosed at atypically early ages. Although having a family history can increase one’s risk of cancer, it does not necessarily mean that one will go on to develop cancer. Inheritance patterns and incidence of cancer in family members: In any discussion of family risk for cancer, it is important to note that individuals can inherit an increased risk of developing cancer, but they do not inherit the disease itself. In fact, a known risk of developing cancer can actually reduce a family member’s susceptibility to cancer by encouraging that individual to adopt healthy behaviors, such as regular medical checkups, good eating and exercise habits, and, for some, prophylactic treatments. Although some individuals may be aware of a family history of cancer, others must be identified by the prudent physician or other health care professional so that they may be appropriately referred for genetic counseling and testing. Cancers have different inheritance patterns, and the risk of a family member who has an affected first-order relative may vary with the type of cancer. For example, research indicates that pancreatic cancer is currently considered attributable to a genetic mutation (an event that changes the genetic structure or genotype of an individual or organism). The majority of genetic mutations that lead to cancer occur in genes that control growth through exposure to carcinogens or errors made by cells when they divide or replicate. Research has shown that patients with hereditary pancreatitis (not to be confused with chronic pancreatitis of common etiology) have a 40 percent increased risk of developing pancreatic cancer. Most research indicates that pancreatic cancer risk involves patients with a paternal inheritance pattern of disease (hereditary pancreatitis), while some research reports evidence of a maternal inheritance pattern. In addition, mutations of BRCA1, a gene known to suppress tumors, have been associated with increased risk of developing pancreatic cancer. Breast cancer is not inherited; rather, it is caused by somatic (environmental) mutations in breast cells during one’s life. BRCA2, another gene known to suppress tumors, has been linked with an increased risk of breast can461
Family history and risk assessment cer, as well as with prostate and pancreatic cancers in men. A higher incidence of the skin cancer melanoma is also more common in individuals with BRCA2 mutations than those without. In addition to BRCA1 and BRCA2 genes, variations of which have been linked to some forms of breast cancer, presence of the following genes in an individual increases the risk of breast cancer by causing syndromes that also increase the risk of developing other types of cancer: CDH1, PTEN, STK11, and TP53. The presence of variations in the following genes has also been associated with breast cancer: AR, ATM, BARD1, BRIP1, CHEK2, DIRAS3, ERBB2, NBN, PALB2, RAD50, and RAD51. Although not all the evidence implicates variations in these genes as risk factors for developing breast cancer, the evidence is strongest for ATM and CHEK2. An accumulation of genetic mutations in genes responsible for cell growth, cell division, or repairing deoxyribonucleic acid (DNA) promotes cancercell proliferation resulting in tumor growth. Inherited patterns or cancer syndromes that increase risk of breast and ovarian cancer include breast-ovarian cancer syndrome, nonpolyposis colorectal cancer syndrome, Cowden syndrome, Peutz-Jegher syndrome, and Li-Fraumeni syndrome, and inherited mutations that increase the risk for other types of cancers. Some cancers follow established hereditary patterns such as autosomal dominant inheritance. An autosomal dominant inheritance pattern consists of one mutated copy of the particular gene in each cell transmitted by one affected parent, occurring in every generation of an affected family. The pedigree of a family affected by a hereditary cancer syndrome will indicate whether that cancer has been inherited as an autosomal dominant disorder—in which case as many as half of the offspring of each carrier may develop a cancer related to the inherited syndrome. Two cancers that follow this pattern are a hereditary form of breast-ovarian cancer syndrome and Lynch cancer family syndrome, which is characterized by increased incidence of cancer of the right colon and increased incidence of endometrial cancer and multiple primary malignant neoplasms. Another type of autosomal dominant hereditary pattern, hereditary nonpolyposis, is responsible for between 2 and 7 percent of all cases of colorectal cancer. Mutations in the genes (including MLH1, MSH2, MSH6, and PMS2) that are responsible for repairing errors made when cells are copied can lead to uncontrolled cell growth and possibly cancer. This condition also increases an individual’s risk for cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, skin, brain, and prostate. Women who inherit this disorder are at greater risk for endometrial and ovarian cancers. 462
Salem Health: Cancer Several hereditary cancer syndromes have been identified for which there are effective diagnostic tests and options for managing the disease, including those for cancers of the breast, ovary, colon, and endometrium, to name a few. These hereditary syndromes include hereditary nonpolyposis colorectal cancer (HNPCC); familial adenomatous polyposis (FAP), an inherited colorectal cancer syndrome; hereditary breast and ovarian cancer (HBOC); and multiple endocrine neoplasia 2 (MEN 2) in conjunction with parathyroid hyperplasia, which has been linked to thyroid cancer. Individuals genetically tested and found to have any of these syndromes can discuss specific options for managing their susceptibility for cancer with a genetic counselor. Genetic screening and testing: Routine screening for most cancers in the general population is neither recommended nor effective in reducing mortality from cancer. Moreover, because incidence of cancer varies in mutation carriers by type of cancer, screening and genetic testing must be approached by the type of inherited cancer and its risk patterns. For example, only 10 to 15 percent of breast cancer cases are thought to be familial, with about onethird caused by an inherited genetic mutation in a BRCA1 or BRCA2 gene. Over a woman’s lifetime, the incidence of breast cancer in a mutation carrier may be more than 50 percent, and an inherited BRCA1 mutation is also associated with increased risk of ovarian cancer. It is therefore recommended that only affected relatives with a family history of an inherited gene mutation BRCA1 or BRCA2 be screened. It should be noted that estimates of how many women with an altered gene will develop breast cancer range from 36 to 85 percent, and estimates of how many women with one of these altered genes will develop ovarian cancer range from 16 to 60 percent. Most research related to BRCA1 and BRCA2 has been done with large families and many affected individuals. Some of the incidence in these affected individuals may be due to other genetic as well as environmental factors; thus, risk estimates may not accurately reflect the risk in the general population of women, or in any individual woman. It must be emphasized, therefore, that genetic screening and testing is primarily for individuals to ascertain their inherited risk of developing cancer. Genetic testing can be used to determine who can benefit from regular, comprehensive cancer screenings, procedures to reduce the risk of acquiring the cancer, lifestyle and behavioral changes, medication, or prophylactic surgery. Genetic counseling: For those individuals who do have a significant inherited risk for cancer, the health professional performing genetic counseling will ask the client
Salem Health: Cancer to gather a family medical history and map a pedigree or family tree to illustrate the family history of the cancer. A variety of health professionals may perform genetic counseling and testing, including genetic counselors, nurses with advanced training and practice, psychologists, social workers, and physicians. The client begins the family-risk-assessment process by talking to relatives, obtaining medical records of relatives, and noting any medical conditions that have occurred in the family and at what ages. It is recommended that the client chart a separate tree for each side of the family, maternal and paternal, recording the country of birth and ethnicity as well. For example, certain breast cancer genes have been associated with Ashkenazi East European descent. The National Society of Genetic Counselors (NSGC) recommends initially talking to first-order relatives (parents and siblings), then contacting second-order relatives going back one generation at a time, collating birth, marriage, and death certificates to form the chart or family tree and document a pedigree. A genetic counselor will often prefer a pedigree with three generations of family history. Some of the facts to include in constructing a pedigree are the name of each relative, age at death and cause of death if deceased, medical conditions and ages when these conditions were acquired, birth defects, fertility problems, learning challenges, and lifestyle patterns (exercise, smoking, drinking, addictions, obesity, and so on). Gathering information on lifestyle behaviors of affected family members is critical; apart from genes, families share lifestyles and environments that may contribute to increased risk of cancer and other disease conditions by altering genes. All this information is useful to the client personally, and it can also help identify inheritance patterns of disorders that may place offspring at risk. After constructing the pedigree, the client will submit it to the counselor, who will thoroughly review the client’s personal, medical, and family history and evaluate the results. The client will meet with the counselor to hear the evaluation, discuss how the results relate to individual risk, and develop a personal prevention program. For example, the counselor will discuss hereditary cancer syndromes and what to look for to see if any syndromes are also present in family members. If the results of the pedigree indicate the utility of genetic testing and the client wishes to go forward, the client will be asked to complete an informed consent form. The form will describe the benefits and limitations of testing for genetic susceptibility, as well as the particular policies and financial procedures associated with the site where the testing will be performed. There are myriad tests for various hereditary cancers; DNA sequencing is the most sensi-
Family history and risk assessment tive and reliable method used to test for a hereditary cancer syndrome. Once the lab informs the physician of the test results, the client will meet with the health professional performing the counseling for disclosure of the test results. These results will be discussed within the context of the family’s history so that risks can be communicated effectively. The counselor will also advise the client on any need to notify family members of a hereditary genetic mutation associated with an elevated risk for cancer. This is the time for the client to discuss perceived and real risks of cancer, emotional issues surrounding cancer, support systems, coping skills, and decision making. Pros and cons of genetic testing: Most cancer is not due to the inheritance of a single genetic mutation. Sporadic cancers—those not due to a known, specific hereditary pattern—comprise the majority, 90 percent of all cancers diagnosed. Nevertheless, those with a hereditary inheritance pattern of a cancer are better positioned to adopt riskreducing behaviors if they know they are at higher risk for certain types of cancer than others in the general population. Moreover, individuals who learn of their risk and begin risk-reduction behaviors at an early age may be able to reduce the risk of passing the mutation to offspring. There are tremendous psychological effects and social costs for an individual who learns of his or her hereditary risk of developing cancer. A risk of family cancer can alter one’s lifestyle, inform family planning, or encourage family members to be tested. Those who are found not to have a hereditary risk may be relieved but may nonetheless be motivated to make healthy lifestyle changes. Specific interventions and potentially life-saving management options are available to individuals found to be at elevated risk of cancer following a genetic screening test. Some of these options include tamoxifen, a chemotherapy for breast cancer; colonoscopy to detect early colon cancer; and removal of ovaries and Fallopian tubes. Some studies have found that prophylactic hysterectomy with bilateral salpingo-oophrectomy (removal of the ovaries and Fallopian tubes) is an effective strategy for preventing endometrial and ovarian cancer in women with Lynch syndrome. Women with a BRCA genetic mutation who have had their ovaries removed reduce their risk of breast cancer by 50 percent or more. Studies have shown that women at increased risk of breast cancer are less likely to develop the cancer if they take tamoxifen, a treatment for advanced breast cancer. For those at greatest risk of developing breast cancer, prophylactic bilateral mastectomy has been shown to greatly reduce (but not eliminate) the risk of developing breast cancer. While genetic tests for cancer risk provide valuable in463
Fanconi anemia formation to the patient and the physician, they are also fraught with controversy. Genetic tests may show increased risk, but they cannot determine degrees of risk or what actual risk an individual will have of developing cancer. A physician must evaluate the benefits and limitations of information on familial risk when deciding who to refer for genetic counseling and testing. The American Cancer Society and other organizations publish guidelines available online; these identify current clinical recommendations, promulgated by the U.S. Department of Health and Human Services, for who should be screened and tested for different types of cancers. Susan H. Peterman, M.P.H. u For Further Information Foulkes, William D., and Shirley V. Hodgson, eds. Inherited Susceptibility to Cancer: Clinical, Predictive, and Ethical Perspectives. New York: Cambridge University Press, 1998. Frank, Thomas S., and Mark H. Skolnick. “Testing for Hereditary Cancer Risk: Pandora or Prometheus?” Journal of Clinical Endocrinology and Metabolism 84, no. 6 (1999): 1882-1885. Hass, Jennifer S., et al. “Do Physicians Tailor Their Recommendations for Breast Cancer Risk Reduction Based on Patient’s Risk?” Journal of General Internal Medicine 19, no. 4 (2004): 302-309. Morrison, Patrick J., Shirley V. Hodgson, and Neva E. Haites, eds. Familial Breast and Ovarian Cancer: Genetics, Screening, and Management. New York: Cambridge University Press, 2002. Schmeler, Kathleen, et al. “Prophylactic Surgery to Reduce the Risk of Gynecological Cancers in the Lynch Syndrome.” New England Journal of Medicine 354 (January 19, 2006): 261-269. U.S. Preventive Services Task Force. “Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement.” Annals of Internal Medicine 143 (2005): 355-361. Utsunomiya, Joji, John J. Mulvihill, and Walter Weber, eds. Familial Cancer and Prevention: Molecular Epidemiology, a New Strategy Toward Cancer Control. New York: Wiley-Liss, 1999. u
Other Resources
American Medical Association Family History http://www.ama-assn.org/ama/pub/category/ 2380.html 464
Salem Health: Cancer National Institutes of Health Genetics Home Reference http://ghr.nlm.nih.gov U.S. Department of Health and Human Services U.S. Surgeon General’s Family History Initiative http://www.hhs.gov/familyhistory See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Childhood cancers; Chromosomes and cancer; Cytogenetics; Gene therapy; Genetic counseling; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Hereditary diffuse gastric cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary mixed polyposis syndrome; Hereditary non-VHL clear cell renal cell carcinomas; Hereditary pancreatitis; Hereditary papillary renal cell carcinomas; Hereditary polyposis syndromes; Latinos/Hispanics and cancer; Mitochondrial DNA mutations; Native North Americans and cancer; Oncogenes; Proto-oncogenes and carcinogenesis; Risks for cancer; Young adult cancers.
u Fanconi anemia Category: Diseases, symptoms, and conditions Also known as: Fanconi’s anemia, FA, aplastic anemia with congenital abnormalities Related conditions: Leukemia, liver tumors, brain tumors, and cancers of the head, neck, esophagus, and female reproductive system Definition: Fanconi anemia is a rare inherited disease that affects bone marrow, resulting in reduced blood cell production. It is not the same as Fanconi syndrome, which is a rare kidney disorder. Bone marrow is the central part of the bones in which blood cells are produced. Red blood cells transport oxygen to the cells, white blood cells protect the body against infection, and platelets cause wounds to clot. Damage to the bone marrow decreases the production of all these types of blood cells. Having this condition predisposes people to developing several kinds of cancers, including acute myelocytic leukemia (AML) and squamous cell carcinoma. These cancers will arise in a person with Fanconi anemia at a much earlier age than the cancers would normally occur. Risk factors: Fanconi anemia is a recessive inherited disease, which means that both parents must have the disease genes for their children to develop it. Each child who has
Salem Health: Cancer two parents with the disease genes will have a 25 percent chance of developing the condition. Etiology and the disease process: Fanconi anemia is an inherited disease that stems from changes, called mutations, in genes. Genes hold the instructions for cells to make different proteins, which carry out various functions throughout the body. In people with Fanconi anemia, defective genes prevent the production of proteins that are needed for cells to work normally. Incidence: Although the exact number of people with Fanconi anemia is unknown, it is estimated that between 1 in 100 and 1 in 600 people carry the genetic defect responsible for the condition. Approximately 1 in 360,000 people are born with the disease. The symptoms of Fanconi anemia most often emerge when a child is between the ages of three and twelve, although symptoms can stay dormant until later in life. The disease occurs equally in both genders and among all races; however, there is a higher risk among people of Ashkenazi Jewish descent. Between 18 and 20 percent of people with Fanconi anemia develop leukemia. Symptoms: Because the disease results in fewer white blood cells, it leaves a person more susceptible to infections. A lower red blood cell count leads to fatigue, and the reduction in platelets can interfere with normal blood clotting. The first signs of the disease are often nosebleeds or bruising. People who have Fanconi anemia may have stunted growth; misshapen, missing, or extra thumbs; abnormal arm, hip, spine, or rib bones; a small head or eyes; kidney problems; an abnormal stomach, esophagus, or intestinal tract; mental retardation; and learning disabilities. Patches of unevenly colored skin (café-au-lait spots) are also common. Men may have smaller than normal genitals. People with Fanconi anemia are more likely to develop leukemia, as well as cancers of the head, neck, and esophagus. Women with the disease are at greater risk for cancers of the reproductive tract. Screening and diagnosis: The primary test for Fanconi anemia is a chromosome breakage test, which mixes the patient’s white blood cells with special chemicals to see whether the chromosomes break more easily than they should. Doctors can also diagnose the disease by removing a sample of bone marrow with a needle through a procedure known as bone marrow aspiration and examining that sample under a microscope to look for signs of low blood cell production. Another method is a bone marrow biopsy, in which a small needle inserted into the bone removes a piece of bone marrow for testing. Often patients will also
Fanconi anemia have a complete blood count to look for low numbers of white blood cells, red blood cells, and platelets. Other screening methods include developmental tests and a kidney ultrasound. If there is a family history of Fanconi anemia, the condition can be diagnosed before a child is born using amniocentesis and chorionic villus sampling (CVS). Treatment and therapy: A bone marrow transplant can treat blood cell problems, although it cannot reduce the risk of developing cancer or other problems (such as bone malformations) associated with Fanconi anemia. The bone marrow transplant is most likely to be successful if taken from a matched sibling. Patients may take artificial versions of male hormones called androgens, which improve red blood cell counts and may also help improve white blood cell counts in certain patients. Taking hemopoietic growth factors, such as erythropoietin, also can increase blood counts, as can having a blood transfusion. Researchers are looking into whether gene therapy to correct the genetic mutation might one day benefit patients with Fanconi anemia. Prognosis, prevention, and outcomes: Because this is an inherited disorder, there is no way to prevent it, although it is possible to screen a fetus for the disease while still in the womb. The average life expectancy for someone with Fanconi anemia is age twenty-two, although survival can vary from one person to another. New research and improved bone marrow transplantation outcomes are prolonging the life spans of many individuals with this disease. Stephanie Watson, B.S. u
For Further Information Frohnmayer, Lynn. Fanconi Anemia: A Handbook for Families and Their Physicians. Eugene, Oreg.: Fanconi Anemia Research Fund, 2000. Schindler, D., and H. Hoehn. Fanconi Anemia: A Paradigmatic Disease for the Understanding of Cancer and Aging. Basel, Switzerland: S. Karger, 2007. Shamin, Ahmad, and Sandra H. Kirk, eds. Molecular Mechanisms of Fanconi Anemia. New York: Springer, 2006.
u
Other Resources
Fanconi Anemia Research Fund http://www.fanconi.org MedlinePlus Fanconi’s Anemia http://www.nlm.nih.gov/medlineplus/ency/article/ 000334.htm 465
Fatigue See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Anemia; Aplastic anemia; Blood cancers; Genetics of cancer; Myelodysplastic syndromes; Nijmegen breakage syndrome; Urinalysis.
u Fatigue Category: Diseases, symptoms, and conditions Also known as: Asthenia, tiredness, exhaustion, lack of energy Related conditions: Anemia
Salem Health: Cancer Medication used as supportive care (for example, to treat depression or vomiting) can cause fatigue. Another cause of fatigue is lack of sleep, which may be caused by pain, emotional issues, depression, and anxiety. Poor nutrition, caused by lack of interest in food or an inability to eat because of mucositis, diarrhea, nausea, or vomiting, has been implicated in fatigue. Surgery for cancer may be the cause of fatigue, which often lessens as the patient recuperates and heals. One way that cancer can cause fatigue is by spreading to bone marrow, where it destroys red blood cell production and leads to anemia, the most commonly reported cause of fatigue. Both chemotherapy and radiation therapy can destroy bone marrow and cause anemia.
Definition: Fatigue describes a condition of tiredness that has many interrelated physical and emotional factors and impairs a patient’s feeling of well-being. Fatigue related to cancer or cancer treatment is a persistent sense of tiredness that can cause distress and depression and affect a patient’s ability to continue normal daily aspects of living. While patients with cancer may have fatigue as a chronic condition, this fatigue is not the same as “chronic fatigue syndrome.” Cancer-related fatigue differs from the fatigue of overwork or excessive exercise as it is not relieved by sleep or rest. It should be noted, however, that each patient is unique and that some cancer patients do not report cancer-related fatigue; other patients report having only mild to moderate cancer-related fatigue for a short period of time.
Incidence: Depending on the type of cancer and its treatment, approximately 15 to 95 percent of patients with cancer report feeling mentally and physically fatigued.
Risk factors: In the setting of cancer, fatigue may be caused by the type of cancer and its stage, chemotherapy or radiation therapy, stress, anemia, depression, chronic pain, lack of sleep, lack of proper nutrition, nausea and vomiting, infections, dehydration and electrolyte imbalance, and weight loss.
Screening and diagnosis: Because of the complex nature of cancer-related fatigue and its many presumptive causes, it is necessary to carefully rule out causes before effective treatment can occur. It is imperative to understand the pattern of fatigue, including when it started, how long it lasted, and how it changed the patient’s daily activity pattern. If fatigue was reported only after radiation therapy, for example, depression and other medications could be ruled out as the cause. The kind of cancer and its stage is important to know, as are known treatment-related symptoms. The side effects of chemotherapeutic agents or other medications may be instructive in determining the cause of fatigue. The health care provider should understand the patient’s sleep patterns before starting treatment for cancer as well as during treatment for cancer. It is important to know if the patient’s eating habits have changed. Patients should be screened for depression, as this is a common cause of fatigue. Patients may be depressed because of their cancer or because they fear losing their jobs, are having financial difficulties, or are upset about their inability to perform their normal daily activities. Anemia, which is a common cause of fatigue, can be
Etiology and the disease process: The causes of fatigue in patients with cancer are not clearly understood and appear to be multiple. Fatigue can be one of the first symptoms of the presence of cancer and can also be an indication of disease progression. The disease of cancer itself can cause fatigue, primarily through the release of cytokines, which are thought to induce fatigue, the increased need of cancer cells to maintain their high rate of metabolism, and the alteration of hormone levels. The stress of having cancer also can be the cause of fatigue. Treatments can lead to fatigue as the body tries to deal with the insult of cytotoxins or radiation and tries to rebuild cells after treatment. Many biological therapies (those that attempt to strengthen the patient’s immune system to fight cancer) have flulike symptoms, including fatigue, as side effects. 466
Symptoms: Fatigue is manifested by extreme tiredness and inability to perform normal daily functions. Fatigue can then lead to other symptoms, such as depression or poor nutrition (if the patient is unable to shop for groceries or cook). Because of the nature of cancer-related fatigue and its interactions with risk factors and other conditions, it is difficult to pinpoint a single symptom. Common symptoms, however, can include dizziness, confusion, inability to think clearly, loss of balance, being bedridden for more than one day, and worsening conditions (for example, increased vomiting, pain, or depression).
Salem Health: Cancer determined through blood tests. Depression scores can be determined through the use of various screens. No staging is available, however, for grading cancer-related fatigue. Treatment and therapy: To be treated properly, the source of fatigue—whether is it physical, emotional, or psychological—must be determined. Because anemia is the most common cause of fatigue, blood tests generally are done to check for low red blood cell counts, low hemoglobin concentration, or both. Anemia can be corrected by blood transfusions or by administration of an erythropoiesisstimulating protein, such as epoetin alfa. Fatigue due to lack of sleep, depression, or poor nutrition generally can be helped by administration of supportive care, such as drugs, or correction of an underlying cause, such as the inability to shop for and prepare food. Patients may be able to help themselves by being aware of what causes their fatigue. It may be important to schedule regular naps or limit the number of visitors. It is important to save energy for important tasks and to ask for help with other tasks. Energy levels may be maintained by scheduling regular eating times, including healthy snacks, limiting caffeine and alcohol, and drinking increased amounts of fluids. Some patients report that mild to moderate exercise also helps fight cancer-related fatigue, allows for a better frame of mind, and increases the ability to sleep at night. Exercise can include aerobic or resistance training. Relief of cancer-related fatigue may also come from practicing yoga or meditation. Research suggests that psychosocial interventions, such as group or individual therapy, education, stress management, or support groups, also have a positive effect on cancer-related fatigue. Prognosis, prevention, and outcomes: Because cancerrelated fatigue is often caused by many overlapping factors, it is difficult to predict which patients will be most affected. Fatigue may subside once treatments are completed and the patient’s bone marrow has recovered. Fatigue may increase as the cancer stage progresses and the cancer spreads in the body. MaryAnn Foote, M.S., Ph.D. u
For Further Information Hofman, Maarten, et al. “Cancer-Related Fatigue: The Scale of the Problem.” The Oncologist 12 (May, 2007): 4-10. Morrow, G. R. “Cancer-Related Fatigue: Causes, Consequences, and Management.” The Oncologist 12 (May, 2007): 1-3. Ryan, J. L., et al. “Mechanisms of Cancer-Related Fatigue.” The Oncologist 12 (May, 2007): 22-34.
Fecal occult blood test (FOBT) u
Other Resources
American Cancer Society Exercise to Keep Active Http://www.cancer.org/docroot/MIT/MIT_2_ 1x_ExerciseToStayActive.asp Anemia.com http://www.anemia.com MedlinePlus Anemia http://www.nlm.nih.gov/medlineplus/anemia.html National Cancer Institute Fatigue http://www.cancer.gov./cancerinfo/pdq/ supportivecare/fatigue/Patient/page2 See also Aids and devices for cancer patients; Anxiety; Chemotherapy; Home health services; Hospice care; Living with cancer; Palliative treatment; Psychosocial aspects of cancer; Radiation therapies; Relationships; Side effects; Stress management; Support groups; Symptoms and cancer.
u Fecal occult blood test (FOBT) Category: Procedures Also known as: Stool occult blood, guaiac smear test Definition: A fecal occult blood test (FOBT) is a simple chemical test on stool (feces) that detects the iron-containing components of hidden or trace amounts of blood. It tests for digestive tract bleeding, a possible indicator of colorectal cancer. Cancers diagnosed: Colon (large intestine) cancer, rectal cancer, gastric (stomach) cancer Why performed: Sometimes hidden blood in the stool is the only sign of cancer in its early stages, before symptoms appear. As a result, the FOBT is most frequently used as a colorectal cancer screening test. Benign (noncancerous) and malignant (cancerous) polyps, tumors, and other tissues that protrude into the intestine can bleed intermittently. The FOBT can detect this abnormal bleeding. It does not diagnose disease. It screens for bleeding that may be caused by gastrointestinal cancer. Other maladies cause blood loss in the digestive tract and anemia, a low red blood cell count. Therefore, the FOBT is sometimes used to determine the cause of unexplained anemia. It is also used to find the cause of abdominal pain. 467
Fecal occult blood test (FOBT)
Salem Health: Cancer with the test by producing misleading results. They should avoid the following foods for two to three days before the test to prevent false positive results: red meats such as beef, cold cuts, lamb, liver, and processed meats; fish; fruits such as apples, oranges, bananas, grapefruit, grapes, lemons, and melons; poultry; and vegetables such as beets, broccoli, cabbage, carrots, cauliflower, cucumbers, horseradish, mushrooms, radishes, and turnips. Patients should stop taking the following medications for seven days before the test to prevent false positive results: aspirin and products that contain aspirin; other nonsteriodal anti-inflammatory drugs (NSAIDS), such as ibuprofen and naproxen; colchicine gout drugs; corticosteroids; oxidizing drugs, such as iodine, bromides, and boric acid; and reserpine. Patients should stop taking dietary iron supplements for seven days before the test to prevent false positive results and should take no more than 250 milligrams of vitamin C per day to prevent false negative results.
A fecal occult blood test can detect blood in the feces, an early sign of cancer. (©IMANE/Image Point FR/Corbis)
Normally, a small amount of blood, a quarter of a teaspoonful or less, leaves digestive tract blood vessels daily and moves into the stool. The FOBT does not react to this small amount of blood. A daily blood loss of at least ten milliliters, or two teaspoonfuls, is required to produce a positive test. Patient preparation: People who prepare for the FOBT pay attention to their health conditions. They avoid the FOBT when their other situations cause digestive or urinary bleeding, which can produce false positive results. Interfering conditions include anal fissures, gum bleeding after dental procedures, colitis, constipation, diverticulitis, esophagitis, gastroesophageal reflux disease (GERD), gastritis, hemorrhoids, inflammatory bowel disease, menstrual periods, nosebleeds, peptic ulcers, severe throat irritation, and urinary tract infections. Before FOBT testing, patients restrict certain food, medications, and dietary supplements that can interfere 468
Steps of the procedure: Medical facility personnel perform FOBT tests, and patients can do their own testing at home. The manufacturer’s instructions must be followed to ensure accurate testing. A small sample of stool is placed onto a chemically treated test card, pad, or wipe. A chemical solution is added to the sample. The appearance of a blue color indicates a positive result—blood in the stool sample. Absence of blue color indicates a negative result—no blood in the stool sample. In one commonly used test, three stool samples are collected on three-part cards over three days, to better detect intermittent bleeding. The collection cards, pads, or wipes must be protected from heat, light, and chemicals during the collection period. The American Cancer Society and other medical organizations recommend an annual screening FOBT for all adults beginning at age fifty. They also recommend that others have the test as needed because of personal or family histories of intestinal polyps or colorectal cancer. These organizations emphasize that negative FOBT tests do not replace regular medical checkups, and they recommend regular medical examinations for everyone. In 2001, immunochemical fecal occult blood test (iFOBTs) became available for detecting blood in the stool. They test for a globelike protein component of blood instead of the iron-containing component detected in the traditional FOBT. They are sensitive and specific for digestive tract bleeding, and they avoid direct stool handling. These new tests have the advantage of eliminating the need to avoid foods, medications, and supplements before testing.
Salem Health: Cancer After the procedure: People who receive positive FOBT results have blood in the stool. They undergo specific follow-up testing, such as sigmoidoscopy, colonoscopy, computed tomography (CT) scans, and X rays, to determine the cause. People who receive negative FOBT results follow medical professionals recommendations for regular cancer screening. Risks: The FOBT is safe and painless and does not cause physical harm, but it is not a foolproof indicator of cancer. Digestive tract bleeding can be intermittent, and negative results can occur in people who have colorectal cancer. Results: A normal FOBT result is negative, which means that blood is not present in the tested stool sample. An abnormal test result is positive, which means that blood is present in the tested stool sample. Occult blood appears in the stool because of colorectal cancer or other medical conditions. It is important to determine the cause and source of bleeding to diagnose, treat, and resolve the situation. Susan E. Ullmann, M.T. (ASCP), M.A. u For Further Information Fishbach, Frances Talaska, with Marshall Barnett Dunning III. A Manual of Laboratory Diagnostic Testing. 7th ed. Philadelphia: Williams & Wilkins, 2004. Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006. Segen, Joseph C., and Joseph Stauffer. The Patient’s Guide to Medical Tests. New York: Facts On File, 1997.
See also Anal cancer; Colon polyps; Colorectal cancer; Colorectal cancer screening; Diverticulosis and diverticulitis; Gastrointestinal cancers; Immunochemical fecal occult blood test (iFOBT); Polyps; Rectal cancer; Screening for cancer; Stomach cancers.
u Fertility drugs and cancer Category: Carcinogens and suspected carcinogens Definition: An association between the use of fertility drugs—clomiphene citrate, follicle-stimulating hormone (FSH), human menopausal gonadotropin (MG), and gonadotropin-releasing hormone analog (GnRH)—and ovarian cancer exists if there is a statistically significant increase in the risk of cancer during the lifetime of the user of fertility drugs. Although the major concern regarding fertility drugs and cancer since the 1990’s has focused on
Fertility drugs and cancer ovarian cancer, some experts have also suggested a possible relationship between fertility drugs and cancers of the breast and uterus. Because fertility drugs evoke changes in hormone levels, the potential risk should be extended to any cancer that can be triggered or modulated by hormones, as well as any indirect effects on the offspring of the user of fertility drugs. Fertility drugs and cancer: A woman’s risk of ovarian cancer is multifactorial; however, it is known that some factors increase the risk for ovarian cancer, while other factors decrease the risk. Specifically, ovarian cancer is known to increase with age, when there is a family history of ovarian cancer, and in women who have never had a child. In contrast, the risk of ovarian cancer is decreased in women who breast-feed, have at least one child, and use oral contraceptives. In considering these risk factors together, current scientific thinking is that ovarian cancer is related to the process of ovulation in most, if not all, cases. It has been suggested, but not proven, that ovarian cancer follows an abnormal repair process on the surface of the ovary following the release of the egg during ovulation. Thus, increasing the number of ovulations (incessant ovulation), either by having no interruption of ovulation due to pregnancy or by inducing ovulation with fertility drugs, would theoretically increase the risk of ovarian cancer. Conversely, inhibiting ovulation vis-à-vis pregnancy or pregnancies, breast-feeding, or through the use of oral contraceptives, would theoretically decrease the risk of ovarian cancer by decreasing the lifetime number of ovulations. In determining the risk of fertility drugs and ovarian cancer, it is important to take into consideration confounding factors. Although some epidemiologic studies have indeed shown an increased risk of ovarian cancer in women who have used fertility drugs, when all factors are accounted for statistically, it has been concluded that it is actually infertility, rather than the fertility drugs, that has led to an increased risk of ovarian cancer. For example, in one study involving more than twelve thousand women who were followed for an average of nearly twenty years, it was found that the risk of ovarian cancer was increased twofold because of infertility alone, and there was no statistical risk of ovarian cancer due to just the fertility drugs. Because the peak onset of ovarian cancer occurs during the seventh decade of life, it will be important to continue such studies longitudinally to verify this finding. It is noteworthy, though, that an association has been demonstrated between the use of clomiphene citrate and cancer of the uterus. Given that clomiphene citrate is chemically similar to tamoxifen (a drug routinely used to 469
Fertility drugs and cancer
Salem Health: Cancer
Common Fertility Drugs Drug Name
Brand Names
Clomiphene citrate
Clomid Serophene Milophene
Human chorionic gonadotropin (HCG) Pregnyl Menotropin
Pergonal Humegon
Urofollitropin
Metrodin
Urofollitropin (highly purified)
Fertinex
Source: U.S. Food and Drug Administration
treat patients with breast cancer after surgery), which is known to be associated with cancer of the uterus, further studies are needed to verify this association. Ovarian cancer: Approximately 25,000 women are diagnosed with ovarian cancer each year in the United States. The current lifetime incidence of ovarian cancer for any given woman is approximately 1 in 70. Unfortunately, the symptoms of ovarian cancer in its early stages are minimal to none. In advanced cases, most women with ovarian cancer complain of abdominal pain, vaginal bleeding, abdominal bloating and distension, or a change in bowel habits. There is no accepted screening protocol for ovarian cancer, unlike cervical cancer (which can be detected by a Pap smear) or breast cancer (which can be found by selfexam, a clinical breast exam, and mammography). It is recommended by the American College of Obstetricians and Gynecologists that all women have a manual pelvic examination as part of their annual well-woman examination. During the manual pelvic examination, the examiner palpates (feels) the ovaries. Although not recommended for women at low risk for ovarian cancer, for those at high risk, a blood test (cancer antigen 125, or CA 125) and a vaginal ultrasound in which the ovarian volume is determined may be beneficial. The standard treatment for ovarian cancer is surgical, in the form of a total abdominal hysterectomy and removal of both ovaries with postoperative chemotherapy. The five-year survival rate for patients with ovarian cancer is 50 percent, depending on the stage at the time of diagnosis and the treatment rendered. The risk of ovarian cancer can
470
be reduced by breast-feeding, using oral contraceptives, and undergoing a tubal ligation, although the mechanism of protection for the latter is unclear. For women who are prescribed fertility drugs, when used as prescribed for less than twelve cycles with monitoring by a specially trained physician (reproductive endocrinologist), there are no convincing scientific studies that have shown an increased risk for ovarian cancer. D. Scott Cunningham, M.D., Ph.D. u
For Further Information Althuis, M. D. “Uterine Cancer After Use of Clomiphene Citrate to Induce Ovulation.” American Journal of Epidemiology 161 (2005): 607-615. Ayhan, A. “Association Between Fertility Drugs and Gynecologic Cancers, Breast Cancer, and Childhood Cancers.” Acta Obstetricia et Gynecologica Scandinovica 83 (2004): 1104-1111. Brinton, L. “Long-Term Effects of Ovulation-Stimulating Drugs on Cancer Risk.” Reproductive BioMedicine Online 15 (2007): 38-44. Brinton, L. A., et al. “Ovarian Cancer Risk After the Use of Ovulation-Stimulating Drugs.” Obstetrics and Gynecology 103 (2004): 1194-1203. Venn, A., D. Healy, and R. McLachlan. “Cancer Risk Associated with a Diagnosis of Infertility.” Best Practice and Research Clinical Obstetrics and Gynaecology 17 (2003): 343-367. u
Other Resources
National Cancer Institute Ovarian Cancer Prevention http://www.cancer.gov/cancertopics/pdq/prevention/ ovarian/healthprofessional Ovarian Cancer National Alliance Q: Do Fertility Drugs Increase Your Risk of Developing Ovarian Cancer? Http://www.ovariancancer.org/index.cfm? Fuseaction=Feature.showFeature&CategoryID= 6&FeatureID=124 See also Childbirth and cancer; Estrogen-receptor-sensitive breast cancer; Fertility issues; Gynecologic cancers; Hormone receptor tests; Hormone replacement therapy (HRT); Infertility and cancer; Ovarian cancers; Ovarian cysts; Pregnancy and cancer; Sterility.
Salem Health: Cancer
u Fertility issues Category: Social and personal issues Definition: Some cancers and cancer treatments pose a risk to a cancer survivor’s fertility. Infertility or sterility can be temporary or permanent. Although in many cases there are few options to address the underlying causes of infertility, patients may be able to preserve their fertility before undergoing cancer treatment and conceive a child after treatment naturally or through the use of assisted reproductive technologies. Infertility and cancer: For natural conception to occur, men must have at least one testicle that produces enough healthy sperm, the hormones to regulate sperm production, the ability to make semen, and the ability to ejaculate the semen. Women need at least one ovary that makes mature and viable eggs, a Fallopian tube through which the egg can move and be fertilized, a uterus capable of maintaining a pregnancy, and the hormones necessary for ovulation and pregnancy. Chemotherapy and radiation in the course of cancer treatments can damage or kill cells required for production of sperm (sperm stem cells) and immature eggs (oocytes) or mature eggs. These treatments can also affect the production and regulation of hormones required for reproduction. Male and female reproductive structures can be damaged by radiation or removed or damaged by surgery. Fertility preservation: Infertility can cause a great deal of psychological distress for cancer survivors. It is advised that cancer patients discuss fertility issues with their oncologists and consult a fertility specialist before treatment. Specialists can inform patients of their risk, if known, of becoming infertile after treatment. In some cases, there are fertility preservation methods that can be undertaken before or during treatment. Patients must weigh the costs and benefits as some preservation methods may alter the efficacy of the cancer treatment, especially if the cancer is hormonally sensitive or affects the reproductive organs. Another possibility in some cases is delaying cancer treatments to pursue fertility preservation. Ferility preservation procedures, including long-term storage of sperm, can be expensive. Assisted reproductive technologies can assist in conception after treatment, but not all patients will want to pursue them or be able to pay for them. Fertility preservation before puberty: Many parents are concerned about protecting a prepubescent child’s fertility from the effects of cancer treatment. Treatments can pre-
Fertility issues vent, delay, or accelerate puberty. The effects on fertility may be permanent or may not be evident until later in life, when they can shorten a person’s reproductive years. Unfortunately, preserving fertility in a child can be a challenge. Fertility-sparing treatment methods that protect reproductive organs from radiation or conservative surgery on reproductive structures may prevent damage to a child’s reproductive systems. Because prepubescent boys and girls cannot make mature sperm or eggs, respectively, researchers are investigating whether testicular or ovarian function can be restored by transplanting back testicular or ovarian tissue that was collected and frozen before treatment. Parenthood for cancer survivors: Cancer survivors confront many issues when considering parenthood after treatment. Oncologists typically advise waiting two to five years after treatment before trying to conceive naturally or through assisted reproduction technologies. Fertility may improve over time as damage to sperm or eggs is naturally repaired. Some cancer treatments also damage the heart and lungs, which can complicate a pregnancy; therefore, women may benefit from waiting. Oncologists also recommend waiting to see if the cancer returns. The likelihood of reoccurrence affects a person’s decision to become a parent. When considering parenthood, many survivors have concerns about the possible impact of the cancer or cancer treatments on the health of a baby. Although it has not been studied extensively, the findings to date do not show any increase in birth defects in children born to cancer survivors. Some are also concerned about their children inheriting a so-called cancer gene or the genetic tendency to develop cancer. Genetic counselors may be able to estimate that risk. Survivors who are unable to conceive a child who is genetically related to both parents still have options for parenthood. A sperm donor can be used to fertilize a partner’s egg. Similarly, donated eggs can be fertilized by a partner’s sperm. In these cases, the child would be genetically related to one parent. Women whose eggs are unable to be fertilized may still be able to carry a pregnancy. These women can use donated embryos created through in vitro fertilization. Survivors may also consider adoption. Many adoption agencies require a letter from an oncologist that the prospective parent is cancer-free and is expected to have a normal lifespan and good quality of life. Some agencies require survivors to be cancer-free for a certain amount of time before being eligible for adoption. Amanda McQuade, Ph.D. 471
Fever u For Further Information Falker, E. S. The Ultimate Insider’s Guide to Adoption: Everything You Need to Know About Domestic and International Adoption. New York: Hachette USA, 2006. Lee, S. J., et al. “American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients.” Journal of Clinical Oncology 24, no. 18 (2006): 2917-2931. Oktay, K. H., L. Beck, and J. D. Reinecke. One Hundred Questions and Answers About Cancer and Fertility. Sudbury, Mass.: Jones and Bartlett, 2008. u
Other Resources
American Academy of Adoption Attorneys http://adoptionattorneys.org/ Fertile Hope http://www.fertilehope.org International Council on Infertility Information Dissemination, Inc. http://www.inciid.org/ Lance Armstrong Foundation http://www.livestrong.org See also Childbirth and cancer; Fertility drugs and cancer; Gynecologic cancers; Hormonal therapies; Infertility and cancer; Ovarian cancers; Ovarian cysts; Pregnancy and cancer; Sterility.
u Fever Category: Diseases, symptoms, and conditions Also known as: Hyperpyrexia Related conditions: Infection and sepsis in cancer treatment, myelosuppression, neutropenia Definition: Fever is a pyrogen-mediated elevation of the core body temperature. This is in distinction to hyperthermia, which is an unregulated rise in core temperature as occurs in heat stroke. Pyrogens may originate outside the body (exogenous) or be produced within the body (endogenous). The exogenous pyrogens are typically microorganisms or their toxins and products but also include drugs, antigen-antibody complexes, and other substances. Endogenous pyrogens are various chemicals produced by host cells and are called cytokines. Risk factors: Fever may be caused by cancer. Although many types of malignant neoplasms may cause fever, 472
Salem Health: Cancer some of the most common are lymphomas, leukemias and preleukemias, and renal cell carcinoma. However, fever in cancer patients is more often a consequence of treatment than of the cancer. The protective barrier provided by the skin and mucous membranes may be breached by surgery or vascular catheter placement, providing entrance points for invading microbes, which produce infection and fever. A similar phenomenon may result from chemotherapeutic cancer drugs that destroy not only the cancer cells but also oral and mucous membrane lining cells, inducing mucositis. Drugs may also kill bone marrow cells (myelosuppression and neutropenia), which impairs bodily defense mechanisms against infectious agents. The vascular catheters used to administer drugs, intravenous fluids, and blood components are risks for infection, and the risk increases the longer the catheter is left in place. Administration of blood components can produce fever through a variety of mechanisms. The antibiotics used to treat infection, like many other drugs, may produce fever, complicating therapy. Some antibiotics, such as sulfonamides and chloramphenicol, can cause neutropenia and fever. Finally, antibiotics may alter the normal flora of the patient, allowing overgrowth of problem organisms. Fungi, such as those of the Candida species, may overgrow on the skin and in the gastrointestinal tract, causing infection. An anaerobic-toxin-producing bacterium called Clostridium difficile can overgrow in the colon, causing fever and diarrhea. Venous thrombosis can also cause fever. Some cancers, especially adenocarcinomas, are associated with a hypercoagulable state. Venous stasis may be a consequence of an obstructing tumor mass or lymphadenopathy, immobility (bedrest or surgery), and dehydration. Some antineoplastic drugs can result in endothelial injury. All these factors can contribute to the formation of fever-associated thrombi. Etiology and the disease process: Fever is a complex process and is not completely understood. The process is initiated by the production of endogenous pyrogens or cytokines. Cytokines are polypeptide proteins that are produced by host cells, probably mononuclear macrophages. Cytokines, including interleukin-1, tumor-necrosis factor, and interleukin-6, produce the rapid onset of fever by acting directly on the brain (hypothalamus). The release of cytokines is induced by the exogenous pyrogens or some endogenous molecules. Exogenous pyrogens are usually microbes and their products (including toxins). An example of an endogenous molecule would be a complement-binding antigen-antibody complex. Finally, the hypothalamus produces prostaglandin E2, which or-
Salem Health: Cancer chestrates physiologic changes that increase core temperature. Fever is an adaptive response that, for the most part, is beneficial. Increased temperature is associated with increased production of antibacterial substances (superoxides and interferon), increased neutrophil migration, and increased T-cell proliferation, all of which are beneficial in the fight against invading microbes. Nonetheless, fever is metabolically demanding, and prolonged fever can be deleterious to the patient. High fever can damage organs and contribute to circulatory collapse or failure. Incidence: The relationship between fever and cancer may be examined by looking first at fever in patients who are not diagnosed with cancer or any other causative disease process and second at fever in patients with a specific cancer that has already been diagnosed. In patients with an undiagnosed fever or fever of undetermined origin, an underlying malignancy has been found to be causative in 9 to 30 percent of patients. Lymphoreticular neoplasms, such as Hodgkin disease and nonHodgkin lymphoma, are the most common. The age of patients with fever of undetermined origin influences the percentage of neoplasms: Children tend to have fewer cancers and more infections, while elderly adults tend to have higher percentages of cancers. The incidence of fever in patients in whom cancer is already diagnosed varies widely, as it depends on many variables, including the type and severity of the cancer, treatments employed, and comorbid illnesses. Fever is a common problem in cancer patients. Symptoms: At the onset of a fever, body heat is conserved by vasoconstriction, and the patient initially feels cool, especially in the hands and feet. Shivering occurs when muscles act to produce heat. Finally, the patient feels warm as the higher setpoint for core temperature is reached. Sweating and vasodilatation (flushing) occur only with heat loss and the subsequent falling temperature. Screening and diagnosis: For patients with fever of undetermined origin, a detailed history and careful physical examination are important and can provide critical information. Sometimes fever patterns themselves can be revealing. A sudden onset of fever, particularly if preceded by rigors or chills, is indicative of bacteremia or fungemia. Pel-Epstein fever is associated with Hodgkin disease and is characterized by three to ten days of fever followed by three to ten days without a fever. An initial battery of laboratory and radiologic tests is followed by an ordering sequence of more tests depending on the results of previous
Fever tests. Ultimately, a biopsy of an abnormal mass, lymph node, or bone marrow is usually required for diagnosis of a specific cancer as a cause of a fever with an undetermined origin. Patients with previously diagnosed cancer present equally challenging problems in the determination of fever etiology. The most serious immediate issue is to determine if the patient has a life-threatening infection, and empiric antibiotic therapy is commonly administered as a safeguard. After a thorough history is taken and a physical examination is conducted, the patient will undergo screening blood and urine tests, radiologic studies, cultures of blood, and other tests to determine the possible sources of infection. If there are no indications of infection and empiric antibiotic therapy has no beneficial effect, then noninfectious causes must be sought. Drugs, venous thrombosis, and neoplastic fever are all possible. When other causes of fever have failed to be detected by any means and neoplastic fever appears likely, treating the patient with the nonsteroidal anti-inflammatory agent naproxen can aid in the diagnosis. Naproxen appears to have a unique ability to suppress tumor fever but not significantly effect fevers of nonneoplastic origin. Treatment and therapy: Antipyretic therapy is generally provided only when the patient is uncomfortable or the fever is causing problems such as cardiovascular failure due to fever-induced tachycardia. The fever is not routinely treated because it is a continuing clue to the underlying diagnosis; treatment of the cause of the fever leads to final resolution. Complicating infections are treated with antibiotics, and associated catheters and other foreign bodies are removed whenever possible. If infection is associated with neutropenia, granulocyte colony-stimulating factor is administered to restore the neutrophil numbers. Drugs are discontinued when necessary, and blood clots are removed or treated. Neoplastic fever can be treated with naproxen while the cancer is being removed or treated with other measures. Prognosis, prevention, and outcomes: The prognosis depends on many factors but is often related to the ability to successfully control infection in the cancer patient with fever. Correspondingly, unresolved immunosuppression or uncontrolled neoplastic growth can render infections difficult or impossible to resolve. For most patients, successful treatment can be accomplished once a specific etiology for the fever has been established. Prevention is mainly directed at infections complicating cancers and antineoplastic therapies. Careful manage473
Fiber
Salem Health: Cancer
ment of vascular catheters, minimization of immunosuppressive periods, and prophylactic antibiotics during critical times can all help prevent infections and fever. H. Bradford Hawley, M.D. u For Further Information Chang, Jae C., and H. Bradford Hawley. “Neutropenic Fever of Undetermined Origin (N-FUO): Why Not Use the Naproxen Test?” Cancer Investigation 13 (1995): 448-450. Cunha, Burke A., ed. “Fever.” Infectious Disease Clinics of North America 10 (1996): 1-222. Dinerello, Charles A., and Jeffrey A. Gelfand. “Fever and Hyperthermia.” In Harrison’s Principles of Internal Medicine, edited by Dennis L. Kasper et al. 16th ed. New York: McGraw-Hill, 2005. Mackowiak, Philip A., ed. Fever: Basic Mechanisms and Management. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 1997. Murray, Henry W., ed. FUO: Fever of Undetermined Origin. New York: Futura, 1988. u
Other Resources
American Cancer Society Fever http://www.cancer.org/docroot/MBC/content/ MBC_2_3X_Fever.asp?sitearea=MBC National Cancer Institute Fever, Sweats, and Hot Flashes http://www.cancer.gov/cancertopics/pdq/ supportivecare/fever/Patient/page2
A diet rich in fiber from complex carbohydrates—grain, fruit, and vegetables—may reduce the risk of cancer. (U.S. Department of Agriculture)
See also Candidiasis; Coughing; Cytokines; Fatigue; Infection and sepsis; Mucositis; Myelosuppression; Nausea and vomiting; Neutropenia; Night sweats; Nonsteroidal anti-inflammatory drugs (NSAIDs); Pneumonia; Side effects; Symptoms and cancer; Tumor lysis syndrome.
Cancers treated or prevented: Colorectal cancers, spastic bowel syndrome
u Fiber Category: Lifestyle and prevention Definition: Fiber is a natural structural chemical component of plants responsible for strength and architectural form. Examples of plant fiber include cellulose, hemicellulose, pectins, and lignins. Most plant fiber is difficult to digest and absorb because it is chemically complex and insoluble. Dietary fiber functions to clean out the digestive tract and move waste quickly through the intestines. 474
Delivery routes: Fruits, vegetables, leafy greens, grains, or oral supplements as tablets or liquid form How this substance works: Fiber in diets helps maintain optimal movement of food and wastes through the lower human digestive tract. Fiber helps cleanse the intestinal tract and colon, preventing the formation of pockets of residue. There are two basic types of dietary fiber, insoluble fiber and soluble fiber. Water-soluble fiber absorbs water in the intestines and via enzymatic activity mixes food into a gel on which intestinal enzymes work. Conversely, insoluble fiber is the more valuable in reducing risk of cancer as it is considerably more difficult to digest; thus carcinogens and toxins in the food are not released in the presence of the metabolically active cells of the intestinal lining but rather pass harmlessly out of the body. It follows
Salem Health: Cancer that the less time carcinogens are in contact with the intestinal walls, the lower the risk of cancer should be because of decreased exposure to carcinogens carried in food and food wastes. Insoluble fiber is sometimes referred to as the “scrub brush” for the human internal digestive tract because it “scrubs” the intestines clean as it passes through the small intestine and colon. This type of fiber acts to absorb many times its own weight in water, which softens the waste in the intestine and facilitates motion through the body, thereby decreasing irritation, constipation, and blockage. Research has shown that fiber increases peristalsis, the involuntary muscular contractions of the digestive system. Regular and efficient peristalsis resulting from increased bulk in soft stools decreases the period of time that toxins are in contact with intestinal tissue. Fiber may also bind to carcinogens, lessening their proximity to internal cells. Water absorbed by fiber dilutes toxins, rendering them less harmful and decreasing the risk of cancer. Fiber can also help absorb intestinal acids such as bile, hydrochloric acid, and other irritants that may predispose cells to disease. Fiber can promote intestinal health by encouraging the growth of beneficial bacteria while discouraging the growth of harmful bacteria. A high-fiber diet may also reduce the incidence of diverticulosis and irritable bowel syndrome, both implicated in intestinal cancer. Human studies suggesting an inverse relationship between insoluble dietary fiber intake and colorectal cancer incidence remain inconclusive because of the complexity of the disease. Many other factors, including heredity and lifestyle, play a role in the appearance of disease. An overwhelming majority of the long-term cohort studies, however, have pointed to dietary fiber as a means of reducing the risk for colorectal cancer. Side effects: Some studies also show that excessive amounts of fiber may interfere with the absorption of certain minerals such as calcium, copper, iron, magnesium, selenium, and zinc. Excessive dietary fiber may also lead to constipation and occasional blockage. The frequency and intensity of both of these negative side affects can be reduced with the use of softening agents such as psyllium. Dwight G. Smith, Ph.D. See also Chemoprevention; Colonoscopy and virtual colonoscopy; Colorectal cancer; Cruciferous vegetables; Diarrhea; Diverticulosis and diverticulitis; Fruits; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Hemorrhoids; Laxatives; Nutrition and cancer prevention; Nutrition and cancer treatment; Polyps; Premalignancies; Prevention; Risks for cancer; Stomach cancers.
Fibroadenomas
u Fibroadenomas Category: Diseases, symptoms, and conditions Also known as: Complex fibroadenomas, juvenile fibroadenomas, giant fibroadenomas Related conditions: Fibrocystic breast disease, cytosarcoma phyllodes, breast cysts Definition: Fibroadenomas are benign breast tumors that are characteristically smooth-surfaced, round or oval in shape, and freely movable on palpation (feeling with the fingers). They can range in size from 1 to 15 centimeters (cm). A fibroadenoma consists of homogeneous (closely related) fibrous tissue. In rare instances, a fibroadenoma can contain a breast cancer. This is more likely in a complex fibroadenoma. A complex fibroadenoma contains several specific tissue changes. They are sclerosing adenosis (hardening of glandular breast tissue) and apocrine metaplasia (conversion of milk-producing cells into an abnormal form). Although a fibroadenoma is not considered a precursor to breast cancer, it is thought that having a complex fibroadenoma slightly increases a woman’s risk of developing breast cancer in the future. Juvenile and giant fibroadenomas occur only in teenagers or young adults and can grow as large as 15 cm. Cytosarcoma phyllodes is a rare type of breast cancer that can occur within a fibroadenoma. Typically, this type of cancer does not spread beyond the breast tissue. Risk factors: Fibroadenomas require the presence of estrogen to develop and grow, so they occur between menarche and menopause. Generally, after menopause, an existing fibroadenoma will stop growing and may even disappear. If a woman takes estrogen after menopause, she can develop a fibroadenoma. Etiology and the disease process: A fibroadenoma arises from a single milk duct in the breast and is made up of both glandular (milk-producing cells) and epithelial cells (skin cells that line the duct). There is no fluid inside a fibroadenoma. It develops from an overgrowth of the affected breast tissue. The cause of the overgrowth of tissue is unknown, although estrogen is required for fibroadenoma development. Fibroadenomas generally stop growing at 2 to 3 cm, although they occasionally grow larger. They may also enlarge during pregnancy and at times of higher estrogen levels during the menstrual cycle. Immunosuppressive medications appear to have an effect on the growth and development of fibroadenomas. Studies have demonstrated that 50 percent of women who 475
Fibrocystic breast changes receive the immunosuppressive drug, cyclosporine, after a kidney transplant will develop one or more fibroadenomas. Incidence: The fibroadenoma is the most common type of benign breast tumor. In women over the age of forty, 8 to 10 percent will develop a fibroadenoma at some time during their lives. Roughly one-third of fibroadenomas are complex fibroadenomas. Symptoms: In women younger than age forty, fibroadenomas usually appear as palpable (can be felt) breast masses. After age forty, they may be discovered as a palpable breast mass, or they may appear on mammography as a breast mass that is not palpable. Fibroadenomas are not painful. Screening and diagnosis: Screening is not carried out specifically for fibroadenomas, but some are picked up while screening for breast cancer in women over the age of forty. Breast fibroadenomas may be diagnosed by breast self-examination if they are palpable, or by mammography. On a mammogram, a fibroadenoma appears as a dense area in the breast, and in women over age forty, it may have areas of calcification (mineral deposits). Since it is not possible to determine whether a breast density is a fibroadenoma or breast cancer on mammography, subsequently, a breast ultrasound is performed. On an ultrasound, a fibroadenoma looks like a clear area with defined edges, much as a breast cyst does. The only way to determine whether a density is, indeed, a fibroadenoma is to biopsy it. A biopsy may be performed using a fine needle, a core needle, or surgical incision. A pathologist examines the tissue under a microscope and decides whether it is cancer or a fibroadenoma. A cancer is present inside 3 percent of fibroadenomas. Typically, these fibroadenomas are larger than usual and have irregular margins that are less clearly defined. In 1 percent of cases, what appears to be a fibroadenoma is actually cytosarcoma phyllodes. Because a fibroadenoma is not cancer, there is no staging for it. If breast cancer is found within a fibroadenoma, it is staged as a breast cancer. Treatment and therapy: A fibroadenoma may be totally removed at the time of biopsy by surgical excision or core needle biopsy. If it is not removed, it will be monitored annually for growth and changes by mammography, magnetic resonance imaging (MRI), or ultrasound. Prognosis, prevention, and outcomes: Since fibroadenomas are benign tumors, the prognosis is excellent for women who develop them. There is a slight increase in the 476
Salem Health: Cancer risk of subsequently developing breast cancer. Before menopause, there is no way to prevent a fibroadenoma from developing. After menopause, a woman can prevent a fibroadenoma by avoiding any type of systemic estrogen therapy. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Chinyama, Catherine N. Benign Breast Disease: Radiology, Pathology, Risk Assessment. New York: Springer, 2004. Ganschow, Pamela, et al., eds. Breast Health and Common Breast Problems: A Practical Approach. Philadelphia: American College of Physicans, 2004. Love, Susan, and Karen Lindsey. Dr. Susan Love’s Breast Book. 5th ed. Cambridge, Mass.: Da Capo Press, 2005.
u
Resources
American Cancer Society http://www.cancer.org Imaginins.com http://www.imaginis.com WebMd Breast, Fibroadenoma http://www.emedicine.com/radio/topic109.htm See also Adenocarcinomas; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Breast ultrasound; Caffeine; Calcifications of the breast; Estrogenreceptor-sensitive breast cancer; Fibrocystic breast changes; Lumps; Phyllodes tumors.
u Fibrocystic breast changes Category: Diseases, symptoms, and conditions Also known as: Fibrocystic conditions of the breast Related conditions: Cysts, mastaglia, trigger-zone breast pain, fibroadenoma, fibrosis, hyperplasia Definition: Fibrocystic changes in the breast are benign (noncancerous) and related to normal hormonal fluctuations during a woman’s menstrual cycle. The word refers to thickening of tissue (fibro) and fluid-filled sacs (cysts) in the breast. The term loosely groups several different benign conditions, some of which can cause physical symptoms of discomfort or pain, known as mastaglia; other conditions may be visible on mammograms but not noticeable physically. In the past, the term “fibrocystic breast disease” was
Salem Health: Cancer used, a misleading label, given that the majority of women experience some breast changes or have mammograms that reveal them. Risk factors: Women in their childbearing years or postmenopausal women taking hormone replacement therapy may be prone to several types of fibrocystic changes. Because these changes are related to menstrual-cycle hormones, they usually cease after natural menopause. Etiology and the disease process: Fibrocystic breast changes are not a disease. They include several different categories of benign changes in breast tissue caused by the fluctuations of hormones during a woman’s menstrual cycle. Each month a woman’s body prepares for pregnancy, and hormones stimulate milk-producing cells, creating as much as three to six teaspoons of fluid within each breast, which is then reabsorbed if pregnancy does not occur. The fluid can collect in sacs and form cysts. Breast pain may be cyclical, appearing at the time of a woman’s ovulation or just before or during her menstrual period. Cyclical breast pain may be related to the presence of cysts and the pressure they cause. However, the number of cysts or the amount of lumpiness a woman has does not necessarily relate to the amount of pain she experiences. Cyclical pain is usually most intense at the beginning and the end of the childbearing years, in a woman’s teens and again in her forties. Pain also may be noncyclical, with no apparent pattern related to the menstrual schedule. Often it is in a specific area of the breast and is known as trigger-zone pain. It can be constant or intermittent. The reasons for noncyclical breast pain are unclear. For some women, old trauma, like a blow to the breast or a biopsy, is sometimes a cause of noncyclical pain. There is some evidence that for some women, different levels of the hormone progesterone or a sensitivity to hormones produced by the thyroid may be the cause of the pain. Other breast changes included under the term “fibrocystic changes” include fibrosis and hyperplasia. Fibrosis occurs in some women when the normal fatty tissue of the breast is replaced over time with fibrous tissue, which may feel firm or rubbery. Some women develop extra cells within the lobules of the breast, the tubes designed to move milk through the breast. These areas of extra cells are called hyperplasia and show up only on mammograms. They are not cause for concern unless the cells begin to change from their normal shape. This rare condition is called atypical hyperplasia. It does not cause cancer. Incidence: Varying estimates indicate that anywhere from 40 to 90 percent of women have some form of fibrocystic
Fibrocystic breast changes changes, which supports the theory that the symptoms are mostly related to normal changes in the breasts. Symptoms: Symptoms of fibrocystic changes vary according to the type of change a woman experiences. She may have feelings of heaviness, tenderness, or swelling of the breasts. Cysts are usually felt as smooth and are generally round and movable when prodded. If they are deep within the breast, they may feel hard because of the breast tissue overlaying them. Cysts may simply cause a feeling of lumpiness throughout the breast, or because of pressure on the breasts caused by collected fluid within the cysts, they may cause tenderness or actual pain. However, pain cannot always be attributed to cysts or other specific causes. The amount of pain may differ between a woman’s right and left breast. The intensity of pain can vary from month to month for the same woman. Breast pain can sometimes be intense enough to interfere with a woman’s normal life. Some women experience no physical symptoms, but breast examinations or mammograms may reveal cysts or areas of fibrosis. Screening and diagnosis: It is important for a woman to become familiar with the way her breasts feel at different times of the month so that she can identify any obvious changes. Annual breast examinations as part of a physical examination are also important to track any changes. Women over age forty should have routine annual mammograms. If breast examination reveals suspect lumps, mammograms may be needed at an earlier age. Women with hyperplasia may need more frequent breast examinations or follow-up mammograms. A woman should bring any defined lumps or masses or persistent breast pain to her doctor’s attention. A doctor may attempt to aspirate a suspect lump with a fine needle to determine whether it is a cyst or a solid lump. If it is a cyst, the doctor can puncture the cyst with the needle and draw the fluid out of the cyst. In this case, generally no further action is needed. However, the doctor may choose to have a pathologist check the fluid for cancer cells. If a lump yields no fluid and proves to be solid, a mammogram is generally done for further diagnosis. The technology of ultrasound has been improved for the creation of diagnostic images of the breast. Although it is generally not a good tool for screening, it is useful in the further diagnosis of areas of concern first identified on mammograms. Because it uses sound waves to create images of the breast, ultrasound is particularly useful for distinguishing between cysts and solid masses and between benign and cancerous lumps. For women with fibrocystic changes in the breast, which often cause the breast tissue to be particu477
Fibrosarcomas, soft-tissue larly dense and may make mammograms difficult for radiologists to read, ultrasound is often a more accurate diagnostic tool. Biopsy may be required to analyze cells to rule out cancer. This can be done by a needle core biopsy, where a doctor removes a sample of cells from the area of the breast. Alternatively, it can be done by surgical biopsy, in which case the whole lump or suspect area is cut out of the breast. Treatment and therapy: Cysts generally need no treatment. If a cyst is very large and therefore creates a lot of pressure resulting in pain, a doctor may use a needle to aspirate it and remove the fluid in the cyst as described above. Once the fluid is gone, this deflates the cyst and resolves the pressure it caused. Most cyclical changes in the breast do not cause enough discomfort to require any treatment. Breast pain generally can be relieved with anti-inflammatory drugs such as ibuprofen or naproxen. A bra with good support, like a sports bra, can relieve pressure and the related pain. Birth control pills can be used to treat more intense breast pain because they level out the fluctuations in hormonal levels. Some women have found relief from symptoms by consuming fewer products that contain caffeine (such as coffee, tea, and chocolate) or using primrose oil or other herbal remedies. However, research has not provided convincing data that these make a difference for women overall. There is some evidence that a low-fat diet may reduce symptoms of cyclical breast pain. Prognosis, prevention, and outcomes: About 54 percent of benign breast conditions go away by themselves over time. None cause cancer. Only one, atypical hyperplasia, is associated with any added risk of cancer. Women with atypical hyperplasia who also have a family history of breast cancer may have a slightly increased risk of cancer over their lifetimes. Charlotte Crowder, M.P.H., ELS u
For Further Information Chinyama, Catherine N. Benign Breast Diseases: Radiology, Pathology, Risk Assessment. New York: Springer, 2004. Love, Susan, and Karen Lindsey. Dr. Susan Love’s Breast Book. 5th ed. Cambridge, Mass.: Da Capo Press, 2005. Mansel, R. E., ed. Recent Developments in the Study of Benign Breast Disease: The Proceedings of the Fifth International Benign Breast Symposium. Park Ridge, N.J.: Parthenon, 1993. 478
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Other Resources
MayoClinic.com Fibrocystic Breast Disease: Any Link to Cancer? http://www.mayoclinic.com/health/ fibrocystic-breast-changes/AN00715 Medline Plus Fibrocystic Breast Disease http://www.nlm.nih.gov/medlineplus/ency/article/ 000912.htm See also Breast cancers; Caffeine; Estrogen-receptorsensitive breast cancer; Fibroadenomas; Lumps.
u Fibrosarcomas, soft-tissue Category: Diseases, symptoms, and conditions Related conditions: Angiosarcoma, alveolar soft part sarcoma, clear-cell sarcoma, dermatofibrosarcoma protuberans, desmoid tumors, desmoplastic small-cell tumor, elastofibroma, epithelioid hemangioendothelioma, epithelioid sarcoma, fibroma, fibrous histiocytoma, fibromatosis, gastrointestinal stromal tumor, glomangiosarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, Kaposi sarcoma, musculoaponeurotic fibromatosis, neurofibrosarcoma, rhabdomyosarcoma, superficial fibromatosis, synovial sarcoma, and malignant versions of fibrous histiocytoma, granular cell tumor, hemangiopercytoma, mesenchymoma, peripheral nerve sheath tumor, and schwannoma Definition: Fibrosarcomas are soft-tissue sarcomas (malignant tumors) of the fibroblasts, the cells that produce the fibrous tissues that connect, support, or surround other organs and tissues in the body (such as those around the joints). They usually occur in the arms, legs, or torso area, most commonly in the legs. They are one of many types of soft-tissue sarcomas. They are called “soft tissue” to distinguish them from osteosarcomas, tumors that develop in the bone. Fibrosarcomas are often grouped together with the other soft-tissue sarcomas because these diseases share certain characteristics and have similar treatment options. Risk factors: Most soft-tissue sarcomas have no known cause. However, there are several factors that may increase the risk of developing these types of cancer. Radiation therapy, usually for other types of cancer, is the bestdocumented risk factor for this disease, possibly because radiation may inactivate the lymph nodes. Surgical removal of the lymph nodes also seems to play a part in development of this disease.
Salem Health: Cancer
Fibrosarcomas, soft-tissue
Another risk factor for this type of disease is exposure to certain chemicals, usually at the workplace. Chemicals that may cause this type of cancer are arsenic, herbicides, vinyl chloride, and wood preservatives. This disease is also associated with certain genetic mutations. People with alterations in the FH gene, the NF1 gene, the TP53 tumor-suppressor gene, or the RB1 gene and who have the diseases associated with these genetic mutations (Li-Fraumeni syndrome and neurofibromatosis, also called von Recklinghausen disease) are much more likely to develop soft-tissue sarcomas, including fibrosarcoma. Other diseases that seem to increase the risk for softtissue sarcomas are basal-cell nevus syndrome, Gardner syndrome, tuberous sclerosis, and Werner syndrome. Etiology and the disease process: Fibrosarcomas begin in the cells that develop fibrous tissues. They start as a lump in these fibrous tissues, usually those that surround the joints in the arms, legs, and torso. The lump is usually painless; however, the tumor may grow, pressing against other tissues such as nerves and muscles, and cause pain. These tumors can spread throughout the body, most commonly to the lungs. Incidence: Soft-tissue sarcomas are rare, and developing fibrosarcoma is even rarer. Only about 9,000 new cases of soft-tissue sarcoma are diagnosed in the United States each year. This type of cancer is most common in people between the ages of twenty and sixty, with most patients being age fifty or older. However, it can occur in people of any age, including infants.
raphy (CT) scan or magnetic resonance imaging (MRI) to help diagnose and stage this disease. These tests can help determine the size of the tumor and whether its location will allow for surgical removal. The stages of this disease depend on how abnormal the cells of the tumor appear, the size of the tumor, and how likely the tumor is to begin to spread and grow. Staging of this disease follows the TNGM system. These letters represent the size of the primary tumor (T), whether the disease has spread to the lymph nodes (N), the grade of the tumor (G), and whether the tumor has spread or metastasized (M). The size of the tumor (T) is assigned a number based on the size of the primary tumor as follows: • T1: Tumor is 5 centimeters or less. • T1a: Superficial (near the surface) tumor • T1b: Deep tumor • T2: Tumor is larger than 5 centimeters. • T2a: Superficial tumor • T2b: Deep tumor Lymph node involvement (N) is assigned a number as follows: • N0: No evidence of cancer is found in nearby lymph nodes. • N1: Evidence of cancer is found in nearby lymph nodes.
Symptoms: This type of cancer is most likely to develop in the arms, legs, or torso. It usually appears as a lump or mass and is not usually painful or swollen. There are generally no other symptoms. Screening and diagnosis: No screening test is available for fibrosarcoma. The only way to accurately diagnose this type of tumor is with a biopsy, surgical removal of part of the tumor. The tumor section is then examined under a microscope to determine whether the cells are cancerous. These cells may also be tested for the genetic mutations that are risk factors in this disease to determine the most effective treatment. Doctors may use a computed tomog-
Fibrosarcoma nodules on the thumb and palm. (Custom Medical Stock Photo)
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Fibrosarcomas, soft-tissue
Salem Health: Cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Soft Tissue Cancer, Including Heart Cancer, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%) Survival Rate (%) 53 25 15 7
84.7 60.0 16.0 54.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
The grade of the tumor is assigned a number as follows: • G0: Grade of tumor cannot be assessed. • G1: The tumor is well defined without reaching into surrounding tissues. • G2: The tumor has moderately reached into surrounding tissues. • G3: The tumor has reached well into surrounding tissues. • G4: The tumor cannot be distinguished from surrounding tissues. The spread of the disease (M) is divided into two categories: • M0: No disease is present elsewhere in the body. • M1: Disease is present in a distant body area. After the TNGM state of the cancer is determined, a stage is assigned. • Stage I: Low grade and either superficial or deep (G1 or G2, any T or N, and M at 0) • Stage II: High grade and either superficial or deep (G3 or G4, any T or N, and M at 0) • Stage III: High grade, large, and deep (G3 or G4, T2b, N and M at 0) • Stage IV: Any spread of disease to lymph nodes or other sites (any G, any T, and either N1 or M1) Treatment and therapy: Treatment for fibrosarcoma usually starts with surgery to remove the tumor and some of the healthy tissue surrounding it. The surgeon must ensure that all edges of the tumor have been removed, and sometimes this involves removing a large amount of tis480
sue. In about 10 to 15 percent of cases, this may even involve amputation of an arm or leg to ensure that the entire tumor is removed; however, surgeons often try to use limb-sparing techniques to avoid amputation. Some patients may need reconstructive surgery after removal of the tumor. Radiation therapy (using high-energy rays to kill the cancerous cells or implanting a tumor with radioactive materials) also may be used with this type of cancer, especially if the cancer’s location makes it difficult to remove the entire tumor or avoid damaging other body parts. Radiation therapy may be used along with surgery to ensure that any cancerous cells that may have been left behind are killed. It may also be used when limb-sparing techniques were used to avoid amputation to ensure that any remaining cancer cells are killed. Chemotherapy (using drugs in the blood stream to kill cancer cells) may also be used with fibrosarcomas. If the cancer has certain gene mutations, it may be treated with drugs specifically developed to target that mutation. Chemotherapy could be used before surgery to try to shrink the tumor before removal. MRIs or CT scans may be used after surgical removal to determine if the entire tumor was removed and to make sure the tumor is not growing back. Prognosis, prevention, and outcomes: Prognosis depends on the patient’s age, the size of the tumor, how deep or superficial the tumor is, and the likelihood of the tumor’s spread at the time of diagnosis. Patients with soft-tissue sarcomas such as fibrosarcoma need to receive follow-up care to ensure that there is no recurrence of the disease. Outcomes are generally better for patients who are less than sixty years old or have tumors smaller than 5 centimeters. Marianne M. Madsen, M.S. u
For Further Information Baker, Laurence H., ed. Soft Tissue Sarcomas. Boston: Martinus Nijhoff, 1983. Montgomery, Elizabeth, and Alan D. Aaron, eds. Clinical Pathology of Soft-Tissue Tumors. London: Informa Healthcare, 2001. Pollock, Raphael E., ed. Soft Tissue Sarcomas. Lewiston, N.Y.: BC Decker, 2002.
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Other Resources
American Cancer Society http://cancer.org
Salem Health: Cancer National Cancer Institute Soft Tissue Sarcomas: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Sites-Types/soft-tissue-sarcoma See also Amputation; Bone cancers; Dermatofibrosarcoma protuberans (DFSP); Limb salvage; Mediastinal tumors; Sarcomas, soft-tissue.
u Financial issues Category: Social and personal issues Definition: Financial issues related to cancer include the financial burden on cancer patients and their families, the costs to insurers and employers, and the financial implications of cancer for the economy and government. Some of the economic issues include the rising costs of new treatments, bankruptcies caused by medical bills, and the high cost to society in terms of lost productivity, excess mortality, and morbidity related to cancer. Overall cost of cancer: In 2005, cancer expenditures in the United States totaled about $209.9 billion. Of that total, about $74 billion was paid for inpatient and outpatient care, drugs, and devices—around $250 for every man, woman, and child. This amount represents less than 5 percent of all medical spending and less than 1 percent of the total U.S. gross domestic product (GDP, a measure of all the goods and services produced in the economy). This may be somewhat surprising, given that cancer accounts for nearly a quarter of all deaths in the United States. However, cancer is mostly a disease of old age and is frequently terminal. Although treating cancer can be expensive compared with the cost of treating many other diseases, the cost of chronic illnesses that require medical care over an extended period (such as diabetes) can be much higher. However, cancer expenditures may be of greater concern in the future, as the baby boomers swell the ranks of Medicare from 42.5 million people in 2005 to about 70 million in 2030. Cancer expenditures are growing at about the same rate as overall medical spending, at 4 to 5 percent per year after adjusting for inflation. This may seem somewhat counterintuitive because the incidence of many types of cancer has been increasing and many intensive and expensive forms of treatment have been introduced in the twentyfirst century. At the same time, the average length of hospital stay has been decreasing, and there has been an increase in the number of early-stage cancers detected because of improved screening programs.
Financial issues Morbidity and premature mortality are called “indirect” costs, because they represent lost resources rather than outgoing payments. Although indirect costs are hard to measure and sometimes controversial, accounting for these costs gives a clearer picture of the total burden of a disease. The additional economic burden of cancer-related morbidity and mortality is estimated at about $135.9 billion per year. This breaks down into $17.5 billion in lost work productivity—including both absenteeism and “presenteeism” (reduced productivity while at work)— and $118.4 billion in lost earnings because of premature deaths. The main measure of premature mortality is years of life lost (YLL), which can be calculated as person-years of life lost in a specified period based on average age at diagnosis and patterns of mortality. Such calculations are then translated into dollar amounts, although doing so requires making assumptions regarding the labor market that are subject to error. In 1997 in the United States, the estimated cost from the top fifteen types of cancer was 6.6 million YLL. Dividing the YLL by the number of deaths for each cancer site produces an additional statistic, the average years of life lost (AYLL), which is a measure of the premature mortality burden of cancer to the individual patient. Prostate cancer patients experience the lowest AYLL at six years, while brain tumor patients have the highest at just over twenty years. Costs of treatment: The cost of medical treatment for a single case of cancer depends mainly on the type of cancer and the seriousness of the disease (size of the tumor, how much the cancer has spread, whether it can be treated with surgery, and so on). Other factors that influence the cost of care include the age and sex of the patient, how many other illnesses the patient has, and where the patient receives care (geographically and by setting, such as an academic hospital or specialty facility). In addition, some patients are charged less than others. Patients with no insurance are often charged full price, which can be many times the cost billed to patients with insurance because of negotiated discounts. In a study of more than 38,000 cancer patients followed for an average of eleven months, the mean cost of treating cancer was about $32,000, with monthly costs ranging from $1,800 for prostate cancer to $7,300 for pancreatic cancer. The largest component of care was inpatient hospital bills, followed by outpatient office visits. The mean monthly cost for drug treatments ranged from $10 for prostate cancer to $750 for ovarian cancer. The cost of drugs used to treat cancer has been the subject of controversy in recent years. Although drug costs ac481
Financial issues
Salem Health: Cancer
cer. More than three-quarters of those who filed for bankruptcy because of medical expenses said that they had health insurance at the time of their diExpenditures Percentage of All Percentage Cancer Treatment (billions; in agnosis. One estimate is that, on averof All New Cancers (1998) 2004 dollars) Expenditures Cancer age, out-of-pocket medical costs consume more than a quarter of the total Lung 12.7 9.6 13.3 annual income of low-income people. Colorectal 10.7 8.4 11.7 Breast 15.9 8.1 11.2 A national survey of cancer patients Prostate 16.8 8.0 11.1 conducted by USA Today, Harvard UniLymphoma 4.6 4.6 6.3 versity, and the Kaiser Family FoundaHead and neck 2.8 3.2 4.4 tion found that about 25 percent had Bladder 4.4 2.9 4.0 used up most or all of their savings. Leukemia 2.4 2.6 3.7 More than 10 percent said they had exOvarian 1.9 2.2 3.1 perienced problems paying for necessiKidney 2.6 1.9 2.7 ties like food and shelter, and 3 percent Endometrial 2.9 1.8 2.5 had declared bankruptcy because of the Cervix 0.8 1.7 2.4 financial cost of dealing with cancer. Pancreas 2.3 1.5 2.1 One in twelve respondents said that they Melanoma 4.0 1.5 2.0 Esophagus 1.0 0.8 1.1 delayed or did not get care because of All other 14.2 13.4 18.4 the cost. Although 95 percent of patients in the survey had health insurTotal 100% $72.1 100% ance, nearly 1 in 4 said that their insurSource: National Cancer Institute ance plan paid less than they expected Note: Based on cancer prevalence in 1998 and cancer-specific costs for 1997-1999, for a bill, 13 percent said their plan projected to 2004 using consumer price index would not cover a treatment they received, and 10 percent reached their maximum allowance for coverage. count for only about 10 percent of total health care spendIn the same survey, 44 percent of cancer patients reing, the prices charged by pharmaceutical companies are ported that they were employed outside the home when more transparent to consumers than prices charged by they were diagnosed. Most said that their employers treated other medical providers because consumers often pay them well. The Americans with Disabilities Act (1990) more out of pocket for drugs. In addition, there is great and the Family and Medical Leave Act (1993) protect cancontroversy over the cost-effectiveness of some of the cer patients to some extent, because they require employnewer drugs. In many cases, using one of the new drugs ers to make reasonable accommodations for the limitawill not extend a patient’s life more than a few months, yet tions of cancer patients on the job and entitle patients and the cost of the drug can be prohibitive. their caregivers up to twelve weeks of unpaid leave with continued benefits. One cost of cancer usually borne by patients and their Financial impact on patients: Cancer can be a very exfamilies is the time and money associated with medical appensive disease. Many types of cancer are complicated to pointments. These costs include transportation to and from treat and often require the services of a team of medical medical offices or clinics, time lost from work and leisure, providers, including surgeons and specialists in radiation child care, and housing and incidental costs for out-ofand chemotherapy. Cancer care may require many abtown trips to specialty care centers. In fact, the nonprofit sences from work for diagnosis and treatment, and long organization CancerCare (www.cancercare.org) reports hospital inpatient stays are required for many interventhat getting help with transportation costs is the most comtions. Patients may find that they need second opinions on monly requested and provided service it offers. biopsies and therapy. Patients with insurance may have to A number of organizations offer financial assistance to fight with insurers to get them to pay for treatments. cancer patients. State Medicaid plans cover the cost of care A recent survey found that more than half of bankfor needy patients, and there is additional assistance availruptcy filings are caused by medical expenses, and the able through some states’ Free Care pools. The Federal highest out-of-pocket expenses were associated with can-
Estimated National Spending on Medical Treatment for the Fifteen Most Common Cancers
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Salem Health: Cancer Breast and Cervical Cancer Early Detection Program covers costs associated with cases of cancer detected through one of the national screening programs. Pharmaceutical companies and nonprofit groups have patient assistance programs in place to help with the cost of cancer drugs, either by providing them free or at heavily discounted rates. Although there are hundreds of these patient assistance programs, they are underpublicized and underused. Financial impact on employers: Cancer-related costs to employers include medical costs paid by employersponsored insurance plans, disability costs, and lost productivity. In addition, other people may have to fill in for the cancer patient, or a part-time or temporary person may need to be hired. In a study of one of America’s largest companies, researchers analyzed insurance claims for medical care, absenteeism, and disability costs for all patients who were diagnosed with cancer between 1995 and 1997 and compared these expenditures with a sample of people who were similar in sex, job function, and type of health plan. They found that the average excess cost of cancer patients was more than $83,000, and total annual health care costs for cancer patients were more than five times higher than for similar people without cancer. The cost of medical care was only about half of the total incremental cost to the employer. The cost of disability payments and absences from work made up the other half of costs borne by the employer. Efforts to contain costs: Most medical care in the United States is paid for by a third party, such as Medicaid (for the poor and disabled), Medicare (for people over the age of sixty-five), or a private or employer-sponsored insurance company. These third-party payers have instituted a number of measures to contain costs associated with treating cancer. For example, most new drugs are required to show cost-effectiveness before payers will add them to their formularies (lists of approved treatments). Other cost-containment measures include cost-sharing, required preauthorizations, and retrospective claim denials. The idea behind cost-sharing is to correct a so-called irrationality in the market: The fact that patients are insulated from the true cost of their health care leads them to have higher demand for goods and services than they otherwise would. Cost-sharing has been criticized as unjust because distributing health care benefits according to the ability to pay discriminates against the poor and lower-middle classes. By law, Medicare is not allowed to set or negotiate prices for reimbursing physicans, hospitals, and drug companies. In the case of cancer drugs, since 2003 Medicare has been overhauling its systems with the intention of eliminating incentives that favor aggressive and expensive
Financial issues treatments over equivalent alternatives. Historically, the problems have arisen because the Medicare reimbursement rate for many drugs was far higher than the actual cost of purchasing them. Medicare was and is required by law to cover cancer drugs if they are being used for their Food and Drug Administration-approved indication or another approved indication. The resulting profits around certain cancer drugs have been shown to influence prescribing patterns. Medicare officials are also concerned about overtreatment, such as screening and monitoring procedures that are conducted more often than the evidence and guidelines recommend. In reaction to these and other issues, Medicare administrators have instituted a number of steps toward increasing the transparency and quality of cancer care. Lisa M. Lines, M.P.H. u
For Further Information Brown, M. L., J. Lipscomb, and C. Snyder. “The Burden of Illness of Cancer: Economic Cost and Quality of Life.” Annual Review of Public Health 22 (2001): 91-113. Brown, M. L., G. F. Riley, N. Schussler, and R. D. Etzioni. “Estimating Health Care Costs Related to Cancer Treatment from SEER-Medicare Data.” Medical Care 40, suppl. 8 (August, 2002): IV-104-117. Chang, S., et al. “Estimating the Cost of Cancer: Results on the Basis of Claims Data Analyses for Cancer Patients Diagnosed with Seven Types of Cancer During 1999 to 2000.” Journal of Clinical Oncology 22, no. 17 (September 1, 2004): 3524-3530. National Institutes of Health. Disease-Specific Estimates of Direct and Indirect Costs of Illness and NIH Support. Bethesda, Md.: Author, 2000.
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Other Resources
American Cancer Society Costs of Cancer http://www.cancer.org/docroot/MIT/content/ MIT_3_2X_Costs_of_Cancer.asp National Cancer Institute Cost of Cancer Care http://healthservices.cancer.gov/areas/economics/ care.html See also Advance directives; Counseling for cancer patients and survivors; Health maintenance organizations (HMOs); Insurance; Living will; Managed care; Medicare and cancer; Poverty and cancer; Preferred provider organizations (PPOs); Survivorship issues. 483
5Q minus syndrome
u 5Q minus syndrome Category: Diseases, symptoms, and conditions Also known as: 5Q-syndrome, 5QMS Related conditions: Myelodysplastic syndrome Definition: 5Q minus syndrome is a rare genetic disorder in which a portion of the long arm (Q) of chromosome 5 is missing. Production of blood cells is affected, and this syndrome can lead to treatment-resistant anemia. 5Q minus syndrome is one in a series of blood disorders collectively called myelodysplastic syndromes (MDS’s). Risk factors: Risk factors are unknown. Gene mutation is probably spontaneous, although there is not enough data to suggest a familial pattern of transmission. Etiology and the disease process: Chromosomes are numbered by size and position of the centromere (point of connection of identical halves). Chromosome 5 is a large chromosome. In 5Q minus syndrome, a portion of the deoxyribonucleic acid (DNA) in the long arm (Q) is absent, leading to lack of output from the missing genes. These genes define growth and differentiation of cells that manufacture most of the blood cells. Thus, bone marrow cells are often deformed and have abnormal growth and maturation. Other missing genes code for interleukins, chemical signals involved in immune protection. Incidence: Although most forms of myelodysplastic syndromes are secondary and show up increasingly with age, 5Q minus syndrome is congenital and shows up early in life. Symptoms: The primary symptoms are anemia, low total white cell count, and increased bone marrow blast cells. Patients with 5Q minus syndrome also have elevated platelet counts, something that distinguishes this group from other myelodysplastic syndromes. Because red blood cells are not manufactured properly, patients are anemic and require regular transfusions of red blood cells. In many cases, this anemia fails to respond to transfusions or other stimuli. Screening and diagnosis: Total white blood cell count, monocyte and platelet count, and bone marrow biopsy are the best diagnostic tools. A definitive karyotype (analysis of chromosome count and pattern) helps to set 5Q minus syndrome apart from other myelodysplastic syndromes. Treatment and therapy: There have been few breakthroughs in therapy. Hematopoietic growth factors and granulocyte-macrophage colony-stimulating factor have been tried with little success. Immunosuppressive drugs 484
Salem Health: Cancer do not help most patients. One study involving the experimental leukemia drug lenalidomide showed substantial improvement to the point of being transfusion independent and going into cytogenic remission (the genetic abnormality was no longer displayed). Studies with bone marrow transplantation in patients with myelodysplastic syndromes have shown positive results, but no specific data on those patients with 5Q minus syndrome have been published. Prognosis, prevention, and outcomes: Due to the rarity of this disease, prognosis is difficult to quantify. Progression to acute leukemia generally occurs, and long-term outcome is poor. Kerry L. Cheesman, Ph.D. See also Acute myelocytic leukemia (AML); Anemia; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Chromosomes and cancer; Colonystimulating factors (CSFs); Interleukins; Leukemias; Leukopenia; Myelodysplastic syndromes; Myelosuppression; Transfusion therapy.
u Flow cytometry Category: Procedures Definition: Cytometry refers to the measurement of the physical and/or chemical characteristics of cells, or, by extension, of other biological particles. Flow cytometry is a process in which such measurements are made while the cells or particles pass, preferably in single file, through the measuring apparatus in a fluid stream. Cancers diagnosed: Hematological (blood) cancers Why performed: Flow cytometry is widely used in the clinical setting for a number of cytometry-based procedures, such as immunophenotyping, cell sorting, enumeration of CD34-positive stem cell precursors, enumeration of lymphocyte subsets (B cells, T cells, and natural killer or NK cells), and fetal bleed tests in fetomaternal hemorrhage. The technique is performed on a sample of cells obtained from blood, bone marrow, or other tissue, such as a lymph node. Flow sorting extends flow cytometry by using electrical or mechanical means to divert and collect cells with one or more measured characteristics falling within a range or ranges of values set by the user. A rapid analysis of a cell sample is possible with an instrument called a cytometer that can count fifty thousand cells per second. Prior to cytometry, cells had to be counted manually under a microscope, a labor-intensive task sub-
Salem Health: Cancer ject to operator error. Components of a cytometer include a fluidics system, an optical system composed of one or more monochromatic lasers or other light source with filters to serve as an excitation beam, electronics to detect emissions from the cells, and a computer to analyze the data collected. The flow cytometry technique is widely used for diagnostics and disease monitoring of hematopoietic malignancies. Immunophenotyping of hematological cancers has developed as a clinically valuable but technically complicated diagnostic procedure. It involves a variety of methodological features, in-process strategic judgments, and an extensive knowledge of clinical, morphological, and other laboratory features of the disease processes. A number of various internal quality-control steps are necessary to guarantee reliable results with respect to instrument setup and calibration, selection and validation of monoclonal antibody panels, and process control. The data provide a wide range of hematological information essential for establishing a diagnosis in blood cancers. In leukemias, for example, knowing cell lineage and maturation helps distinguish specific forms of leukemia. Testing by flow cytometry is performed to distinguish an abnormal population of hematopoietic cells and to determine the cellular lineage of malignant cells, clonality, cellular maturation, and heterogeneity within the cancerous cell populations. Flow cytometric analysis, called immunophenotyping, allows cells to be characterized by their size, complexity, and patterns of expression of surface and cellular markers. Multiparameter flow cytometry is the simultaneous use of multiple fluorochromes, which allows completion of the full diagnostic test with fewer cells, thus reducing the size of the specimen needed. Immunophenotyping by flow cytometry is used for the initial diagnosis of hematopoietic malignancies, for monitoring the response to treatment administered for the malignancy, and for determining the presence of minimal residual disease that may indicate recurrence of the cancer. Patient preparation: The specimen, on which the process of cytometry is performed, is generally bone marrow aspirate, although a sample of peripheral blood can also be used. The patient is given instructions by the health care provider based upon the need for a bone marrow procedure versus blood collection. Steps of the procedure: The procedure of immunophenotyping is based on the ability of hematopoietic cells of different lineages and different levels of differentiation to present specific surface, cytoplasmic, or nuclear markers. These markers, called clusters of differentiation (CD), are molecules on the cell surface, as recognized by specific
Flow cytometry sets of antibodies, that are used to identify the cell type, stage of differentiation, and activity of a cell. The procedure of immunophenotyping consists of three main steps: sample preparation, flow cytometric data acquisition, and analysis and interpretation of results. To prepare a sample, cells are labeled with the antibodies tagged by specific fluorochromes, which includes staining with fluorochrome-bound monoclonal antibodies, lysis of red blood cells, and fixation in a formalin-containing reagent. This staining protocol is used for all directly conjugated reagents. A so-called whole blood lysing system is used to prepare immunologically stained leukocytes for flow cytometry analysis. In the process of flow cytometric data acquisition, cells are run through a fluidic stream so that single cells can be analyzed one at a time. Then multiple parameters are collected on each cell and analyzed for forward-angle light scatter, ninety-degree light scatter, and fluorescent signal information from up to six different fluorochromes simultaneously. All data can be stored in the form of list-mode files for later reanalysis. After the procedure: Patients receive aftercare instructions according to how the sample is obtained. If sedation is used, then limitations and restrictions are communicated to the patient by health care practitioners. Risks: Potential risks of a bone marrow biopsy and aspirate or blood collection are incorporated into a consent form explained at the facility where the procedure is accomplished and signed by the patient prior to obtaining the sample for analysis. Results: Data can be analyzed and displayed in a variety of formats, such as single-parameter histograms, dot-plots (display of distribution of two antigens on an x-y plot), or three-dimensional plots of three antigens. Data are analyzed using a gating strategy, in which specific gates are set around the subpopulations of cells based on common parameters measured on all cells. The quantification of each cell type, its light-scatter properties, its intensity of fluorescence, and certain patterns of surface or cytoplasmic marker expression serve as an indication of hematopoietic abnormalities. The pattern of antigen expression on all the cells is analyzed and compared with the distribution of normal cells. Data interpretation is based on the knowledge of specific cell phenotypes affiliated with certain types of leukemia and lymphomas. Abnormal phenotypes, however, are not always associated with disease progression. Therefore, results of flow cytometric analysis have to be used in conjunction with other diagnostic procedures and clinical evaluations. Linda August Vrooman, R.N., B.S.N., O.C.N. 485
Folic acid u For Further Information Givan, Alice Longobardi. Flow Cytometry: First Principles. 2d ed. New York: Wiley-Liss, 2001. Langdon, Simon P., ed. Cancer Cell Culture: Methods and Protocols. Totowa, N.J.: Humana Press, 2004. McCarthy, Desmond A., and Marion G. Macey, eds. Cytometric Analysis of Cell Phenotype and Function. New York: Cambridge University Press, 2001. Radbruch, Andreas, ed. Flow Cytometry and Cell Sorting. 2d ed. New York: Springer, 2000.
See also Immunocytochemistry and immunohistochemistry; Myelodysplastic syndromes.
u Folic acid Category: Lifestyle and prevention Also known as: Folate, pteroylglutamic acid Definition: Folate is a water-soluble B vitamin found naturally in foods such as lentils, green leafy vegetables, broccoli, cereals, citrus fruits, and liver. It is an essential cofactor for deoxyribonucleic acid (DNA) synthesis and replication and is necessary for the production of normal red blood cells. Folic acid is the synthetic, oxidized form used in commercial vitamin supplements and food fortification. Cancers treated or prevented: Colorectal cancer, breast cancer Delivery routes: Natural dietary sources, fortified foods, oral supplements How this substance works: Folate is an essential cofactor in the de novo synthesis of purines and thymidylate and therefore plays a role in DNA synthesis, replication, stability, and repair. Evidence suggests that folate deficiency can lead to DNA damage and is associated with macrocytic anemia, neural tube defects, and cancer. In 1998, the U.S. Food and Drug Administration (FDA) began requiring the fortification of all flour and cereal grains with folic acid. These products are thus a major source of folic acid in the U.S. population. Large epidemiological studies that followed subjects for many years have found that higher dietary intake of folate and folic acid supplementation decreased the risk of colon and breast cancer. A possible explanation for its protective effect is that folate prevents DNAdamage that may lead to the development of cancer. Side effects: Research results on the benefits of folate in preventing cancer are inconsistent. Despite population studies showing positive effects of higher folate intake, 486
Salem Health: Cancer studies in animals and humans also have shown that folic acid supplementation increased the risk of breast cancer and the development of colon polyps. These mixed results suggest that folate has a dual role in the development of cancer. In normal tissues, folate appears to suppress the development of cancer, presumably by preventing mutations. Once early lesions or tumors have developed, however, folate appears to promote their progression in colorectal and breast cancers. In these cases, folic acid may provide a source of nucleotides for rapidly proliferating tissues, including tumors. Indeed, antifolate drugs are sometimes used in the treatment of cancer. Thus, the timing, dose, and form of folate appear to be critical in whether this substance prevents or actually promotes certain types of cancers. For these reasons, the National Institutes of Health (NIH) do not currently recommend folic acid supplements to reduce the risk of cancer. Linda Hart, M.S., M.A. See also Anemia; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Antioxidants; Colon polyps; Dietary supplements; Free radicals; Fruits; Mesothelioma; Myelofibrosis.
u Formaldehyde Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1981 Also known as: Formalin, formic aldehyde, methaldehyde, methanol, methyl aldehyde, methylene glycol, methylene oxide Related cancers: Squamous cell carcinomas of the upper respiratory tract Definition: Formaldehyde is a flammable, colorless gas at standard temperature and pressure with a strong, irritating odor. It is highly soluble in water and is most commonly encountered as a 37 percent aqueous solution known as formalin, which usually also contains 10 to 15 percent methanol to prevent formaldehyde polymerization. Because of its simple molecular structure and reactivity, formaldehyde is widely used as a starting material in plastics manufacturing. Because it irreversibly links proteins and nucleic acids to one another, it is useful as a disinfectant and a fixative/ preservative in biomedical applications. Exposure routes: Inhalation Where found: Manufacturing plants, prefabricated dwellings, hospitals, mortuaries, smog
Salem Health: Cancer At risk: Workers involved in tissue fixation and in manufacturing plastics, particleboard, wood paneling, and furniture; occupants of prefabricated dwellings Etiology and symptoms of associated cancers: When formaldehyde reacts with adjacent primary amine groups in proteins or other biomolecules, the resulting covalent bond prevents normal mobility and functioning of the joined molecules. Repeated or sustained exposure to high concentrations (greater than 15 parts per million) of inhaled formaldehyde is sufficient to cause tissue damage, mutations, and increased cell turnover, which can result in malignant transformation. Cells in the upper respiratory tract (the nasopharynx) are especially liable to formalininduced cancers, which take the form of squamous cell carcinomas. Formaldehyde’s carcinogenicity has been demonstrated only in rodents exposed to very high gas concentrations over long periods of time, and extrapolation to human carcinogenicity is speculative. History: Formaldehyde was first described and chemically synthesized in the 1800’s, although it exists in small quantities in the atmosphere naturally and is a product of amino acid metabolism in the body. Its widespread adoption in the chemical industry prompted several large studies to search for diseases associated with exposure. More than thirty epidemiologic studies have addressed formaldehyde carcinogenicity in humans, and no consistent pattern of response has been found. One expert panel concluded that no evidence existed to show a relationship between formaldehyde exposure and human cancer and if a risk did exist, it had to be very small. Because of its many other adverse health effects, formaldehyde is subject to occupational and residential monitoring, with variable exposure limits in different jurisdictions. John B. Welsh, M.D., Ph.D. See also Air pollution; Artificial sweeteners; Astrocytomas; Chewing tobacco; Coke oven emissions; Lung cancers; Mineral oils; Nasal cavity and paranasal sinus cancers; Occupational exposures and cancer; Tobaccorelated cancers.
u Fox Chase Cancer Center Category: Organizations Definition: The Fox Chase Cancer Center is a cancer research facility and treatment hospital in Philadelphia, Pennsylvania. The one-hundred-bed hospital of Fox Chase Cancer Center is one of the few hospitals in the United States devoted solely to cancer care.
Fox Chase Cancer Center History and founding: In 1974 the Fox Chase Cancer Center was formed when the American Oncologic Hospital combined with the Institute for Cancer Research. The American Oncologic Hospital, established in 1904, is notable as the first cancer hospital in the United States. The Institute for Cancer Research, founded in 1927, was established for basic research of normal and abnormal cell growth. The Institute for Cancer Research (ICR), later known as the Fox Chase Cancer Center, contributed significantly to the field of cancer research and treatment. Many important discoveries, including the identification of vitamin B12 by Mary Bennett in 1946, were made in the Fox Chase research laboratories. The Nobel Prize in Physiology and Medicine was awarded to Baruch Blumberg in 1976 for his discovery of the hepatitis B virus (HBV) and development of the HBV vaccine. Considered the first anticancer vaccine, the HBV vaccine has reduced the incidence of liver cancer. Fox Chase Cancer Center established the Partners program in 1986 to unite a group of community hospitals with the center to make the most current cancer treatments available in a wide geographic area. In 1995 Fox Chase Cancer Center was a founding member of the National Comprehensive Cancer Network (NCCN), a program of twenty-one nonprofit academic centers working on cancer research, treatment, and prevention. The Research Institute for Cancer Prevention was opened at Fox Chase in 2000 and includes the Prevention Pavilion of Fox Chase, where individuals have access to prevention-oriented resources. Current facilities: The Fox Chase Cancer Center research facilities and hospital are in the northeast section of Philadelphia. The hospital is one of the few in the United States that is solely devoted to the care of cancer patients. Its Partners program includes a group of community hospitals in Pennsylvania, New Jersey, and Delaware, where patients can receive treatment closer to home yet still have access to the most up-to-date cancer treatment based on the translation of cancer research results. The program also provides access to participation in clinical trials. Other collaborative programs with which Fox Chase is involved are a bone marrow transplantation program with Temple University, the National Comprehensive Cancer Network, and the Oncology Physicians Network (OPN). Fox Chase operates a mobile mammography van as part of its corporate and community outreach program; additional outreach programs provide screening services for other cancers. More than eighty research laboratories are part of Fox Chase. Research programs are structured in three divi487
Fred Hutchinson Cancer Research Center sions: medical science, basic science, and population science. The medical science research programs include breast cancer, developmental therapeutics, ovarian cancer, and prostate cancer. The basic science research programs include biomolecular structure and function, cellular and developmental biology, genome stability, immunobiology, tumor cell biology, and viral pathogenesis. Fox Chase’s population science program studies groups of people with high risk for cancer, works to build approaches for risk reduction, and is involved with cancer prevention trials; the specific research programs include a cancer prevention and control program and a human genetics program. Specialization: Cancer prevention and early detection of cancers are Fox Chase priorities; patient services include the Prostate Risk Assessment Program as well as risk assessment programs for familial melanoma and gastrointestinal tumors. The Internet Risk Assessment Program was developed at Fox Chase to address the need for risk assessment and counseling of family members who are geographically separated. Cancer prevention and screening programs are offered by Fox Chase outreach services at low or no cost to the community. Community partners, such as the Black Women’s Health Alliance and local churches, work with Fox Chase to reach underserved minority populations. The outreach programs at Fox Chase also provide cancer awareness, screening, and education services in corporate settings. Fox Chase provides multidisciplinary treatment centers for adult patients with solid tumors and hematologic malignancies. A multidisciplinary pain management center is located at Fox Chase, and the Lippincott Hospice Program provides home-based care to terminally ill adult cancer patients and their families. An additional area of renown is a Fox Chase collaboration with Temple University Health System, forming the Fox Chase-Temple Bone Marrow Transplant Program. A special clinical studies wing of the hospital has ten patient beds for individuals enrolled in phase I clinical trials, which enroll small numbers of individuals for assessment of the safety of a new drug treatment and the determination of its maximum safe dose and optimal dosing schedule. Fox Chase is known for its oncology nursing and has achieved American Nurse Credentialing Center Magnet status. Vicki Miskovsky, B.S., R.D. u
For Further Information Eyre, Harmon, and Dianne Partie Lange, eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002. 488
Salem Health: Cancer Hoffman, Barbara, ed. A Cancer Survivor’s Almanac: Charting Your Journey. Minneapolis: Chronimed, 1996. Morra, Marion, and Eve Potts. Choices. 4th ed. New York: HarperCollins, 2003. Teeley, Peter, and Philip Bashe. The Complete Revised and Updated Cancer Survival Guide: The Most Comprehensive, Up-to-Date Guide for Patients and Their Families. Rev. ed. New York: Broadway Books, 2005. u
Other Resources
Fox Chase Cancer Center http://www.fccc.edu National Comprehensive Cancer Network Fox Chase Cancer Center http://www.nccn.org/members/profiles/fccc.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Fred Hutchinson Cancer
Research Center Category: Organizations Definition: The Fred Hutchinson Cancer Research Center is a nonprofit biomedical research institution in downtown Seattle, Washington. A partnership of the Hutchinson Center with the University of Washington and Children’s Hospital and Regional Medical Center forms the Seattle Cancer Care Alliance (SCCA), which provides clinical care to adult and pediatric patients. History and founding: William B. Hutchinson, a native of Seattle, attended the University of Washington, where he was captain of the baseball team. Hutchinson was offered a contract with a Class AAA baseball team in California after graduation but chose instead to attend medical school at McGill University in Montreal. After he came back to Seattle in 1940 to practice medicine, he returned to baseball as team physician to the Seattle Rainiers baseball team. His love for baseball and other sports was also mani-
Salem Health: Cancer fest in his work with local youth athletic programs. In 1956 he founded the Pacific Northwest Research Foundation, an institution for research into heart surgery, diseases of the endocrine system, and cancer. Hutchinson’s brother Fred shared his brother’s talent for baseball. He was a major league pitcher for the Detroit Tigers from 1939 through 1953 and later was the team manager for the Tigers, the St. Louis Cardinals, and the Cincinnati Reds. In 1964 Fred Hutchinson was diagnosed with lung cancer, and he died of the illness the same year. In memory of his brother, William B. Hutchinson established the Fred Hutchinson Cancer Research Center (FHCRC) in 1965 as a division of the Pacific Northwest Research Foundation. The FHCRC separated from the Pacific Northwest Research Foundation in 1972, and the independent FHCRC opened its facility in 1975. Current facilities: The Fred Hutchinson Cancer Research Center is one of thirty-nine centers nationwide designated by the National Cancer Institute (NCI) as a comprehensive cancer center. The National Cancer Institute designation is awarded to cancer centers deemed to have earned scientific excellence in cancer research and that provide a full range of cancer diagnostic and treatment services. The Seattle Cancer Care Alliance (SCCA) was formed in 1998 as a partnership of the Fred Hutchinson Cancer Research Center, University of Washington Medicine (made up of the University of Washington School of Medicine, Harborview Medical Center, University of Washington Medical Center, and University of Washington Neighborhood Clinics), and Children’s Hospital and Regional Medical Center. The mission of the Seattle Cancer Care Alliance is to unite research and outstanding patient care to provide state-of-the-art cancer treatment. Another collaboration, formed in 2002, between the Fred Hutchinson Cancer Research Center, the University of Washington, and Children’s Hospital and Regional Medical Center is the Fred Hutchinson/University of Washington Cancer Consortium. The consortium allows participating institutions to combine their expertise to further cancer research with the development of leading research programs spanning many types of cancer. A large faculty of researchers involved in basic, clinical, and public health disciplines contribute efforts in seventeen research programs. The National Cancer Institute designation as a comprehensive cancer center now includes the consortium. The Fred Hutchinson Cancer Center is the only comprehensive cancer center in the Pacific Northwest designated by the National Cancer Institute. The institute contracts with the Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center through the Partnership Program to provide services to the states of Alaska, Idaho, Nevada, Oregon, and Washington, and to operate as one of four contact centers. A contact center serves as a clearinghouse of cancer information for the United States, Puerto Rico, the U.S. Virgin Islands, and the U.S. Associated Pacific Territories. Research: Three Nobel Prize winners in medicine have come from the Fred Hutchinson Cancer Research Center. E. Donnell Thomas received the prize, shared with Joseph E. Murray, in 1990 for research into cell and organ transplantation in treating people. Lee Hartwell received the prize along with R. Timothy Hunt and Paul M. Nurse for research into the key regulators of the cell cycle. Linda B. Beck shared the prize in 2004 with Richard Axel from Columbia University for research into odorant receptors and the organization of the olfactory system. Research at the FHCRC focuses on improving the quality of life for people worldwide through its initiatives in cancer prevention and early detection of cancers and by focusing on new therapies, such as immunotherapy (fighting cancer by using the individual’s own immune system) and organ and cell transplantation, carrying on the research of Nobel Prize winner Thomas. Specialization: Direct patient services offered through the Seattle Cancer Care Alliance (SCCA) include adult and pediatric oncology services using multidisciplinary teams. Some areas of special expertise at the FHCRC include treatment of leukemias (cancers of the blood and the bone marrow, where blood cells are made) and treatment of lymphomas (cancers of the lymph nodes). The FHCRC is known internationally for its early work with bone marrow transplants and performs all types of donor transplants for bone marrow, peripheral blood stem cells, and umbilical cord blood from related and unrelated donors. Vicki Miskovsky, B.S., R.D.
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For Further Information Dollinger, M. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 4th ed. Kansas City, Mo.: Andre McMell, 2002. Eyre, Harmon, and Dianne Partie Lange, eds. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment, and Recovery. 2d ed. Atlanta: American Cancer Society, 2002. Raju, Tonse N. K. The Nobel Chronicles: A Handbook of Nobel Prizes in Physiology or Medicine, 1901-2000. Bloomington, Ind.: AuthorHouse, 2002. 489
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Other Resources
Fred Hutchinson Cancer Research Center http://www.fhcrc.org National Comprehensive Cancer Center Fred Hutchinson Cancer Research Center http://www.nccn.org/members/profiles/ hutchinson.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Free radicals Category: Carcinogens and suspected carcinogens Also known as: Radicals, reactive species Related cancers: Cancers of the skin, airways, gastrointestinal tract, liver, bladder, prostate, and kidney, as well as leukemia and other cancers Definition: Free radicals are molecules with one or more unpaired electrons. Although there are stable radical species, the most common of which is oxygen, the presence of unpaired electrons most frequently confers high reactivity and oxidizing potential to free radicals. The most abundant free radicals in biological systems are molecules in which the unpaired electron belongs to an oxygen atom. They are known as reactive oxygen species and are mainly, but not exclusively, derived from the incomplete reduction of oxygen during mitochondrial respiration, which generates the superoxide anion radical (O2-). Superoxide is converted to hydrogen peroxide (H2O2) in a reaction driven by the enzyme superoxide dismutase. Hydrogen peroxide is converted to water and detoxified by glutathione peroxidase and catalase. Hydrogen peroxide is not a free radical; however, when produced in excess (for example, in leukocytes during the respiratory burst that takes place in inflammatory processes) or when its enzymatic detoxifying mechanisms are deficient, hydrogen peroxide can be converted to hydroxyl radical (OH) in the presence of transition metals such as iron or copper. The hydroxyl radical is the most deleterious of the reactive oxygen species be490
Free radicals. (Custom Medical Stock Photo)
cause it can hydroxylate or abstract an electron from most macromolecules, including enzymes, membrane lipids, and DNA, the latter sometimes resulting in mutagenesis. In addition to reactive oxygen species, another significant free radical in the cell is nitric oxide (NO), which is synthesized from arginine by nitric oxide synthase. Nitric oxide fills essential physiological functions but it can also act as an oxidant. Living organisms have developed enzymatic and nonenzymatic mechanisms to neutralize free radicals. When the generation of free radicals overpowers the capacity of the natural antioxidant defense systems, however, oxidative stress occurs. Signs of oxidative stress have been found in many forms of human cancer. Exposure routes: The pathologically related free radicals originate within the body as a product of normal aerobic metabolic processes and inflammatory reactions, but some environmental agents, such as radiation and pollutants, with diverse routes of exposure, can increase the production of free radicals. Where found: Free-radical-generating agents are diverse, as are their sources. The most common are tobacco smoke,
Salem Health: Cancer sunlight, X rays, and automobile exhausts. Others include the carcinogens benzene, inorganic arsenic compounds, cadmium compounds, aflatoxins, and asbestos. At risk: Populations at highest risk are those with a low dietary intake of antioxidants or genetic deficiencies in antioxidant enzymes (for example, glutathione peroxidase) or deoxyribonucleic acid (DNA) repair mechanisms, along with tobacco smokers, people who spend a long time in areas of heavy traffic or who are directly exposed to sunlight, and those with chronic inflammatory conditions. Etiology and symptoms of associated cancers: The carcinogenic potential of free radicals arises from their ability to damage DNA, modify proteins by oxidation, and induce lipid peroxidation. The most frequently found form of oxidative DNA damage is hydroxylation of purine and pyrimidine bases. Other consequences of free radical actions for DNA are the generation of strand brakes, deamination, and formation of etheno adducts. Oxidative modifications of proteins include nitration, nitrosylation, and acetylation, among others. In addition, one of the most damaging effects of free radicals is lipid peroxidation because of its self-propagating nature, which greatly affects the properties and functioning of cell membranes. Furthermore, lipid peroxidation products, such as the reactive aldehydes malondialdehyde and 4-hydroxynonenal, can damage DNA and proteins in the same way as free radicals. DNA oxidative damage can cause mutations in cancerrelated genes, such as tumor-suppressor genes or oncogenes, and lead to the initiation and progression of cancer. Likewise, carcinogenesis can be induced by posttranslational oxidative modification of proteins involved in the regulation of cell growth, signal transduction pathways, DNA repair, or other mechanisms of cellular homeostasis. For instance, free radicals are known to induce the transcription of the proto-oncogenes FOS (also known as c-fos), JUN (c-jun), and MYC (c-myc), which stimulate cell growth. Also, posttranslational oxidative modifications of TP53 (p53), a tumor-suppressor protein, can inhibit its antiproliferative activity. Lastly, free radicals can promote not only tumor growth but also tumor migration and metastasis, by activating matrix metalloproteinases and stimulating the release of vascular endothelial growth factor. A current view of free radical actions supports the notion that these species do not act in a purely stochastic manner but are second messengers in redox-sensitive mechanisms of regulation of gene expression and enzyme activity. Aberrant and sustained redox signaling in oxidative stress situations leads to pathological changes, including cancer.
Fruits History: The relevance of free radicals in biological systems was first proposed by Denham Harman in 1956 in his classic article “Aging: A Theory Based on Free Radical and Radiation Chemistry.” Harman viewed age-related diseases as the result of an accumulation of oxidative damage. In the same year, in vitro studies showing the ability of oxygen reactive species to induce chromosome fragmentation in the presence of iron suggested for the first time the hypothesis of free-radical-induced carcinogenesis. Since then, the concept has been extended and free radicals have been found to be involved in most pathological conditions. Reyniel Cruz-Aguado, Ph.D. u
For Further Information Halliwell, B. “Oxidative Stress and Cancer: Have We Moved Forward?” Biochemistry Journal 401 (2007): 1-11. Hussain, S. P., L. J. Hofseth, and C. C. Harris. “Radical Causes of Cancer.” Nature Reviews. Cancer 3 (2003): 276-285. Wu, W. S. “The Signaling Mechanism of ROS in Tumor Progression.” Cancer Metastasis Reviews 25 (2006): 695-705.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Antioxidants and Cancer Prevention: Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ antioxidantsprevention See also Antioxidants; Beta-carotene; Bone cancers; Carotenoids; Coenzyme Q10; Curcumin; Diethanolamine (DEA); Fruits; Green tea; Helicobacter pylori; Herbs as antioxidants; Liver cancers; Lutein; Lycopene; Mesothelioma; Nutrition and cancer prevention; Phenolics; Resveratrol; Wine and cancer.
u Fruits Category: Lifestyle and prevention Definition: Botanically, a fruit is defined as the ripened ovary of an angiosperm, or flowering plant. In the human diet, fruit generally refers to sweet and fleshy parts of certain plants. Examples of fruits include cherries, peaches, plums, apples, strawberries, and oranges. 491
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Salem Health: Cancer mation of cancer cells by regulation of communication between cancer cells. Ascorbic acid, or vitamin C, functions in a similar manner and can be found in citrus fruits and strawberries. Folic acid, also found in citrus fruits, is involved in the synthesis, repair, and function of deoxyribonucleic acid (DNA), while dietary fiber encourages peristalsis and, in turn, the elimination of harmful wastes and estrogens.
How fruits help: Overall, the benefits of moderate fruit intake in the diet include cell differentiation (which decreases cell proliferation), antioxidant potential, increase in activity of naturally protective enzymes, lower estrogen levels, and enhanced immune function. Research shows a strong relationship between overall health and fruit consumption. Total cancer risk is often reported to decrease by at least 12 percent in populations that receive adequate amounts of fruit per the dietary guidelines Fruits, like the cherries from which this supplement is made, contain compounds thought to help prevent cancer. (AP/ Wide World Photos) of the U.S. Department of Health and Human Services and the U.S. Department of Agriculture. The correlation is almost certainly stronHow phytochemicals work: Fruits contain many phyger than results indicate, as studies on the relationship betochemicals that are believed to have an inverse relationtween increased fruit intake and reduced cancer rates must ship to cancer incidence or at least act as a protective agent track a healthy person over many years to assess the relaagainst cancer-causing substances in the human body. tionship to subsequent cancer incidence—this involves reSome of these chemicals believed to be active include liance on memory before the cancer diagnosis. Additional allium compounds, carotenoids, coumarins, dietary fiber, studies analyzing the relationship between increased fruit dithiolthiones, flavonoids, folic acid, endole-3-carbinol, in diet and reduction of various cancers have begun. inositol hexaphosphate, isoflavones, isothiocyanates, Dlimonene, phytosterols, protease inhibitors, saponins, seSide effects: Generally no side effects are experienced lenium, and vitamins, especially vitamins C and E. by eating fruit. However, excessive dietary intake of fruit Carotenoids, including alpha- and beta-carotene, lutein, may cause gastrointestinal discomfort in some individand lycopene, are found in yellow and orange vegetables uals and increase the incidence or extent of diarrhea in and fruits and act as antioxidants to maintain the functionothers. ing of the immune system. Antioxidants bind to free radiDwight G. Smith, Ph.D. cals in the human body. Free radicals are unstable molecules that lack a sufficient number of electrons and can See also Antioxidants; Beta-carotene; Bioflavonoids; Cadamage genetic material and proteins. This disrupts cell rotenoids; Chemoprevention; Coenzyme Q10; Dietary supmolecules and chemical processes, making cells more susplements; Fiber; Folic acid; Free radicals; Herbs as antioxceptible to cancer. When the amount and availability of idants; Isoflavones; Lutein; Lycopene; Macrobiotic diet; free radicals in cells and tissues is decreased, the likeliNutrition and cancer prevention; Phytoestrogens; Prevenhood of cells becoming cancerous is similarly decreased. tion; Resveratrol; Saw palmetto; Sun’s soup; Wine and Studies have also suggested that carotenoids stimulate the cancer. manufacture of detoxifying enzymes and inhibit the for-
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u Gallbladder cancer Category: Diseases, symptoms, and conditions Also known as: Gallbladder carcinoma Related conditions: Bile duct cancer (cholangiocarcinoma) Definition: Gallbladder cancer is a rare cancer that starts in the lining of the gallbladder. The gallbladder stores bile, a liquid necessary for the breakdown of fat. The vast majority of gallbladder cancers—more than 80 percent— are of a type known as adenocarcinoma. Other types of gallbladder cancer include squamous cell carcinoma and small-cell carcinoma. Risk factors: Gallbladder cancer occurs more frequently in women than in men (a 4:1 ratio) and usually in people older than age fifty, with most patients in their mid- to late sixties. In the United States, Native Americans and Hispanics are at the highest risk for the disease. Worldwide, high incidence of the disease occurs in Chile, Bolivia, and parts of Asia. Obesity and a sedentary lifestyle have been identified as risk factors for gallbladder cancer. About 80 percent of gallbladder cancer patients have gallstones. However, only 0.5 percent of patients with gallstones will go on to develop gallbladder cancer. Cysts in the bile ducts also raise the risk of gallbladder cancer. Calcification (hardening) in parts of the gallbladder increases the risk of gallbladder cancer. People with calcifications throughout the entire gallbladder wall have no higher risk than the general population. Etiology and the disease process: There is strong circumstantial evidence that gallbladder cancer results from constant inflammation of the gallbladder. Gallstone disease causes repeated irritation and inflammation of the gallbladder. Most patients with gallbladder cancer have gallstones in addition to their cancer. Patients with large gallstones (greater than 3 centimeters, or cm) are at ten times the risk for developing gallbladder cancer. Also supporting the inflammation theory is the fact that repeated infections in the gallbladder seem to increase a person’s risk of this cancer. Gallbladder cancer spreads through the lymph nodes and lymph vessels as well as the blood vessels. Lymph vessels, which extend into every organ in the body, collect abnormal or foreign cells into the lymph nodes. This is why gallbladder cancer surgery often includes removal of the lymph nodes in the area of the gallbladder, liver, and pancreas. Another route through which the cancer spreads is directly into the liver. Because there is no separation be-
Gallbladder cancer tween the gallbladder and liver tissues, a gallbladder tumor can directly enter the liver. Incidence: The disease is rare. There are approximately 7,000 new cases of gallbladder cancer each year in the United States. According to the American Cancer Society, the incidence of the disease decreased by 50 percent between 1973 and 2007. On average, there are 2.5 cases of the disease for every 100,000 people in the United States. Symptoms: Unfortunately, symptoms of gallbladder cancer do not appear until the disease is advanced. When they do appear, they are not specific and are often identical to symptoms of other (benign) gallbladder or liver problems. Symptoms of gallbladder cancer may include the following: • Enlarged liver • Fever • Jaundice (yellowing of the skin and whites of the eyes) • Loss of appetite • Nausea or vomiting • Pain in the upper right part of the abdomen • Severe itching • Swelling of the stomach due to fluid accumulation (ascites) • Weight loss Screening and diagnosis: There is no test to screen for gallbladder cancer. Because the symptoms are often the same as for other liver or biliary diseases, unless doctors find the cancer during surgery to remove gallstones, diagnosis is usually delayed until the cancer is advanced and symptoms appear. Tests for suspected gallbladder cancer include the following: • A complete physical examination • Liver function tests • Cancer antigen (CA) 19-9 assay (while this test identifies a marker that is not specific for gallbladder cancer, it may focus suspicion in combination with other test results) • Endoscopic retrograde cholangiopancreatography (ERCP), an X ray of the bile ducts that uses a lighted tube (endoscope) passed from the mouth to the small intestine; a smaller tube inside the endoscope delivers a special dye into the bile ducts, and X rays of the dye can help diagnose blockage or narrowing of the ducts • Blood tests, which may show abnormal amounts of certain chemicals in the blood • Percutaneous transhepatic cholangiography (PTHC), an X ray of the liver and bile ducts during which a special dye is injected into the liver and X rays follow the dye 493
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through the bile ducts; PTHC helps diagnose blockage or narrowing of the bile ducts • Biopsy, the examination of a tissue sample under a microscope • Computed tomography (CT) scan and magnetic resonance imaging (MRI), usually the best diagnostic tools to verify gallbladder cancer In the United States, staging of gallbladder cancer is done according to the criteria of the American Joint Commission on Cancer (AJCC). These criteria use the TNM (tumor/lymph nodes/metastasis) staging system, which looks at the tumor location, whether the cancer has invaded any near or distant lymph nodes, and whether the cancer has spread (metastasized) to other parts of the body. The TNM system for gallbladder cancer is as follows: • TX: Primary tumor cannot be evaluated. • T0: No evidence of primary tumor is found. • Tis: The cancer is limited to the innermost layer of the gallbladder (mucosa). • T1a: The tumor invades the lamina propria (the layer next to the mucosa). • T1b: The tumor invades the muscle layer (the next layer). • T2: The tumor invades the layer surrounding the muscle; it does not extend beyond the outer covering of the gallbladder (serosa) or into the liver. • T3: The tumor goes through the serosa or into the liver or one other organ, such as the stomach, small intestine, or pancreas. • T4: The tumor invades the main portal vein (connecting the digestive tract to the liver) or hepatic artery, or invades multiple organs outside the liver. • NX: Regional lymph nodes cannot be assessed. • N0: No regional lymph node spread is found. • N1: Regional lymph node spread is found. • MX: Distant metastasis cannot be assessed. • M0: No distant metastasis is found. • M1: Distant metastasis is found. Staging is as follows: • Stage 0: Tis, N0, M0 • Stage IA: T1, N0, M0 • Stage IB: T2, N0, M0 • Stage IIA: T3, N0, M0 • Stage IIB: T1, N1, M0; T2, N1, M0; or T3, N1, M0 • Stage III: T4, any N, M0 • Stage IV: Any T, any N, M1
There are several types of gallbladder removal surgery (cholecystectomy): • Simple cholecystectomy: Removal of the gallbladder alone • Extended cholecystectomy: Removal of the gallbladder, a small area of the liver right next to the gallbladder, and area lymph nodes • Radical cholecystectomy: Removal of the gallbladder, a wedge-shaped part of the liver, the common bile duct, tissues between the liver and the small intestine, and the lymph nodes along the path between the liver and the small intestine The type of surgery a patient will have depends on how the cancer was found and how advanced it is. When surgery is not a treatment option, palliative surgery may help relieve symptoms. Palliative surgery is not intended to treat or control the disease. Follow-up radiation after surgery helps prolong survival in some patients. Chemotherapy may be added to surgery and radiation. Two chemotherapy drugs that show some success in treating gallbladder cancer are 5-fluorouracil (5-FU) and gemcitabine. Radiation and chemotherapy (alone or in combination) can also be used before surgery to try to shrink a large tumor. When surgery is no longer an option, patients should consider enrolling in clinical trials of new treatments.
Treatment and therapy: Currently, the only realistic treatment option is surgery. Removal of the gallbladder can cure patients with Stage 0 or I cancer, and the cure rate is 80 to 100 percent.
Prognosis, prevention, and outcomes: Because the disease is often diagnosed at an advanced stage, the prognosis is usually poor. The median survival time from diagnosis is less than six months. The five-year survival rate is 5 per-
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Stage at Diagnosis and Five-Year Relative Survival Rates for Gallbladder Cancer, 1988-2001 Stage a
Localized Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
21.5 39.9 35.9 2.7
41.7 13.6 1.2 13.1
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
Salem Health: Cancer cent. However, the prognosis depends on the stage of the cancer at diagnosis. When diagnosed early (usually during surgery to remove gallstones), patients can be completely cured. Lifestyle modifications, such as weight loss and an exercise program, may help prevent gallbladder cancer. Adi Ferrara, B.S. u For Further Information Icon Health. Gallbladder Cancer: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. Sarg, M. J., and A. D. Gross. The Cancer Dictionary. 3d ed. New York: Facts On File, 2006. u
Other Resources
American Cancer Society Detailed Guide: Gallbladder Cancer Http://www.cancer.org/docroot/CRI/CRI_2_3x .asp?rnav=cridg&dt=68 Clinical Trials Registry http://clinicaltrials.gov/ National Cancer Institute Gallbladder Cancer http://www.cancer.gov/cancertopics/types/ gallbladder/ See also Bile duct cancer; CA 19-9 test; Cholecystectomy; Endoscopic retrograde cholangiopancreatography (ERCP); Endoscopy; Gastrointestinal cancers; Hepatic arterial infusion (HAI); Laparoscopy and laparoscopic surgery; Nuclear medicine scan; Obesity-associated cancers; Pancreatitis; Percutaneous transhepatic cholangiography (PTHC); Ultrasound tests.
u Gallium scan Category: Procedures Also known as: Nuclear medicine scan, radioisotope scan Definition: A gallium scan is a nuclear medicine imaging study that evaluates specific tissues based upon their uptake of an administered radioactive isotope. During a gallium scan, the tracer (gallium 67 citrate) is injected into a vein. It travels through the bloodstream into
Gallium scan the tissues—primarily the bones, liver, and intestines. It usually takes a few days for the tracer to accumulate in the tissues, so in most cases a scan is done two days after an injection of the tracer and repeated at three days. Areas of increased tracer uptake show up as bright, or “hot,” spots on an X ray. Delineated problem areas may be caused by infection, inflammation, or tumor (rapid cell division). The gallium scan was the standard for cancer diagnosis and staging until it was replaced by positron emission tomography (PET) scans. Gallium 67 is often used in conjunction with a bone scan (using technetium 99m phosphate) as “a double tracer” technique to overlay areas of inflammation within organ systems. Gallium is less dependent on blood flow than technetium and may identify foci that would otherwise be missed. Cancers diagnosed: Major cancers such as lymphoma, malignant bone tumors, and soft-tissue sarcomas; can be used to identify most neoplasms, whether benign or malignant Why performed: A gallium scan is performed to detect the presence of cancerous tissue. It may be employed to determine whether a cancer has spread (metastasized) to other parts of the body or to monitor the effectiveness of cancer treatment. It can also be used to diagnose inflammatory conditions such as pulmonary fibrosis or sarcoidosis; to monitor the response to antibiotic treatment; to detect an abscess or certain infections, especially in the bones; and to detect an unknown source of infection that is causing a fever. Patient preparation: Gallium accumulates in the large intestine (colon) before being eliminated in the stool. Patients may need to take a laxative the night before the scan and have an enema one to two hours prior to the scan to prevent gallium in the colon from interfering with pictures being taken of the area. The doctor and radiologist should also be informed of possible pregnancy, breast-feeding activity, and the use of a barium enema within the previous four days or medicine (such as Pepto-Bismol) that contains bismuth, as barium and bismuth can interfere with the test results. Steps of the procedure: A gallium scan is performed by a nuclear medicine technologist. The scan pictures are interpreted by a radiologist or nuclear medicine specialist. The arm is cleaned with soap, betadine, and/or alcohol around the injection site. A small amount of the radioactive chemical is then injected through a vein. After administration of the tracer, the patient is brought back to the radiology facility and scans are completed at forty-eight hours and repeated at seventy-two hours. 495
Gallium scan
Salem Health: Cancer The protocol for scanning requires the removal of all jewelry. Most clothes are removed, and the patient is provided with a cloth gown or paper covering. The patient lies in a supine position (on the back) upon a table. A large scanning (gamma) camera will be positioned closely above the patient. After the initial injection, the camera will scan for radiation released by the tracer and produce pictures of the tracer in the tissues. These images serve as a baseline to compare subsequent scan data completed in the next two to three days. The camera will move slowly above and around the body. The camera does not produce any radiation, so the patient is not exposed to any additional source of radioactive material. Different positioning may be attempted so that an area of interest can be viewed from different angles. Restricted movement is necessary during each scan to avoid blurring of the acquired images. Often, the patient will be asked to hold his or her breath briefly during some of the scans to minimize chest movement that occurs with respiration. Each scan can take approximately sixty to ninety minutes. After the procedure: A gallium scan is painless. There are no activity restrictions postscan. Risks: There is a risk of damage to cells and tissues exposed to any level of radiation, including the low level of radiation released by a radioactive tracer such as gallium. Allergic reactions to radioactive tracers are rare. Most of the tracer will be eliminated from the body (in the urine or stool) within four days. Occasionally, some soreness or swelling can develop at the injection site. These symptoms can be relieved by applying moist, warm compresses to the affected area. Results: A gallium scan utilizes a special radiographic camera to obtain pictures of certain tissues in the body after a radioisotope makes them visible. The results of the scan are available within forty-eight hours after the scans are completed. The entire process takes approximately five days. John L. Zeller, M.D., Ph.D. u
Full-body gallium scan showing cancer that has spread from the lungs to the rib and vertebra. (Scott Camazine/Photo Researchers, Inc.)
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For Further Information Hussain, R., D. Christie, V. Gebski, et al. “The Role of the Gallium Scan in Primary Extranodal Lymphoma.” Journal of Nuclear Medicine 39, no. 1 (1998): 95-98. Maderazo, E., N. Hickingbotham, C. Woronick, et al. “The Influence of Various Factors on the Accuracy of Gallium-67 Imaging for Occult Infection.” Journal of Nuclear Medicine 29, no. 5 (1988): 608-615. Mettler, Fred A., Jr., and Milton J. Guiberteau. Essentials
Salem Health: Cancer
Gamma Knife
of Nuclear Medicine Imaging. 5th ed. Philadelphia: Saunders/Elsevier, 2006. Ziessman, Harvey A., Janis P. O’Malley, and James H. Thrall. Nuclear Medicine: The Requisites. 3d ed. Philadelphia: Mosby Elsevier, 2006. u
Other Resources
American College of Radiology http://www.acr.org Society of Nuclear Medicine http://www.snm.org See also Burkitt lymphoma; Imaging tests; Nuclear medicine scan; Radionuclide scan.
u Gamma Knife Category: Procedures Also known as: Radiosurgery, stereotactic radiosurgery (SRS), stereotactic radiotherapy Definition: The Gamma Knife, not actually a knife, is a large precision system that delivers 201 intensely focused gamma-radiation beams to treat tumors and other problems of the brain and nervous system. It resembles a computed tomography (CT) scanner. Gamma Knife technology was developed by Lars Leskell (1907-1986), a Swedish neurosurgeon.
A nurse explains how the Gamma Knife works. (AP/Wide World Photos)
Cancers treated: Cancerous tumors that originate elsewhere in the body but have spread to the brain Why performed: Gamma Knife “surgery” is a noninvasive alternative to traditional open-brain surgery. The precisely focused radiation beams of the Gamma Knife allow surgeons to treat very small, deep-seated tumors without damaging nearby brain tissue. Patient preparation: Patients should not eat or drink anything after midnight the night before the procedure. They should inform their doctor if they are taking medication to control diabetes, are allergic to shellfish or iodine, or have implanted medical devices in the body. Patients must remove glasses, contact lenses, jewelry, makeup, nail polish, wigs, and dentures. Steps of the procedure: Surgeons apply a local anesthetic and use four screws to attach a lightweight frame to the patient’s head. The frame prevents the head from moving and allows surgeons to identify the treatment target accurately.
With the head frame in place, surgeons take electronic images of the brain to establish the exact size, shape, and location of the target. From the images, surgeons develop a specific treatment plan. For the treatment, the patient lies on a couch. A helmet is attached to the head frame. The couch slides into the Gamma Knife unit, where radiation destroys the tumor. The patient is awake during the procedure, which lasts from a few minutes to more than an hour, depending on the size and location of the tumor. After the procedure: When the treatment is completed, the head frame is removed. In most cases, the patient goes home the same day and returns to a normal routine in a day or two. Risks: Because surgeons make no incisions, the risk of complications from use of the Gamma Knife is low. Some patients feel minor soreness from the head frame. Some patients experience mild headache, dizziness, or nausea, which last only a short while. 497
Gardner syndrome The dose of radiation outside the target is very low and poses little risk. Occasionally, patients experience swelling in the brain, which is temporary and treatable. Results: The effects of radiation treatments take time: weeks, months, or even years. Wendell Anderson, B.A. See also Acoustic neuromas; Astrocytomas; Cobalt 60 radiation; Meningiomas.
u Gardner syndrome Category: Diseases, symptoms, and conditions Also known as: Gardner’s syndrome, familial adenomatous polyposis, familial polyposis coli, hereditary adenomatosis of the colon and rectum, bone tumor-epidermoid cyst-polyposis Related conditions: Colon and rectal polyps, cancer Definition: Gardner syndrome is a rare, genetically linked disorder that is classified as a variant form of familial adenomatous polyposis (FAP), a group of disorders most commonly identified by the growth of numerous polyps in the large intestine or colon. In Gardner syndrome, large amounts of benign tissue form in multiple organs. As with FAP, this includes colon polyps as well as skull tumors, cysts and fibrous tumors in the skin, extra teeth, and a congenital eye condition. Gardner syndrome significantly increases an affected person’s risk of developing colorectal cancer, small bowel cancer, pancreatic cancer, and papillary thyroid cancer. Early diagnosis of the disorder is essential as colon polyps resulting from Gardner syndrome have a 100 percent chance of becoming cancerous. Risk factors: Gardner syndrome is genetically linked, meaning that it is associated with a defect, or mutation, in one or more genes. A person with family members with the disease or with the defective gene is at high risk of developing this disorder. It is estimated that 20 percent of patients do not have a family history of Gardner syndrome or FAP, which indicates a spontaneous mutation of the gene. Etiology and the disease process: Normally, during conception, the body receives two copies of every gene, one each from the mother and the father. It takes only one copy of a defective gene, from either the mother or father, for a person to be affected by Gardner syndrome. This disease is caused by a mutation in the gene called APC (adenomatous polyposis coli). The defective APC gene initiates changes 498
Salem Health: Cancer in at least three other genes, causing what is known as the adenoma-to-carcinoma sequence, which allows cells in the colon to increase in number and causes the lining of the colon to thicken. Most people who receive this defective gene develop the disease. Although the way Gardner syndrome develops varies from person to person, it always presents a high risk of developing polyps, tumors, and cancer, especially in the colon. Other physical changes that occur (with their percentage of risk when known) include congenital hypertrophy of the retinal pigmented epithelium (55 to 88 percent), epidermoid cysts (53 percent), stomach and small intestine polyps (90 percent), thyroid cancer, desmoids (10 to 35 percent), dental abnormalities (70 percent), hepatoblastoma, and bone tumors. Incidence: Gardner syndrome is considered to be rare, with only 1 case per 1 million people, whereas the incidence of FAP is 1 case per 8,000 people. An increased risk for the development of thyroid cancer and desmoid tumors has been noted in women with Gardner syndrome. Most patients with Gardner syndrome have already been diagnosed with polyps when they reach puberty. From 80 to 90 percent of polyps are located in the left colon, including the splenic flexure and descending, sigmoid, and rectosigmoid colons. Cancers typically develop between ages twenty and thirty but can occur at any age. Symptoms: The patient with Gardner syndrome may experience a wide variety of symptoms, depending on the body systems affected. The most common are gastrointestinal symptoms and include rectal bleeding, pain, diarrhea or constipation, nausea, and vomiting. Multiple cysts may be found on the patient’s body, particularly on the face, scalp, and extremities. They usually cause no symptoms but may become itchy or inflamed. Screening and diagnosis: When a person has a family history of Gardner syndrome, blood tests can be performed for deoxyribonucleic acid (DNA) analysis and to look for mutations in the APC gene. A positive test result for an APC mutation is sufficient for diagnosis. Laboratory testing to determine the extent of the disease includes stools for occult blood, thyroid function studies, and liver function tests as well as basic chemistries, blood counts, and electrolyte levels. Imaging studies include upper and lower gastrointestinal series, esophagogastroduodenoscopy, colonoscopy, computed tomography (CT) scanning, magnetic resonance imaging (MRI), and ultrasonography to screen for polyps and tumors, as well as skull, facial, and dental X rays to evaluate oral abnormalities and screen for tumors. Most testing procedures should be performed on an annual basis after initial diagnosis.
Salem Health: Cancer Treatment and therapy: Extensive surgery is indicated when colon polyps are identified in a patient with Gardner syndrome because of the risk of colon cancer. Osteomas of the skull and dental abnormalities should be removed if they interfere with normal function or are deforming. Cysts on the skin may require removal if they are producing symptoms or are disfiguring. The necessity of surgery to remove other tumors is evaluated based on their location, type of tumor, patient’s surgical risk, and potential risks of not removing them. Chemotherapy, using doxorubicin with dacarbazine or high-dose tamoxifen, has been shown to reduce polyps following colon surgery. Treatment with sulindac, a nonsteroidal anti-inflammatory drug, is recommended for every patient following a total colectomy; oral calcium has been shown to reduce the colon cancer risk; and sulindac, tamoxifen, or a combination of both is recommended for other manifestations of the disease. Research into other treatments, including gene therapy, is ongoing. Prognosis, prevention, and outcomes: The five-year survival rate for patients older than forty-five who do not have surgery to remove the colon is 0 percent; with surgery, it is nearly 100 percent. The recurrence rate after surgery ranges from 30 percent in twenty years to 45 percent in thirty years. There is no prevention for Gardner syndrome. Dorothy P. Terry, R.N.
Garlic and allicin
u Garlic and allicin Category: Lifestyle and prevention Also known as: Allium sativum Definition: Garlic (Allium sativum) is a nontoxic plant bulb in the Allium genus, which includes onions, leeks, and shallots. Allicin, a chemical created by enzymes when garlic is processed, produces garlic’s odor and taste. Cancers treated or prevented: Gastric (stomach) cancer, colon cancer, breast cancer, prostate cancer, throat cancer Delivery routes: Oral ingestion by pill or in food How this compound works: Historically, humans have consumed garlic for medicinal purposes to soothe digestive and circulatory problems. Aware of nutritional strategies to prevent and control diseases, scientists initiated cancer research exploring garlic and its allyl sulfur components in the mid-twentieth century. Researchers identified allicin as garlic’s most significant chemical that could fight cancer. Allicin is created as the enzyme alliinase reacts with alliin when garlic bulbs are sliced or crushed. Scientists hypothesized that biochemical processes in garlic which boost distribution of antioxidants might prevent cancerous cells from forming and increasing. Studies regarding use of garlic and allicin for cancer prevention and treatment have given rise to both skepti-
u For Further Information Butler, Jonathan, et al. “Gardner Syndrome: Review and Report of a Case.” Oral Oncology Extra 5, no. 41 (May, 2005): 89-92. Hansmann, A., et al. “High-Dose Tamoxifen and Sulindac as First-Line Treatment for Desmoid Tumors.” Cancer 100, no. 3 (February 1, 2004): 612-620. Pomery, Chris. DNA and Family History. Toronto, Ont.: Dundurn Press Limited, 2004. u
Other Resources
MedicineNet.com Gardner Syndrome http://www.medicinenet.com/gardner_syndrome/ article.htm National Cancer Institute http://www.cancer.gov See also Bone cancers; Colon polyps; Desmoid tumors; Fibrosarcomas, soft-tissue; Hereditary polyposis syndromes; Sarcomas, soft-tissue; Thyroid cancer; Turcot syndrome.
Garlic has been studied for cancer prevention and treatment. (Object Gear)
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Gastric polyps cism and optimism. In 1990, the National Cancer Institute (NCI) studied the potential use of allium vegetables, including garlic, for stomach cancer. That year, researchers attended the First World Congress on the Health Significance of Garlic in Washington, D.C. Despite some scientists’ suggestion that garlic and its allyl sulfur components could prevent or inhibit malignancies, experts emphasized that garlic’s anticancer effectiveness had not been scientifically proven. By the early twenty-first century, international researchers had published several thousand scientific journal articles discussing allium plants. Studies focused on garlic’s effect on gastric, colon, breast, prostate, and throat cancers. Investigators achieved promising laboratory results regarding allicin use in mice. At the Weizmann Institute of Science at Rehovot, Israel, scientists delivered alliinase and alliin to malignant tumors, where they produced allicin that entered and destroyed those cells. When researchers combined allicin with rituximab, an anticancer drug, they found that this mixture killed 95 percent of cancerous cells in mice. In October, 2006, the University of California, Berkeley Wellness Letter noted that the cancer-fighting properties of garlic and allicin remained uncertain because tests had been limited to animal subjects and cell cultures and were inconclusive. That newsletter discounted previous studies as presenting minimal evidence, stressing that clinical scientific trials using humans were necessary to declare definitively anticancer properties expressed by garlic and allicin. Although garlic and allicin have not been scientifically shown to cure cancer in humans, they contribute to healthy diets. People with cancer often consume garlic to strengthen their immune systems and receive other health benefits relevant to cholesterol and heart concerns. Garlic can be consumed raw, cooked, or in synthetic formats, providing people varying amounts and versions of allyl sulfur compounds. Side effects: Garlic, when ingested regularly as part of diet, may cause halitosis and body odors. These effects are mitigated by taking it in pill form. Some people develop gas, bloating, diarrhea, or heartburn when taking garlic, which can be mitigated by taking enteric-coated supplements. Finally, because garlic and allicin can increase prothrombin time (PT), a measure of how long it takes for blood to form clots, people taking blood thinners such as warfarin (Coumadin) and anyone about to undergo surgery should consult their physicians before taking these substances. Elizabeth D. Schafer, Ph.D. See also Fruits; Herbs as antioxidants; Nutrition and cancer prevention; Phytoestrogens; Prevention. 500
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u Gastric polyps Category: Diseases, symptoms, and conditions Also known as: Stomach polyps Related conditions: Gastritis, familial adenomatous polyposis, Peutz-Jeghers syndrome, gastric carcinoid tumors Definition: Gastric polyps are small tissue growths on the lining of the stomach. Risk factors: Risk factors for gastric polyps are chronic inflammation and the long-term use of proton pump inhibitors. Etiology and the disease process: The cause of gastric polyps is not completely understood. Hyperplastic polyps are thought to arise from irritation or chronic inflammation of the stomach lining. The nature of the causative agent has not been clearly established; suggested irritants include coffee, tea, and gastric acid. Long-term use of proton pump inhibitors is associated with development of hyperplastic and carcinoid polyps; this may be related to the decrease in stomach acid, which in turn causes an in-
Stomach cancer often develops near the bottom and top of the stomach. Some types of gastric polyps have the potential to become cancerous. (Kairos, Latin Stock/Photo Researchers, Inc.)
Salem Health: Cancer
Gastrinomas
crease in gastrin, a hormone that supports cell growth. Familial cancer syndromes such as familial adenomatous polyposis and Peutz-Jeghers syndrome have been linked with gastric polyps, suggesting that genetic mutations have a role in polyp formation.
u Gastrinomas
Incidence: The largest endoscopic study, of almost 13,000 patients during a four-year period, showed that gastric polyps were found in 157 patients (1.2 percent). About 66 percent of the gastric polyps were in patients over age sixty. The gastric polyps were hyperplastic (75.6 percent), inflammatory (17.8 percent), and adenomatous (6.6 percent). No correlation with stomach cancer and no gender preponderance were found with gastric polyps.
Related conditions: Peptic ulcers, gastroesophageal reflux disease (GERD), multiple endocrine neoplasia type 1 (MEN 1), liver cancer
Symptoms: Patients usually have no symptoms. However, if they are symptomatic, they may develop bleeding from the stomach or obstruction (blockage of the digestive tract). Screening and diagnosis: Most gastric polyps are discovered and diagnosed incidentally when endoscopy of the stomach is performed for an unrelated reason. Upper endoscopy is a procedure using an endoscope, a flexible tube with a small camera and an instrument for biopsy that is introduced through the upper digestive tract; it allows visual examination of the esophagus, stomach, and upper duodenum, the first part of the small intestine. No staging is applicable for gastric polyps. Treatment and therapy: Gastric polyps can be removed during endoscopy and examined in the laboratory. Multiple polyps may require removal of the largest polyp and sampling from the remaining polyps; there is no need to remove all polyps. Treatment will be based on the nature of these polyps. Prognosis, prevention, and outcomes: The majority of gastric polyps are benign. Hyperplastic polyps are also generally benign. The polyps associated with familial adenomatous polyposis and Peutz-Jeghers syndrome can become adenomatous in nature. Adenomatous polyps have an increased risk for cancer transformation; therefore, regular surveillance with upper endoscopy is warranted for these familial conditions. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. See also Achlorhydria; Adenocarcinomas; Adenomatous polyps; Barium swallow; Gastrinomas; Gastrointestinal cancers; Gastrointestinal oncology; Gastrointestinal stromal tumors (GISTs); Helicobacter pylori; Krukenberg tumors; Small intestine cancer; Stomach cancers.
Category: Diseases, symptoms, and conditions Also known as: Gastrin-secreting tumors, ZollingerEllison syndrome, nonislet cell pancreatic cancer
Definition: Gastrinomas are slow-growing tumors that secrete large quantities of the peptide hormone gastrin. Gastrinomas most often arise in the wall of the duodenum, the pancreas, or the pancreatic lymph nodes. Risk factors: Gastrinomas arise spontaneously or in association with the rare genetic disorder multiple endocrine neoplasia type 1 (MEN 1). Men have double the risk of developing gastrinoma relative to women. Approximately 60 percent of all MEN 1 patients will develop pancreatic gastrinomas. Etiology and the disease process: The large amount of gastrin produced by gastrinomas causes the stomach to produce massive quantities of acid. The acid causes ulcers to form in the stomach and duodenum and can irritate and inflame the esophagus. The acid also produces water and ion imbalances in the small intestine, resulting in diarrhea. More than 50 percent of gastrinomas are malignant, usually metastasizing to nearby lymph nodes and the liver. Incidence: Gastrinomas are exceedingly rare tumors, occurring in 1 to 3 people per million. Gastrinomas are usually diagnosed when people are in their forties but can occur at any age. Symptoms: The most common symptom of gastrinoma is persistent upper abdominal pain due to severe or recurring ulcers. Chronic diarrhea is the second most frequent symptom, followed by heartburn. Other symptoms include nausea, vomiting, weight loss, and ulcer-related gastrointestinal bleeding. Screening and diagnosis: Initial diagnosis is made by measuring gastrin levels in the blood and acid output by the stomach after an overnight fast. Elevated levels of both are a presumptive diagnosis of gastrinoma. Somatostatin receptor scintigraphy is the preferred imaging technology to locate the tumor and check for metastasis. Treatment and therapy: Treatment of gastrinoma involves controlling acid production and surgical removal of tumors. Proton pump inhibitor medications are the most potent agents to block acid secretion. Chemotherapy with streptomycin, 5-fluorouracil, and doxorubicin can shrink 501
Gastrointestinal cancers tumors and control metastasis-associated symptoms but does not prolong survival time. Prognosis, prevention, and outcomes: The five-year survival rate for patients with isolated, operable tumors is 86 percent, and surgery is curative in 20 to 30 percent of cases. For patients with liver metastasis or numerous, diffuse tumors, the five-year survival rate is 20 percent. Tumors that have spread to the liver are usually inoperable and are the main cause of death in gastrinoma patients. Tumor recurrence is monitored by regular screening of fasting gastrin levels. Lifelong treatment with medications to control acid production is often necessary. Pamela S. Cooper, Ph.D. See also Cyclin-dependent kinase inhibitor-2A(CDKN2A); Endocrinology oncology; Gastrointestinal cancers; Islet cell tumors; Liver cancers; Multiple endocrine neoplasia type 1 (MEN 1); Neuroendocrine tumors; Pancreatic cancers; Small intestine cancer; Stomach cancers; ZollingerEllison syndrome.
Salem Health: Cancer Exposure to rubber, leather, or certain dyes increases the risk of esophageal cancer, while industrial dusts and fumes increase the risk for gastric cancer. Exposure to nitrosamine is a factor for cancer of the small intestine. A family history of polyps increases risk for gastric cancer. A history of some types of polyps; ulcerative colitis; cancer of the breast, ovary, or uterus; and cancer among firstdegree relatives are risk factors for colon cancer. Diet is a greater risk factor for gastric cancer in Japan, Korea, parts of Eastern Europe, and Latin America than in the United States, possibly because of diets high in dried, smoked, salted, and pickled foods. Diets high in fat and low in fruits, vegetables, and other high-fiber foods are risk factors for colorectal cancer. Although cancer of the small intestine is unusual, certain inherited disorders may be risk factors. A history of genital warts, fistulas, fissures, genital herpes, gonorrhea, radiation dermatitis, homosexuality, symptomatic human immunodeficiency virus (HIV) disease, hemorrhoids, or anal degenerative skin changes increases the risk of anal cancer.
Definition: Gastrointestinal cancers are malignant tumors in the various organs of the gastrointestinal tract—the esophagus, stomach, colon, small intestine, rectum, and anus—formed when normal cells enlarge and divide abnormally.
Etiology and the disease process: Although the causes of many gastrointestinal cancers are unknown, for some of these cancers, causative agents or factors have been found. Alcohol and tobacco abuse appear to be causes of esophageal cancer in North America; in other parts of the world, exposure to environmental carcinogens and diets deficient in riboflavin, magnesium, nicotinic acid, and zinc are causative factors. Chewing betel nuts and smoking bidi are major factors in India. The exact cause of stomach cancer is unknown, but carcinogens, notably nitrites found in smoked foods or used as preservatives, are suspect. Risk factors for colorectal cancer are diets high in saturated fat and low in fiber and calcium, a lack of exercise, and parasitic infestation of Schistosomiasis japonicum. Cancer of the small intestine is rare, and its causes are unknown. The primary cause of anal cancer is chronic irritation.
Risk factors: Major risk factors for developing gastrointestinal cancers are age, gender, race, tobacco use, exposure to carcinogens, family history, and diet. Esophageal cancer and cancer of the small intestine usually appear after a person reaches the age of sixty; stomach, over fiftyfive; colorectal, over fifty; and anal, over forty. Four times as many men as women develop esophageal cancer, and twice as many men as women get stomach cancer. More women are likely to have anal cancer of the inner part of the anus, while more men have outer involvement. African Americans are more likely to have gastric cancer than white Americans. Tobacco use may put people at risk for esophageal and gastric cancer.
Incidence: Incidence rates vary by the affected digestive tract organ. Esophageal cancer occurs much more often in China, Singapore, Iran, Puerto Rico, Switzerland, and France than in North America. In the United States, three times as many men as women are stricken, and blacks outnumber whites 3.5 to 1. Stomach and colorectral cancer is most common in industrialized countries with high living standards; colorectal cancer is uncommon in Asian and Third World countries. Environmental and dietary factors in westernized countries probably account for the higher incidence. Cancer of the small intestine is almost twice as common in men as in women, and blacks are almost twice as likely to have it as whites. It is rare among American In-
u Gastrointestinal cancers Category: Diseases, symptoms, and conditions Also known as: Abdominal and intestinal neoplasms Related conditions: Cancer of the gallbladder and bile duct, pancreas, and liver; a Helicobacter pylori infection; pernicious anemia; acid reflux disease; gastric polyps; familial polyposis; ulcerative colitis; Crohn disease
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Gastrointestinal cancers
Estimated New Cases and Deaths from Gastrointestinal Cancers in 2008 Cancer Esophagus Stomach Colon and rectum Small intestine Anus
Newly Diagnosed Cases
Deaths
16,470 21,500 148,810 6,110 5,070
14,280 10,880 49,960 1,100 680
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008
dians and native Alaskans, and relatively rare among Hispanics and Asians and Pacific Islanders. Anal cancer accounts for only 1 percent or 2 percent of gastrointestinal cancers worldwide. Symptoms: Symptoms vary depending on the part of the gastrointestinal tract that is affected. Esophageal cancer is marked by difficulty in swallowing; a feeling of fullness, pressure, or burning as food passes down the tract; indigestion; heartburn; vomiting; choking on food; weight loss; coughing and hoarseness; and pain behind the breastbone or in the throat. Stomach cancer may present no symptoms in the early stages; later, they are often vague and include indigestion or heartburn; abdominal pain or discomfort; nausea and vomiting; diarrhea or constipation; bloating after meals; loss of appetite; weakness and fatigue; and vomiting of blood or bloody stools. Colorectal cancer symptoms result from local obstruction or, in more advanced stages, from extension to adjacent organs. In early stages, symptoms are usually vague and vary according to the location of the tumor. In later stages, symptoms include pallor, cachexia, ascites, enlarged liver, and dilatation of lymphatic vessels. About 10 percent of people with cancer of the small intestine experience no symptoms, but most patients have abdominal pain or distension because of obstruction, as well as weight loss, nausea and vomiting, fever, change in bowel habits, and general malaise. Anal cancer may exhibit no symptoms in early stages; later, there may be bleeding, pressure, pain, itching, and a palpable mass. Screening, diagnosis, and staging: Routine screening tests for gastrointestinal cancers are not generally performed, but a colonoscopy is used in people over the age of fifty to look for signs of polyps that might lead to colon cancer. People should monitor digestive symptoms, particularly if these change or if they develop gastrointestinal re-
flux desease (acid reflux, or GERD), and immediately discuss such symptoms with their doctor. After symptoms have appeared, diagnosis usually begins with the physician performing a physical examination and taking a family medical history. Endoscopy, biopsy, and imaging tests such as a barium swallow, computed tomography (CT), and magnetic resonance imaging (MRI) are used for further study. When symptoms of esophageal cancer appear, a thorough family medical history is done and a complete physical examination is performed. An X-ray study (barium swallow) or an esophagoscopy can find changes in the shape of the esophagus. The doctor can do a tissue biopsy through the endoscope and brush cells from the esophageal wall for examination by a pathologist. If cancer is found, additional tests to determine the extent of involvement include a CT scan, an MRI scan, a laryngoscopy, or a bronchoscopy. These tests will determine staging, or classification of the extent of the cancer. For esophageal cancer the stages are as follows: • Stage I: Cancer is in only a small part of the esophagus; it has not spread to nearby tissues, lymph nodes, or other organs. • Stage II: Cancer is in a large portion of the esophagus; it has spread to all sides of the esophagus but not to other tissues. • Stage III: Cancer has spread to tissues or lymph nodes near the esophagus but not to other parts of the body. • Stage IV: Cancer has spread to other parts of the body. When symptoms of stomach cancer appear, the doctor will take a medical history, do a physical examination, and order additional tests: a fecal occult blood test, an upper gastrointestinal series (barium swallow), and an endoscopy. If cancer is identified, staging is as follows: • Stage 0: Cancer is only in the innermost layer of the stomach wall. • Stage I: Cancer is in the second or third layers of the stomach wall but has not spread to nearby lymph nodes, or it is in the second layer and nearby lymph nodes. • Stage II: Cancer is in the second layer of the stomach wall and in more distant lymph nodes; in only the third (muscle) layer and the nearby lymph nodes; or in all four stomach wall layers but not in lymph nodes or other organs. • Stage III: Cancer is in the third layer and more distal lymph nodes; in all four layers of the stomach wall and nearby or more distant lymph nodes; or in all four layers and nearby tissues, with or without nearby lymph node involvement. • Stage IV: Cancer has spread to nearby tissues and to distant lymph nodes or to other parts of the body. 503
Gastrointestinal cancers
Salem Health: Cancer
Although only tumor biopsy can verify colorectal cancer, several other tests that can aid in detection include digital examination, proctoscopy or sigmoidoscopy, colonoscopy, computed tomography scan, and barium X rays. The staging is as follows: • Stage I: Cancer is present in the innermost and middle tissue layers of the colon. • Stage II: Cancer has spread beyond the middle layers and into nearby tissues around the colon or rectum, or has spread through the peritoneum or to nearby organs.
•
Stage III: Cancer has spread from the innermost layer to the middle layers and is in as many as three lymph nodes; or has spread to three lymph nodes and beyond the middle layers, to tissues nearby the colon or rectum, or into nearby organs or through the peritoneum; or to four or more lymph nodes and to or beyond the middle layers of the colon wall, to tissues nearby the colon or rectum, or to nearby organs or through the peritoneum. • Stage IV: Cancer has spread to nearby lymph nodes and distant sites such as the lungs or liver.
Esophagus Liver Liver (hepatic) ducts Gallbladder
Pancreas
Stomach Cystic duct
Duodenum
Bile/pancreatic duct opening
Small intestine
Colon Appendix Rectum
Cancer can affect most parts of the gastrointestinal system.
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Salem Health: Cancer Treatment for cancer of the small intestine is usually determined by cell type: adenocarcinomatous, lymphomatous, sarcomatous, or carcinoid. However, staging is done for lymphoma: • Stage I: Cancer in only one lymph node area or one area or organ outside the lymph nodes • Stage II: Cancer found either in two or more lymph nodes on the same side of the diaphragm or in only one area or organ outside the lymph nodes • Stage III: Lymph node involvement on both sides of the diaphragm and possible spread to an area or organ near the lymph nodes • Stage IV: Metastasis to one or more organs outside the lymph system or to only one organ outside the lymph system, but to lymph nodes far away from the organ involved The following stages are used for anal cancer: • Stage 0 (carcinoma in situ): Cancer is only in the top layer of anal tissue. • Stage I: Cancer has spread beyond the top layer of anal tissue but involves less than an inch. • Stage II: Cancer has spread beyond the top layer and is larger than an inch; no lymph node or organ is involved. • Stage IIIA: Cancer involves lymph nodes around the rectum or has spread to nearby organs such as the vagina or bladder. • Stage IIIB: Cancer has invaded lymph nodes in the middle of the abdomen or in the groin, or has spread to both nearby organs and lymph nodes around the rectum. • Stage IV: Cancer has spread to distant lymph nodes within or outside the abdomen. Treatment and therapy: Treatment of gastrointestinal cancers may vary depending on the tumor’s location, size, extent, and cell type, as well as the patient’s age and general health, but usual treatments include surgery to remove the tumor and nearby lymph nodes, radiation therapy to shrink the tumor before surgery or to destroy any cancerous cells remaining after surgery, and chemotherapy, alone or combined with radiation therapy. The ideal treatment for stomach cancer is radical surgery, involving a total or subtotal gastrectomy and the removal of a portion of tissue around the stomach. Another treatment option is biological therapy (immunotherapy), designed to help the body’s immune system attack and destroy the malignant cells With colorectal cancer, after surgery, if the healthy sections of the colon cannot be reconnected, a colostomy may be performed, allowing evacuation of body waste through an opening (stoma) in the abdomen. The small intestine is very sensitive to radiation, limiting the usefulness of this therapy, however. The size of the tumor may determine the method
Gastrointestinal cancers of treatment of anal cancer. Superficial in situ tumors (less than 1 inch) may require only local excision or radiotherapy alone. Tumors 1 to 2 inches are best treated by chemotherapy and radiation. Larger tumors may require chemotherapy, radiation, and surgery. Prognosis, prevention, and outcomes: Five-year survival rates for gastrointestinal cancers are as follows: • Esophageal cancer: Stage 0, excellent; Stage I, over 50 percent; Stage II, 10 to 15 percent; Stage III, less than 10 percent; Stage IV, unusual. • Stomach cancer: Stage 0, over 90 percent; Stage I, a 52 to 85 percent rate for distal cancers (stomach outlet), but only 10 to 15 percent for proximal cancers (stomach entry); Stage II, 20 percent or less; Stage III, 17 percent for distal cancers, less for proximal tumors; Stage IV, less than 5 percent. • Colorectal cancer: Stage I , 80 percent; Stage II, 50 percent; Stage III, about 25 percent; Stage IV, only 5 percent. • Cancer of the small intestine: Adenocarcinoma type, 20 percent if it is resectable; sarcoma type, about 50 percent if surgical removal is possible; lymphoma type, 25 percent for diffuse lymphoma, but 50 percent or higher for nodular lymphoma; and for the carcinoid type, about 54 percent. • Anal cancer: Stage 0 (in situ), 100 percent; Stage I, over 95 percent; Stage II, 75 percent; Stage IIIA, 60 percent; Stage IIIB, 10 percent; Stage IV, unusual. Prevention of cancer involves trying to reduce risk; lifestyle, environment, and heredity help determine risk. To help prevent gastrointestinal cancers, people can stop or avoid smoking, reduce the amount of fat in the diet while increasing fruit and vegetable consumption, control acid refux and request testing if it persists, and undergo colon cancer screening after the age of fifty. Victoria Price, Ph.D. u
For Further Information Bellenir, Karen, ed. Cancer Sourcebook. 4th ed. Detroit: Omnigraphics, 2003. Cook, Allan R., ed. The New Cancer Sourcebook. Vol. 12. Detroit: Omnigraphics, 1996. Dollinger, Malin, Ernest H. Rosenbaum, and Greg Cable. Cancer Therapy. Kansas City: Andrews and McMeel, 1994. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006.
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Other Resources
Abramson Cancer Center of the University of Pennsylvania http://www.oncolink.com 505
Gastrointestinal complications of cancer treatment American Society of Clinical Oncology Gastrointestinal Cancer http://gicancers.asco.org National Cancer Institute Digestive/Gastrointestinal http://www.cancer.gov/cancertopics/ cancersbodylocation/page5 See also Achlorhydria; Anal cancer; Appendix cancer; Appetite loss; Ascites; Barrett esophagus; Bile duct cancer; Cachexia; Carcinosarcomas; Colon polyps; Colorectal cancer; Crohn disease; Desmoid tumors; Desmoplastic small round cell tumor (DSRCT); Diarrhea; Diverticulosis and diverticulitis; Duodenal carcinomas; Enteritis; Esophageal cancer; Esophagitis; Gallbladder cancer; Gardner syndrome; Gastric polyps; Gastrinomas; Gastrointestinal complications of cancer treatment; Gastrointestinal stromal tumors (GISTs); Helicobacter pylori; Hematemesis; Hemorrhoids; Hereditary diffuse gastric cancer; Hereditary mixed polyposis syndrome; Hereditary pancreatitis; Hereditary polyposis syndromes; Inflammatory bowel disease; Islet cell tumors; Juvenile polyposis syndrome; Krukenberg tumors; Leiomyomas; Leiomyosarcomas; Leptomeningeal carcinomas; Liver cancers; Nausea and vomiting; Obesity-associated cancers; Pancolitis; Pancreatic cancers; Pancreatitis; Peutz-Jeghers syndrome (PJS); Polyps; Rectal cancer; Small intestine cancer; Stomach cancers; Taste alteration; Turcot syndrome; Weight loss; Yolk sac carcinomas; Zollinger-Ellison syndrome.
u Gastrointestinal complications
of cancer treatment Category: Diseases, symptoms, and conditions Also known as: Lower gastrointestinal complications, upper gastrointestinal complications Related conditions: Nausea, vomiting, oral mucositis, diarrhea, constipation, impaction, bowel obstruction, radiation enteritis Definition: Upper gastrointestinal complications of cancer treatment include nausea and vomiting, decreased appetite, mouth sores or inflammation (mucositis), and thrush (yeast infection of the mouth). Lower gastrointestinal complications of cancer treatment include diarrhea, constipation (infrequent passage of dry, hard stools), fecal impaction (accumulation of dry, hardened feces in the rectum or colon), bowel obstruction (blockage), and radiation 506
Salem Health: Cancer enteritis (inflammation of the bowel lining due to radiation therapy). Risk factors: Upper and lower gastrointestinal complications may occur as a result of cancer treatment, such as chemotherapy or other medications given to treat cancer, radiation therapy to the pelvis or abdomen, or surgery. These symptoms also may be the result of an underlying condition, including cancer, central nervous system disorders, bowel obstruction, diverticulitis (outpouchings of the colon), and hernia. Upper gastrointestinal symptoms may occur as signs or symptoms of esophageal, laryngeal, and other cancers. Lower gastrointestinal symptoms may occur as signs or symptoms of gastric cancer, colon cancer, rectal cancer, bowel cancer, and other cancers. These symptoms also may occur upon the growth or spread of these types of cancer. Anxiety about cancer or cancer treatment can contribute to the development of gastrointestinal symptoms. In addition, a history of lactose intolerance can increase the patient’s risk of developing lower gastrointestinal complications associated with cancer treatment. Aging and declining health are other contributing factors. Etiology and the disease process: Chemotherapy and radiation therapy can cause changes in the function of the intestines, including increased or decreased peristalsis (the wavelike contraction of the muscles to propel contents through the digestive tract). An increase in peristalsis can cause stool to move more quickly through the intestines, leading to diarrhea and cramping. A decrease in peristalsis can cause stool to move more slowly through the intestines, leading to constipation, difficulty passing stool, and, in severe cases, fecal impaction, a condition requiring emergency attention. Chemotherapy can also change the normal bacteria in the intestines, causing abdominal pain, cramping, or gas. Fungal, parasitic, or viral pathogens also may contribute to diarrhea. Partial or complete intestinal or bowel obstructions may occur as the result of a tumor, postoperative adhesion, or a hernia. Nausea is controlled by part of the central nervous system, and vomiting is a reflex controlled by the brain and stimulated by various triggers, including inflammation in the body. Chemotherapy drugs as well as radiation therapy directed to the gastrointestinal tract, liver, or brain can cause nausea and vomiting. Nausea can also be caused by constipation. Incidence: Gastrointestinal complications are very common among patients undergoing cancer treatments. The rate of gastrointestinal complications is variable, depend-
Salem Health: Cancer
Gastrointestinal complications of cancer treatment
Prescribed Techniques to Manage Gastrointestinal Complications Symptom
Medications
Nausea, vomiting
serotonin-receptor antagonists such as granisetron, ondansetron, dexamethasone, and aprepitant (given intravenously before the administration of a chemotherapy agent) prochlorperazine metoclopramide promethazine dronabinol
Decreased appetite
dexamethasone prednisone megestrol
Diarrhea
loperamide and diphenoxylate/atropine (first-line treatment) octreotide subcutaneous injections (second-line treatment for persistent, chronic cases) antibiotics, may include fluoroquinolone
Constipation
bisacoyl lactulose
ing on the type of cancer as well as the extent of the treatment. Side effects may not be the same for each patient or even for patients having the same treatments. In addition, a patient’s side effects may change from one treatment session to the next. The National Cancer Institute reports that 70 to 80 percent of patients undergoing cancer treatment experience nausea and vomiting, and 25 percent of patients experience severe diarrhea. Symptoms: Gastrointestinal symptoms range from moderate to severe and vary among patients. Symptoms can impede cancer treatment, resulting in a delay, dose reduction, or discontinuation of therapy. Symptoms of nausea and vomiting may occur during chemotherapy treatment and last a few hours to a few days after treatment. If vomiting occurs for more than twentyfour hours, it is important for patients to notify their physician right away, especially if it is accompanied by abdominal pain or cramping. Changes in stool frequency, consistency, or volume, or the presence of blood, mucus, or pus in the stool may indicate an underlying disease. If diarrhea occurs more than six times a day or does not resolve within twenty-four hours after taking prescribed antidiarrheal medications, patients should call their physician. Screening and diagnosis: A thorough review of the patient’s medical history and a physical exam are performed to diagnose gastrointestinal problems. Blood tests can be performed to identify neutropenia, electrolyte imbalances, and renal insufficiency. Stool tests can be performed to identify blood and bacterial, fungal, parasitic, or viral
pathogens. Diagnostic tests include upper endoscopy, upper gastrointestinal series (barium swallow), abdominal X rays, sigmoidoscopy, and colonoscopy. Treatment and therapy: Symptom management is critical to avoid an interruption in the delivery of cancer treatment. Aregistered dietitian can provide nutritional therapy to help patients develop eating plans that meet dietary requirements while reducing upper and lower gastrointestinal side effects, helping to make treatment more tolerable. In some cases, antinausea or antidiarrheal medications may be prescribed to help prevent or reduce these troublesome side effects. It is important for patients to ask their physician first before self-treating these side effects, as some over-the-counter remedies could interfere with cancer treatment. Conservative self-management techniques can be used to manage gastrointestinal complications in many cases. Techniques to manage nausea, vomiting, and diarrhea include the following: • Increasing fluid intake to prevent dehydration • Eating bland foods in small amounts • Following a clear liquid diet of juices and broth until symptoms subside • Avoiding spicy, high-fat, and sugary foods • Eating small, frequent meals • Eating slowly and chewing food completely before swallowing • Drinking cool beverages after meals • Taking medication with food, unless advised otherwise • Eating foods at room temperature 507
Gastrointestinal oncology Many of these guidelines are also helpful in managing decreased appetite. Nutritional supplements may be recommended to ensure sufficient caloric and nutrient intake. Additional tips for managing diarrhea include avoiding high-fiber foods, dairy products, caffeine, and alcoholic beverages and including high-potassium foods, as advised by the doctor. Techniques for managing abdominal pain include avoiding aspirin and other nonsteroidal anti-inflammatory drugs, unless prescribed; avoiding alcohol and nicotine; and limiting caffeine. Techniques for managing constipation include exercising and increasing consumption of fluids and high-fiber foods. In addition to these recommendations, relaxation techniques such as deep breathing and guided imagery may help. Patients should follow their physician’s specific guidelines for managing treatment side effects and should call the doctor when symptoms are severe or persist for more than twenty-four hours. Hospitalization is recommended for patients with dehydration, fever, neutropenia, bowel obstruction, fecal impaction, and nausea, vomiting, or diarrhea that results in the inability to maintain adequate hydration or nutrition. Hospitalization is also recommended for patients with chronic diarrhea that does not resolve within twenty-four hours after taking prescribed antidiarrheal medications. Intravenous fluids can be given, and the patient can be closely monitored in the hospital. Treatment for a bowel obstruction includes surgical removal, a nasogastric tube to relieve a partial obstruction, or a gastrostomy tube to relieve fluid and air buildup. In some cases, an ileostomy or a colostomy may be recommended. Prognosis, prevention, and outcomes: Gastrointestinal symptoms can be effectively managed with conservative treatments and medications, and they are generally relieved when cancer treatments are completed. There usually are no long-term effects of gastrointestinal symptoms that are properly managed, according to the American Cancer Society. Left untreated, chronic gastrointestinal symptoms, particularly diarrhea and vomiting, can cause significant morbidity and mortality due to nutritional deficiencies and fluid and electrolyte imbalances that may result in lifethreatening dehydration or impaired kidney function. Constipation can lead to fecal impaction, which can be a life-threatening condition requiring immediate medical attention. Although cancer treatments can create gastrointestinal complications that are temporarily unpleasant to the pa508
Salem Health: Cancer tient, the potential side effects should be measured against the cancer-fighting benefits of a particular treatment. Angela M. Costello, B.S. u
For Further Information American Society of Clinical Oncology. Optimizing Cancer Care: The Importance of Symptom Management. Dubuque, Iowa: Kendall/Hunt, 2001. Moore, Katen, and Libby Schmais. Living Well with Cancer: A Nurse Tells You Everything You Need to Know About Managing the Side Effects of Your Treatment. New York: Putnam’s, 2001. National Cancer Institute. Chemotherapy and You. NIH Publication No. 07-7156. Bethesda, Md.: National Institutes of Health, U.S. Department of Health and Human Services, 2007. Sharma, R., et al. “Management of ChemotherapyInduced Nausea, Vomiting, Oral Mucositis, and Diarrhea.” Lancet Oncology 6 (2005): 93-102. Tyson, Leslie B., and Joanne Frankel Kelvin. One Hundred Questions and Answers About Cancer Symptoms and Cancer Treatment Side Effects. Sudbury, Mass.: Jones & Bartlett, 2005.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/index.htm See also Antidiarrheal agents; Antinausea medications; Ascites; Candidiasis; Chemotherapy; Colorectal cancer; Diarrhea; Drug resistance and multidrug resistance (MDR); Enteritis; Fatigue; Gastrointestinal cancers; Infection and sepsis; Inflammatory bowel disease; Living with cancer; Medical marijuana; Motion sickness devices; Mucositis; Nausea and vomiting; Overtreatment; Pain management medications; Side effects; Stress management; Taste alteration; Weight loss.
u Gastrointestinal oncology Category: Medical specialties Also known as: Gastroenterology oncology Definition: Gastrointestinal oncology is the medical specialty for the diagnosis, treatment, and prevention of pol-
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Gastrointestinal oncology
yps, tumors, and cancers affecting the digestive system, including the esophagus, stomach, liver, gallbladder, pancreas, small intestine, colon, rectum, and anus.
cluding an annual educational conference and the publication of the journals Gastroenterology and Clinical Gastroenterology and Hepatology.
Subspecialties: Medical oncology and hematology, radiation oncology, surgical oncology, gastrointestinal cancer research Cancers treated: Gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, esophageal cancer and adenocarcinoma, gallbladder cancer, gastric (stomach) cancer, liver cancer, pancreatic cancer, colorectal cancer, anal cancer
Services and procedures performed: Gastroenterology oncologists work closely with gastroenterologists who perform patient risk assessments and endoscopic exams for gastrointestinal cancer prevention and early detection. Gastroenterologists also identify hereditary syndromes and perform genetic testing when necessary for high-risk patients. Gastroenterology oncologists diagnose and stage digestive cancers and provide cancer treatment, including surgery, chemotherapy, and radiation therapy.
Training and certification: The field of gastroenterology oncology has evolved rapidly in the twenty-first century. Gastroenterology oncologists may have a background in gastroenterology or oncology with additional training in malignant conditions of the digestive system. After receiving a four-year medical degree from an accredited program and board certification from the American Board of Internal Medicine, gastroenterologists with a specialty interest in oncology complete a one-year internship, followed by three or more years of postgraduate residency training in tumors and other cancerous conditions affecting the digestive system. Gastroenterology oncologists are trained in the areas of histological examination, endoscopic screening procedures, the biology and pathology of gastrointestinal cancer, gastrointestinal imaging procedures, chemotherapy including adjunctive treatment, radiation oncology, surgical oncology, palliative care, gastrointestinal cancer research, and alternative medicine. Gastrointestinal clinical practice guidelines, quality care standards, and quality assurance measures in the United States have been established by these organizations: • American College of Gastroenterology (ACG): The ACG is a professional organization that represents more than 10,000 digestive health specialists from seventy-five countries. It publishes clinical practice guidelines on malignant gastrointestinal diseases in the American Journal of Gastroenterology and provides up-to-date scientific information on digestive health and the etiology, symptomatology, and treatment of gastrointestinal disorders. • American Gastroenterological Association (AGA): A professional association with 15,500 members, including physicians and scientists who research, diagnose, and treat disorders of the gastrointestinal tract and liver. The AGA consists of two nonprofit organizations: the AGA and the AGA Institute. The AGA administers all membership and public policy activities, while the AGA runs the organization’s practice, research, and educational programs, in-
Related specialties and subspecialties: Gastroenterology oncologists work with a multidisciplinary team of cancer health care providers whose goals are to provide early detection; accurately diagnose the condition; offer prompt, appropriate state-of-the-art treatment to reduce morbidity and improve quality of life and survival; provide psychological guidance through complex treatment phases; reduce long-term effects of chemotherapy and radiation therapy; and provide long-term follow-up. Multidisciplinary team members include the patient’s gastroenterologist, primary care physician, medical oncologist, oncologist surgeon, diagnostic radiologist, and radiation oncologist. Others involved may include infectious disease specialists; pathologists; oncology nurses; physical therapists; and oncology social workers and other allied health care professionals, such as educational specialists, registered dietitians, and pharmacologists. Gastroenterologists are physicians who specialize in disorders and conditions of the gastrointestinal tract. After completing their general medical education, they train for at least two years to become board certified in internal medicine. Then, gastroenterologists receive additional training in conditions of the gastrointestinal tract for two to three more years to become board certified in gastroenterology. Medical oncologists are often the main health care providers for adults diagnosed with cancer. They determine the appropriate systemic or adjunctive drug regimens to treat the patient’s condition and supervise the dosage, schedule, and administration of cancer drugs to treat localized or metastatic malignancies. Medical oncologists are trained and skilled in chemotherapy drug indications and toxicities so that they can safely administer these therapies while minimizing side effects and appropriately managing complications. Oncologist surgeons use laparoscopy, thoracoscopy, and other surgical techniques to diagnose and treat cancers. In addition to having a four-year medical degree from 509
Gastrointestinal oncology an accredited program and board certification from the American Board of Surgery, oncologist surgeons have completed five years of residency training in an accredited general surgery program and at least two years of fellowship training in oncological surgery. Diagnostic radiologists obtain and interpret medical images to diagnose diseases. In addition to having a fouryear medical degree from an accredited program and board certification from the American Board of Radiology or the American Osteopathic Board of Radiology, the radiologist must have passed a licensing examination and completed at least four years of residency training in an accredited radiology program. Radiation oncologists, sometimes referred to as clinical oncologists, treat cancers using radiation. In the United States, most radiation oncologists have completed residency training in radiation oncology in a program approved by the American Council of Graduate Medical Education or the American Board of Radiology. Infectious disease specialists are physicians who are experts in the diagnosis and treatment of infectious diseases. In addition to having a four-year medical degree from an accredited program and board certification from the American Board of Pediatrics, infectious disease specialists have completed three or more years of residency training and two to three years of additional training in infectious diseases. Pathologists are physicians who are experts in the pathology of hematologic malignancies and solid tumors. They are skilled in immunochemistry and molecular techniques to assess malignancies. In addition to having a fouryear medical degree from an accredited program and board certification from the American Board of Internal Medicine, pathologists have completed three or more years of residency training and one to two years of additional training in pathology. Oncology nurses administer medications and provide medical care as well as family and patient education. Oncology clinical nurse specialists are registered nurses with a master’s degree in oncology nursing. They prepare and administer medications, including chemotherapy; possess knowledge about treatment protocols; and have experience in managing treatment complications. Oncology nurse practitioners are registered nurses with a master’s or doctoral degree. The Oncology Nurses Society facilitates the professional development of oncology nurses. Angela M. Costello, B.S. u
For Further Information Ajani, Jaffer A., et al., eds. Gastrointestinal Cancer. New York: Springer, 2005. 510
Salem Health: Cancer Blay, J. Y., et al. “Consensus Meeting for the Management of Gastrointestinal Stromal Tumors: Report of the GIST Consensus Conference of 20-21 March 2004, Under the Auspices of ESMO.” Annals of Oncology 16, no. 4 (2005): 566-578. Kochman, M. L., ed. The Clinician’s Guide to Gastrointestinal Oncology. Thorofare, N.J.: Slack, 2005. Wang, K. K., et al. “American Gastroenterological Association Medical Position Statement: Role of the Gastroenterologist in the Management of Esophageal Carcinoma.” Gastroenterology 128 (2005): 14681470. u
Organizations and Professional Societies
American College of Gastroenterology http://www.acg.gi.org P.O. Box 342260 Bethesda, MD 20827-2260 American Gastroenterological Association http://www.gastro.org 4930 Del Ray Avenue Bethesda, MD 20814 American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 National Comprehensive Cancer Network http://www.nccn.org 275 Commerce Drive, Suite 200 Fort Washington, PA 19034 Oncology Nurses Society http://www.ons.org 125 Enterprise Drive Pittsburgh, PA 15275 u
Other Resources
American Cancer Society All About Stomach Cancer Http://www.cancer.org/docroot/CRI/CRI_2x .asp?sitearea=&dt=40 CancerCare http://www.cancercare.org Cancer.Net http://www.cancer.net/portal/site/patient
Salem Health: Cancer International Foundation for Functional Gastrointestinal Disorders http://www.iffgd.org National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/index.htm See also Abdominoperineal resection (APR); Anoscopy; Barium enema; Barium swallow; Cholecystectomy; Colectomy; Coloanal anastomosis; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Colostomy; Endoscopy; Esophagectomy; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Ileostomy; Laparoscopy and laparoscopic surgery; Liver biopsy; Pancreatectomy; Paracentesis; Percutaneous transhepatic cholangiography (PTHC); Polypectomy; Sigmoidoscopy; Splenectomy; Tracheostomy; Upper gastrointestinal (GI) endoscopy; Upper gastrointestinal (GI) series.
u Gastrointestinal stromal
tumors (GISTs) Category: Diseases, symptoms, and conditions Also known as: Gastrointestinal sarcomas Related conditions: Soft-tissue sarcomas Definition: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors, forming in the connective tissue of the gastrointestinal system. The most common forms of GISTs occur in the stomach, although tumors may also develop in the small intestine, the esophagus, and the colon or rectum. GISTs are differentiated from similar gastrointestinal tumors by an overexpression of the C-KIT protein, a tyrosine kinase receptor protein that, on activation, triggers protein-signaling pathways that initiate cell proliferation. Risk factors: Currently, there are no well-defined risk factors for the development of gastrointestinal stromal tumors. Neurofibromatosis, a disease characterized by the formation of numerous benign tumors in nerves throughout the body, may be associated with the formation of GISTs. Most GISTs occur sporadically, but there have been a few reported cases of these tumors developing in members of the same family, perhaps due to inheritance of a mutation within the C-KIT gene. Additionally, familial gastrointestinal stromal tumor syndrome is an inherited disorder that predisposes individuals to the formation of
Gastrointestinal stromal tumors (GISTs) GISTs. This rare condition is caused by mutations in the C-KIT gene. However, unlike people with sporadic GIST in which only the tumor expresses C-KIT mutations, individuals with gastrointestinal stromal tumor syndrome have C-KIT mutations in all the cells of their bodies. Etiology and the disease process: Gastrointestinal stromal tumors arise because of activating mutations of one of two tyrosine kinase proteins important for triggering cell proliferation. The majority of GISTs occur subsequent to mutations within the gene encoding for the C-KIT protein, although mutations in the gene encoding the plateletderived growth factor receptor (PDGFR) also may cause a GIST. The specific type of cell in which GISTs originate is what differentiates a GIST from similar gastrointestinal tumors. Most investigators believe that GISTs begin in specific cells within the connective tissue of the gastrointestinal tract, called interstitial cells of Cajal. Many GISTs are found not to be malignant and are instead benign growths within the gastrointestinal system. Incidence: A gastrointestinal stromal tumor is considered to be a relatively rare cancer and is estimated to occur in 10 to 20 individuals per 1 million people. Each year, approximately 4,500 to 6,000 Americans have a GIST. Of these cases, 20 to 30 percent of the tumors are diagnosed as malignant. Most GISTs occur in people over the age of fifty, with the majority of tumors diagnosed between the ages of fifty-five and sixty-five. GISTs rarely occur in children or people younger than forty years. While GISTS are thought to affect both genders equally, some studies have suggested that there may be a slight prevalence of GIST development in men. Symptoms: Depending on the size of the gastrointestinal stromal tumor, an individual may or may not experience any symptoms. As the tumor enlarges, patients often feel abdominal pain or develop intestinal bleeding. Upon examination, a GIST may be found to be the cause of these symptoms. Other symptoms that have been associated with GISTs include nausea, vomiting, and appetite or weight loss. Screening and diagnosis: There are currently no effective screening tests to detect gastrointestinal stromal tumors. Some GISTs are diagnosed by chance, during abdominal surgery or a routine colonoscopy. Also, GISTs may be identified by radiological screening tests, such as a computed tomography (CT) scan, a barium X ray, or magnetic resonance imaging (MRI). In some cases, a doctor may perform a biopsy if a mass is detected. However, biopsies are often impractical, and instead surgery is performed to remove the mass, at which time a biopsy of the tumor tis511
Gene therapy
Salem Health: Cancer
sue is removed to determine if it is malignant or benign. Using a biopsy sample, GISTs are histologically graded to determine the malignant potential of the tumor.
u Gene therapy
Treatment and therapy: The primary treatment for GIST is surgery, in which the goal is to remove as much of the tumor as possible. Surgery is more likely to be successful when the GIST is small. Most general anticancer chemotherapeutics previously used to treat GISTs were largely ineffective. The approval of the targeted therapy imatinib (Gleevec) has caused this drug to become part of the front-line therapy for the treatment of GISTs. Imatinib specifically inhibits both C-KIT and PDGFR, the two main proteins responsible for the development and survival of GIST cells. Although imatinib does not necessarily cure the GIST, it is often used to shrink the tumor size.
Definition: Gene therapy is a technique that corrects deleterious, defective, and disease-inducing genes through genetic modifications. Modifications include restoration, substitution, or supplementation of the defective gene. Therapeutic approaches involve introduction of altered genetic material into either normal cells (to develop immunity against cancer) or cancer cells (to combat the disease). Gene therapy is sometimes aimed at augmenting results from other existing treatment options. It is still in experimental stages, and no gene therapies are available outside clinical trials. However, there are exceptionally large numbers of ongoing clinical trials using gene therapy as their primary clinical approach, and about 60 percent of all these clinical trials aim at addressing cancer-related questions.
Prognosis, prevention, and outcomes: The prognosis for patients diagnosed with a GIST depends on several factors. These include the size and grade of the tumor, as well as the degree to which the tumor has spread, if at all. For people diagnosed and treated between 1992 and 2000, the overall five-year survival rate of patients with GIST was approximately 45 percent. This survival increases to 64 percent if the tumor has not spread but decreases to 13 percent if the tumor has spread to distant sites. However, because of the addition of new therapies to treat GIST, these survival rates have begun to increase. Lisa M. Cockrell, B.S. u For Further Information DeMatteo, R., et al. One Hundred Questions and Answers About Gastrointestinal Stromal Tumor (GIST). Boston: Jones & Bartlett, 2006. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. Rubin, B. P., et al. “Gastrointestinal Stromal Tumor.” Lancet 369 (2007): 1731-1741. u
Other Resources
American Cancer Society http://www.cancer.org GIST Support International http://www.gistsupport.org See also Angiogenesis inhibitors; Barium swallow; Duodenal carcinomas; Fibrosarcomas, soft-tissue; Gastrointestinal cancers; Gastrointestinal oncology; Leiomyosarcomas; Mesenchymomas; Small intestine cancer; Stomach cancers; Tyrosine kinase inhibitors. 512
Category: Procedures
How this therapy works: Success with gene therapy depends on multitudes of factors: how an altered gene is introduced into the body, how efficiently the modified (recombined) gene is able to restore or resuscitate normal function, how specific the targeting of a particular region is, how sustained the response of the body is, how low the immunological response of the host is, and the extent to which the other associated risks are eliminated. Gene therapy is ideal only for diseases that are caused by mutations of a single gene. In general, it is impossible to introduce a gene directly into cells, and therefore, special carriers called vectors are used to aid in the transfer of genes. Most commonly used vectors are viruses. Viruses have the remarkable capacity to recognize specific cells and integrate themselves into those cells. Specific classes of viruses called retroviruses have been used extensively in many clinical trials involving gene therapy, although studies using other types of viruses, such as adenoviruses, adeno-associated viruses, lentiviruses, poxyviruses, and herpesviruses, also abound. The reasons for using viruses as vectors are multifold. First, viruses possess a relatively simple genome (genetic makeup). Only a handful of genes exist in a viral genome (as opposed to the approximately 30,000 genes, for example, in the human genome), and therefore, it is relatively easy to handle. Second, viruses have evolved ways of surpassing natural barriers that cells put forth, gaining access across membranes into the cytoplasm as well as to the nuclei of the cells. Third, viruses can be engineered with relative ease to stop replication, gain integration into host deoxyribonucleic acid (DNA), and exit without causing
Salem Health: Cancer destruction of the host cell. Fourth, viruses have remarkable specificity to infect certain types of cells. This particular characteristic affords greater reliability and hope for better outcomes. However, there are various complications associated with the use of viral vectors, such as host immune response, and therefore, use of nonviral vectors is preferred in certain cases. Numerous types of genes are delivered using viral vectors. Enhancing host immune responses: Different approaches have been attempted to use gene therapy as a treatment option for patients. Of these, major focus has been on improving the body’s immunological responses to cancer. The body’s immunological system consists of populations of different kinds of cells (broadly called white blood cells or lymphocytes) whose function is to fight against multitudes of foreign bodies that invade the cells. In cancer patients, however, this immunological response is highly compromised either because of deficiency or improper functioning of lymphocytes. Immune therapy for cancer generally falls under a few specific categories: injection of cytokines (special proteins secreted by the immune system), addition of lymphokine-associated killer cells (LAK cells, which are special immune cells) to existing treatment options, addition of activated peripheral lymphocytes, and infusion of antigen-presenting cells to increase the antigen-recognizing capacity of immune cells. The gene therapy approach employs the idea of enhancing the capacity of normal lymphocytes to become aggressive combatants of cancer by using any of these techniques. Specific retroviruses are manipulated to incorporate certain proteins called T-cell receptors (a kind of lymphocyte), which when introduced into the body engender the required confirmation for lymphocytes to destroy cancer cells. Some ongoing clinical trials use this approach to treat melanoma. T lymphocytes exert their immunogenicity through secretion of specific proteins called cytokines. Human cells possess different kinds of cytokines, most of which have been used in gene therapy studies. The major advantage of using cytokines in gene transfer studies is that they help not only in tumor destruction but also in eliciting immune memory. Most known cytokines such as interleukins (ILs), interferons (IFNs), granulocyte-macrophage colonystimulating factors (GM-CSF), and tumor necrosis factoralpha (TNF-α) are used in immunotherapy and gene therapy experiments. In fact, cytokines constitute about 25 percent of the genes used in experiments in gene therapy around the world. Preclinical studies using IL-2, IL-12, IL-24, GM-CSF, TNF-α, and IFN are extremely promising, and all these compounds are used in clinical trials. Cy-
Gene therapy tokines can be delivered using both viral and nonviral modes of entry into the cells. They can be administered directly into tumor cells in vivo (inside cells) or can be engineered with lymphocytes ex vivo (outside cells) and then implanted in stem cells. There are some sporadic reports of vectors themselves contributing to antitumor effects in studies involving cytokine gene transfers. However, gene therapy experiments using cytokines face similar challenges as those of other comparable experiments, where determination of optimal doses of cytokines and elimination of immunosuppressive agents still hamstring progress. Introduction of normal tumor-suppressor cells: Other approaches to gene therapy include replacement of mutated (altered) or deleted genes with healthy copies of genes. For example, a tumor-suppressor gene called TP53 is mutated in a wide array of tumors. The TP53 protein, under normal conditions, suppresses the activation of genes contributing to uncontrolled cell division and proliferation. Replacement of normal, wild type TP53 genes using a retroviral TP53 expression vector is used in gene therapy trials. Inhibition of oncogenes: An alternative strategy is to alter the oncogene or cancer-inducing gene directly. Genes belonging to the RAS family of oncogenes, such as HRAS, NRAS, and KRAS, and others such as MYC are examples of oncogenes. These genes are activated by mutations or modifications that change the composition of their protein products, resulting in the development of cancer. A common approach to inactivate such oncogenes uses a method called antisense technology. A ribonucleic acid (RNA) sequence complementary to that targeted for inactivation is introduced into the cell, then binds and thereby blocks translation of that RNA. Thus, inhibition is ensured at a level before the protein is formed, reducing its opportunities to induce tumor development. Insertion of suicide genes: A novel approach of gene therapy is to transplant what are called suicide genes in the body; these help convert generally nontoxic substances called prodrugs into physiologically active forms, thereby triggering death of cancer cells. The popular gene and prodrug combination is the herpes simplex virus (HSV) thymidine kinase (HSV-tk)/ganciclovir (GCV). Ganciclovir is a prodrug that is inactive in its dephosphorylated (no phosphate group attached to the protein) form. When it is phosphorylated by HSV-tk introduced through an adenovirus, it attains the capability of inducing so called “death pathways” and triggering cell death. The effect is accentuated by a process called “by-stander effect,” whereby sur513
Gene therapy rounding cells receive the toxic metabolites and join the race of combating tumor cells. This strategy has yielded very promising results in clinical trials. Aiding antiangiogenesis: Tumors require a copious supply of oxygen for sustenance and access to blood vessels for spread. The process of formation of new blood vessels is called angiogenesis. It is a multistep process that includes proliferation of endothelial cells, cellular migration, membrane degradation, and reorganization of cell cavity or lumen. Some factors that aid in angiogenesis are growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and hepatocyte growth factor (HGF). Gene therapy experiments focus on introducing viruses containing inhibitors of some of these growth factors and attempt to block angiogenesis in tumor cells. Interaction with other treatment techniques: A commonly employed gene therapy strategy is to insert genes that will facilitate or augment some existing therapeutic intervention. In the case of patients undergoing radiotherapy or chemotherapy, for example, introduction of certain beneficial genes could afford resistance to multiple drugs or protection of bone marrow. Tumor cells have the capacity to efflux drugs, and this capacity is a challenge to overcome in therapeutic procedures. The strategy is to use drug-resistance genes for overcoming drug efflux. A gene that has been approved in protocols for breast or ovarian cancer treatments is multiple-drug-resistance gene (MDR1). This gene is inserted into normal bone marrow to select for cells that are particularly resistant to the specific chemotherapeutic agent in a treatment regimen. Other approaches: The use of small inhibitor ribonucleic acid (siRNA) technique for silencing oncogenes is gaining momentum in gene therapy studies. Experiments have begun using viral vectors incorporating siRNA in animal models to examine their efficacy in targeting and silencing specific genes. Attempts have also been made to introduce a forty-seventh, artificial chromosome with relevant beneficial genes through a large viral vector. Using nonviral vectors: The use of viral vectors for delivering specific genes poses some palpable problems such as interaction of the introduced virus with other viruses that it might encounter in the body and nonspecific target stimulation. Therefore, use of nonviral material to transfer genes is preferred in certain cases. Some examples of nonviral vectors are cationic liposomes, polyethylenimines, DNA-liposome complexes, and synthetic polymers. Liposomes are lipid particles possessing the innate ability to traverse cell membranes. The strategy behind gene therapy is to harness this property to deliver desired DNA to 514
Salem Health: Cancer cancer cells via lipid-DNA complexes. Naked DNA or plasmids and transposable elements called transposans are other examples of nonviral vectors. Electrotransfer of DNAhas been used in experiments as a physical method of transfer of DNA. In this process, the transfer of genetic material is achieved by local application of electric pulses after introducing DNA into the extracellular medium. Nanomaterials are temperature-sensitive polymers capable of binding and complexing with DNA to form nanorods. The stability of nanorods at physiological temperatures and their capacity to expand when heated make them attractive alternatives to deliver and trap genetic materials. Once inside tumor cells, they disintegrate and make the delivery complete and competent. Recent experiments have used both naturally occurring polymers like chitosans and synthetic, biocompatible compounds called propyleneimines for DNA-binding experiments. Side effects: Major side effects for gene therapy include host immune responses to foreign genes introduced into the body. Immune responses can include inflammation, allergic reactions, and, rarely, death. It is worth mentioning that gene therapy studies have reported minimal side effects and encouraging responses. The challenge lies in improving efficiency and producing sustainable responses. Progress and perspectives: Due to its ability to alter genes, which are the basic units of heredity and variation, gene therapy encounters multitudes of social and ethical concerns. The ability to alter genes confers the ability to change the genetic makeup and ultimately the genetic composition of the human population. It might become difficult then to determine what is legitimate and ethical to manipulate. Some of the issues concerning germ-line gene therapy and genetic enhancement are serious concerns and need to be tackled. In the United States, there are stringent procedures and regulations for conducting gene therapy studies and clinical trials. Various government organizations, including the Food and Drug Administration (FDA) and the Recombinant DNA Advisory Committee (RAC), need to provide approval for protocols. However, as with any other approach, the benefits of gene therapy in curing life-threatening diseases have to be weighed appropriately against any possible misuses or abuses of this approach. Geetha Yadav, Ph.D. u
For Further Information George, L. Gene Therapy. Woodbridge, Conn.: Blackbirch, 2003. Gerl, R., and D. L. Vaux. “Apoptosis in the Development and Treatment of Cancer.” Carcinogenesis 26 (2005): 263-270.
Salem Health: Cancer Panno, J. Gene Therapy: Treating Disease by Repairing Genes. New York: Facts On File, 2005. Podajcer, O. L., M. V. Lopez, and G. Mazzolini. “Cytokine Gene Transfer for Cancer Therapy.” Cytokine and Growth Factor Reviews 18 (2007): 183-194. Roth, J. A., and R. J. Cristiano. “Gene Therapy for Cancer: What Have We Done and Where Are We Going?” Journal of the National Cancer Institute 89 (1997): 21-39. u
Other Resources
American Society of Gene Therapy http://www.asgt.org Centers for Disease Control and Prevention National Office of Public Health Genomics http://www.cdc.gov/genomics Human Genome Project Information Gene Therapy http://www.ornl.gov/sci/techresources/ Human_Genome/medicine/genetherapy.shtml National Cancer Institute http://www.cancer.gov Office of Biotechnology Activities http://www4.od.nih.gov/oba See also Adenoviruses; Family history and risk assessment; Genetic counseling; Genetic testing; Genetics of cancer.
u Genetic counseling Category: Medical specialties; social and personal issues Definition: Genetic counseling in terms of cancer is the activity of health care professionals who have received specialized training in genetics and therapy or counseling in helping people determine, evaluate, and understand their individual risk of the occurrence or recurrence of cancer. Genetic counselors also help people cope with this information and plan a course of action. Why performed: Genetic counseling is intended to provide information to people about their risk for the occurrence or recurrence of a specific type or types of cancer. Genetic counselors are not able to determine the risk that a specific individual will develop any type of cancer but
Genetic counseling rather can determine the risk of specific cancers for which the person is believed to be at increased risk. People are usually considered good candidates for genetic counseling if they have an unusually high number of close relatives with a certain type of cancer, have relatives who have had multiple types of cancer, have had very unusual cancers, or have developed cancer at an unusually young age. The risk assessment done during genetic counseling can give people important information that can help them make the best possible medical and lifestyle choices. For example, if a woman finds out that she has an extremely elevated risk of developing breast cancer, she may consider the option of preventive breast tissue removal. People found to have an increased likelihood of developing cancer can work with their physician and other medical professionals to help develop more intensive screening regimens to ensure that the cancer will be caught as early as possible if it does develop. Steps of the procedure: The genetic counselor discusses and explains the possible risks and benefits of testing and also what kind of results people can expect to receive. The genetic counselor also evaluates people to determine if they are suitable for genetic counseling, in terms of both possible cancer risk and mental health. If a genetic consultation does take place, the first thing that a genetic counselor does is develop a pedigree for the individual. This is a type of family tree that lists information relating to cancer and health. These trees usually go back three generations, if possible. Developing a pedigree can be a complex and time-consuming process, as the person may need to contact extended family, find old medical records, and search for death certificates to provide as much detailed information as possible. The genetic counselor also determines which genetic tests are appropriate and helps set up all necessary appointments. Often the genetic counselor provides support services just before testing is done to help prepare the person for the results and to provide an opportunity to rethink the decision to undergo testing. Similarly, often the genetic counselor engages in counseling before presenting the result of the pedigree and genetic testing to the individual. The person may decline to view the results at any time during the entire process, right up until the genetic counselor actually discloses the results. After the results have been disclosed, the genetic counselor will help the individual identify what feelings and emotions the results have caused, and help the individual work through them. The counselor will also provide information and referrals for further services, such as preven515
Genetic counseling tive options and additional mental health resources. The genetic counselor can also help the individual work through the important decisions that need to be made, such as who should be told and how best to share the news. Benefits: There are many possible benefits to genetic counseling. People who decide to undergo genetic counseling and testing are provided with information that can help them make important decisions that can significantly improve lifetime health. If the results of the genetic testing and the pedigree show that a person is at an increased risk, knowing this information can be very beneficial, even if extremely upsetting. The person can work with a physician and other health care team members to come up with a plan to reduce any environmental factors that are believed to also lead to an increased risk of developing the cancer. The health care team can also help the person ensure that regular screening is done so that if the cancer develops it will be diagnosed as early as possible. Family members of the person can also be informed that they may be at an increased risk of developing the cancer so that they can seek genetic counseling themselves or can work with their health care team to take appropriate preventive and screening measures. If the results show that the person is not at an increased risk of developing the type of cancer of concern, this can have significant positive benefits. The relief felt by the person may lead to better mental health, especially if the likelihood of developing cancer was believed to be extremely high. The person may also feel at ease knowing that any children will not inherit the genetic predisposition to develop the cancer. Risks: If the results of the genetic testing and pedigree show that a person is at an increased risk of developing cancer, it can cause significant emotional upset, turmoil, and fear. It is important for the genetic counselor to help the person explore and work through some of the emotions that a determination of increased risk causes. Emotions such as hopelessness, fear, and depression are not uncommon after the results of a genetic test are revealed. The genetic counselor can also make referrals or recommendations for additional mental health care if it is indicated. A determination of a high level of risk can also place a significant strain on family relationships. People have to decide with whom to share the newly received information. Finding out that a family member is at an increased risk of developing cancer can cause feelings of fear and sadness. It is very important to help family members understand that having an increased risk of developing cancer does not mean that the person will definitely develop 516
Salem Health: Cancer cancer. People must also decide whether to share the information with extended family members. This can cause strained relationships as difficult issues are brought up. There are risks to genetic counseling even if the eventual determination is that the person is not at an increased risk. This determination does not mean that the person will definitely not get cancer; it means only that the person’s risk of developing the cancer is not believed to be above that of the general population. There is still some chance that cancer will develop. One risk of genetic counseling is that people who are found not to be at an increased risk may neglect important, normal screening procedures, such as regular mammograms. There are some risks that those who undergo genetic counseling will be subjected to discrimination in employment or have problems obtaining life or health insurance. The legislation concerning these issues is complex and developing, so people should discuss these risks with a genetic counselor or other knowledgeable health care professional before undergoing genetic counseling. People may also want to consult other sources of information such as insurance companies, a lawyer, or government Web sites. Helen Davidson, B.A. u
For Further Information Pupecki, Sandra R., ed. Genetic Screening: New Research. New York: Nova Science, 2006. Schneider, Katherine A.. Counseling About Cancer: Strategies for Genetic Counseling. 2d ed. New York: WileyLiss, 2002. Skirton, Heather, Christine Patch, and Janet Williams. Applied Genetics in Healthcare: A Handbook for Specialist Practitioners. New York: Taylor & Francis Group, 2005. Young, Ian D. Introduction to Risk Calculation in Genetic Counseling. 3d ed. New York: Oxford University Press, 2007.
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Other Resources
American Board of Genetic Counseling http://www.abgc.net/english/view.asp?x=1 National Society of Genetic Counselors http://www.nsgc.org See also Cancer education; Epidemiology of cancer; Family history and risk assessment; Gene therapy; Genetic testing; Hereditary cancer syndromes; Oncology social worker.
Salem Health: Cancer
u Genetic testing Category: Procedures; social and personal issues Also known as: Deoxyribonucleic acid (DNA) testing, gene testing, genetic screening, molecular genetic testing Definition: Genetic testing is a medical test identifying genetic composition. DNA for genetic testing can be extracted from the cells of many different body fluids or tissues. The majority of genetic tests are completed by using DNA from blood cells. Other sources include cells obtained from the cheek lining using swabs or a mouthwash, hair root cells, or the cells in the fluid surrounding a fetus in the womb (amniotic fluid). Gene analysis is accomplished by examining chromosomes, DNA codes, or the proteins produced by genes. Why performed: Typically, genetic testing is used to find inherited genetic disorders. Genetic testing can determine an individual’s genetic composition and can help determine if the tested person has an inherited disorder. Genetic testing can also help establish whether a person can develop genetic diseases or pass them on to subsequent generations. Sometimes genetic tests are used to assess disease risk. A genetic test can help assess genetic predisposition to colon and breast cancer. This test can determine whether a person has an increased likelihood or propensity to develop colon or breast cancer. Such a test gives an idea of an individual’s risk of having the disease but does not determine with absolute certainty whether a person will get breast or colon cancer. A person with a negative test (lacking the genetic marker) could still get breast or colon cancer. Conversely, a person with a positive test (possessing the genetic marker) may not get breast or colon cancer. A person with a positive test will, however, have an increased chance of getting breast or colon cancer compared with a person with a negative test. Many genetic tests are available, and descriptions of most of them are provided by the National Library of Medicine and the National Genome Research Institute. Some of these genetic tests determine chromosomal abnormalities, such as those resulting in Down syndrome, and some identify DNA genetic code changes, such as those occurring with sickle cell anemia. Some of the more common types of tests are described here. Newborn screening: Infant screening after birth identifies treatable genetic disorders. This type of genetic screening has been done for decades in the United States and is routinely completed on millions of newborns yearly in all
Genetic testing fifty states. For example, infants are screened for phenylketonuria, a disorder that causes mental retardation if unrecognized and untreated, and other genetic disorders such as congenital hypothyroidism. Diagnostic testing: Genetic testing to determine if a particular disease is present is called diagnostic testing. Usually, these types of tests are used to diagnose a disease suspected on the basis of the patient’s family health history, personal health history, physical examination, or symptoms. Carrier testing: Normally, people have two copies of almost all the genes in the body; one copy comes from the father and the other from the mother. Some diseases, known as recessive disorders, will express themselves (cause a disorder) only if both copies of the gene have the disease trait. An example is sickle cell anemia. Carrier testing can determine if a person has one or two copies of the recessive gene. The person who has two copies of the gene with the disease trait will have the disease. The person who has one copy of the gene with the trait and one normal copy of the gene is known as a carrier of the disease. This person does not have the disease itself but carries the disease trait and has a 50 percent chance of passing the trait (gene) to any offspring. This type of testing is useful for individuals with a family history of a genetic disorder. Testing couples who plan to have a child for recessive genetic disorders helps establish their risk of having a child with a genetic disease. Prenatal testing: Some birth defects and inherited disorders, such as spina bifida and Down syndrome, can be detected with prenatal testing. This type of information can help parents make important decisions regarding the care of a disabled child or the progress of a pregnancy. Predictive testing: This type of genetic test can determine potential risk for some diseases such as colon cancer, breast cancer, ovarian cancer, or hemochromatosis (an iron metabolism disorder resulting in too much iron in the body). For example, the presence of BRCA1 and BRCA2 genes indicate a higher risk for breast and ovarian cancer. Forensic testing: Forensic testing, such as DNA fingerprinting or paternity testing, is used for criminal investigations or to establish biological parenthood. DNA fingerprinting is accomplished by breaking down DNA into smaller segments. The technique involves using compounds that attack DNA sequences at particular points, splitting the DNA into several fragments. These break points are different in each person because everyone has a unique DNA sequence (unless the person is one of a pair of identical twins). The fragments are lined up and com517
Genetic testing
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pared with DNA left at crime scenes (and usually with that of people who are not suspects and serve as controls). Matches are very evident visually. Pharmacogenomics: Genetic testing to determine response to therapy is known as pharmacogenomics. Many tests to predict how effective a medicine will be in a particular person are being developed, and some of these types of genetic tests are available. For example, a medication called trastuzumab treats breast cancer but is effective only when the breast tumors have estrogen receptors. A genetic test determines if a woman’s breast tumors have estrogen receptors and, therefore, trastuzumab will help treat them. More tests that predict how a specific person may respond to medications for cancer, asthma, heart disease, and other diseases have entered into development. Preimplantation genetic diagnosis: In vitro reproduction occurs when egg cells are removed from a woman’s ovaries and fertilized with sperm outside the body. The embryos formed this way are then implanted in a woman’s uterus. Before implantation, cells are taken from the embryos and screened for specific genetic disorders. This ensures that embryos lacking the specific genetic disorders are implanted. Direct-to-consumer genetic testing: Some genetic testing laboratories sell genetic tests directly to consumers through print, television, and Internet advertisements. A test for the BRCA1 and BRCA2 genes that have been associated with breast and ovarian cancer was marketed directly to consumers, as were tests for markers for hemochromatosis and cystic fibrosis. Although this type of marketing can raise awareness of the tests, concerns have been raised about the accuracy of information presented in advertisements. One form of direct-to-consumer genetic test arouses particular concern. Some Web sites have begun selling genetic tests for aging, behavior, and nutrition. The tests provide genetic profiles that are matched to consumer goods such as creams and dietary supplements. Little scientific study supports the commercial pairing of these types of genetic tests with the goods offered. Regardless of the type of direct-to-consumer genetic test, the lack of genetic counseling and the absence of health care professionals in the process raise concerns about how well these genetic tests are interpreted and applied. Often, genetic tests have great implications for not only the person taking the test but also relatives of the person taking the tests. These types of concerns have caused some to advocate more government oversight and regulation of direct-to-consumer genetic testing. 518
Results from genetic tests, which can help assess one’s genetic predisposition to several cancers. (Digital Stock)
The case of breast cancer genes: A closer look at BRCA1 and BRCA2, the breast cancer genes, provides some background information and shows how testing relates to the science of genetics. The human body is constantly replacing cells in a process called mitosis. Mitosis is the orderly duplication of cells that ensures each cell has the exact same genetic information. Over the course of many years, some mutations or changes in the genetic code can appear, and these changes may result in uncontrolled cell division. When mitosis is not carefully regulated, tumors or cancers can develop. The majority of cancers are due to noninherited changes in the genetic code that occur during life. However, 5 to 10 percent of all breast and ovarian cancers may have a genetic basis. A person can inherit a mutation in a tumor-suppressor gene, which controls cell division and growth and therefore protects against cancer. From birth, the person who inherits the mutated tumorsuppressor gene does not have carefully controlled cell division. Many factors play a role in determining if the per-
Salem Health: Cancer son who inherits the mutated gene will actually develop cancer. People have two copies of every gene (one from the mother and one from the father), and the normal copy of that tumor-suppressor gene may prevent cancer from developing. Additional tumor-suppressor genes may also prevent the development of cancer. A person inheriting a mutated tumor-suppressor gene has an increased risk of developing cancer but not an absolute (100 percent) risk of getting cancer. The cancer itself is not inherited, but a defective gene that does not adequately protect against cancer is inherited. If a person inherits one of these defective genes and develops cancer, the condition is called hereditary cancer. Ovarian or breast cancer are regulated by many genes, but two of them have been named and can be found through genetic testing. BRCA1 is short for breast cancer 1 gene, and BRCA2 is short for breast cancer 2 gene. BRCA1 and BRCA2 are tumor-suppressor genes, and they keep cell reproduction from getting out of control. BRCA1 and BRCA2 genes are present in both men and women. If a person inherits a faulty or mutated copy of BRCA1 or BRCA2, that person has an increased risk of developing breast or ovarian cancer, along with a slightly higher risk of developing any type of cancer. Because half of all genes are inherited from the mother and half are inherited from the father, a mutated BRCA1 or BRCA2 gene can be inherited from either parent. If a person has a faulty BRCA1 or BRCA2 gene, each of the person’s children has a 50 percent chance of inheriting the faulty gene. Although inheriting a faulty BRCA1 or BRCA2 gene increases a person’s genetic predisposition for breast or ovarian cancer, environmental factors still play a large role in determining whether the person develops breast or ovarian cancer. More mutations in other tumor-suppressor genes need to occur for the person to develop cancer. The causes of the mutations acquired during a lifetime are largely unknown and subject to much speculation and scientific research. One branch of genetic research involves looking not only at the genetic code present in DNA but also into how ribonucleic acid (RNA), another molecule that carries genetic information, may be contributing to cancers. This BRCA1 and BRCA2 example shows how one of the nearly one thousand available genetic tests relates to the science of genetics. It demonstrates the complex relation between genes and disease, and it underscores the necessity of accurate genetic information and competent and caring counseling. As the number of genetic tests grows, it becomes more important to understand the science behind the tests as well as their social implications and applications. Richard P. Capriccioso, M.D.
Genetics of cancer u
For Further Information Institute of Medicine of the National Academies. CancerRelated Genetic Testing and Counseling: Workshop Proceedings. Washington, D.C.: National Academies Press, 2007. Langreth, Robert. “Genetic Report Card.” Forbes, June 18, 2007, pp. 58-59. Lorenz, Eva. “Predictive Testing in the Workplace: Could the German Model Serve as a Blueprint for Uniform Legislation in the United States?” North Carolina Journal of Law and Technology 7, no. 2 (Spring, 2006). Schoonmaker, Michele, and Erin D. William. Genetic Testing: Scientific Background and Nondiscrimination Legislation. New York: Novinka Books, 2006. Sharpe, Neil F., and Ronald F. Carter. Genetic Testing: Care, Consent, and Liability. Hoboken, N.J.: WileyLiss, 2006.
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Other Resources
Centers for Disease Control and Prevention National Office of Public Health Genomics http://www.cdc.gov/genomics Centre for Genetics Education http://www.genetics.com.au Genetics Home Reference http://ghr.nlm.nih.gov National Institutes of Health National Human Genome Research Institute http://www.genome.gov See also Cancer education; Epidemiology of cancer; Family history and risk assessment; Gene therapy; Genetic counseling; Hereditary cancer syndromes; Oncology social worker.
u Genetics of cancer Category: Cancer biology Definition: Genetics of cancer can be defined as the study of heredity and variation in the development of cancer. Description: Inheritance of characters or traits occurs through basic units of heredity called genes. Each human cell consists of twenty-three pairs of chromosomes containing genes inherited from both biological parents. Of these, some genes are dominant, requiring only one copy to exert their effects, while others are recessive, requiring both copies to be in place to cause any changes. Aberra519
Genetics of cancer tions in chromosomes on the whole or mutations in specific genes without chromosomal modifications could lead to cancer development. However, only about 5 to 10 percent of cancers are attributed to heredity. Most cancers are acquired during the course of a person’s life, primarily because of changes (called mutations) that occur in normal genes. Exposure to chemicals (for example, in smoking) and radiation (emitted by various sources, including the sun) poses a high probability of inducing mutations in genes. Chromosomal aberrations such as deletion of an entire chromosome, multiplication of certain chromosomes, or translocation of certain parts of chromosomes are probable causative agents for cancer. A normal cell gets transformed into a malignant cancer cell in a multistep process and as a consequence of a concatenation of events leading to modifications in many of its genes. These changes primarily enable normal cells to acquire uncontrolled growth potential, resulting in the formation of tumors. Tumor development culminates in metastasis, a process in which cancerous cells travel through blood vessels and invade other organs of the body. Genetic changes suggested as hallmarks of cancer include the following: • Self-sustained growth that is independent of availability of external growth factors • Resistance to signals controlling cell growth and proliferation • Methods to evade mechanisms of the programmed cell death pathway (apoptosis) • Uncontrolled capacity to replicate • Sustained capability to produce new blood vessels (angiogenesis) required for growth and survival of tumors and resistance to antiangiogenesis factors • Capability to overcome stringent physiological barriers and get transported to other regions of the body and spread (metastasis) Broadly, these properties can be encompassed within three categories of gene mutations: mutations occurring in proto-oncogenes, mutations of tumor-suppressor genes, and mutations in deoxyribonucleic acid (DNA) repair genes. Mutations of proto-oncogenes: Proto-oncogenes are genes that are responsible and required for normal growth and development. Normal growth and development are complex physiological processes that require activation of a number of genes, which is made possible by signal transduction mechanisms that are inherent in cells. Signal transduction is a process whereby a signal received by the cell from its external environment is processed and transduced to the internal milieu, resulting in activation 520
Salem Health: Cancer of a variety of genes. Physiological processes such as cell division and proliferation are initiated by many signal transduction pathways. Of the approximately thirty thousand genes that have been mapped in the human genome, nearly one hundred have been identified as proto-oncogenes. Mutated or damaged proto-oncogenes are called oncogenes. Presence of oncogenes in cells has been directly correlated with development of most types of cancers. A wide array of genes have been identified as oncogenes in humans. These genes are called gain-of-function genes, as they gain the capacity to induce tumor development as a result of mutations. They become hyperactivated in the mutated state and, consequently, initiate multitudes of cell signal transduction pathways, ultimately resulting in uncontrolled cell division and growth. The mitogen-activated protein kinase (MAPK) pathway is one such signal transduction pathway that has been implicated in most cancers. Mutations occurring in genes involved in this signal transduction cascade impede communication within and between cells, resulting in abnormal growth and ultimately in tumor development. Specific examples include the RAS and BRAF gene families. About 25 percent of all cancers have recorded some kind of mutation in RAS family members. The MAPK signal transduction cascade is initiated by the activation of cell-surface receptors such as tyrosine kinase and epidermal growth factors that traverse cell membranes. Inhibitors of receptor activation are being tried as possible therapeutic agents for cancer. Mutations of tumor-suppressor genes: Tumor-suppressor genes are a class of genes whose protein products control cell division and death. Most often, the protein products of these genes act directly on cells and usher them toward the so-called “suicidal” or apoptotic pathway. In cancer cells, such an entry into the apoptotic pathway is rendered impossible because of mutations in tumorsuppressor genes. Tumor-suppressor genes are called lossof-function genes because mutations in these genes result in the loss of their normal function of tumor suppression. It is noteworthy that these genes belong to the recessive class of genes. The significance of this is that a single copy of a normal tumor-suppressor gene is enough to exert a beneficial effect. Mutations in both copies of the genes could result from hereditary or environmental factors or aging. Most tumor developments document mutations in tumorsuppressor genes. A classic example of a tumor-suppressor gene is TP53. A majority of the cancers reported in human cells exhibit either an abundance of abnormal TP53 genes or the ab-
Salem Health: Cancer sence of normal TP53 genes and signaling pathways. There is also overwhelming evidence to show that mutant TP53 protein acquires novel oncogenic traits that provide a favorable environment for development, sustenance, and resistance of tumor cells. Replacement of the normal, wild-type TP53 gene using a retroviral TP53 expression vector is an attempted method of controlling cancer cell growth in gene therapy. In addition to the TP53 gene, its homologs TP73 and TP63 have also been identified in the induction of cancer. Mutations in DNA-repair genes: Exposure to certain types of radiation such as ultraviolet (UV) light can induce damage in DNA. Cells have evolved normal repair mechanisms that can detect and correct such damage through specific genes called DNA-repair genes. Therefore, most mistakes usually go unnoticed. However, when mutations occur in DNA-repair genes, damaged and malfunctioning DNA accumulates in cells, interfering with normal processes and inducing tumor development. Mistakes occurring in genes such as tumor-suppressor genes, if not repaired in time, can lead to cancer formation. DNA-repair genes are recessive genes, and therefore it is imperative to have mutations in both copies of the gene to have visible effects. Examples for this category of mutations are observed in the skin cancer condition xeroderma pigmentosum, as well as in some forms of colon cancer. In these colon cancers, DNA-repair genes MLH1 and MSH2, located on chromosomes 3 and 2, respectively, are mutated and damaged. Chromosomal aberrations: Chromosomes have distinct sizes and characteristics, and accordingly, each chromosome has been designated a unique number and can be distinguished easily in modern karyotyping tests. Sometimes, for various reasons, including being fertilized by more than one sperm, cells can acquire an abnormal number of chromosomes, a condition called aneuploidy. In other cases, the number of chromosomes may not be different from the normal forty-six, but portions of chromosomes may be deleted, added, or translocated to a different chromosome. Some of these modifications could shuffle relevant genes, leading to cancer development. Chronic myeloid leukemia (CML) is a classic example of such a cancer. In this case, a small portion of genetic material from chromosome 22 is translocated to chromosome 9 and vice versa (a condition called reciprocal translocation). A consequence of this translocation is the transfer of a normal proto-oncogene called ABL1 from chromosome 9 to chromosome 22. Movement of ABL1 to chromosome 22 is responsible for its conversion to an oncogene and ulti-
Genetics of cancer mately to malignancy. Other cancers resulting from a similar translocation between chromosomes 9 and 22 are acute lymphoblastic leukemia and adult acute myelogenous leukemia. Burkitt lymphoma, a B-lymphocyte malignancy most common in African children, is induced by translocation of genetic materials between chromosomes 8 and 14, resulting in activation of the oncogene MYC. Heritability of cancer: Whether the incidence of cancer is caused by alterations of whole chromosomes or of specific genes, its inheritance is variable. In some cancers such as retinoblastoma, a childhood eye cancer, tumor development occurs only with deletions in both copies of chromosome 13. Children with deletion in one copy of the chromosome are at risk for the disease because every cell in these patients possesses this deletion, but a second mutation, in the remaining complete copy of the chromosome, is required for disease development. Similar is the case of Wilms’ tumor, a childhood kidney cancer condition, in which the abnormality in chromosome 11 is inherited in one copy, but a second mutation is necessary for tumor expression. Other kinds of cancers that have genetic predispositions include xeroderma pigmentosum, Paget disease of bone, ataxia telangiectasia, and Fanconi anemia. There are several common examples of familial cancer syndromes that predispose subsequent generations of patients to cancers. Common examples are colon cancers, breast cancers, and prostate cancers. Colon cancers occur because of two kinds of hereditary conditions: familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC). FAP involves mutations of a tumor-suppressive gene called APC and interactions between TP53 and KRAS genes. HNPCC occurs as a result of mutations in MLH1 and MSH2 genes that are involved in DNA repair. Approximately 80 percent of patients with familial early-onset breast and ovarian cancers exhibit mutations in a tumor-suppressor gene called BRCA1. This and another gene called BRCA2 are examples in which mutations have penetrated into the reproductive cells (germ-line mutations) and therefore are inherited, predisposing women to these cancers. Similarly, mutations in the gene HPC1 (hereditary prostate cancer 1), located on chromosome 1, are responsible for most familial cases of prostate cancer. Epigenetics and cancer: Epigenetics can be defined as the study of those factors other than traditional DNA sequences that are inherited during cell division. These can be monogenic (involving a single gene) or multigenic (involving multiple genes). The most prevalent epigenetic disease is due to loss of phenotypic plasticity (the ability of 521
Geography and cancer cells to alter their behavior as a response to alterations in internal or external environments). This loss of genomic imprinting is the first reported molecular evidence that epigenetics plays a role in cancer. Considerable attention is therefore being focused on epigenetic aspects of cancer development. Progress and perspectives: Progress in discovering, analyzing, and profiling genetic determinants of cancer has been excellent. Advances in molecular biological techniques and the cracking of the human genome have enabled forays into various aspects of cancer. Techniques such as array comparative genomic hybridization (aCGH), which can measure DNA copy number alterations (CANs), are important contributions toward correlating genetic factors with human diseases. The advent of therapeutic strategies such as gene therapy has advanced researchers’ ability to overcome various impediments posed by traditional treatment strategies. Previously unimaginable approaches, such as introduction of a supernumerary artificial chromosome with relevant beneficial genes to cure cancer and other diseases, have begun to be attempted. However, because of its ability to alter genes, which are the basic units of heredity and variation, gene therapy encounters multitudes of social and ethical concerns. Similarly, other benefits offered by diagnostic tools such as genetic testing should be handled with caution. Statistics show that only about 5 percent of cancers are inherited or due to heredity; therefore, being aware of and cautious about various risk factors such as carcinogens and viruses remains the recommended way of preventing cancer. Geetha Yadav, Ph.D. u
For Further Information Hanahan, D., and R. A. Weinberg. “Hallmarks of Cancer.” Cell 100 (2000): 57-70. Hartage, P. “Genes, Cancer Risks, and Clinical Outcomes.” New England Journal of Medicine 2 (2007): 115-123. McKinnell, G. R., R. E. Parchment, A. O. Perantoni, and G. Barry Pierce, eds. The Biological Basis of Cancer. New York: Cambridge University Press, 1998. Nguyen, D. X., and J. Massague. “Genetic Determinants of Cancer Metastasis.” Nature Reviews (Genetics) 8 (2007): 341-352. Pianno, J. Cancer: The Role of Genes, Lifestyle, and Environment. New York: Facts On File, 2005. Rosman, Diana S., Virginia Kaklamani, and Boris Pasche. “New Insights into Breast Cancer Genetics and Impact on Patient Management.” Current Treatment Options in Oncology 8, no. 1 (February, 2007): 61-73. 522
Salem Health: Cancer u
Other Resources
Cancer Genetics Web http://www.cancerindex.org/geneweb Centers for Disease Control and Prevention National Office of Public Health Genomics http://www.cdc.gov/genomics Genetics Home Reference http://ghr.nlm.nih.gov Human Genome Project Information Genetic Disease Information http://www.ornl.gov/sci/techresources/ Human_Genome/medicine/assist.shtml National Cancer Institute Cancer Genetics http://www.cancer.gov/cancertopics/ prevention-genetics-causes/genetics See also APC gene testing; BRAF gene; BRCA1 and BRCA2 genes; Cancer biology; Childhood cancers; Chromosomes and cancer; Cytogenetics; DPC4 gene testing; Family history and risk assessment; Gene therapy; Genetic testing; Hereditary cancer syndromes; HRAS gene testing; Mitochondrial DNA mutations; MLH1 gene; MSH genes; MYC oncogene; Oncogenes; PMS genes; Proteomics and cancer research; Proto-oncogenes and carcinogenesis; RB1 gene; RhoGD12 gene; SCLC1 gene; TP53 protein; Tumor markers; Tumor-suppressor genes.
u Geography and cancer Category: Social and personal issues Definition: Cancer geography is concerned with the geographic distribution of various forms of the disease. By mapping the location of cancer incidence and identifying such things as cancer clustering, it aims to improve the understanding of the various factors that affect the health of individuals. It is akin to epidemiology, the study of the causes, distribution, and control of disease in populations. Cancer and world populations: Although there is much to be discovered about the biological causes of cancer, it has been determined that cancer affects populations differently in various parts of the world. The incidence of cancer may be strikingly different even among regions inside a given country or quite similar between populations in countries that are widely separated geographically. A number of factors enter into identifying how particular kinds of cancer affect world populations. Certain kinds of cancer
Salem Health: Cancer may occur in differing patterns between men and women, white or black populations, northern or southern areas, urban or rural groups, poor or affluent populations, Western or Eastern peoples, developed or developing countries, and among ethnic subgroups. An examination of the distribution of some of the more common types of cancer will reveal the wide variations that appear throughout the world. Reporting of cancer incidence is typically made as age-standardized incidence rates per 100,000 persons. Lung cancer: Worldwide, the cancer most often diagnosed and the one with the highest mortality rate is lung cancer. In the United States, only 14 percent of lung cancer patients survive five years after diagnosis. International variations in lung cancer incidence are wide, ranging from an incidence rate of below 10 per 100,000 in parts of Africa, China, and South America to over 100 per 100,000 in some black populations in the United States. Although the greatest risk factor is cigarette smoking, atomic radiation and air pollution are risks associated with geography. The incidence of lung cancer is higher worldwide among men than in women and rises sharply with age. Among men, lung cancer incidence rates in Middle Eastern populations are much lower than in Western populations, except for male Israeli Arabs. The incidence rates in Canada and Ireland are similar to the rate in the United States. Cancers of the digestive tract: Worldwide, esophageal cancer ranks seventh in incidence, appearing most often in central and western Asia. The geographical differences in the incidences of esophageal cancer are more marked than for any other type of cancer. One especially high-risk area ranges from northern Iran to north-central China and consequently has been labeled the “esophageal cancer belt.” However, the rate of incidence of esophageal cancer in some of the countries in the same general part of the world, such as Syria, Jordan, and Israel, is among the lowest worldwide, possibly attributable to low levels of alcohol consumption; however, these same countries have a high prevalence of smoking, a major risk factor. Worldwide, incidence rates are higher in men than in women (7:1), and they increase with age. Unlike in the United States, where adenocarcinoma is the most common type, 95 percent of all esophageal cancer in the rest of the world is squamous cell carcinoma. In England, esophageal cancer is found more often in rural than in urban areas, but the opposite is true in Denmark. The incidence rate of adenocarcinoma is twice as high for white as for Hispanic men and four times as high as that for blacks, Asian and Pacific Islanders, and Native Americans. Female rates are lower across the board. On the other hand, squamous cell carcinoma rates are highest in African Americans.
Geography and cancer
Age-Adjusted Incidence Rates for Stomach Cancer in Men by Geographical Area Geographical Area Eastern Asia Central and Eastern Europe Polynesia South America Southern Europe Central America Caribbean Middle Africa Western Europe Northern Europe Western Asia Australia/New Zealand Southeastern Asia Southern Africa Northern America Eastern Africa South-Central Asia Melanesia Micronesia Western Africa
Rate per 100,000 People 46.1 29.6 24.7 24.3 18.0 15.2 13.6 13.4 12.8 12.4 11.7 9.9 8.6 8.2 7.7 7.4 6.9 6.3 5.5 3.4
Source: Data from GLOBOCON 2002, CancerMondial, and International Agency for Research on Cancer Note: Populations are estimated for the middle of 2002; however, disease data are from most recent data, not 2002, available at the International Agency for Research on Cancer
The incidence of stomach cancer, also called gastric cancer, is second only to that of lung cancer worldwide. The areas of highest risk are East Asia, South America, and Eastern Europe. In fact, about 38 percent of stomach cancer cases worldwide are in China. Incidence rates in Japan are the highest in the world. Interestingly, Chinese laborers in Sumatra, an Indonesian island in East Asia, have a high rate of both stomach and liver cancer, but Javanese laborers, who work alongside the Chinese, have almost no stomach cancer, though they, too, have a high liver cancer rate. Second-generation immigrants who come from highto low-risk areas are less likely to develop stomach cancer than were their parents. Incidence rates for men are double those for women. Globally, the incidence rate for colorectal cancer is 20.1 per 100,000 men and 14.6 per 100,000 women; however, this cancer is much more common in the Western world, higher both in incidence and in mortality (incidence 523
Geography and cancer rates of 40.0 per 100,000 in men and 26.6 per 100,000 in women), while the incidence rates are only 10.2 per 100,000 for men and 7.7 per 100,000 for women in Asia and Africa. The highest incidence rates in men are found in Australia and New Zealand (48.4), followed by North America (44.4) and Western Europe (42.9). The lowest rates worldwide are in South-Central Asia (4.7) and Central Africa (2.3). Migrants from low-risk areas to highrisk Western countries experience a rapid increase in colorectal cancer risk within a generation, possibly because of changes in dietary habits. Low consumption of red meat and dietary fat in Asian and African countries seems to play a role in the low incidence there. Some studies suggest that tobacco and alcohol use may also play a role. Genetic risk factors have also been identified; for example, Ashkenazi Jews and Israeli Ashkenazi Jews (Jews of European origin) have a significantly increased risk of having colorectal cancer. The low incidence in some areas, such as Egypt, could be because of low detection rates or local protective nutritional factors. Incidence of pancreatic cancer ranks thirteenth worldwide, but this cancer ranks considerably higher in its mortality rate, partly because of late diagnosis. The highest incidence is in African American men and in Hawaiians, but there are also high rates among Korean, Czech, Latvian, and New Zealand Maori men. The Scandinavian countries have the highest rates of incidence in Europe. In some areas of the world, notably India, pancreatic cancer is rare. Kidney and urinary tract cancer: Kidney cancer is found mainly among white populations from developed countries in which risk factors are unusually prevalent. Worldwide, the Czech Republic has the highest incidence, with an incidence rate of 22.25 per 100,000 in men, followed by Estonia, Hungary, Slovakia, Lithuania, Uruguay, Latvia, Germany, Iceland, Finland, Israel, the United States, and Canada. In general, rates are considerably lower in Asian, African, and some South American countries. The bladder is one of the most common sites of cancer worldwide, but the highest incidence is in industrialized countries. Incidence rates of more than 40 per 100,000 have appeared in Europe, notably in Belgium and Italy. In the United States and Canada, the rate is about half of that in Europe. The lowest incidence rates are in Asia and South America. More men than women develop bladder cancer, but the geographical pattern for women is the same as for men. Breast cancer: Globally, breast cancer is the second leading cause of death in women. It is the most common cancer among women, excluding nonmelanoma skin cancer. The 524
Salem Health: Cancer incidence is highest in Northern America, followed by East Asia, South-Central Asia, Western Europe, and Eastern Europe; the lowest rates are in Micronesia and Polynesia. In the United States, the estimated incidence of new cases is highest in California, Florida, and New York, while Alaska, Wyoming, and Utah are projected to have the fewest. Interestingly, in Massachusetts, which is estimated to have a rather modest number of new cases, Cape Cod has a rate 20 percent higher than that of the rest of the state, attributed to aerial spraying with the now-banned dichloro-diphenyl-trichloroethane (DDT). Similar “hot spots” occur in Long Island, New York; San Francisco; Puget Sound, Washington; and Brownsville, Texas. In India, there is a wide variance in breast cancer incidence between women in the Parsi (or Parsee) sect of the Zoroastrian community in the Mumbai (formerly Bombay) area and Hindu women; Parsis have three times the incidence of breast cancer as of cervical cancer, but the opposite is true among Hindu women. Cancers of reproductive system organs: Among women, globally, cervical cancer is the second most common form of cancer: It is estimated that there were 493,000 new cases (compared with 1.15 million of breast cancer) and 274,000 deaths (compared with 411,000 from breast cancer) in 2002. In general, cervical cancer is much more common in developing countries (15 percent of all new female cancers) than in developed countries (3.6 percent of all new female cancers). It is the most common form of malignancy in parts of Africa, Asia, and South America. Researchers suggest that the world differences in incidence are attributable in part to socioeconomic and behavioral differences among countries. Screening programs may account for substantial declines in incidence and mortality in Western developed countries over the past several decades. Throughout the 1990’s, the major risk factor for developing cervical cancer was human papillomavirus (HPV) infections; however, this finding has been questioned by some researchers. Uterine cancer, also called corpus (body of the uterus rather than the mouth, or cervix) or endometrial cancer, has a distribution pattern similar to that for ovarian cancer. The highest incidence appears in North America, with incidence rates of 18 per 100,000 in whites in the United States and about 15 per 100,000 in whites in Canada. Eastern European countries such as the Czech Republic, Slovakia, and Latvia have rates comparable to those in the United States. There are low rates (less than 6 per 100,000) in eastern and southern Asia and in most of Africa. However, among Middle Eastern countries, the incidence rate in Israeli Jews was similar to those in Japan, Kuwait, the
Salem Health: Cancer Venetian region of Italy, Switzerland, and Spain; the low rate found among Israeli Arabs was similar to rates observed in the Beijing, Shanghai, and Tianjin areas of China (no cases were found in some parts of China). Although Africa generally enjoys low rates, the highest rates there were found in Zimbabwe (55.4 per 100,000) and Uganda (41.7 per 100,000). Much research indicates that ovarian cancer occurs more often among middle- and upper-class women from industrialized nations, especially those in Western and Northern Europe and North America, and is uncommon in less developed countries. Among cases diagnosed in Middle Eastern countries, female Israeli Jews have the highest incidence rate (9.4 per 100,000). One possible explanation is differing dietary factors. Ovarian cancer ranks fifth among cancers found in women. The majority of ovarian cancers are diagnosed at an advanced stage because few symptoms are visible in the early stages. Although there are a number of risk factors, those related to geography are being white (although some studies maintain that race is not a factor) and living in a sunlight-deficient area (with consequent deficiency in vitamin D). Generally, it was found that the higher the latitude, the higher the risk. For example, incidence in Iceland and Norway was about five times that in equatorial regions such as Asia, South America, and Africa. Prostate cancer is one of the most prevalent cancers among men, especially in Western countries such as Norway, Sweden, and the United States. There is marked variation in incidence worldwide, with a ratio of 1:100 between low- and high-incidence countries. The lowest rates are found in parts of China and in other Asian countries. Genetic factors may explain some of the geographical variation, but environmental factors probably explain why Chinese and Japanese who emigrate to Hawaii and California have higher rates than are found in their native countries. Thyroid cancer: Although the incidence of endocrine gland malignancies, such as thyroid cancer, is relatively low worldwide, the rate has been on the increase for several decades. Among women in the United States, thyroid cancer is the eighth most common malignancy. In the Middle East, the rates are highest for Israeli Jews and lowest for Egyptians. The major risk factor for the most common types is radiation exposure in childhood. Thus, survivors of the Japanese atomic bombings, those exposed to radioactive fallout in the Chernobyl disaster in the Ukraine, and people exposed to radiation from nuclear testing account for geographical differences in the incidence rates. Follicular thyroid cancer incidence is related to iodine defi-
Germ-cell tumors ciency and endemic goiter. However, an iodine-rich diet may be associated with higher incidence of the papillary type of cancer. The incidence rate is highest in Iceland, for both women and men, although the disease is much more prevalent in women than men worldwide. Victoria Price, Ph.D. u
For Further Information American Cancer Society. Cancer Facts and Figures for African Americans. Atlanta: American Cancer Society, 2007. Gatrell, A. C. Geographies of Health: An Introduction. Malden, Mass.: Blackwell, 2002. Howe, G. Melvyn, ed. Global Geocancerology: A World Geography of Human Cancers. New York: Churchill Livingstone, 1986. Meade, M. S., and R. J. Earickson. Medical Geography. 2d ed. New York: Guilford, 2005.
u
Other Resources
Cancer Research UK Cancer Worldwide http://info.cancerresearchuk.org/cancerstats/ geographic/world/ Centers for Disease Control and Prevention National Center for Disease Statistics http://www.cdc.gov/nchs/gis.htm International Agency for Research on Cancer CancerMondial http://www-dep.iarc.fr World Health Organization Cancer http://www.who.int/topics/cancer/en See also Cancer clusters; Developing nations and cancer; Epidemiology of cancer; Ethnicity and cancer; Poverty and cancer; Statistics of cancer.
u Germ-cell tumors Category: Diseases, symptoms, and conditions Also known as: Seminoma, nonseminoma, embryonal cell cancer, teratoma, endothermal signal tumor, mature and immature teratomas Related conditions: Testicular cancer, ovarian cancer Definition: Germ-cell tumors (GCTs) are tumors of cancerous or noncancerous cells that arise from germ cells during embryonic development. 525
Germ-cell tumors Risk factors: The only confirmed risk factors of germ-cell tumors involve birth defects. Male infants with undescended testis (chryptorchidism) are ten to forty times more likely to develop germ-cell tumors than male infants with normally descended testes. Children with the genetic disease Klinefelter syndrome are also at an increased risk for germ-cell tumors. Etiology and the disease process: Germ cells are the cells that develop in the embryo and become the cells that make up the reproductive system in men and women. These germ cells follow a midline path through the body after development and descend into the pelvis as ovarian cells or into the scrotal sac as testicular cells. Most ovarian tumors and testicular tumors are of germ-cell origin. Germ-cell tumors can spread (metastasize) to other parts of the body. The most common sites for metastasis are the lungs, liver, lymph nodes, and central nervous system. Rarely, germcell tumors can spread to the bone, bone marrow, and other organs. Types of germ-cell tumors include the seminoma (in testis), dysgerminoma (in ovary), teratoma, endodermal sinus tumor, embryonal, and choriocarcinoma. Extragonadal germ-cell tumors form from developing sperm or egg cells that travel from the gonads to other parts of the body. Extragonadal germ-cell tumors can be benign (noncancerous) or malignant (cancerous). Benign extragonadal germ-cell tumors are called benign teratomas. These are more common than malignant extragonadal germ-cell tumors and often are very large. Teratomas can be further classified into mature (lining resembles that of skin) and immature (cancer cells look like cells from a developing fetus). Incidence: Germ-cell tumors are diagnosed in about 900 children each year. Germ-cell tumors account for 16 percent of all cancers diagnosed in adolescents between the ages of fifteen and nineteen and nearly 4 percent of cancers diagnosed in children younger than fifteen. In women, germ-cell tumors account for 30 percent of ovarian tumors, but in patients under the age of twenty-one, 60 percent of ovarian tumors are of the germ-cell type. Most male adolescents are diagnosed with germ-cell tumors after puberty; these tumors are usually malignant. The incidence in whites is five times higher than in blacks. For unknown reasons, worldwide incidence has more than doubled in the past forty years. The incidence of germ-cell tumors varies by geographic area. The highest incidence is in Scandinavia, Germany, and New Zealand; it is lower in the United States and lowest in Asia and Africa. 526
Salem Health: Cancer Symptoms: Patients with germ-cell tumors usually complain of a tumor, swelling, or mass that can be felt or seen, and abnormal shape, or irregularity in, testicular size. Additional symptoms can include elevated levels of alphafetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). Constipation, incontinence, and leg weakness can occur if the tumor is compressing structures in the sacrum (a segment of the vertebral column that forms the top part of the pelvis). Malignant extragonadal germ-cell tumors may cause symptoms such as chest pain or breathing problems. Screening and diagnosis: Diagnostic procedures for germcell tumors may include biopsy of the tumor; blood tests, including a complete blood count (CBC) to determine the size, number, and maturity of different blood cells within the blood; and multiple imaging studies such as computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and X ray. Scientists have identified a tumor marker in the blood called lactate dehydrogenase isoenzyme 1 (LD1); increased levels of this enzyme indicate seminoma in more than 60 percent of patients. Staging of the disease depends on its development in the ovary or testis. Treatment and therapy: Specific treatment for germ-cell tumors is determined by the patient’s age, overall health, medical history, and extent of the disease. The treatment plan will also rely heavily on whether the tumor is extragonadal and whether it is malignant. Treatments for germcell tumors are similar to those for ovarian tumors and testicular tumors, usually involving surgery to remove the tumors. If cells are malignant, patients may undergo chemotherapy or radiation to reduce the risk of recurrence of cancerous cells. In some cases, patients will require a bone marrow transplant or hormone replacement therapy. Prognosis, prevention, and outcomes: Prognosis greatly depends on the extent of the disease, the size and location of the tumor, whether the cancer has spread, and the age and overall health of the patient. Prompt medical attention and aggressive therapy are important for the best prognosis. Continuous follow-up care is essential for a child diagnosed with a germ-cell tumor. Side effects of radiation and chemotherapy as well as second malignancies can occur in survivors of germ-cell tumors. New methods are continually being discovered to improve treatment and to decrease side effects. Robert J. Amato, D.O. u
For Further Information Johanson, Paula. Frequently Asked Questions About Testicular Cancer. New York: Rosen, 2007.
Salem Health: Cancer Kurth, Karl H., Gerald H. Mickisch, and Fritz H. Schroder, eds. Renal, Bladder, Prostate, and Testicular Cancer: An Update. New York: Parthenon, 2001. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Testicular Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. u
Other Resources
CureSearch Germ Cell Tumors http://www.curesearch.org/for_parents_and_families/ newlydiagnosed/article.aspx?ArticleId= 3190&StageID=1&TopicId=1&Level=1 National Cancer Institute Extragonadal Germ-Cell Tumors http://www.cancer.gov/cancertopics/types/ extragonadal-germ-cell/ See also Brain and central nervous system cancers; Embryonal cell cancer; Klinefelter syndrome and cancer; Lactate dehydrogenase (LDH) test; Mediastinal tumors; Ovarian cancers; Spermatocytomas; Teratocarcinomas; Teratomas; Testicular cancer; Thymomas; Yolk sac carcinomas; Young adult cancers.
u Gerson therapy Category: Procedures; complementary and alternative therapies Also known as: Gerson diet, Gerson regime, Gerson method Definition: Gerson therapy is an alternative treatment therapy developed by Max Gerson that is used to treat chronic debilitating diseases as well as cancer. This treatment involves a specialized diet, vitamin supplements, and coffee enemas that are aimed at cleansing the body, strengthening the immune system, and increasing metabolic activity. Cancers treated: All Why performed: The theory behind Gerson therapy is that the body needs to be detoxified frequently in order to treat a disease’s underlying cause. It is theorized that people with cancer may contain levels of sodium in their bodies that are too high relative to the levels of potassium. Eating organic fruits and vegetables and taking supplements are believed to help restore a balance in the body.
Gestational trophoblastic tumors (GTTs) Patient preparation: Patients with diabetes, brain metastases, kidney damage, and foreign bodies such as pacemakers and implants and those undergoing chemotherapy should consult a certified Gerson practitioner before beginning treatment. Steps of the procedure: The therapy is based on maintaining a diet high in vitamins and minerals, which is achieved by consuming juices made from fresh, organic fruits and vegetables, as well as vegetarian meals. Medications are taken orally or injected. In addition, in order to rid the body of toxins, enemas are administered. They are thought to increase bile flow, which facilitates the removal of toxins as well as the elimination of tumor and diseased tissue that is being broken down. Some items prohibited by the therapy include salt, oil, berries or nuts, coffee, drinking water, animal protein, and bottled, canned, preserved, or frozen food, as well as the use of aluminum utensils. After the procedure: No special steps are taken following Gerson therapy. Risks: The solutions used for enemas in Gerson therapy (such as coffee) can cause infections, dehydration, constipation, colitis, electrolyte imbalance, heart and lung problems, and even death. Some additional side effects that have been reported by those using Gerson therapy include dizziness or weakness, abdominal cramps, loss of appetite, diarrhea, aching, fever and sweating, and cold sores. The therapy can be especially problematic in women who are pregnant or breast-feeding. Results: No conclusive scientific evidence has shown that this therapy is effective in preventing or treating cancer. Lindsay Lewellyn, B.S. See also Complementary and alternative therapies; Dietary supplements; Integrative oncology; Macrobiotic diet; Nutrition and cancer treatment; Sun’s soup.
u Gestational trophoblastic
tumors (GTTs) Category: Diseases, symptoms, and conditions Also known as: Gestational trophoblastic neoplasia (GTN), gestational trophoblastic disease (GTD), metastasizing mole, invasive mole, chorioadenoma destruens Related conditions: Hydatidiform mole (H. mole), molar pregnancy, placental site trophoblastic tumor (PSTT), choriocarcinoma 527
Gestational trophoblastic tumors (GTTs) Definition: Gestational trophoblastic tumors (GTTS) refer to a group of benign tumors and malignant cancers in the uterus originating from the trophoblast layer that begins to develop after conception and forms the embryonic placenta. GTTs can be classified as hydatidiform mole (complete or partial molar pregnancy), invasive mole (chorioadenoma destruens), choriocarcinoma, and placental site trophoblastic tumor (PSTT). Some 60 percent of gestational trophoblastic tumors are persisting hydatidiform moles. Although hydatidiform moles are classified as benign while invasive moles, choriocarcinoma, and PSTTs are classified as malignant, their behavior in real life may be similar, especially when aggressive benign tumors mimic malignant ones. Risk factors: A number of factors may contribute to a woman’s susceptibility to developing gestational trophoblastic tumors. All women of childbearing age are at risk, with women over age forty and under age twenty at highest risk for having a complete molar pregnancy. According to the American Cancer Society, women who have had a previous molar pregnancy, have blood type of A or AB (rather than B or O), used birth control pills, smoked or drank alcohol (although some studies failed to support this), had more than ten sexual partners, and are of lower socioeconomic status have a higher risk of developing a gestational trophoblastic tumor. The risk factor of being Asian or Native American is controversial. Conflicting figures preclude this as a solid risk factor, suggesting other factors (poor record keeping regarding numbers of births, diet) may falsely raise the incidence. Etiology and the disease process: A hydatidiform mole arises from the fusion of an ovum and one or more sperm. The trophoblast, a layer of cells surrounding the embryo, produces finger-like villi that attach to the uterus. In a hydatidiform mole, the villi swell and grow in clusters to resemble bunches of grapes. One of three scenarios is possible in the creation of a hydatidiform mole. The first involves the union of the ovum (unfertilized egg) with two sperm instead of one. The second scenario may involve a single sperm whose complement of 22 chromosomes and one sex chromosome (23 total) is duplicated. These moles contain fetal material and are known as partial moles. Only about 2 percent of partial moles become malignant. The third scenario involves the union of an ovum without a nucleus with one or two sperm. No fetal tissue is present in a complete molar pregnancy. Invasive moles (chorioadenoma destruens) are hydatidiform moles, most commonly complete moles, that have 528
Salem Health: Cancer invaded the myometrium (muscular wall of the uterus). Some 20 percent of women who have had a complete mole removed by scraping the uterus develop invasive moles. These moles usually must be treated with chemotherapy and sometimes spread to other organs such as the lungs or brain. Choriocarcinoma are malignant tumors that usually develop from complete hydatidiform moles (50 percent), although they can result after a normal pregnancy (25 percent) or an abortion (25 percent). This type of cancer often spreads past the uterus. Placental site trophoblastic tumor is a rare form of gestational trophoblastic tumor. It develops after a normal pregnancy or abortion in which the placenta attaches to the uterus. This type of tumor tends to be confined to the uterus and is usually removed by surgery, as it does not respond to chemotherapy. Incidence: In the United States, hydatidiform moles occur in 1 out of every 2,000 deliveries, with progression to malignancy in 9 to 20 percent of women. It is estimated that 1 in 850 to 1 in 1,300 pregnancies are molar. A disproportionate number of complete moles is reported in nonwhite women. Complete moles were reported to arise in 1 in 400 Korean, Indonesian, or Native American women compared with 1 in 1,500 white women in the United States. However, data from multiple sources are conflicting. Choriocarcinomas are rare, occurring in 0.133 per 100,000 women in the United States and as many as 1 out of 50,000 live births in the United Kingdom. Symptoms: Patients often complain of delayed menses, and gestational trophoblastic tumors can mimic a pregnancy. However, abnormalities such as painless uterine bleeding during the first trimester or the passing of grapelike material from deformed chorionic villi through the vagina suggest the presence of a gestational trophoblastic tumor. The condition may also mimic preeclampsia (elevated blood pressure, swelling, headache, blurring of vision) and persisting hyperemesis gravidarum (frequent bouts of nausea and vomiting initially associated with rapidly rising hormone levels). Hyperthyroidism symptoms (palpitations, diarrhea, heat intolerance, sweating, tremors, nervousness/irritability) from a molar analog of thyroid-stimulating hormone (human molar thyrotropin) or direct stimulation by beta-human chorionic gonadotropic hormone (β-HCG) can also occur. Symptoms of spread to other parts of the body develop according to the involved organs. On physical examination, a disparity between gestational age and fundic height (length of uterus along its long axis) of four or more weeks
Salem Health: Cancer is suggestive. A screening β-HCG of greater than 100,000 million international units per milliliter (mIU/ml) is highly suggestive of neoplasia. Screening and diagnosis: No specific screening is recommended. The single most important laboratory test for diagnosis of GTT is a quantitative assay of HCG and all its subcomponents. Diagnosis is confirmed by pelvic ultrasound, where the grapelike vesicles may be seen, and partial moles may be found by the absence of a fetal heart and blood flow. A “snowstorm” appearance also may be described. Other imaging studies include a chest X ray and computed tomography (CT) scan or magnetic resonance imaging (MRI) of the head and abdominal and pelvic regions to find evidence of metastases. The criteria needed to diagnose gestational trophoblastic tumors are at least four values of persistently elevated HCG, a sequential rise of HCG for two weeks or longer, and lung metastases as seen on chest X ray. The International Federation of Gynecology and Obstetrics (FIGO) has created the following staging system: • Stage I: Gestational trophoblastic tumors strictly confined to the uterine corpus • Stage II: Tumors extending to the adnexa or vagina but limited to the genital structures • Stage III: Tumors extending to the lungs, with or without genital tract involvement • Stage IV: All other metastases The World Health Organization (WHO) created a prognostic scoring system which is used to further classify the stages used by FIGO into high and low risk. Point values are assigned to various factors present at the time of diagnosis. Prognostic factors include the following: • Age: Being older than forty, 1 point • Prior pregnancy: Hydatidiform mole, 0 points; abortion, 1 point; full-term pregnancy, 2 points • Time from pregnancy to manifestation of the tumor: Less than four months, 0 points; four to six months, 1 point; seven to twelve months, 2 points; more than twelve months, 4 points • HCG levels in blood (mIU/ml): Less than 1,000, 0 points; 1,000-9,999, 1 point; 10,000-100,000, 2 points, more than 100,000, 4 points • Tumor size: Less than 3 centimeters (cm), 0 points; 3 to 5 cm, 1 point; more than 5 cm, 2 points • Site of metastases: Lungs, 0 points; spleen, kidney, 1 point; gastrointestinal tract, 2 points; brain, liver, 4 points • Number of metastases: One to four, 1 point; five to eight, 2 points; more than eight, 4 points • Earlier failed chemotherapy: Single drug, 2 points; multiple drugs, 4 points
Gestational trophoblastic tumors (GTTs) Low-risk patients have a WHO score of seven or less; high-risk patients have a score of eight or more. This stratification determines the best treatment course. Metastasis to only the lungs with disease duration less than four months can be considered low risk. Treatment and therapy: Treatment includes evacuation of the uterus by suction dilation and curettage, along with monitoring of HCG with the overall goal of achieving undetectable levels. A hysterectomy is avoided unless extensive invasion is present. Metastatic lesions are resected if possible. Evacuation is usually followed by chemotherapy according to risk stratification. Low-risk patients undergo any of several single-drug therapies, which may use methotrexate with or without leucovorin rescue or actinomycin-D given as intramuscular or intravenous injections at regular intervals. High-risk patients are given combination chemotherapy. The main regimen, known as the EMA-CO protocol, uses etoposide, methotrexate, and actinomycin D, given before cyclophosphamide and vincristine (Oncovin). Resistant disease utilizes the EMA-EP protocol in which EMA alternates with etoposide and cisplatin (EP). Other drugs used include pacliataxel (Taxol), 5-fluorouracil (FU), or vinblastine in various combinations with EP. Levels of HCG are monitored even after treatment, with two additional chemotherapy sessions after undetectable levels are seen. A minimum of twelve disease-free months is recommended prior to pregnancy, after which early monitoring is done. Prognosis, prevention, and outcomes: Cure rate is excellent with surgery followed by chemotherapy, approaching 100 percent in low-risk patients and 75 percent for highrisk patients. Recurrence rates are low, at less than 1 percent. A second molar pregnancy may occur 1 to 2 percent of the time, but the likelihood of another molar pregnancy increases tenfold if the patient has had two molar pregnancies. Aldo C. Dumlao, M.D. u
For Further Information Haas, Adelaide, and Susan L. Puretz. The Woman’s Guide to Hysterectomy: Expectations and Options. Berkeley, Calif.: Celestial Arts, 2002. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Gestational Trophoblastic Tumors. San Diego, Calif.: Icon Health, 2002. Rosenthal, Sara M. The Gynecological Sourcebook. 4th ed. New York: McGraw-Hill Professional, 2003. 529
Giant cell tumors (GCTs) u
Other Resources
American Cancer Society Detailed Guide: Gestational Trophoblastic Disease http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_are_gestational_trophoblastic_ disease_49.asp?rnav=cri American College of Obstetricians and Gynecologists http://www.acog.org National Cancer Institute Gestational Trophoblastic Tumor http://www.cancer.gov/cancertopics/types/ gestationaltrophoblastic WebMd Gestational Trophoblastic Neoplasia http://www.emedicine.com/med/TOPIC866.HTM See also Choriocarcinomas; Computed tomography (CT) scan; Gynecologic cancers; Gynecologic oncology; Human chorionic gonadotropin (HCG); Hydatidiform mole; Ultrasound tests.
u Giant cell tumors (GCTs) Category: Diseases, symptoms, and conditions Also known as: Osteoclastomas Related conditions: Differential diagnosis includes other giant cell lesions, such as the brown tumor seen in hyperparathyroidism, giant cell reparative granuloma, chondroblastoma, pigmented villonodular synovitis, and giant cell tumor of the tendon sheath. Definition: Giant cell tumors (GCTs) are relatively uncommon benign but locally aggressive bone neoplasms. The tumors are large, red-brown, and subject to frequent cystic degeneration. They are composed of uniform oval mononuclear cells with scattered osteoclast-type giant cells containing one hundred or more nuclei. The mononuclear cells are the proliferating component of the tumor. Necrosis, hemorrhage, hemosiderin (iron) deposition, and reactive bone formation are common secondary features. Risk factors: There are no known predisposing factors that place a person at risk for having a giant cell tumor. Genetic changes (mutations) trigger the condition, but researchers do not know what conditions or factors might promote such mutations. Those diagnosed with this condition, however, will have an increased risk for joint collapse 530
Salem Health: Cancer and degeneration and pathologic fractures. The incidence of metastasis is rare. Etiology and the disease process: The tumor is located in the metaphysis or epiphysis of long bones, with 50 percent of the lesions occurring around the knee. The proximal humerus and distal radius are also common locations, as well as the pelvis and sacrum. Typically, the lesion presents as a painful, slowly enlarging mass. With proliferation of the mononuclear cells, tissue expansion creates a bone defect that is described as lytic (bringing about disintegration or dissolution), with sharply circumscribed margins. The lesion is often described as having an “eccentric soap bubble” pattern. There may be thinning of the cortex (outer ring of bone), and the lesion may extend into subchondral bone of the adjacent joint. Most tumors are solitary; however, multiple tumors do occur, especially in the distal extremities. Malignant degeneration is rare. Basic science data strongly suggest a close molecular genetic relationship between the benign giant cell tumors of bone and the malignant osteosarcomas (bone cancer). Indeed, these two conditions have similar genetic alterations in the oncogenes (genetic material incorporated into chromosomes associated with various malignancies). Molecular genetic studies have found a higher incidence of p53 protein and alterations in the MYC gene in both tumors. Incidence: Giant cell tumors usually arise in people from their early twenties to forties, with a slight female predominance. Giant cell tumors are exceedingly rare in patients younger than age thirteen, and only about 10 percent of cases occur in individuals older than sixty-five. The majority of giant cell tumors arise around the knee, but any bone may be involved, including the sacrum, pelvis, spine, and small bones of the hands and feet. Symptoms: The location of these tumors in the ends of bones near joints frequently causes patients to complain of arthritic symptoms. Individuals may complain of pain, show signs of local swelling, or have a pathologic fracture through the lesion. Screening and diagnosis: Diagnosis is based on X-ray evidence and confirmed by tissue biopsy. Magnetic resonance imaging (MRI) scans are often employed to define bone margins and soft-tissue involvement. The current staging system is based on imaging studies. Stage I (latent-quiescent) delineates a lesion in cancerous bone with minimal cortical involvement. The most common stage is Stage II (active), which denotes extensive cortical thinning and creation of the “soap bubble” pattern. Stage III (aggressive) has a greater risk of recurrence. A
Salem Health: Cancer more aggressive surgical approach is recommended for tumors in this stage. Treatment and therapy: Watchful conservative care and treatment may be a reasonable approach if the lesion is small, localized, contained, and not painful. The use of radiation therapy is restricted to difficult lesions in the pelvis and spine, where an adequate surgical resection is not feasible because of anatomical considerations. For a majority of Stage II and III lesions, surgical excision is the treatment of choice. This involves extensive exteriorization (removal of a large cortical window over the lesion), curettage with hand and power instruments, and chemical cauterization with phenol (a caustic chemical that destroys cells) or hydrogen peroxide, cryosurgery, or other methods of cavity sterilization. The large resulting defect is usually reconstructed with subchondral bone grafts and methylmethacrylate cement. Surgery with only limited curettage is associated with a 40 to 60 percent recurrence rate. Although benign, up to 4 percent of operative cases will metastasize to the lungs after surgery, suggesting dislodgement of tumor emboli. Lesions with significant extension into adjacent soft tissue require en bloc resection (complete removal of affected bone and surrounding tissue). In this more radical procedure, modified arthrodesis (fusion of a joint), allograft (replacement of bone segment with donor bone), or prosthetic reconstruction (artificial joint implant) is indicated. In the knee, this operation may require extensive bone resection, necessitating a total knee replacement. Prognosis, prevention, and outcomes: Malignancy may occur in two forms: primary malignant giant cell tumor and secondary malignant giant cell tumor. Secondary tumors occur following radiation to a giant cell tumor or following multiple local recurrences. The most common scenario is associated with a patient who has a large aggressive giant cell tumor that is inoperable. These individuals receive irradiation for local control, but an osteosarcoma (bone cancer) may subsequently develop (15 percent incidence rate) in the irradiated field over an extended latency period of three to fifty years. John L. Zeller, M.D., Ph.D. u
For Further Information Campanacci, M. Bone and Soft Tissue Tumors. New York: Springer, 1990. Campanacci, M., et al. “Giant Cell Tumor of the Bone.” Journal of Bone Joint Surgery 69A (1987): 106-114. Manaster, B. J., and A. J. Doyle. “Giant Cell Tumors of the Bone.” Radiologic Clinics of North America 31, no. 2 (1993): 299-323.
Ginseng, panax Pals, S. D., and R. M. Wilkins. “Giant Cell Tumor of the Bone Treated by Curettage, Cementation, and Bone Grafting.” Orthopedics 15 (1992): 703-708. Rooney, R. J., et al. “Giant Cell Tumor of the Bone: A Surgical Approach.” International Orthopaedics 17, no. 2 (1993): 87-92. Schajowicz, F. Tumors and Tumorlike Lesions of the Bone: Pathology, Radiology, and Treatment. Berlin: Springer-Verlag, 1994. u
Other Resources
American Academy of Orthopedic Surgeons http//www.aaos.org Bonetumor.org Giant Cell Tumor of Bone http://bonetumor.org/tumors/pages/page106.html See also Bone cancers; Dermatofibrosarcoma protuberans (DFSP); Malignant fibrous histiocytoma (MFH); Spinal axis tumors.
u Ginseng, panax Category: Lifestyle and prevention; complementary and alternative therapies Also known as: Asian ginseng, Chinese ginseng, Korean ginseng, Oriental ginseng Definition: Panax ginseng C. A. Meyer, more commonly known as Panax ginseng, is a perennial plant of Asia and northern Europe. Other types of ginseng include the related Panax quinquefolius, or American ginseng, and Siberian ginseng, with activity that differs from Panax varieties. The root of Panax ginseng is associated with many medicinal claims; “panax” translates as “all-healing.” Panax ginseng’s most widely reported claims encompass energizing effects. Cancers treated or prevented: Purported general anticarcinogenic and cell-protective agent; potential treatment of chemotherapy-related side effects Delivery routes: Oral by capsule, tea, or powder How this substance works: Panax ginseng has a history of more than two thousand years of medicinal use and has been formally studied for health claims since the 1960’s. The plant root contains numerous pharmacologically active entities called ginsenosides, also known as saponins. The ginsenoside content of each root, however, varies with root age, harvest season, and preservation method, 531
Gleason grading system which contributes to an uneven effect of ginseng wholeroot products. Ginsenoside effects vary between species as well. Ginseng’s pharmacologic claims include altered blood pressure effects, analgesic effects, increased mental and physical capacities, and anti-inflammatory effects. Among the early claims now supported by studies is a general adaptogenic, or strengthening, effect. This effect helps the body fight disease, reduce stress or fatigue, and enhance recovery from illness, depression, or anxiety. Ginsenosides in the plant root are similar to steroid hormones and are the likely source of many of these medicinal effects. Possible mechanisms of ginseng’s reported anticarcinogenic effect include direct cytotoxicity, cancer cell growth inhibition, inhibited metastases and cell adhesion, and increased antibody production. Clinical studies for cancer use have been conducted, primarily in Asia; however, ginseng’s use in cancer remains unsupported by solid evidence. Because of its steroidal anti-inflammatory activity and overall strengthening effect, trials are evaluating the possible use of Panax and American ginsengs for cancer-related fatigue or as a supplemental treatment to improve responses to chemotherapy. Side effects: Ginseng is generally considered safe; the adverse effects possible with high doses include increased heart rate, nausea, headache, restlessness, and trouble sleeping. Women may experience swollen breasts and vaginal bleeding; the safety of Panax ginseng during pregnancy and lactation is unknown. Because of its steroidlike effects, ginseng should not be used in women with breast or endometrial cancers. Ginseng may decrease blood sugar and increase bloodclotting times. Nicole M. Van Hoey, Pharm.D. See also Dietary supplements; Herbs as antioxidants; PCSPES.
u Gleason grading system Category: Procedures Also known as: Gleason score Definition: The Gleason grading system is the most common system used in the United States to evaluate, or “grade,” prostate cancer. The Gleason grade describes the appearance of prostate cancer tissue when observed under a microscope. The grade assigned describes how closely the tumor cells in the prostate tissue resemble normal pros532
Salem Health: Cancer tate cells and can predict how quickly the tumor is expected to grow. Typically, prostate cancer tissue has different patterns within the cells. The first Gleason grade describes the most common pattern. The second Gleason grade is assigned to the next most common pattern of cells in the tissue. Together, these two numbers combined make the Gleason score. Cancers diagnosed: Prostate cancer Why performed: Assigning a Gleason grade or score allows the doctor to predict the behavior of the prostate cancer—that is, whether it will be a slow- or fast-growing tumor. This information can have an impact on the treatment choices available to the patient. Patient preparation: No patient preparation is needed. This evaluation is performed in a laboratory by a pathologist, a doctor who specializes in identifying diseases by examining tissues and cells to determine if cancer cells are present and, if they are, how aggressive the disease may be. Steps of the procedure: After the patient undergoes a prostate biopsy, the biopsy samples are sent to a pathologist to determine the Gleason grade and score of the prostate cancer tissue. After the procedure: It may take anywhere from a few days to a couple of weeks to obtain the results. After the results are received, the patient can discuss the best treatment options available based on the type of prostate cancer cells present in the biopsy samples. Risks: No risks are associated with this procedure. Results: There are five Gleason grades. Grade 1 appears similar to normal prostate tissue, which means that the tumor is most likely a slow-growing tumor. Grades 2, 3, and 4 reflect increasingly faster-growing tumors. Grade 5 indicates a fast, aggressive prostate cancer. The Gleason score is determined by adding the two Gleason grades together. The Gleason score is a number between 2 and 10 that reflects how closely the cancer cells resemble normal prostate tissue. In general, a low Gleason score suggests less aggressive tumors and a higher Gleason score suggests more aggressive tumors. Vonne Sieve, M.A. See also Grading of tumors; Prostate cancer; Staging of cancer; Watchful waiting.
Salem Health: Cancer
u Gliomas Category: Diseases, symptoms, and conditions Also known as: Malignant gliomas, brain tumors, astrocytomas, ependymomas, glioblastomas, oligodendrogliomas Related conditions: Central nervous system tumors, primary brain tumors Definition: A glioma is a brain tumor that develops from a neuroglia, commonly known as a glial cell. Glial cells are support cells for the neurons that send and receive signals in the nervous system. There are six types of glial cells— astrocytes, oligodendrocytes, and ependymal, Schwann, microglia, and satellite cells—that can grow into a glioma. Gliomas are categorized and named based on their glial cell of origin, are considered primary central nervous system tumors, and occur in both children and adults. A glioma is a primary brain tumor, meaning that the tumor started in the brain. An astrocytoma is the most common glioma and occurs in children and adults. Brain stem gliomas form at the connection between the brain and the spinal cord and are most common in children between the ages of three and ten but do occur in adults. Glioblastoma multiformae is the most aggressive of gliomas and accounts for almost 25 percent of all primary brain tumors.
Gliomas diagnosed each year in the United States. The average age at diagnosis for adults is fifty-four. Children with brain tumors are diagnosed evenly over the ages from birth to nineteen years. Symptoms: Depending on the type and grade of the tumor, tumors may grow one to two years before symptoms develop. The brain can adjust to a slow-growing, lowgrade tumor and may adapt over time, but symptoms eventually will occur. A high-grade or aggressive tumor may cause dramatic symptoms that develop quickly. The most common symptoms are headache, seizures or convulsions, weakness or paralysis, nausea or vomiting, difficulty walking due to poor balance, behavior changes, confusion, and vision changes. Screening and diagnosis: There are no screening tests for gliomas. Diagnosis begins when the patient complains of symptoms suggestive of a glioma. A physician with a specialty in neurology or neurosurgery should be involved in a comprehensive physical examination of the patient. Diagnostic radiology procedures such as computed tomogra-
Risk factors: Most brain tumors have no known risk factors. Exposure to radiation or radiation of the brain may cause a brain tumor. There are no studies that prove brain tumors are caused by cell phone use, electric lines, injury or accidents, exposure to toxic fumes, hair dyes, or any food or food product. The National Cancer Institute reports that exposure to vinyl chloride, a gas used in making plastic, may increase the chance of developing glioma. Etiology and the disease process: There is no known cause for glioma. Malignant gliomas are aggressive tumors that may spread quickly throughout the brain. Because the brain controls almost all body functions, a rapidly growing tumor may cause problems with breathing, sight, hearing, smell, balance, body temperature, and other functions, creating life-threatening conditions. As the glioma increases in size, the symptoms progress, leading to difficulty with activities of daily living. Gliomas are considered incurable, and once diagnosed, a survival time of less than one year is not unusual. Incidence: Gliomas account for approximately 42 percent of all central nervous system (CNS) tumors and 77 percent of all malignant CNS tumors. Just over 9,000 gliomas are
CT scan of a glioma. (Scott Camazine/Photo Researchers, Inc.)
533
Glomus tumors
Salem Health: Cancer
Five-Year Relative Survival Rate by Histologic Type for Adult Brain Cancers, 1988-2001 Histologic Type
Survival Rate (%)
a
45.2 36.3 71.6 35.8 2.7 68.2 66.4 50.3
Glioma Glioma, otherb Ependymoma Astrocytoma Glioblastoma Oligodendroglioma Medulloblastoma Germ-cell neoplasms, other
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Nasal glioma, subependymal glioma, missed gliomas b Choroid plexus papilloma, malignant; primitive polar spongioblastoma; primitive neuroectodermal tumor
Prognosis, prevention, and outcomes: The prognosis depends on the type of the glioma, the age of the patient, and the symptoms of the patient when diagnosed. Gliomas are difficult to treat, and survival time is often limited. Slower growing, low-grade tumors, even when treated successfully at first, have the potential to grow back and progress. Avoiding radiation to the head is the only documented prevention. If the tumor is treated successfully, which is rare, there may still be major physical limitations that exist from side effects of the tumor or its treatment. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Ashby, L. S., and T. C. Ryken. “Management of Malignant Glioma: Steady Progress with Multimodal Approaches.” Neurosurgical Focus 20, no. 4 (2006): E6. Barnett, Gene H., ed. High-Grade Gliomas: Diagnosis and Treatment. Totowa, N.J.: Humana, 2007. Berger, Mitchel S., and Charles B. Wilson, eds. The Gliomas. Philadelphia: W. B. Saunders, 1999.
u
phy (CT) and magnetic resonance imaging (MRI) of the head are most commonly used when a patient exhibits symptoms. A positron emission tomography (PET) scan may be used as it can assist in determining if the tumor is malignant. Abiopsy is generally not done for diagnosis because of inability to reach the tumor, but one is usually done at the time of surgery to determine the specific cell type. Staging is based on identifying the location of the primary tumor (T X-4), evidence of metastasis (M X-1), and grade (G I-IV). Treatment and therapy: Treatment for gliomas is difficult and usually combines surgery (if the tumor can be reached) and radiation. Radiosurgery is an option if the tumor is inoperable. Chemotherapy has limited use because of the difficulty of getting the drugs into the brain in the proper amounts to kill cells. Carmustine (BCNU) is one drug that is able to penetrate into the brain and has shown some activity against gliomas. It does have toxicity that limits its use. Recommendations for treatment are consistently moving toward surgery, radiation, and systemic chemotherapy. Advances in the treatment of gliomas include a wafer with carmustine that is placed into the surgical site after removal of the tumor. Temozolomide (Temodar), an oral drug with few side effects, has shown activity when a glioma returns. Clinical studies are ongoing to determine other chemotherapy combinations that may be useful in treating gliomas. 534
Other Resources
American Cancer Society http://www.cancer.org National Brain Tumor Foundation http://www.braintumor.org National Cancer Institute http://www.cancer.gov See also Astrocytomas; Boron neutron capture therapy (BNCT); BRAF gene; Brain and central nervous system cancers; Carcinomatous meningitis; Cell phones; Craniotomy; Cyclin-dependent kinase inhibitor-2A (CDKN2A); Ependymomas; Meningeal carcinomatosis; Mitochondrial DNA mutations; Neurofibromatosis type 1 (NF1); Neurologic oncology; Oligodendrogliomas; Orbit tumors; Pheochromocytomas; Spinal axis tumors; Spinal cord compression; Turcot syndrome; Von Hippel-Lindau (VHL) disease.
u Glomus tumors Category: Diseases, symptoms, and conditions Also known as: Glomangiomas Related conditions: Benign tumors of blood vessels and lymphatics (hemangiomas, lymphangiomas) Definition: Glomus tumors are benign but often exquisitely painful tumors that are formed from nests of special-
Salem Health: Cancer ized cells from the glomus body, a specialized arteriovenous structure involved in thermoregulation (temperature control via the skin). They manifest as round, slightly elevated, firm nodules, and when visible, the lesion appears as a small reddish-blue discoloration of the skin. Solitary or multiple in number, they are generally less than 1 centimeter (cm) in diameter. Microscopically, a tumor consists of collections of uniform cells that appear epithelial in nature and lie along the outside of abundant, branching blood vessels. Smooth muscle fibers are seen as part of the connective tissue matrix along with nerve fibers. These nerve fibers are intermixed with thick-walled capillaries and are responsible for the lancinating pain. Risk factors: There are no known risk factors for glomus tumors. Etiology and the disease process: Although the initiating event is unknown, the disease process is clearly an abnormal proliferation of glomus cells. These cells are differentiated perivascular cells from the arterial portions of the glomus body (Sucquet-Hoyer canal), which is a common arteriovenous shunt located in the dermis. Most hereditary glomangiomas are associated with defects in the glomulin gene, located on chromosome 1. Incidence: Although glomus tumors are more frequent in adults, the exact incidence is unknown. The skin and subcutaneous tissues of the hands and feet are usually affected, but a tumor may develop in any location in which a glomus body is found. These vascular tumors occur more often in the hand (75 percent) than elsewhere and are located beneath the fingernail (subungual) in 25 to 65 percent of patients. In the head and neck areas, glomus tumors account for 0.6 percent of all neoplasms. Symptoms: Pain, cold sensitivity, and point tenderness are the characteristic symptoms of a glomus tumor. Direct pressure on the tumor can cause excruciating pain. Screening and diagnosis: Because of this tumor’s rarity and small size, a diagnosis may be problematic. In subungual tumors, X rays can demonstrate bony erosion in 14 to 60 percent of patients. Whereas bone scans and ultrasound scans have been helpful, high-resolution magnetic resonance imaging (MRI) remains the standard for imaging diagnostics. Treatment and therapy: Nonoperative treatment is chosen if local measures such as nonsteroidal anti-inflammatory drugs (NSAIDs) and activity modification adequately control discomfort. For resistant tumors, surgery involves a meticulous and complete excision of the encapsulated lesion.
Glossectomy Prognosis, prevention, and outcomes: Wide excision is curative, although reoperation rates of 12 to 24 percent have been reported. John L. Zeller, M.D., Ph.D. See also Benign tumors; Endotheliomas; Eye cancers; Hemangiosarcomas; Nuclear medicine scan; Orbit tumors; Spinal axis tumors.
u Glossectomy Category: Procedures Also known as: Hemiglossectomy, partial glossectomy Definition: A glossectomy is a surgical procedure to remove all or part of the tongue. Cancers treated: Cancers of the tongue Why performed: A glossectomy is performed to take out the abnormal tissue (tumor) and enough of the surrounding tissue so that the edges, or margins, around the tumor do not contain cancer cells. Patient preparation: In addition to the usual preoperative preparation (physical examination, blood testing, and consultation with an anesthesiologist), the patient should meet with a speech-language pathologist for a consultation regarding the changes in speech and swallowing that happen when all or part of the tongue is removed. Glossectomies are done in a hospital, and the patient is given general anesthesia. The surgical team will be specialists in head and neck cancer surgeries, including an ear, nose, and throat surgeon, an oral-maxillofacial surgeon, and a plastic surgeon. Steps of the procedure: Small cancers may require only a biopsy if the surgeon is able to remove enough tissue so that the edges around the tumor have no cancer cells. The tissue is tested tableside during the surgery to determine if the margins are negative (without cancer cells). If the cancer is small, then the surgeon sews up the tongue or uses a small skin graft to repair the tongue. For larger skin grafts, the skin is frequently taken from the wrist along with the surrounding blood vessels; this type of skin graft is a radial forearm free flap. The graft is sewn into the hole in the tongue, and the blood vessels are connected to supply the graft. A total glossectomy is rarely done. The neck lymph nodes are tested to see if the cancer has spread. If lymph nodes are positive for cancer cells, then additional surgery may be done during the same operation for a limited dissection of the neck. 535
Glutamine After the procedure: An inpatient hospital stay of about a week after a glossectomy procedure is expected. A nasogastric tube (from the nose to the stomach) may be used for feeding until food can be taken orally. Subsequent reconstructive surgeries, fitting with prosthetic devices (an artificial tongue), radiation therapy, and rehabilitation therapy may be necessary. Risks: Possible risks of a glossectomy include bleeding and/or swelling of the tongue, failure of the skin graft, formation of a new opening between the mouth and the skin (a fistula), and difficulty swallowing and talking. Results: The results depend on the amount of the tongue that was removed; if one-third or more of the tongue remains, then good swallowing and talking function is expected. Vicki Miskovsky, B.S., R.D. See also Arterial embolization; Erythroplakia; Laryngeal cancer; Leukoplakia; Multiple endocrine neoplasia type 2 (MEN 2); Oral and oropharyngeal cancers; Stomatitis.
u Glutamine Category: Chemotherapy and other drugs; lifestyle and prevention Definition: Glutamine is the most abundant amino acid in the body and is found in most proteins. Glutamine is considered a nonessential amino acid since the body is normally able to synthesize an adequate amount for its needs. Cancers treated or prevented: All cancers currently treated with chemotherapy or radiation Delivery routes: Glutamine can be taken orally by capsules, powder, or tablets. In the clinical setting, glutamine can be part of an enteral liquid formula given by feeding tube through the nose, stomach, or small intestine. Glutamine can also be given intravenously. How this compound works: Although glutamine is found largely as a component of proteins (skeletal muscle in particular), it serves a variety of functions in the body. Stress conditions such as injury, burns, critical illness, or highintensity exercise cause a greatly increased need for glutamine. Glutamine is considered a conditionally essential amino acid under these stress conditions, since dietary supplementation of glutamine is necessary. The gastrointestinal tract is the largest user of glutamine, particularly as a source of energy. Glutamine is important in wound healing and helps to mobilize components of the immune sys536
Salem Health: Cancer tem. It also helps to maintain the integrity of the intestinal lining to prevent entry of bacteria and fungi. Cancer cells have a great demand for glutamine as an energy source, which can deplete glutamine stores in muscle and other body tissues. Laboratory studies indicate that glutamine is necessary for the functioning of T lymphocytes and natural killer cells, which are components of the immune system. The depletion of body glutamine, therefore, could compromise the role of the immune system in the protection against cancer. Some researchers were concerned about supplementing cancer patients with glutamine, thinking that supplementation could increase tumor growth. Such supplementation has been found, however, to increase glutamine stores in the body and to improve intestinal and immune function. In addition, studies have indicated that glutamine may alleviate the side effects of chemotherapy and radiation therapy. Glutamine supplementation has resulted in decreased intestinal mucosa ulceration and mouth inflammation. Peripheral neuropathy (numbness in extremities, motor weakness) often limits chemotherapeutic dosages. Glutamine may reduce the severity of neurological disorders, thereby permitting more effective dosages. Researchers believe that glutamine may work by restoring cellular levels of glutathione, a molecule that contains a sulfur group which binds to drugs and carcinogens. Glutamine supplementation increases the glutathione level in the body, thereby helping to reduce toxic drug levels. Glutamine supplementation has been shown to increase the accumulation of the chemotherapeutic drug methotrexate inside tumor cells, thereby increasing its killing effect. Side effects: Since glutamine is so abundant in the body, even doses of up to 21 grams daily are well tolerated. Side effects are mainly gastrointestinal and include constipation and bloating. David A. Olle, M.S. See also Antimetabolites in chemotherapy; Antinausea medications; Antineoplastics in chemotherapy.
u Gonioscopy Category: Procedures Definition: Gonioscopy is a procedure used by eye health professionals to examine the interior of the eye to check the drainage angle for growths, problems, and obstructions.
Salem Health: Cancer
Grading of tumors
Cancers diagnosed: Cancers of the eye
u Grading of tumors
Why performed: Gonioscopy is performed to allow the doctor to see into the patient’s eye to examine the area in which fluid drains in order to check for problems.
Category: Procedures
Patient preparation: A patient who wears contact lenses will have to remove them. Steps of the procedure: Gonioscopy is usually performed in a doctor’s office, although it can be performed in other settings as well. It is usually performed by an ophthalmologist. The doctor begins by applying eyedrops to the patient’s eye to numb it, allowing the doctor and instruments to touch the eye without the patient feeling it. The patient may be asked to lie down or may be asked to rest the head on a headrest if the procedure is performed while the patient is sitting up. The patient is asked to try to refrain from blinking during the procedure. The doctor uses a special lamp and a special lens to look inside the patient’s eye and examine the area between the cornea and the iris. Problems with this area can cause the eye not to drain fluid correctly, which can lead to many eye and vision problems, including eventual loss of vision. In total, gonioscopy usually takes between five and ten minutes for the doctor to perform. After the procedure: The patient should refrain from rubbing the eye for a period after the procedure. The patient’s eye may need to be dilated during the procedure, so he or she may experience loss of vision quality for a few hours afterward. Risks: In general, no significant risks are associated with gonioscopy. There is a small risk of an allergic reaction to the eyedrops that are used by the ophthalmologist to numb the eye. There is also a very small chance of eye infection. Results: Gonioscopy allows the doctor to see into the area of the eye where fluid drainage occurs. This can help the doctor see whether normal drainage is occurring or if a growth or other blockage is preventing normal drainage. Normal results for this procedure will show a drainage angle that is wide and open. Abnormal results will show a drainage angle that is blocked or closed. Robert Bockstiegel, B.S. See also Childhood cancers; Computed tomography (CT) scan; Eye cancers; Eyelid cancer; Genetics of cancer; Ophthalmic oncology.
Definition: The grading of tumors is a system devised to classify malignant tumors. The grade is determined by how aberrant (different from what is expected) the tumor cells are in relation to normal tissue cells when viewed under a microscope. The grading of tumor cells is performed by a medical doctor who specializes in pathology. This system also considers how aggressive the tumor is in regard to growth and metastases (the spread of cancer cells to other organs). Cancers diagnosed: All Why performed: Tumors are graded so that physicians have information about the tumor to use in developing a treatment plan for the patient. The higher the grade of the tumor, the more aggressively it is treated. A tumor grade can also give an indication of the likelihood that the cancer can be cured, as well as of the prognosis of the patient. Patient preparation: Tumor grade is determined by analysis of tissue cells from the tumor. The patient is not directly involved with the grading of the tumor, which is performed by a pathologist. Steps of the procedure: Specimens (small samples) to be used for grading a tumor are extracted through biopsy (removal of tissue from a tumor) or tissue scraping. An example of a tissue scraping procedure is the Papanicolaou smear (Pap smear), in which cells are scraped from the cervix of the uterus. The tissue samples are then placed in a container with a preservative solution, such as formaldehyde. The pathologist takes thin slices of tumor tissue and prepares slides for viewing under a microscope. Then the slides are examined as to cell structure and growth pattern. Each type of cancer has its own characteristics, although there is a similarity between cells of tumors from similar types of tissue. For example, all sarcomas (cancer of the muscle) are similar no matter the muscle in which they are discovered. Two important factors identified by the pathologist are histologic grade and nuclear grade. Histologic grade refers to the amount of differentiation between the tumor cells and the cells of the tissue where the tumor resides. Cancer cells that appear quite similar to the tissue cells are low grade, whereas cancer cells that are large and oddly shaped, bearing little resemblance to normal cells, are considered higher grade. Nuclear grade considers the size, shape, and activity of the nucleus of each cancer cell. Nuclei that resemble closely those of normal cells would be low grade. 537
Graft-versus-host disease (GVHD) Nuclei that are large and oddly shaped, bearing little resemblance to normal nuclei, would be higher grade. Nuclear grade also considers the relative number of cancer cells that are dividing, as evidenced by the signs of cell mitosis (cell division). In cell mitosis, it is possible to see the genetic material of the cells duplicating and splitting into two cells. After the procedure: After examining the cancer cells, the pathologist writes a report that describes what the tumor cells look like and the pathologist’s impression as to the type and grade of the tumor. Commonly used terms are metaplasia, hyperplasia, and atypical hyperplasia. Metaplasia of cells describes the reversible transformation of normal cells to a slightly different form by injury or stress. It is thought that metaplasia could lead to cancer. Hyperplasia of cells indicates that the cells are reproducing at an abnormally high rate. Atypical hyperplasia signifies that, in addition to the fact that cells are reproducing at a high rate, there are also cells that appear different from normal cells. Risks: The risk for the grading of tumors is that the pathologist is incorrect in judgments about the tumor cells. The more experience that a pathologist has with a type of tumor cells, the more accurate he or she is likely to be in an assessment of the cells. As a result, pathologists often specialize in certain types of tumors. Results: The American Joint Commission on Cancer (AJCC) has developed generic (basic) guidelines for the grading of tumors. They are as follows: • Grade X: tumor cell grade cannot be assessed • Grade 1: tumor cells appear quite similar to normal cells (low grade) • Grade 2: moderate differences exist between the tumor cells and normal cells (intermediate grade) • Grade 3: substantial differences exist between the tumor cells and normal cells (high grade) • Grade 4: tumor cells bear little or no resemblance to normal cells (high grade) In practice, variations of this generic tumor grading scale are used. A tumor grading scale has been developed for each type of cancer. For example, prostate cancer is graded by the Gleason scale, which includes grades 2 through 10. Christine M. Carroll, R.N., B.S.N., M.B.A. u For Further Information American Cancer Society. “How Are Lung Carcinoid Tumors Staged?” Available online at http://www .cancer.org.
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Salem Health: Cancer Answers.com. “Tumor Grading.” In Oncology Encyclopedia. Available online at http://www.answers.com/ topic/tumor-grading. Damjanov, Ivan, and Fang Fan, eds. Cancer Grading Manual. New York: Springer, 2007. National Cancer Institute. “Tumor Grade: Questions and Answers.” Available online at http://www.cancer.gov. See also Breslow’s staging; Gleason grading system; Staging of cancer; TNM staging.
u Graft-versus-host disease
(GVHD) Category: Diseases, symptoms, and conditions Related conditions: Bone marrow transplantation, stem cell transplantation, allogeneic transplant Definition: Following an allogeneic bone marrow transplant or umbilical cord blood transplant, graft-versus-host disease (GVHD) may develop. GVHD is a complication that occurs when white blood cells (or immune cells, also known as T cells) from the donor or cord blood, administered to the patient during the transplant, attack the patient’s own cells as foreign. The donor cells are called the “graft” and the patient’s body is considered the “host,” hence the name graft-versus-host disease. Risk factors: Those who have undergone an allogeneic bone marrow transplant or an umbilical cord blood transplant are at risk for this condition. Etiology and the disease process: When patients have an allogeneic bone marrow transplant, they receive stem cells from a relative, usually a parent, sister, or brother. An unrelated person’s stem cells may also be used if the donor’s cells match the patient’s. Umbilical cord blood, collected from the umbilical cord and placenta at the birth of a baby and stored in a cord blood bank, is rich in stem cells and may be used if a match to the patient is found. The transplant’s success is often related to how well the proteins on the surface of the donated cells match the cells of the patient. These proteins are called human leukocyteassociated (HLA) antigens and are identified by a blood test. Acute GVHD can develop within a few weeks of the transplant but always within the first one hundred days after the transplant. Patients who get acute GVHD are more likely to develop chronic GVHD. Chronic GVHD develops well after the transplant, usually during or after
Salem Health: Cancer the third month post transplant in patients who may or may not have developed acute GVHD. Chronic GVHD can last for years after the transplant and, like acute GVHD, can be mild to life-threatening. Incidence: The incidence rate of acute GVHD varies from 33 percent in HLA identical siblings to 75 percent in unrelated, HLA matched, or related, partially matched transplants. Chronic GVHD may occur in one-third to twothirds of transplant patients. Incidence rates vary with the initial use and aggressiveness of immunosuppressive therapy, and use of T-cell depleted stem cells. Incidence is generally thought to be lower in patients receiving matched cord blood. Symptoms: Symptoms of GVHD depend on the part of the body affected by the disease. The skin, eyes, stomach, intestines, and liver are the most commonly affected organs in the body. In acute GVHD, skin symptoms include the development of a rash on the palms of the hands and soles of the feet. If GVHD is severe, blisters may appear. Cramping, nausea, and diarrhea may occur with digestive tract involvement, and jaundice (a yellowing of the skin) may occur with liver involvement. Chronic GVHD symptoms include skin changes, including rash, pain in the mouth, dry mouth and eyes, and digestive tract symptoms. Advanced chronic GVHD may cause a hardening or tightness in the skin, and joints may become stiff. Screening and diagnosis: Screening and diagnosis are made based on symptoms occurring after transplant, including fever, rashes, and organ involvement. A definitive diagnosis is made by skin or organ biopsy. There are four stages of acute GVHD, with rankings based on skin, liver, and gastrointestinal changes. Five grades are given to the acute version, ranging from none to life-threatening. A higher stage and grade means a more aggressive, acute GVHD. Chronic GVHD is based on a grading related to skin involvement and liver function. An early diagnosis may provide a better chance for treatment. Treatment and therapy: Because up to 75 percent of patients may develop acute GVHD, early diagnosis is critical so that treatment may begin promptly. The initial treatment is steroids for both acute and chronic GVHD. Prednisone and cyclosporine are the usual drugs of choice, along with symptom management. New agents are under study that may have a role in managing acute GVHD, including monoclonal antibodies and alemtuzumab (Campath). Chronic GVHD is usually treated with steroids every other day. Additional treatment manages the symptoms of GVHD, such as diarrhea and fever.
Graft-versus-host disease (GVHD) Prognosis, prevention, and outcomes: If steroids fail to control GVHD, the prognosis is poor, as there is no other proven therapy. Development of higher stage, acute GVHD is linked to increased morbidity and mortality. Chronic GVHD may be associated with longer term survival, as presence of chronic GVHD may protect a patient from relapse. Prevention includes drug prophylaxis with corticosteroids, and in some cases methotrexate and other drugs or agents; more accurate HLA typing with as strong a match as possible; and depletion of T cells prior to administration of the donor cells. Using umbilical cord blood may also be preventive for GVHD, as the stem cells are immature and less likely to cause GVHD. The disease can range from very mild to life-threatening. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Couriel, Daniel, et al. “Ancillary Therapy and Supportive Care of Chronic Graft-Versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-VersusHost Disease—V. Ancillary Therapy and Supportive Care Working Group Report.” Biology of Blood and Marrow Transplantion 12, no. 4 (2006): 375-396. Lee, Stephanie J., Georgia Vogelsang, and Mary E. D. Flowers. “Chronic Graft-Versus-Host Disease.” Biology of Blood and Marrow Transplantion 9, no. 4 (2003): 215-233.
u
Other Resources
Bone and Marrow Transplant Information Network http://www.bmtinfonet.org National Cancer Institute Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Therapy/bone-marrow-transplant National Marrow Donor Program Graft-Versus-Host Disease http://www.marrow.org/PATIENT/ Plan_Life_after_Tx/Managing_Long-Term_ Effects_of_/Graft-Versus-Host_Disease/index.html See also Bone marrow transplantation (BMT); Cyclosporin A; Pheresis; Stem cell transplantation; Transfusion therapy; Umbilical cord blood transplantation. 539
Granulosa cell tumors
u Granulosa cell tumors Category: Diseases, symptoms, and conditions Related conditions: Endocrine imbalances, endometrial hyperplasia, endometrial adenocarcinoma Definition: Granulosa cell tumors are slow-growing tumors almost always found in the ovaries. They have a low potential for becoming malignant. These tumors usually secrete large amounts of estrogen, although occasionally they secrete androgens (male hormones). Risk factors: Granulosa cell tumors are evenly distributed among women of all races and ethnicities. Most tumors occur in postmenopausal women and are diagnosed between the ages of fifty and fifty-five. Only 5 percent are found in women under age thirty. Etiology and the disease process: Researchers are unclear about how these malignancies arise. One theory is that they are related to chromosomal abnormalities. Another is that they are caused by a defect in hormonal regulation. These tumors grow slowly. Incidence: Granulosa cell tumors make up about 5 to 8 percent of malignant tumors of the ovaries. Between 1,500 and 2,000 cases are diagnosed each year in the United States. Symptoms: Granulosa cell tumors usually secrete estrogen. In children this tends to cause abnormally early signs of puberty. In reproductive-age women, it disrupts the menstrual cycle, and in postmenopausal women, the most common symptom is uterine bleeding. Other symptoms include an increase in the size of the abdomen and abdominal or pelvic pain. Screening and diagnosis: Most women seek medical attention because of the side effects of increased estrogen. On physical examination, the physician can feel the tumor in more than 90 percent of women. Average diameter of the tumor at diagnosis is 4.7 inches (12 centimeters). Physical findings are confirmed with blood tests, imaging tests, and biopsy. Some 90 percent of tumors are diagnosed in Stage I with malignancy confined to only one ovary. In Stage II, the tumor has begun to extend into the tissues near the ovary. In Stage III, it has metastasized to the abdomen, and in Stage IV to distant sites. Treatment and therapy: Treatment is always surgical removal of the affected ovary. Postmenopausal women may also have a hysterectomy. Chemotherapy and radiation 540
Salem Health: Cancer treatment are used in the 10 percent of women whose cancer has advanced beyond Stage I. Prognosis, prevention, and outcomes: Prognosis is excellent for tumors in Stage I, with ten-year survival rates of 90 to 96 percent. The ten-year survival rate for more advanced cancers is about half this rate. Tumors diagnosed in women under age thirty tend to recur within three years, but in postmenopausal women years or even decades may pass before recurrence. Martiscia Davidson, A.M. See also Dilation and curettage (D&C); Endometrial cancer; Endometrial hyperplasia; Hormone replacement therapy (HRT); Ovarian cancers; Ovarian cysts.
u Green tea Category: Lifestyle and prevention; complementary and alternative therapies Also known as: Camellia sinesis Definition: Green tea is a beverage made from fresh leaves of the evergreen Camellia sinesis plant. These leaves are rich in antioxidants, including polyphenols and flavonoids, that have been implicated in such general body health as suppressing aging; deterring food poisoning; controlling blood pressure, glucose, and cholesterol levels; and preventing cancer. One class of flavonoids, the catechins, have recently become the focus of study for their anticancer potential. Cancers treated or prevented: Implicated in both the treatment and the prevention of several cancers Delivery routes: Most commonly oral by liquid; green tea tablets and capsules containing its main ingredients also are widely marketed How this substance works: Studies have suggested relationships between green tea intake in the diet and the reduction of stomach cancer in Asians. Laboratory studies of animal subjects strongly suggest that green tea may also help reduce the incidence of a number of cancers. The cancer-fighting components of green tea are antioxidants, which are the body’s defense against free radicals that precipitate cell dysfunction that in turn leads to cancer. Antioxidants in green tea include polyphenols and flavonoids such as EGCG (epigallocatechin gallate) and other catechins. EGCG binds with laminin receptors on the surface of cancer cells, thereby dramatically reducing their growth
Salem Health: Cancer
Grief and bereavement Side effects: Side effects from drinking large amounts of green tea in the diet are normally rare among most of the population. Green tea has a high caffeine content, however, and physicians routinely warn that people with heart conditions or high blood pressure and women who are pregnant or breast-feeding should not drink green tea in excess. Some side effects of caffeine may include nausea, insomnia, frequent urination, irritability, or diarrhea. In excessive doses, caffeine can cause seizures or heart irregularities. Green tea also contains vitamin K, which can decrease the effectiveness of anticoagulant drugs. Dwight G. Smith, Ph.D. See also Antioxidants; Chemoprevention; Dietary supplements; Phytoestrogens; Prevention.
u Grief and bereavement Category: Social and personal issues
Green tea is being studied as a cancer preventative. (©Monkey Business Images/Dreamstime.com)
and survival. It may also restrict blood flow to cancerous cells and restrict or eliminate the formation of new blood vessels, both of which contribute to the death of cancer cells, which are unable to obtain needed nutrients for growth. Laboratory studies have also suggested that catechins may inhibit the formation and operation of specific enzyme activities that lead to cancer development. Human studies have been much less consistent. Some studies support laboratory findings regarding green tea cancer-fighting benefits, but other studies suggest little or no benefit. Studies in China, where green tea is a staple in the diet, generally find lower incidences of cancer among tea drinkers when compared to non-tea drinkers. The National Cancer Institute (NCI), however, conducted its own study of the antitumor effect among prostate cancer patients. This study concluded that there was little to no benefit. In response to these differing results, the Food and Drug Administration (FDA) has denied that green tea has antitumor benefits and suggests that further controlled studies on the relationships between green tea and cancer are needed.
Definition: Grief is the normal reaction to loss, which can be physical, mental, or emotional. Bereavement is the period of time after a loss in which a person experiences grief and mourning. Many cancer patients experience grief, and their families and friends experience both grief and bereavement. The universal experience of loss: Everyone experiences loss at some time in life. Loss can come as the death of a spouse, child, or friend; the loss of a marriage through divorce; the loss of a job or position at work; the loss of a home; or the loss of a pet. Loss is a universal experience that occurs when some meaningful part of a person’s life has been taken away. Loss comes in many ways to cancer patients and their families and friends. Dying patients face loss of function and independence, their role in the family unit, relationships, dreams and possibilities, and finally life itself. They may worry about those left behind. Spouses may show concern for their mates and want to be sure that they will be all right. Some may grieve that they worked too late and too much, that they spent too little time with their spouse and children, that they never got that new car or never took that dream vacation, or that they did not accomplish their life goals—and now it is too late. Watching a person’s health deteriorate because of cancer is difficult. Family and friends may experience anticipatory grief with increased anxiety, fear, or depression. The patient’s family and friends experience tremendous stress as they work through what being without the person may mean to them. They may find themselves unable to 541
Grief and bereavement
The Kübler-Ross Model Elisabeth Kübler-Ross, in her 1969 book On Death and Dying, identified five stages of grief experienced by a dying person. She noted that the stages are not always experienced in this order and that the dying person always experiences at least two of these stages. 1. Denial and isolation (this cannot be happening) 2. Anger (why me?) 3. Bargaining (if I do this, then . . . ) 4. Depression (I do not care about anything anymore) 5. Acceptance (I will face reality)
concentrate or make decisions. Their work performance may suffer. Physical illness occurs, and aches and pains crop up for no apparent reason. They may imagine how death may happen and hover over the dying person. Family struggles may surface when people are tired and uncertain about their family member’s life. Anticipatory grief can be useful, as the family can begin to adjust to the death before it actually occurs. Unfinished business can be addressed, and families can say their good-byes. Family roles may be reassigned to fill the anticipated void. Differences in grief, bereavement, and mourning: Although grief and bereavement are used interchangeably, they are separate concepts. Grief is the normal reaction to death and can be experienced many ways. The person with grief may display mental reactions such as anxiety, guilt, anger, depression, or despair. Grief can produce physical problems such as insomnia, loss of appetite, and illness. The intensity of the grief and symptoms depend on the closeness of the relationship with the deceased person, the impact that the death has on the survivor, and any feelings left unexpressed or unresolved after the person’s death. Bereavement is the time after the death occurs when the remaining person is grieving. After all the arrangements are made and the funeral is completed, the survivor is left alone in a changed environment. The severity and length of bereavement depend on the closeness of that person to the deceased and whether there was time to process the death through anticipated grief. Survivors process grief through mourning. Mourning allows the survivor to adapt to the death of another person. Survivors may take part in rituals that vary among cultures and religious beliefs. A funeral or memorial service may be held to honor the memory of the deceased person. Some may wear black or other special clothes, send the family 542
Salem Health: Cancer flowers or other gifts, or prepare food. Time may seem to stand still as normal activities of daily living seem to have been put on hold. Survivors may pull away from their usual activities and struggle to resume minimal tasks. Energy to process grief is emotionally and physically draining, so survivors feel tired. They may relive past experiences of loss and find themselves hurting again. Phases of bereavement: When people experience the death of someone close to them, most go through four predictable phases of grief. Stage one is shock and numbness. Survivors are stunned and cannot fully grasp that death has occurred. Numbness buffers the harsh realities as what has been lost begins to become evident. Stage two is yearning and searching. The reality of the death is unacceptable, so anxiety surfaces because of separation from the deceased person. Survivors may desire to see the deceased person again and have dreams about the person. They may find themselves looking for or calling to the deceased person. Feelings of disappointment surface because the deceased person cannot return. Stage three is disorganization and despair. Depression sets in, and survivors may see no future. Making plans seems hopeless. Focusing or concentrating proves difficult or impossible. Stage four is reorganization and resolution. Slowly survivors find their way through their desire to have the deceased person back in their lives, through sadness and disorganization, to reorganization and resumption of daily life. Grief counseling and therapy: Grief counseling provided by trained professionals offers survivors the opportunity to process normal grief reactions. Counseling can help survivors accept the loss by talking about the deceased person. Discussions give survivors time and a forum to express any feelings about the loss, such as sadness, helplessness, or anger. Sessions assist survivors to begin to live without the deceased person and feel strong enough to make decisions for themselves. Separating emotionally from the deceased person can be difficult, but with help the transition may be softened. The counselor can teach survivors to anticipate heightened feelings of loss during holidays or on birthdays or anniversaries. Grief counseling makes resuming normal life easier. Grief counseling can be provided in a group setting. Sometimes several people who have lost someone to cancer come together and support each other by sharing their experiences. Sometimes they become friends with others who can provide positive support when the group sessions end. Churches, home health and hospice agencies, or fu-
Salem Health: Cancer neral homes may offer group grief counseling to support the friends and family of the deceased person. Grief therapy is needed when survivors have serious difficulty separating from the deceased person. The mourner is encouraged to identify strong feelings such as anger or resentment and to allow those negative thoughts to surface and be spoken. Sometimes guilt is present, or uncomfortable and unresolved thoughts still linger. Mourners can work though their grief to recognize the finality of the death and see a future. Complicated or unresolved grief results when the survivor cannot progress to reorganization and resolution. Problems develop with major unrelieved depression, severe anxiety, substance abuse, or post-traumatic stress syndrome such as flashbacks of the death, panic, nightmares, work instability, parenting or marital problems, family difficulties, memory and concentration loss, sleep disturbances, or suicidal thoughts. Complicated grief requires more intense work from professional therapists. Grief and bereavement in children: Children and their grief may be overlooked by adults when a death occurs. How children react to a death will depend on their age, stage of development, and personality; any previous experience with death; and the intensity of the lost relationship. Children may wonder if they somehow caused the death, if they too will die, and who will care for them or love them now that the deceased person is gone. Children express their grief in different ways from adults. Initially some children may throw tantrums or have pronounced mood swings. They may misbehave and seek attention as they wrestle with their feelings. However, other children may withdraw and become reclusive. They may show signs of depression and lose interest in school or normal social activities. Still others may become aggressive, and some seem sad one minute and happy the next. Though children may appear to show symptoms for only a brief time, their grief may actually last longer than that of an adult. Unresolved grief can surface later in the child’s life and may need grief therapy by a trained counselor. Marylane Wade Koch, M.S.N., R.N. u
For Further Information James, John W., Russell Freidman, and Leslie Matthews. When Children Grieve: For Adults Who Help Children Deal with Death, Divorce, Pet Loss, Moving, and Other Losses. New York: HarperCollins, 2001. Lewis, C. S. A Grief Observed. New York: HarperCollins, 1961. Rando, Therese A. How to Go on Living When Someone You Love Dies. Lexington, Mass.: Bantam, 1991.
Gynecologic cancers Westberg, Granger E. Good Grief. Minneapolis: Augsburg Fortress, 2006. Worden, J. William. Children and Grief: When a Parent Dies. New York: Guilford Press, 1996. u
Other Resources
American Cancer Society Coping with Grief and Loss http://www.cancer.org/docroot/MBC/ MBC_4x_CopingGrief.asp National Cancer Institute Coping with Grief and Loss http://www.cancer.gov/cancertopics/pdq/ supportivecare/bereavement/Patient See also Advance directives; Anxiety; Caregivers and caregiving; Counseling for cancer patients and survivors; End-of-life care; Hospice care; Living will; Palliative treatment; Prayer and cancer support; Psychosocial aspects of cancer; Stress management.
u Gynecologic cancers Category: Diseases, symptoms, and conditions Also known as: Cervical cancer, uterine cancer, ovarian cancer, gestational trophoblastic disease, and cancers of the vulva, vagina, and Fallopian tubes Related conditions: Cancer of the colon and rectum, cancer of the bladder, peritoneal carcinomatosis Definition: Gynecologic cancers are cancers that arise in one of the anatomic structures of the female reproductive tract: the Fallopian tubes, the ovaries, the uterus, the cervix, the vagina, and the vulva. Historically, cancer of the breast has not been considered to be a gynecologic cancer. Risk factors: Risk factors have been identified for many of the gynecologic cancers. For cervical cancer, they include a woman’s having her first sexual encounter at less than age fifteen, multiple sexual partners, promiscuous male partners, a history of sexually transmitted diseases, an impaired immune system, and cigarette smoking. Risk factors for uterine cancer are use of medications containing estrogen without the addition of progesterone (the so-called unopposed estrogen effect), use of the medication tamoxifen for more than two years, onset of late menopause (at greater than age fifty-two), obesity, never having had children (nulliparity), diabetes, high blood pressure, and increased dietary fat intake as well as having 543
Gynecologic cancers had estrogen-secreting ovarian tumors, polycystic ovarian syndrome, or radiation therapy to the pelvis. Risk factors for ovarian cancer are not having been pregnant, incessant ovulation (ovulation not interrupted by use of oral contraceptives or by pregnancy), a family history of ovarian cancer, breast cancer, Western lifestyle, and exposure to talc. A risk factor for cancer of the vulva is exposure to the human papillomavirus (HPV). Risk factors for cancer of the vagina include age, HPV infection, exposure to diethylstilbestrol (DES), a history of cervical cancer, vaginal adenosis, uterine prolapse, cigarette smoking, chronic vaginal irritation, low socioeconomic status, hysterectomy at an early age, and vaginal trauma. The major risk factors for cancer of the Fallopian tube are chronic inflammation in the form of endometriosis or pelvic infections, a history of infertility, and low parity (no children or only one or two). The primary risk factors for gestational trophoblastic disease are being over age forty or less than age twenty and having a history of a prior molar pregnancy. Etiology and the disease process: What is known about the etiology of gynecological cancers varies. Cancer of the Fallopian tube and ovary share abnormalities of the cancer genes TP53 and ERBB-2, suggesting similar genetic risks and environmental factors. HPV causes cervical cancer and is believed to cause changes that progress to cancer of the vulva. If left untreated, up to one-third of women infected with HPV will develop cervical cancer. Women who have long-term unopposed estrogen stimulation undergo benign changes in the endometrium that can precede the development of uterine cancer. Most vaginal cancers are metastatic, originating from cancers of the cervix or vulva and spreading to the vagina, although metastases have been reported to occur from the uterus, ovaries, colon, rectum, breast, and even the kidney. Gestational trophoblastic disease, which can mimic a normal pregnancy, progresses rapidly and is fatal if not treated but has a good prognosis with treatment. Ovarian cancer is an insidious disease, and with the lack of screening and the associated vague symptoms, most cases are advanced at the time of diagnosis. Incidence: Cancer of the uterus is the most frequent cancer involving the female reproductive tract in the United States, and the fourth most frequent cancer affecting women, behind breast, lung, and colorectal cancer. There are approximately 41,000 new cases of uterine cancer each year, with about 7,300 deaths. An individual woman’s lifetime risk of cancer of the uterus is about 1 in 50. Ovar544
Salem Health: Cancer
Age Groups with the Highest Incidence of Specific Gynecologic Cancers Type of Cancer Gestational trophoblastic Cervical Uterine Ovarian Fallopian tube Vulva
Age at Diagnosis
Women Diagnosed (%)
20-29 40-49 50-59 50-59 60-69 70-79
43.9 27.0 27.9 23.1 28.7 29.7
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
ian cancer is the second most common cancer involving the female reproductive tract and is the leading cause of death of all gynecologic cancers. There are approximately 26,000 new cases diagnosed each year and 16,000 deaths. The lifetime risk for ovarian cancer is 1 in 70. The third most common gynecologic cancer is cervical cancer, with 12,800 new cases per year and 4,600 deaths. Less common cancers are those of the vagina, with about 2,000 new cases each year, and cancer of the vulva, with 1,000 to 1,500 new cases per year. About 5 percent of all gynecologic cancers are vulvar, and 1 to 2 percent of malignancies involving the female reproductive tract are vaginal cancer. Fallopian tube cancer is the rarest cancer involving the female genital tract, accounting for approximately 1 percent of all gynecologic malignancies. There are approximately 300 cases diagnosed in the United States each year. Gestational trophoblastic disease occurs in 1 in 850 to 1,300 pregnancies and 1 in 2,000 deliveries. Symptoms: Many gynecologic cancers share symptoms such as abnormal bleeding; however, some are much harder to detect. Abnormal bleeding through the vagina is the most common symptom associated with cancer of the uterus, occurring in approximately 90 percent of cases. For premenopausal women, this may take the form of socalled breakthrough bleeding, prolonged bleeding, or heavy bleeding, all of which generally reflect an underlying hormonal imbalance and can be treated as such. For postmenopausal women, any bleeding should be considered abnormal and should be evaluated by a gynecologist. Abnormal uterine bleeding is the most frequent symptom of gestational trophoblastic disease. The most common symptoms associated with cancers of the vagina are abnor-
Salem Health: Cancer mal bleeding or an excessive, nonodorous, watery discharge; less frequent symptoms include pelvic pain, an increased frequency of urination or pain with urination, and constipation. Cancer of the Fallopian tube, for the most part, is a disease without specific symptoms. Symptoms that are associated with cancer of the Fallopian tube include an abnormal, watery vaginal discharge or excessive bleeding. Pain and a palpable pelvic mass are infrequently associated with Fallopian tube cancer. For cancer of the vulva, irritation and itching are the most common symptoms. Cervical and ovarian cancer are harder to detect through symptoms. An abnormal Pap smear is the earliest “symptom” of cervical cancer, as most patients with cervical cancer are physically asymptomatic. In more advanced cases of cervical cancer, bleeding after intercourse (postcoital bleeding), intermenstrual bleeding, or postmenopausal bleeding may occur. The symptoms of ovarian cancer are nonspecific, and because of this, the diagnosis is often delayed. The most common symptoms include bloating, abdominal fullness (necessitating an increase in clothing size), early fullness after eating, heartburn, and abdominal pain. Screening and diagnosis: Screening for gynecologic cancers ranges from the common Pap smear to visual inspection to no screening for rarer cancers. Pap smears are used to screen for cervical cancer. The diagnosis of cervical cancer is established by consistent findings on an abnormal Pap smear with a large biopsy of the cervix (conization), performed as an outpatient in the hospital. Stage I cervical cancer is confined to the cervix, Stage II involves spread to the upper two-thirds of the vagina, Stage III involves spread to the lower one-third of the vagina, and Stage IV involves cancer that has spread to the bladder or rectum, or outside the pelvis. No routine screening test exists for cancer of the uterus, but those at high risk for the cancer can be screened by endometrial sampling and measurement of the endometrial thickness (or lining). Endometrial sampling is an office-based procedure in which a small, flexible plastic catheter is inserted into the uterus and the cells lining the uterus (endometrial cells) are drawn into the catheter. Endometrial sampling can also serve as the diagnostic test for endometrial cancer. In some cases, if the diagnosis of uterine cancer is in question based on endometrial sampling, a dilation and curettage (D&C) can be performed as an outpatient procedure in which more extensive sampling of the uterine cavity can be performed. Measurement of the endometrial thickness is also an office-based procedure, but in some cases is done by a radiologist. Using an
Gynecologic cancers ultrasound probe through the vagina (transvaginal ultrasound), the thickness of the lining of the uterus is measured. Stage I cancer is limited to the uterus, Stage II involves extension from the body of the uterus to the cervix, Stage III occurs when the tumor protrudes through the uterus or metastasizes to the vagina, pelvis, or lymph nodes adjacent to the aorta, and Stage IV cancer exists when metastases involve the bladder, the bowel, or organs outside the pelvis in the abdomen. Other than an annual well-woman examination with palpation of the ovaries, no specific screening is recommended for ovarian cancer. However, for women at high risk or those specifically concerned about ovarian cancer, a transvaginal ultrasonogram (in which the volume of the ovaries is determined), combined with a cancer antigen (CA) 125 blood test, can be performed. The diagnosis of ovarian cancer is made at the time of surgery, although abdominal ultrasonography and computed tomography (CT) scans of the pelvis generally are obtained first. Ovarian cancer is staged as follows: Stage I involves a tumor limited to one or both ovaries, Stage II ovarian cancer exists when the tumor has extended to the pelvis, Stage III cancer involves a tumor outside the pelvis, and Stage IV cancer is characterized by distant metastases (lungs or liver). For cancer of the vulva, no screening is recommended other than visual inspection during an annual well-woman examination. The diagnosis is made by biopsy of any suspicious lesion. Stage I cancer is less than 2 centimeters (cm) in diameter and confined to the vulva, Stage II cancer is greater than 2 cm in diameter and confined to the vulva, Stage III cancer extends to the anus or urethra or lymph nodes on one side, and Stage IV involves spread to the bladder, rectum, bones of the pelvis, or lymph nodes on both sides. Screening for vaginal cancer should be performed in the context of the annual well-woman examination. Stage 0 vaginal cancer is referred to as carcinoma in situ, referring to cancer that is localized without apparent spread. Stage I vaginal cancer is limited to the vaginal wall. Stage II vaginal cancer has extended to the subvaginal tissues but not to the pelvic wall. Stage III vaginal cancer involves the pelvic wall. Stage IV vaginal cancer has spread beyond the pelvis or has extended to the bladder or rectum. No screening exists for cancer of the Fallopian tube. Stage 0 is cancer limited to the lining of the Fallopian tube. Stage I is cancer limited to one tube with extension into the muscular layer of the tube but not to the external surface of the tube. Stage II cancer involves one or both tubes with extension beyond the Fallopian tube. Stage III cancer involves one or both tubes with spread beyond the pelvic cavity. Stage IV cancer involves one or both Fallo545
Gynecologic cancers pian tubes with distant metastases, for example, the lungs. Specific screening is not recommended for gestational trophoblastic disease. With the advent of obstetric ultrasonography, few cases of gestational trophoblastic disease are diagnosed in advanced stages when symptoms occur. The diagnosis is made when the pregnancy blood test shows that the level of beta-human chorionic gonadotropin (β-HCG) is elevated beyond what is expected and the ultrasound shows no fetus (exhibits a snowstorm pattern). Gestational trophoblastic disease is staged as follows: Stage I is limited to the uterus, Stage II involves the female reproductive tract, Stage III has spread to the lungs, and Stage IV has spread elsewhere. Treatment and therapy: Most gynecologic cancers are treated first with surgery and then by radiation therapy or chemotherapy; however, uterine cancer is treated primarily by surgery. Cervical cancer and cancer of the vulva are treated by surgery with or without radiation therapy. Cancer of the vagina is treated by surgery or radiation or a combination of the two, depending on the type of tumor. Ovarian cancer is treated by surgery with chemotherapy, and cancer of the Fallopian tube is treated by surgery, with or without chemotherapy. Gestational trophoblastic disease is treated by evacuation of the uterus with chemotherapy. Prognosis, prevention, and outcomes: Gynecologic cancers range from cancers with excellent prognoses, such as low-risk gestational trophoblastic disease, to those with less favorable prognoses, such as ovarian cancer, which is usually detected in an advanced state. The prognosis of gestational trophoblastic disease is based on the woman’s age, pregnancy history, β-HCG level, tumor size, metastases, and response to chemotherapy. For those at low risk, the cure rate is 100 percent; for those at high risk, the cure rate is 75 percent. Prognostic factors for uterine cancer include the woman’s age at the time of diagnosis, race, tumor stage, type of tumor, size of the uterus at the time of diagnosis, depth of invasion of the tumor into the layer of uterine muscle, presence of tumor in the blood vessels supplying the uterus, and spread of the tumor outside the uterus to other organs or lymph nodes. The overall five-year survival rates for cancer of the uterus are 87, 72, 51, and 9 percent for stages I, II, III, and IV, respectively. The prognosis for cervical cancer depends on tumor stage, size of tumor, depth of invasion, and lymph node spread. The availability of a vaccine against HPV has provided a means for the prevention of cervical cancer. Fiveyear survival rates for Stages I to IV are 80 to 95, 64, 38, and 14 percent, respectively. 546
Salem Health: Cancer Prognosis of cancer of the vulva is related to the tumor stage, size of the lesion, and lymph node involvement. Five-year survival rates for Stages I to IV are 71, 61, 44, and 8 percent, respectively. The prognosis for vaginal cancer is directly related to the stage at the time of diagnosis. The five-year survival rates for Stages I to IV are 68, 54. 35, and 20 percent, respectively. The overall five-year survival for cancer of the vagina is approximately 45 percent. The five-year survival rate for all stages of Fallopian tube cancer combined is approximately 40 to 50 percent. Women with Stage I Fallopian tube cancer have five-year survival rates of 65 percent, Stage II disease is 50 to 60 percent, and Stages III and IV are 10 to 20 percent. Prognosis of ovarian cancer is related to tumor stage as well as the amount of residual tumor after surgery. Because most patients are diagnosed in advanced stages, the five-year survival rate is approximately 50 percent. D. Scott Cunningham, M.D., Ph.D. u
For Further Information Grimes, D. A. “Economy KE: Primary Prevention of Gynecologic Cancers.” American Journal of Obstetrics and Gynecology 172 (1995): 227. Hartmann, Lynn C., and Charles L. Loprinzi, eds. Mayo Clinic Guide to Women’s Cancers. Rochester, Minn.: Mayo Clinic, 2005. Krychman, Michael L. One Hundred Questions and Answers for Women Living with Cancer: A Practical Guide for Survivorship. Sudbury, Mass.: Jones and Bartlett, 2007. Sutton, Amy, ed. Cancer Sourcebook for Women. 3d ed. Detroit: Omnigraphics, 2006.
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Other Resources
American Association for Cancer Research Support and Advocacy Groups: Gynecologic Cancers http://www.aacr.org/home/survivors—advocates/ cancer-resources—organizations,-agencies-andwebsites/support-and-advocacy-groups/us-andcanadian-groups-by-focus/gynecologic-cancers.aspx American Society of Clinical Oncology Gynecologic Cancers http://gyncancers.asco.org Eyes on the Prize.org http://www.eyesontheprize.org/links/gynca.html See also Amenorrhea; Breast cancer in pregnant women; Cervical cancer; Childbirth and cancer; Choriocarcinomas; Colposcopy; Dilation and curettage (D&C); Endocrine
Salem Health: Cancer cancers; Endocrinology oncology; Endometrial cancer; Endometrial hyperplasia; Fallopian tube cancer; Fertility drugs and cancer; Fertility issues; Gestational trophoblastic tumors (GTTs); Gynecologic oncology; Hormone replacement therapy (HRT); Hysterectomy; Hysterography; Hystero-oophorectomy; Hysteroscopy; Infertility and cancer; Oophorectomy; Ovarian cancers; Ovarian cysts; Ovarian epithelial cancer; Pap test; Pelvic examination; Placental alkaline phosphatase (PALP); Pregnancy and cancer; Salpingectomy and salpingo-oophorectomy; Sterility; Transvaginal ultrasound; Uterine cancer; Vaginal cancer; Vulvar cancer.
u Gynecologic oncology Category: Medical specialties Also known as: Gynecology oncology Definition: Gynecologic oncology refers to a subspecialty of obstetrics and gynecology that deals with the diagnosis and comprehensive surgical and chemotherapeutic treatment of cancers originating from the female reproductive system and the complications thereof. Gynecologic oncology utilizes traditional surgical as well as chemotherapeutic and technological innovations to accomplish this. Additional (adjuvant) treatment before or after surgery is carried out as needed with other oncologic specialties such as radiotherapy oncology. Cancers treated: All cancers of female reproductive system origin, including vulvar, vaginal, cervical, endometrial, tubal, and ovarian cancers; hydatidiform moles (gestational trophoblastic disease) Training and certification: To be recognized and certified as a gynecologic oncologist, a candidate (fellow) must first finish an accredited four-year postgraduate residency training program in obstetrics and gynecology. An aspiring candidate must not only demonstrate excellent surgical technique and skill in carrying out procedures but also have extensive knowledge of the behavior of cancer clinically as well as at the cellular level. The candidate must be able to carry out clinical and laboratory research during the fellowship, which requires a comprehensive understanding of not only research designs and biostatistics, but also how to evaluate research articles, carry out original research, and write. In the United States, the American Board of Obstetrics and Gynecology (ABOG) is the regulatory organization responsible for graduate medical education programs for gynecologic oncology. The board requires training pro-
Gynecologic oncology grams to be at least thirty-six months in duration and cover knowledge and skills the board deems essential for providing the most effective care for patients. Education is accomplished through formal subspecialty teaching conferences, seminars, didactics, teaching rounds, supervised management of patients in both inpatient and outpatient settings, and performance of subspecialty-specific procedures. Clinical or laboratory research projects are also a part of the curriculum, and time is allotted for this during training. For certification, the board evaluates candidates’ knowledge base through written and oral examinations as well as skills through case lists and experience logs kept by the candidate. Certifications in gynecologic oncology are renewed every six years. Services and procedures performed: Gynecologic oncologists evaluate patients and conduct the diagnostic tests necessary to ascertain the type and stage of cancer, with the ultimate aim of implementing a definitive intervention. These tests may include a pregnancy test in women of reproductive age, chest X rays, an intravenous pyelogram when kidney involvement is suspected, computed tomography (CT) scans or magnetic resonance imaging (MRI) of the pelvis and other areas where cancer is clinically suspected to have spread, tumor marker tests, a colposcopy, and biopsies of suspicious lesions that do not require major surgery. The intervention, based on the initial diagnostic findings, may consist primarily of a surgical procedure with the intent to assess the spread of the cancer, remove as much tumor as possible, and repair any damage caused by the spread. At other times, a combination of chemotherapy and radiation therapy before or after the surgical procedure may be used, with radiotherapy coordinated with the radiation oncologist. A female patient in whom a cancer specific to the reproductive organs is suspected is typically referred to a gynecologic oncologist by her primary care physician. The gynecologic oncologist focuses on the management of cancer. Gynecologic oncologists must be able not only to recognize cancer but also to derive the most effective treatment plan for the patient while minimizing unnecessary harm that can lower quality of life. An essential part of planning treatment is surgical staging of the cancer. This is generally an extension of the diagnostic plan but at the same time is therapeutic in that as much tumor is removed as possible. Not only can the prognosis be known, but also the most appropriate, research-based intervention can be determined based on the stage of the cancer. The most common major surgical procedure performed by gynecologic oncologists is a hysterectomy, often with a salpingo-oophorectomy (removal of ovaries and Fallopian 547
Gynecologic oncology
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tubes). Women with preinvasive and less extensive disease who still wish to bear children may elect to have only the diseased cervix or adnexa (ovary and Fallopian tube) removed. Other procedures performed include biopsies of small masses and wide excision of the external genitalia (vulva) and the surrounding skin and tissue in extensive tumors suspected of spreading microscopically, often through lymph drainage. These are often complex and complicated surgeries, where removing tumors arising from these organs can be challenging, especially with bulky tumors and tumors that have spread outside the reproductive system. A part of the staging procedure is the excision of specific groups of lymph nodes that drain the affected organs, as they can serve as accumulation points for cancer cells. Lymph node involvement often signifies a poorer prognosis, which means that radiation, chemotherapy, or both may have to be instituted postoperatively. Complications can arise from encroachment into nearby organs such as the bowel, urinary bladder, and urethra. These are an inevitable part of practice, and gynecologic oncologists are competent in surgical repair of these organs as well as reconstructive surgery of the external genitalia and vagina, as necessary. Reconstructive surgery seeks to preserve as much functionality as possible. Seri-
ous psychological effects on the patient’s self-image can result with disfigurement of the genitalia if left untreated. Another part of a gynecologic oncologist’s experience is the palliative care of women with terminal conditions. Palliative treatments include surgery to remove as much tumor as possible, followed by radiation therapy to kill off remaining tumor cells and to alleviate pain. Related specialties and subspecialties: Although the gynecologic oncologist is involved in specialized treatment, other specialists such as medical oncologists, radiation oncologists, gynecologic pathologists, and oncology nurses collaborate with the gynecologic oncologist in formulating an individualized treatment plan for the patient. Oncology nurses are specialized registered nurses who care for the patient as well as prepare and administer chemotherapy or biotherapy (for example, antibodies) to patients in as safe a manner as possible. They act as the main points of contact for the patient and family, monitor the patient’s progress during therapy, and educate the patient regarding his or her disease. Oncology nurses may be oncology certified nurses (O.C.N.s). Aldo C. Dumlao, M.D.
Ampulla
Fundus Isthmus Ovarian Ligament
Infundibulum
Uterine Cavity Body
Ovary Isthmus of Uterus Internal Os
Fimbriae
Cervix External Os Fornix
Vagina
Female reproductive system. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams & Wilkins. All rights reserved.)
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Salem Health: Cancer u For Further Information Betancourt, Marian, and Joseph F. Dooley. The Coming Cancer Breakthroughs: What You Need to Know About the Latest Cancer Treatment Options. New York: Kensington Books, 2003. Likis, Frances E., and Kerri Durnell Schuiling. Women’s Gynecologic Health. Sudbury, Mass.: Jones and Bartlett, 2005. Null, Gary. Women’s Health Solutions. New York: Seven Stories Press, 2002. u
Organizations and Professional Societies
American Board of Obstetrics and Gynecology (ABOG) http://www.abog.org 2915 Vine Street Dallas, TX 75204 International Federation of Gynecologists and Obstetricians (FIGO) http://www.figo.org Suite 3, Waterloo Court 10 Theed Street London SE1 8ST United Kingdom
Gynecologic oncology Oncology Nursing Society (ONS) http://www.ons.org 125 Enterprise Drive Pittsburgh, PA 15275 Society of Gynecologic Oncologists http://www.sgo.org 230 W. Monroe, Suite 710 Chicago, IL 60606 See also Amenorrhea; Breast cancer in pregnant women; Cervical cancer; Childbirth and cancer; Choriocarcinomas; Colposcopy; Dilation and curettage (D&C); Endocrine cancers; Endocrinology oncology; Endometrial cancer; Endometrial hyperplasia; Fallopian tube cancer; Fertility drugs and cancer; Fertility issues; Gynecologic cancers; Hormone replacement therapy (HRT); Hysterectomy; Hysterography; Hystero-oophorectomy; Hysteroscopy; Infertility and cancer; Oophorectomy; Ovarian cancers; Ovarian cysts; Ovarian epithelial cancer; Pap test; Pelvic examination; Placental alkaline phosphatase (PALP); Pregnancy and cancer; Salpingectomy and salpingo-oophorectomy; Sterility; Transvaginal ultrasound; Uterine cancer; Vaginal cancer; Vulvar cancer.
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Hair dye
u Hair dye Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogens include 2,4-diaminotoluene (since 1981), 2,4diaminoanisole sulfate (since 1983), 4-chloro-ophenylenediamine (since 1985), Disperse Blue 1 (since 1998) Also known as: Hair color, coloring agent Related cancers: Bladder, breast, endometrial, and urinary tract cancers; non-Hodgkin lymphoma; hematopoietic cancers; myelodyplasia; multiple myeloma; leukemia; preleukemia Definition: Hair dye is a usually soluble substance for staining or coloring to change or enhance the color of hair. Synthetic hair dye falls into one of three categories: permanent, semi-permanent, and temporary. Darker hair dyes have more carcinogens than lighter dyes because more chemicals are used in the dyes. Exposure routes: Skin contact Where found: Hair salons, barber shops, hair dye manufacturing plants, individual residences At risk: Hairdressers, barbers, hair dye manufacturers, individuals using hair dye either in a salon or at home. Of the three types of synthetic hair dye—permanent, semipermanent, and temporary—carcinogens are more prevalent in permanent and semi-permanent dyes. Etiology and symptoms of associated cancers: There appears to be an increased risk for those who use darker shades of hair color because darker shades have more chemicals than do lighter shades. In addition, the frequency and duration of use may also increase carcinogen exposure. Older versions of dyes may have a greater risk associated with them than newer versions; however, death rates from all cancers combined appear to be about the same for hair dye users and nonusers. Most evidence does not show hair dyes to be a significant cancer risk factor, and studies indicating otherwise have been inconsistent. For example, some studies have shown an association between hair dye use and bladder or blood cancers, while others have found no association. Of all studies conducted, none has shown a direct link, only an association. Potential cancer risk relates mostly to permanent and semi-permanent dyes as opposed to temporary ones. History: Ancient civilizations used plants to dye hair. The first synthetic dye was created in 1907. It is estimated that 550
Salem Health: Cancer 45 percent of women and 6 percent of men use hair dye. Chemicals in hair dye have been shown to cause cancer in lab animals; however, these animals were fed high levels of dye over a long period, leaving the relevancy of these studies to humans unclear. Jennifer M. Hickin, B.S. See also 4-Aminobiphenyl; Benzidine and dyes metabolized to benzidine; Diethanolamine (DEA); Gliomas; Occupational exposures and cancer.
u Hairy cell leukemia Category: Diseases, symptoms, and conditions Also known as: Leukemic reticuloendotheliosis Related conditions: Anemia, thrombocytopenia (excessive bleeding and bruising) Definition: Hairy cell leukemia is a rare, chronic, slowprogressing cancer of the blood and bone marrow that is most often found in people over age forty and does not occur in children. Risk factors: Although there is some debate about the role of risk factors in hairy cell leukemia, the following appear to increase the likelihood of developing this cancer: a family history of blood cancers, Ashkenazi Jewish heritage, a previous diagnosis of cancer, and exposure to radiation, sawdust, and toxins, especially those in agricultural chemicals and petrochemicals. Etiology and the disease process: Researchers have not yet determined exactly what changes in deoxyribonucleic acid (DNA) cause the development of hairy cell leukemia. They do know that hairy cell leukemia begins in the bone marrow. The bone marrow makes stem cells that develop into three types of blood cells: red blood cells, white blood cells, and platelets. Hairy cell leukemia is a defect in white blood cell production. White blood cells are part of the immune system. Their function is to produce antibodies (proteins) and fight infection. Hairy cell leukemia affects the type of white blood cells called lymphocytes. There are three kinds of lymphocytes. In response to foreign organisms (bacteria, viruses, fungi), B lymphocytes produce antibodies that help destroy these foreign organisms. They are helped by two other types of lymphocytes, T lymphocytes and natural killer (NK) cells. All three types of lymphocytes must function properly to control infections. In people with hairy cell leukemia, too many stem cells turn into B lymphocytes. These B lymphocytes de-
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Hairy cell leukemia
velop abnormal threadlike projections that make them look “hairy.” Hairy lymphocytes are defective and do not function correctly in fighting infections. Because an abnormally large number of stem cells turn into hairy B lymphocytes, the number of other blood cells is smaller than usual. A decrease in red blood cells leads to anemia. A decrease in platelets makes it difficult for the blood to clot. The increase in hairy B lymphocytes occurs gradually and at first produces no obvious signs. Nevertheless, as the bone marrow produces more and more defective B lymphocytes, these cells collect in the spleen (an organ in the abdomen) and sometimes in the liver. The spleen begins to swell and become tender. Incidence: About 600 to 800 people in the United States are newly diagnosed with hairy cell leukemia each year. Five times more men than women develop this cancer. Most are diagnosed in their early fifties. Symptoms: Hairy cell leukemia usually produces gradual, very general symptoms that initially are not very noticeable. A decrease in the number of red blood cells causes anemia, which results in unusual tiredness, weakness, and shortness of breath. A decrease in platelets causes easy bruising and difficulty getting blood to clot. Defective B lymphocytes lead to increased infections and sometimes a low-grade fever associated with chronic infection. The individual may feel bloating or tenderness below the ribs. This is caused by swelling of the spleen (splenomegaly) as masses of hairy B lymphocytes collect there and sometimes in the liver. Individuals may lose weight for no obvious reason. Screening and diagnosis: Hairy cell leukemia is rare, so there are no routine screening tests for this cancer. Most people first see a physician for symptoms related to anemia or because of repeated infections due to malfunctioning B lymphocytes. Hairy cell leukemia is usually discovered during testing to determine the cause of these symptoms. Diagnosis of hairy cell leukemia begins with a physical examination. About 80 percent of people with hairy cell leukemia have a spleen so enlarged that the physician can feel it by pressing on (palpating) the abdomen. However, an imaging scan (computed tomography, ultrasound) may be done to determine the size of the spleen, especially if the individual complains of bloating and tenderness. A
complete blood count (CBC) determines the number and type of blood cells. If the lymphocyte count is high, a peripheral blood smear is done. This test looks at a thin layer of blood under a microscope to check for abnormal or “hairy” cells. About 20 percent of people with hairy cell anemia show abnormalities on liver function tests. Diagnosis continues with a bone and bone marrow biopsy. Under local anesthetic, a small piece of bone and marrow is removed from the hip bone and examined in the laboratory for cancer cells. Definitive diagnosis of hairy cell leukemia comes from examining under the microscope the pattern of proteins on the surface of B lymphocytes. This is called immunophenotyping, and it helps distinguish between hairy cell leukemia and other blood cancers. Since hairy cell leukemia is a chronic, slow-growing cancer, it is not staged using the standard TNM (tumor/ lumph node/metastasis) system. The staging of hairy cell leukemia is as follows: • Untreated or newly diagnosed hairy cell leukemia: Hairy B lymphocytes are found in the blood and bone marrow. Other blood cell levels may be decreased, and the spleen is enlarged. • Progressive hairy cell leukemia: The cancer has been treated with chemotherapy or removal of the spleen (sple-
A scanning electron micrograph of a hairy cell. (Professor Aaron Polliack/ Photo Researchers, Inc.)
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Hand-foot syndrome (HFS) nectomy). There is an increased number of hairy cells, or other blood cell levels are below normal. • Relapsed or refractory hairy cell leukemia: Hairy cell leukemia has returned after treatment (relapsed) or has not responded to treatment (refractory). Treatment and therapy: Because hairy cell leukemia progresses very slowly and sometimes not at all, the patient and physician may decide to wait and monitor the blood to see if conditions worsen. Early treatment—although imperative for most other cancers—does not improve the chance for remission, survival, or cure, so if symptoms are not too burdensome, waiting does not harm the patient. Eventually most people need treatment, but some individuals go ten or more years before treatment becomes necessary. One course of chemotherapy puts as much as 80 percent of hairy cell leukemia cases into complete remission and the remainder in partial remission. Remission is a condition in which symptoms disappear, but the cancer is still present in the body and can reoccur. The chemotherapy drug of choice is cladribine (Leustatin), and the alternative is pentostatin (Nipent). About 10 percent of patients do not improve with chemotherapy, and others have health conditions that prohibit chemotherapy treatments. These individuals may receive biological therapy (immunotherapy). The goal of biological therapy is to boost the immune system and make cancer cells more recognizable to healthy immune system cells so that they will be destroyed. Interferon alpha and rituximab (a monoclonal antibody made in the laboratory) are the standard biological therapies for hairy cell leukemia. Biological therapy is frequently successful in bringing about remission. Surgery to remove the spleen may also be done when the spleen is so enlarged that it may burst. This does not cure hairy cell leukemia but does restore the blood count to normal, which helps the body fight infection. Clinical trials are under way to test new treatments for hairy cell leukemia. There is no cost to the patient to participate in a clinical trial. Prognosis, prevention, and outcomes: Hairy cell leukemia rarely is cured but usually can be put into remission through treatment. Remission can last many years before symptoms recur. Recurring symptoms are often successfully treated. Overall survival rate at twelve years is about 87 percent, with more than half of individuals showing no progression of symptoms. About 17 percent of people with hairy cell leukemia eventually go on to develop other types of cancer. Martiscia Davidson, A.M. 552
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For Further Information Icon Health. Hairy Cell Leukemia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Parker, James N., and Phillip M. Parker, eds. The Official Patient’s Sourcebook on Hairy Cell Leukemia. San Diego, Calif.: Icon Health, 2002. Ravandi, F., and S. O’Brien. “Chronic Lymphoid Leukemias Other than Chronic Lymphocytic Leukemia: Diagnosis and Treatment.” Mayo Clinic Proceedings 80, no. 12 (December, 2005): 1660-1674.
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Other Resources
Hairy Cell Leukemia Research Foundation http://www.hairycellleukemia.org The Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org MayoClinic.com Hairy Cell Leukemia http://www.mayoclinic.com/health/ hairy-cell-leukemia/DS00673 National Cancer Institute Hairy Cell Leukemia Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ hairy-cell-leukemia/Patient See also Aleukemia; Biological therapy; Blood cancers; Cytokines; Leukemias; Lymphocytosis; Oncogenic viruses; Splenectomy; Staging of cancer; Watchful waiting.
u Hand-foot syndrome (HFS) Category: Diseases, symptoms, and conditions Also known as: Palmar-plantar erythrodysesthesia (PPE), hand-to-foot syndrome, Burgdorf’s reaction, chemotherapy-induced acral erythema Related conditions: Hand-foot skin reaction (HSFR) Definition: Hand-foot syndrome (HFS) is a chemotherapyinduced skin reaction characterized by swelling, tingling, redness, tenderness, pain, and possibly peeling and blistering of the palms of the hands and soles of the feet. Occurrence of HFS in patients receiving chemotherapy may result in lowering of dosage levels and interruption or discontinuation of treatment. Risk factors: HFS is a common side effect of high-dosage treatment of certain traditional cancer chemotherapeutic
Salem Health: Cancer agents, including 5-fluorouracil (5-FU), capecitabine, liposomal doxorubicin, and docetaxel. HFS typically occurs within the first few weeks of chemotherapy but may also occur after several weeks or months of treatment. Etiology and the disease process: The cause of HFS is not completely understood. The most widely accepted theory is that capillaries in the palms and soles break because of several factors including overuse, pressure, or increased temperature. Breakage of the blood vessels may release small amounts of the chemotherapeutic agent into the surrounding tissue, resulting in an inflammatory reaction in the affected areas. Another theory is that the drugs pass from the body through sweat secretion, and the hands and feet are more susceptible to HFS due to the large number of sweat glands present in those areas. The hands tend to be more commonly affected than the feet; in some patients, they may be the only areas affected. HFS may also occur elsewhere on the skin, such as the neck and chest, but it is much less common. HFS is distinct from hand-foot skin reaction (HSFR), a condition reported with the use of various targeted kinase inhibitors (such as sunitinib) that is characterized by more localized, thicker, callus-like lesions. Incidence: The occurrence of HFS is known to depend on agent, dose, and administration of the chemotherapeutic drug responsible. For example, in early phase II studies of capecitabine monotherapy for metastatic colorectal and breast cancer patients, HFS occurred in approximately 50 percent of patients; severe HFS was noted in approximately 10 percent of these patients. Symptoms: HFS typically begins as a feeling of numbness or tingling in the palms or soles. These symptoms may rapidly progress in three to four days to swelling, redness, tenderness, and burning pain in the affected areas. If treatment with the chemotherapeutic agent is not promptly interrupted or the dose of the agent reduced, blisters may develop, causing increased pain and interfering with general activities of daily living such as walking and handling objects. Screening and diagnosis: Histological examination of affected tissue does not discern from normal inflammation processes, preventing a true diagnostic marker for HFS. The National Cancer Institute has a general system for classifying HFS and HFSR based on three grade levels of severity: • Grade 1: Skin changes or dermatitis without pain, for example, erythema, peeling • Grade 2: Skin changes with pain, not interfering with function
Hand-foot syndrome (HFS)
•
Grade 3: Skin changes with pain, interfering with function Treatment and therapy: Control of symptomatic pain may occur through the use of cold compresses, particularly those that conform to the shape of the hands and feet (such as ice packs or bags of frozen corn or peas). Frequent but gentle application of highly moisturizing lotions and creams is also recommended. Elevation of the hands and feet may reduce swelling, and pain may be controlled through the use of pain relievers such as acetaminophen. Systemic corticosteroids, vitamin B6 (pyridoxine), and dimethyl-sulfoxide (DMSO) has been proposed to reduce or relieve symptoms, but conclusive evidence for these treatments has yet to be demonstrated. The only proven means to reverse the signs and symptoms of HFS is through interruption or dose reduction of chemotherapeutic therapy. Prognosis, prevention, and outcomes: Patient education in the early phases of treatment is vital to prevent complications brought on by HFS. Patients should be instructed to contact their doctor immediately if symptoms develop, as a quick reaction can often prevent development of more severe effects. Patients receiving agents known to cause HFS are instructed to avoid wearing tight-fitting clothes (gloves, socks, stockings) and shoes as well as to avoid excessive sun exposure, hot baths and showers, steam rooms, and excessive rubbing of the soles and palms. Comfortable slippers, sandals, or shock-absorbing shoe liners should be worn to relieve painful pressure points. Moisturizing creams and lotions should be applied liberally but gently to the hands and feet. However, creams or lotions containing alcohol, perfumes, or glycerin should be avoided. Sunscreen (SPF 30 or higher) and long-sleeved shirts and pants should be worn during prolonged exposure to the sun. Strenuous physical activity and long-term alcohol use should be avoided. Once actions to interrupt or reduce the dose of chemotherapy are undertaken, reversal of symptoms is typically rapid and without long-term consequences. Chemotherapeutic treatment can typically resume at a lower dose once symptoms improve. Scott A. Boerner, M.S.
u
For Further Information Chu, Edward, and Vincent T. DeVita. Physicians’ Cancer Chemotherapy Drug Manual 2007. Sudbury, Mass.: Jones and Bartlett, 2007. Lassere, Yvonne, and Paulo Hoff. “Management of HandFoot Syndrome in Patients Treated with Capecitabine (Xeloda).” European Journal of Oncology Nursing 8 (2004): S31-S40. 553
Head and neck cancers Nagore, Eduardo, Amelia Insa, and Onofre Sanmartín. “Antineoplastic Therapy-Induced Palmar Plantar Erythrodysesthesia (‘Hand-Foot’) Syndrome: Incidence, Recognition, and Management.” American Journal of Clinical Dermatology 1, no. 4 (2000): 225234. Yarbro, Connie H., Michelle Goodman, and Margaret H. Frogge, eds. Cancer Symptom Management. 3d ed. Sudbury, Mass.: Jones and Bartlett, 2004. u
Other Resources
American Cancer Society http://www.cancer.org Cancer.Net http://www.cancer.net/portal/site/patient See also Chemotherapy; Side effects.
u Head and neck cancers Category: Diseases, symptoms, and conditions Also known as: Cancers of the mouth, sinuses, nose, salivary glands, throat, lymph nodes in neck Related conditions: Squamous cell carcinoma, adenocarcinoma, oral cancer, laryngeal cancer, nasal cavity cancer, parasinus cancer, nasopharyngeal cancer, oropharyngeal cancer, hypopharyngeal cancer, salivary gland cancer Definition: Head and neck cancers refers to a wide variety of cancers occurring in the head and neck region, including cancers of the throat, mouth, voice box (larynx), salivary glands, lips, nose, and sinus cavities. Cancers of the scalp, skin, bones, muscles, brain, eye, and thyroid are not usually referred to as head and neck cancers. Risk factors: Smoking or using chewing tobacco is the greatest risk factor for head and neck cancers; in fact, tobacco use can be linked to 85 percent of these cancers. Cigarette smokers have a markedly increased chance of developing these cancers, up to a 25 percent greater risk than nonsmokers. Smoking cigars or marijuana also increases one’s risk of getting these cancers. Alcohol use increases risk, and using alcohol and tobacco in combination increases risk even further. Use of betel (a seed chewed as a stimulant, mainly in Southeast Asia) or maté (a beverage consumed like tea, generally in South America) also increases the risk of head and neck cancer. These substances damage the squamous cells that form a lining of many structures in the head and neck. 554
Salem Health: Cancer Diet may also increase the risk of head and neck cancers. Processed meats, red meat, and salted fish have all been linked to increased risk of cancers of the head and neck. White patches or spots in the mouth, called leukoplakia, are also a risk factor. About one-third of the time, these spots will turn into cancer. Other risk factors include sun exposure, radiation to the head and neck, and environmental exposure to wood dust, paint fumes, asbestos, nickel refining, textile fibers, and chemicals used by the petroleum industry. Poor oral hygiene, poor nutrition (especially low levels of vitamins A and B), a weakened immune system, gastroesophageal reflux disease (GERD), and exposure to secondhand smoke may also play a role. Medical experts are currently exploring the relationship between oral cancers and certain strains of human papillomavirus (HPV) infection. Epstein-Barr virus has also been associated with higher risk of cancer of the nose and throat. Etiology and the disease process: Most head and neck cancers are squamous cell carcinomas, cancers that begin in the cells lining the mucosal tissues in the mouth and throat. If the cancer is limited to these cells, it is called carcinoma in situ. If it has spread into deeper tissues or to other sites in the body, it is called invasive squamous cell carcinoma. Other head and neck cancers begin in the glands and are called adenocarcinomas. These types of cancer are much rarer than squamous cell carcinomas. Any tumors in these glands are usually benign and occur in people in their sixties and seventies. Another very rare type of head and neck cancer can begin in connective tissues. Incidence: Head and neck cancers account for 3 to 5 percent of all types of cancer in the United States. Experts estimate that about 45,000 people per year in the United States will develop these types of cancer, and these cancers will cause more than 11,000 deaths. (These numbers do not include skin cancers that occur in the head and neck, which account for many more cases and deaths.) In the United States, cancers involving the mouth and throat are the most common type. These cancers are more common in people over age fifty. They are slightly more common in men than in women and somewhat more common in African Americans than in those of other genetic backgrounds. Men are more than twice as likely as women to die of these cancers. Symptoms: Symptoms of these types of cancers include a sore throat, neck pain, trouble swallowing, pain when
Salem Health: Cancer
Head and neck cancers
swallowing, a red or white patch in the oral cavity, bad breath, swelling of the jaw, hoarseness or a change in voice, bloody sputum, bleeding from the mouth, unexplained weight loss, fatigue, sinus congestion that does not go away, loose teeth or dentures that no longer fit properly, or a lump or sore that does not heal. Cancer of the nasal cavity or throat area may involve nosebleeds or ear pain. A less common symptom is numbness of facial muscles. Screening and diagnosis: Many of the symptoms of head and neck cancers can be caused by other conditions, so people who use alcohol and tobacco should be screened at least yearly for head and neck cancers. Some types of tests that doctors or dentists may use to screen for these cancers are a visual inspection of the oral or nasal cavity using a small mirror and light, a physical examination for lumps, an endoscopy of the nasal or oral cavities, laboratory tests, X rays, ultrasounds, computed tomography (CT) scans, magnetic resonance imaging (MRI), positron emission tomography (PET) scans, fine-needle aspirations, or biopsies of tissue. Surgery may be required to see if cancer has spread to lymph nodes in the neck. Microscopic examination of a tissue sample is required to confirm a diagnosis. After diagnosis is confirmed and the extent of the tumor or cancer has been assessed, a stage is assigned to the cancer. Staging of head and neck cancers is rather complicated. Basically, the staging system uses the extent of the tumor’s spread as the primary basis of assigning a stage, but information on how large the tumor is and whether and to what extent lymph nodes are involved is also used. A commonly used staging division is the TNM system. This system uses letters and numbers to describe the size of the tumor (T), how many lymph nodes are involved (N), and whether the cancer has spread or metastasized (M). The tumor (T) is most often assigned a number based on the size of the primary tumor. In some cases (for example, in a tumor in the sinus cavity), a number is assigned based on the extent to which the tumor has invaded and destroyed tissues. Designations based on the size of the tumor are as follows: • T1: Tumor is 2 centimeters (cm) or less. • T2: Tumor is larger than 2 cm but smaller than 4 cm. • T3: Tumor is larger than 4 cm or multiple smaller tumors have spread to a single lymph node. • T4: Tumors larger than 4 cm have spread to distant areas of the body. Lymph node involvement (N) is assigned a number as follows: • N0: No evidence of cancer exists in nearby lymph nodes.
Age-Adjusted Incidence Rates for Invasive Head and Neck Cancers by Site Site Lip Tongue Salivary gland Floor of mouth Gum and other mouth Nasopharynx Tonsil Orophaynx Hypopharynx Other oral cavity and pharynx Nose, nasal cavity, and middle ear Larynx
Rate per 100,000 Adults 0.7 2.8 1.2 0.7 1.5 0.5 1.6 0.4 0.8 0.2 0.7 4.1
Source: U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2004 Incidence and Mortality WebBased Report (Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute, 2007)
•
N1: A tumor measuring 3 cm or less is found in one lymph node on the same side as the primary tumor. • N2: Either a tumor measuring between 3 and 6 cm is found in a lymph node on the same side as the primary tumor, tumors are in multiple lymph nodes on the same side but measure less than 6 cm, or tumors are found in lymph nodes on both sides, with the largest tumor measuring less than 6 cm. • N3: Tumor greater than 6 cm is found in any lymph node. The spread of the disease (M) is divided into two categories: • M0: No disease is present elsewhere in the body. • M1: Disease is present in a distant body area. After determining the TNM state of the cancer, a stage is assigned. • Stage 0: The cancer is only in the layer of cells lining the lips, mouth, or throat. • Stage I: T1 N0 M0 tumors • Stage II: T2 N0 M0 tumors • Stage III: T3 N0 M0 or T1-3 N1 M0 tumors • Stage IV: Any T4 tumor, any N2 or N3 tumor, and any M1 tumor This staging process is complex and certainly not foolproof. For example, a small primary tumor that has spread to a lymph node on the opposite side and a large tumor that 555
Head and neck cancers has not spread at all may be assigned the same disease stage. However, assigning a stage to the cancer can help determine treatment options. Treatment and therapy: Treatments for head and neck cancers depend on the type of cancer, location of tumors, severity of symptoms, age and general health of the patient, stage of the cancer, and preference of the patient. These treatments often include surgery and may also involve radiation therapy or chemotherapy. Some types of head and neck cancer may require surgery to remove the cancer and perhaps surrounding tissue or lymph nodes; in fact, surgery is the type of treatment most often used for these cancers. In some cases, nerves, muscles, glands, and veins in the neck must be removed. These removals can significantly affect a patient’s quality of life. Any surgical treatment plan should consider how surgery and removal of tissues will affect how a person breathes, eats, talks, or looks. If it is possible that the cancer has spread, radiation treatment may also be necessary following surgery. Radiation therapy can involve either a beam of radiation or implantation of tiny radioactive “seeds” to destroy the cancerous tissues. Chemotherapy may also be used depending on where the cancer is located and whether it has spread. Sometimes chemotherapy is used to enhance radiation therapy. Rehabilitation or occupational therapy can be an important part of treatment for patients who are recovering from surgery or other types of treatment for these cancers. Patients may need to relearn how to chew, swallow, or speak. Reconstructive surgery to improve the patient’s physical appearance, ability to function, or quality of life may also be part of a patient’s rehabilitation. Physical therapy may also be involved in a follow-up treatment plan, and education for patients and families, especially education about smoking cessation and any necessary diet changes, is helpful in recovery and future prevention efforts. Prognosis, prevention, and outcomes: Even though some people with no risk factors develop head and neck cancers, most of these cancers are caused by smoking and can be prevented. When found early, these cancers are often curable. However, up to 50 percent of patients with head and neck cancers have advanced cancers by the time they are discovered. For example, more than 70 percent of throat cancers are at an advanced stage when discovered. An advanced stage on discovery reduces the chances of a cure or the ability to halt the progression of the disease. A person who has had a cancer of the head or neck is at increased risk for developing a new cancer in the head, neck, esophagus, or lungs. Usually, a recurrence or sec556
Salem Health: Cancer ondary cancer will happen in the first two to three years following diagnosis of the first cancer, but a cancer may recur even up to twenty years later. These secondary tumors are a major cause of death even after a successful course of therapy has eliminated the primary tumor. Medical professionals are currently investigating a vitamin-like substance called isotretinoin and whether it can reduce the risk of tumors recurring in the head and neck. The most effective way to reduce the chance of another head and neck cancer occurring is to stop tobacco use. Other prevention tactics include using sunscreen and eating a diet low in fat, moderate in alcohol, and high in whole grains, fruits and vegetables. Caring properly for dentures can also help. Dentures that do not fit properly can trap cancer-causing substances and keep those substances in the mouth for a long time, increasing the chances that tissues will be damaged by those substances. Marianne M. Madsen, M.S. u
For Further Information Carper, Elise. One Hundred Questions and Answers About Head and Neck Cancer. Sudbury, Mass.: Jones and Bartlett, 2007. Myers, Eugene N., Michael R. Smith, Jeffrey Myers, and Ehab Hanna. Cancer of the Head and Neck. Philadelphia: Saunders, 2003. Ward, Elizabeth C., and Corina J. Van As-Broosk, eds. Head and Neck Cancer: Treatment, Rehabilitation, and Outcomes. San Diego, Calif.: Plural, 2006.
u
Other Resources
National Cancer Institute Head and Neck Cancer http://www.cancer.gov/cancertopics/types/ head-and-neck Oral Cancer Foundation http://www.oralcancerfoundation.org Support for People with Oral and Head and Neck Cancer http://www.spohnc.org Yul Brynner Head and Neck Cancer Foundation http://www.headandneck.org See also Epidermoid cancers of mucous membranes; Glossectomy; Hypopharyngeal cancer; Lip cancers; Lymphedema; Metastatic squamous neck cancer with occult primary; Nasal cavity and paranasal sinus cancers; Oral and oropharyngeal cancers; Otolaryngology; Parathyroid cancer; TP53 protein.
Salem Health: Cancer
u Health maintenance
organizations (HMOs) Category: Social and personal issues Definition: A health maintenance organization (HMO) is a company that provides, arranges, or pays for coverage of comprehensive medical services with specific health care providers, using a fixed payment structure. The term “health care providers” refers to physicians, hospitals, or outpatient facilities. Prevalence of HMOs: Health maintenance organizations have their roots in prepaid health care systems established in the 1920’s and 1930’s. Members of defined groups of people, such as rural communities or workers in particular industries, would prepay physicians set fees in exchange for health care services. Modern HMOs began to take shape in the 1960’s and 1970’s, and their development became a national priority in the early 1970’s with the passage of the HMO Act of 1973. Enrollment in HMO plans did not significantly increase until the early 1980’s. It peaked in 1996 and then began to decline. According to the Kaiser Family Foundation, in 2005 there were 411 HMOs in the country, providing coverage to approximately 70 million people. The number of people covered under an HMO varies widely state to state. In 2005, less than 1 percent of the populations of Mississippi and North Dakota were covered under an HMO, while 49.9 percent of Californians were covered by an HMO. Characteristics of HMOs: Health maintenance organizations were the first to develop and use managed care as a way to provide health insurance coverage. Persons covered under an HMO plan have to choose their health care providers from a list provided by the HMO. Approved health care providers are either on the staff of or under contract with the HMO, depending on the organizing model of the HMO plan. The staff model describes an HMO plan in which covered people obtain their medical care from health care providers who are employees of the HMO. Their offices are typically in health care facilities that are owned by the HMO, and the providers see only people covered by the HMO. The group model is one in which an HMO contracts with a large physician group or a large health care facility that will provide comprehensive care to persons covered under the HMO plan. Under the independent physician association (IPA) model, by contrast, independent physicians form an IPA for the purpose of entering into a contract with the HMO.
Health maintenance organizations (HMOs) The physicians maintain their own offices and can see any patients they want to see. The network model describes the situation in which the HMO contracts with physician groups, IPAs, individual physicians, and health care facilities to provide comprehensive services to covered persons. Health care providers that are under contract with an HMO are either paid retrospectively for services or prepaid for services. Retrospective payment is are usually on a fee-for-service basis according to a negotiated fee schedule usually based on discounted rates. Prepayments are made through capitation payments, which are negotiated per-capita rates to be paid by the HMO. The capitation payment covers all services delivered to the covered person, regardless of the number or the complexity of services. HMO plans: Health maintenance organizations typically offer two different plans to covered persons. The traditional HMO plan will cover only services delivered by a health care provider on the staff of or under contract with the HMO. The covered person usually pays a copayment at the time services are rendered. Health care is provided and coordinated by a primary care physician, who is usually a family doctor, internist, pediatrician, or obstetrician/ gynecologist. The primary care physician provides preventive and routine care to covered people and acts as a gatekeeper to arrange for and authorize care from other health care providers. Those covered normally are required to obtain a referral from their primary care physicians before they can seek nonemergency medical care from a specialist, hospital, or outpatient facility. For example, to consult an oncologist, a patient wishing to receive full coverage would not allowed to identify and directly contact any oncologist but instead would be limited to those oncologists working within the HMO system. Some health maintenance organizations do, however, offer point-of-service (POS) plans. A POS plan is also called an “open-ended” HMO plan because the covered person can receive services from a health care provider who is not an employee of or under contract with the HMO. These services are available at higher cost to the covered person through a deductible and coinsurance, and frequently they do not require a referral from a primary care physician. Coinsurance is an amount expressed as a fixed amount or as a percentage that a covered person is required to pay after meeting the deductible. The deductible is the amount a covered person must pay (usually on a yearly basis) before the HMO starts paying for services. Regulation of HMOs: Health maintenance organizations are not typically licensed as insurers but rather are licensed under special state laws and overseen by both state insur557
Helicobacter pylori
Salem Health: Cancer
ance and health regulators. This is historically the case because HMOs operate as insurers by protecting against financial loss due to illness or bodily injury and are uniquely involved in actually providing or arranging for medical care. Today, the distinctions between HMOs and insurers are narrowing, and most of the state and federal laws applying to insurance companies also apply to HMOs. These laws regulate access to and coverage provided under HMO plans and institute certain consumer protection measures. Amanda McQuade, Ph.D. u For Further Information Coombs, Jan G. The Rise and Fall of HMOs: An American Health Care RevScanning electron micrograph of Helicobacter pylori bacteria. (Dr. Gary Gaugler/ Photo Researchers, Inc.) olution. Madison: University of Wisconsin Press, 2005. Marcinko, David E., and Hope R. Hetico, vironment. It possesses four to six flagella that give the oreds. Dictionary of Health Insurance and Managed ganism its motility, allowing it to penetrate the mucus gel Care. New York: Springer, 2006. layer of the stomach. Certain strains produce the cagA Mitka, Mike. “AQuarter Century of Health Maintenance.” toxin, which has been associated with a higher risk for deJournal of the American Medical Association 280 veloping cancer. (1998): 2059-2060. u
Other Resources
Kaiser Family Foundation http://www.kff.org National Association of Insurance Commissioners http://www.naic.org See also Insurance; Managed care; Medicare and cancer; Preferred provider organizations (PPOs); Second opinions.
u Helicobacter pylori Category: Carcinogens and suspected carcinogens Also known as: Helico-bacter pylori, H. pylori, previously known as Campylobacter pylori, Campylobacter pyloridis Related cancers: Gastric cancer (cancer of the stomach, adenocarcinoma), B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma, pancreatic cancer Definition: Helicobacter pylori is a curved, helical-shaped gram-negative bacterium that produces urease, an enzyme that enables the organism to modify the stomach’s acid en558
Exposure routes: Ingestion of contaminated food and water. Transmitted person to person by oral-oral and oralfecal routes. Where found: Distribution of the organism is worldwide. There is a higher incidence in developing countries and where overcrowded and unsanitary conditions exist. At risk: Elderly, children Etiology and symptoms of associated cancers: Gastric cancer associated with H. pylori occurs in the antrum (lower) portion of the stomach and involves the inner lining of the stomach mucosa. Symptoms are nonspecific. Heartburn, bleeding into the stomach, loss of appetite, fatigue, and abdominal discomfort or pain is also associated with gastritis and peptic ulcer. A biopsy of the stomach is required for a definitive diagnosis. H. pylori infection alters the gastric epithelial cells triggering the body’s defense mechanisms. It is this response— production of interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and free radicals—that may cause cancerous cells to develop, replicate, and spread. Stomach cancer can spread directly through the stomach wall to adjacent organs or through the lymphatic system to the lymph nodes. MALT is a rare form of non-Hodgkin lymphoma, a
Salem Health: Cancer slow-growing cancer of the B-cell lymphocytes that develop in the stomach in response to a H. pylori infection. Not all H. pylori infections will lead to cancer. History: For much of the twentieth century, it was thought that bacteria were unable to survive in the acid environment of the stomach. In 1981 pathologist J. Robin Warren with Barry J. Marshall isolated H. pylori from the human stomach mucosa and established a link between H. pylori and gastritis and peptic ulcers. Marshall proved their theory by infecting himself with the organism, developing gastritis, and recovering the organism from his stomach lining. In 1994 H. pylori was categorized as carcinogenic to humans (Group 1) by the World Health Organization’s International Agency for Research on Cancer (IARC). Carol Ann Suda, B.S., M.T. (ASCP), S.M. See also Achlorhydria; Bacteria as causes of cancer; Gastrointestinal cancers; Hematemesis; Infectious cancers; Mucosa-associated lymphoid tissue (MALT) lymphomas; Non-Hodgkin lymphoma; Pancreatic cancers; Premalignancies; Stomach cancers.
u Hemangioblastomas Category: Diseases, symptoms, and conditions Also known as: Lindau tumors Related conditions: Von Hippel-Lindau disease Definition: Hemangioblastomas are benign tumors of the nervous system. These tumors form a knot of blood vessels and may be surrounded by a hollow cyst containing a yellowish fluid. The most common location for hemangioblastomas is the cerebellum. The cerebellum is the part of the brain located at the base of the back of the head. Its primary function is to coordinate voluntary movement. The second most common location for hemangioblastomas is on the spinal cord. Only rarely are hemangioblastomas found on other nerves. Although hemangioblastomas are not usually cancerous, their growth can increase pressure in the brain and interfere with brain and spinal cord functions. Risk factors: Men develop hemangioblastomas at twice the rate of women. Most hemangioblastomas are diagnosed in people between the ages of twenty and fifty. Etiology and the disease process: Genetic abnormalities are thought to be the underlying cause of hemangioblastomas. About 25 percent of people who develop these tumors have von Hippel-Lindau (VHL) disease. VHL is a hereditary disorder in which hemangioblastomas form
Hemangiopericytomas along with other tumors of the adrenal gland, pancreas, and kidney. Incidence: Hemangioblastomas are rare. They make up only about 2.5 percent of all abnormal growths (neoplasms) on the brain and spinal cord. Symptoms: Symptoms depend on the location of the tumor. In the cerebellum, hemangioblastomas can cause lack of coordination, problems with balance, dizziness, and headache. On the spinal cord, they can cause pain and progressive dysfunction. Screening and diagnosis: There is no routine screening for hemangioblastomas. These tumors are diagnosed by magnetic resonance imaging (MRI) studies. If a hemangioblastoma is suspected, imaging studies such as a computed tomography (CT) scan, angiography, and ultrasound are done to provide additional information before surgery. There is no staging for hemangioblastomas. Treatment and therapy: Hemangioblastoms are surgically removed unless the risks of the operation are greater than the expected benefits. Damage to surrounding brain tissue may occur during surgery depending on the location of the tumor. After surgery, regular follow-up visits are needed to check for recurrent tumors. Prognosis, prevention, and outcomes: The outcome of surgery depends largely on the location of the hemangioblastoma but is usually good. About 25 percent of patients develop additional hemangioblastomas. The recurrence rate is higher in younger individuals and in those with VHL disease. Martiscia Davidson, A.M. See also Benign tumors; Brain and central nervous system cancers; Brain scan; Pheochromocytomas; Spinal axis tumors; Von Hippel-Lindau (VHL) disease.
u Hemangiopericytomas Category: Diseases, symptoms, and conditions Also known as: Perithelioma, myopericytoma Related conditions: Soft-tissue sarcomas Definition: Hemangiopericytomas are soft-tissue sarcomas derived from pericytes (cells of the connective tissue surrounding capillaries and other small blood vessels). Malignancy is variable and unpredictable, and the disease is most commonly encountered in adults. Risk factors: There are no readily identifiable risk factors particular to hemangiopericytoma, although several risk 559
Hemangiosarcomas
Salem Health: Cancer
factors associated with soft-tissue sarcomas in general have been identified. These include exposure to chlorophenols in wood preservatives and phenoxyacetic acid in herbicides, exposure to ionizing radiation, and very rare genetic predispositions in some families.
u Hemangiosarcomas
Etiology and the disease process: Etiology is not at all well understood, and connections with diet, smoking, alcohol, or preexisting conditions have not been established.
Related conditions: Soft-tissue sarcomas
Incidence: Less than 1 percent of newly diagnosed cancers are soft-tissue sarcomas, and fewer than 5 percent of these are hemangiopericytomas. They typically arise in the fifth or sixth decade of life, and only 5 to 10 percent of the cases are found in children. A distinct rare infantile form is known in children less than one year in age. Symptoms: Tumors usually develop as a deep soft-tissue mass, most commonly in the legs, pelvis, and retroperitoneum (back of the abdominal cavity), although one study reports that 16 to 25 percent of new cases manifest as lesions in the head and neck. Detection is often first noted as a painless swelling of the soft tissue, although growing abdominal tumors may cause painful intestinal or urinary symptoms. An occasional symptom is pronounced hypoglycemia resulting from tumor secretion of insulin-like growth factors.
Category: Diseases, symptoms, and conditions Also known as: Angiosarcomas, malignant hemangiotheliomas, hemangiomas
Definition: Hemangiosarcomas are rare soft-tissue sarcomas affecting the endothelial cells that line blood vessels. These tumors can develop anywhere, but they most commonly are associated with the skin of the head and neck. Visceral hemangiosarcomas of the liver, heart, spleen, bowel, and bone marrow are also known. Risk factors: Hemanagiosarcoma of the liver is known to be associated with exposure to genotoxic compounds such as vinyl chloride, vinyl fluoride, vinyl bromide, thorium dioxide, and arsenic. External irradiation for another ma-
Screening and diagnosis: The existence of hemangiopericytoma as a distinct class of sarcomas is controversial, because other related neoplasms show a very similar vascular growth pattern. Diagnosis is always based on direct histological examination of tumor tissue. No screening tests exist, and hemangiopericytoma is sufficiently rare and unpredictable that uniform staging criteria have yet to be developed. Treatment and therapy: In adults, complete surgical removal and resection is favored whenever possible. Radiotherapy and chemotherapy have proven effective, and these are particularly recommended for patients with incomplete resection or large invasive tumors. Prognosis, prevention, and outcomes: Malignant hemangiopericytoma is prone both to local recurrence and to metastasis to distant sites, most commonly the lungs and bones. Tumors of the head, neck, and trunk seem far more likely to recur locally than do tumors of the extremities. One study reported a ten-year survival rate of 70 percent, but local and distant recurrences are known to occur after a prolonged disease-free interval. Jeffrey A. Knight, Ph.D. See also Nasal cavity and paranasal sinus cancers; Sarcomas, soft-tissue. 560
Hemangiosarcoma. (Biophoto Associates/Photo Researchers, Inc.)
Salem Health: Cancer lignancy has been shown to predispose rare hemangiosarcomas of the bowel. Etiology and the disease process: The mechanisms giving rise to these tumors are poorly understood, although activated mutations in known oncogenes have been detected in some cases. Once initiated in the lining of the blood vessels, the tumor spreads rapidly and builds its own blood vessel network. The tumor itself is often filled with blood, since the blood vessels grow directly into it. Incidence: Less than 1 percent of newly diagnosed cancers are soft-tissue sarcomas, and only about 2 percent of these are classified as hemangiosarcomas. An incidence rate of 0.21 cases per 100,000 people (0.00021 percent) has been reported. Symptoms: Dermal hemangiosarcomas usually appear as a rosy red or purple growth on the skin, which is often raised. When the tumors arise as a deep soft-tissue mass, a painless swelling is often the first indication. Hemangiosarcomas of the heart, liver, bowel, and pulmonary aorta may become quite large before organ function is compromised and symptoms develop. Screening and diagnosis: Diagnosis is based on surgical biopsy and direct histological examination of tumor tissue. The characteristic network of blood vessels usually provides an unambiguous identification. Screening tests for industrial workers exposed to vinyl chloride are available, but hemangiosarcomas are sufficiently rare and unpredictable that uniform staging criteria are unavailable. Treatment and therapy: Treatment varies considerably depending on tumor location, although surgical removal is always recommended whenever possible. Immunotherapy with recombinant interleukin-2 and chemotherapy (docetaxel or ifosfamide-doxorubicin) have proven effective in some cases. Prognosis, prevention, and outcomes: Patients with excised dermal hemangiosarcomas have an excellent prognosis if the cancer is detected early. The prognosis for patients with deep tissue or visceral tumors is relatively poor. A frequent cause of death is tumor rupture, which can cause the victim to rapidly bleed to death. Jeffrey A. Knight, Ph.D. See also Endotheliomas; Lymphangiosarcomas; Sarcomas, soft-tissue; Veterinary oncology.
Hematemesis
u Hematemesis Category: Diseases, symptoms, and conditions Also known as: Vomiting of blood Related conditions: Esophageal, stomach (gastric), and duodenal ulcers, esophagitis; gastritis; esophageal and stomach varices; melena; Mallory-Weiss tears; Dieulafoy’s lesion; blood-clotting problems; cirrhosis; portal hypertension Definition: Hematemesis is vomiting of blood or material that resembles coffee grounds from the upper gastrointestinal (UGI) tract, which includes the mouth, part of the throat, the esophagus, the stomach, and the first part of the small intestine (called the duodenum) up to the ligament of Treitz, a tough fibrous-muscle band tissue supporting the duodenum. Risk factors: Risk factors for hematemesis include prolonged vomiting, bleeding ulcers, Helicobacter pylori infection, nosebleeds, and use of nonsteroidal anti-inflammatory drugs, alcohol, and tobacco. Etiology and the disease process: Hematemesis and melena (black, tarry stools) are common symptoms of upper gastrointestinal bleeding (UGIB). The most common causes of UGIB include esophagitis, gastritis, peptic ulcer disease, esophagogastric varices, arteriovenous malformations (abnormal blood vessels in the digestive tract), Mallory-Weiss tears (lacerations on the lining of the junction of the esophagus and stomach), tumors (cancers), and nonspecific abnormalities of the upper gastrointestinal lining. Incidence: Approximately 100 cases of upper gastrointestinal bleeding occur per 100,000 hospitalizations annually; this bleeding causes hematemesis. Symptoms: Vomiting of blood is the result of upper gastrointestinal bleeding. Although not all cases can cause a major medical problem, it is necessary to seek medical help immediately. If large quantities of blood are lost, the patient could develop low blood pressure, increased heart rate, and shock. Screening and diagnosis: A flexible tube extending from the nose or mouth to the stomach and into the duodenum will be inserted to remove blood and prevent blood going into the lungs. Blood tests will include blood-clotting factors, liver function tests, and a complete blood count, which evaluates how much blood was lost. Upper endoscopy will be performed to visualize the upper gastrointes561
Hematologic oncology tinal tract and to treat the bleeding. If endoscopy fails to identify the site of bleeding, other methods such as angiography (radiographic visualization of blood vessels) and radioactive scan of tagged red blood cells can be employed. Treatment and therapy: Endoscopic treatments to stop bleeding include injection methods with absolute alcohol, salt solution, or epinephrine, or mechanical methods such as applying heat directly and placing hemoclips (metal clips for grasping blood vessels or surrounding tissues). A combination of injection followed by mechanical methods is another treatment modality. If H. pylori infection is present, the bacteria will be eradicated with antimicrobials, proton pump inhibitors, and acid suppressors. Aspirin and nonsteroidal anti-inflammatory drugs will be stopped. If large volumes of blood are lost, emergency measures may include intravenous fluids, blood transfusions, and medications such as proton pump inhibitors and acid suppressors. Consultations will include a gastroenterologist and a surgeon, who may operate if bleeding does not stop. Prognosis, prevention, and outcomes: Repeated hematemesis due to upper gastrointestinal tract bleeding increases the mortality rate. Associated factors that increase the mortality rate include age, poor nutrition, and having other medical problems and blood-clotting disorders. Related medical conditions such as ulcers should be appropriately treated and risk factors addressed for prevention. Miriam E. Schwartz, M.D., M.A., Ph.D., and Colm A. Ó’Moráin, M.A., M.D., M.Sc., D.Sc. See also Coughing; Esophageal cancer; Esophagitis.
u Hematologic oncology Category: Medical specialties Also known as: Blood and bone marrow treatment Definition: Hematologic oncology is the medical specialty for the diagnosis, treatment, and prevention of disorders and cancerous conditions affecting the blood, bone marrow, and lymphatic system. As defined by the American Society of Hematology, a hematologist is a physician who specializes in the diagnosis, treatment, prevention, or investigation of disorders of the hematopoietic, hemostatic, and lymphatic systems, and disorders of the interaction between blood and the blood vessel wall. Hematologic oncology practices can be found in university medical centers, community hospitals or clinics, specialized can562
Salem Health: Cancer cer hospitals, comprehensive cancer centers, and laboratories. Subspecialties: Medical oncology/hematology, pediatric oncology/hematology Cancers treated: Many cancers, particularly leukemia, lymphoma, multiple myeloma, hemophilia, sickle cell disease, thalassemia, aplastic anemia and other anemias, hemochromatosis, Hodgkin disease, marrow failure syndromes, platelet disorders, idiopathic thrombocytopenic purpura and other thrombotic disorders, and von Willebrand disease and related conditions Training and certification: Hematologists may be internists or pathologists who further specialize in disorders of the blood. In addition to having a four-year medical degree from an accredited program and board certification from the American Board of Internal Medicine, hematologists complete a one-year internship, followed by three or more years of postgraduate residency training in hematological disorders. Hematology fellows are eligible to take a certification exam in hematology, offered by the American Board of Internal Medicine or the American Board of Pathology, after completing a minimum of three years of successful training. They become board certified after passing this exam. Once certified, hematologists often further their training by participating in one or more years of clinical or laboratory research. Hematologists are trained in the basic science principles and techniques, pathophysiology of normal and abnormal hematologic processes, and the tools needed to diagnose and manage patients with hematologic disorders. Specific areas of study include basic laboratory concepts and techniques, pharmacology, clinical laboratory techniques, transfusion medicine, radiation therapy, diagnostic imaging, hematopoiesis, red and white blood cell disorders, hemochromatosis, platelet and megakaryocyte disorders, bone marrow failure states, hemostasis, hematologic neoplastic disorders, palliative care, bone marrow transplantation, stem cell transplantation, and hematologic manifestations of infectious diseases. Hematologic clinical practice guidelines, quality care standards, and quality assurance measures in the United States have been established primarily by the American Society of Hematology (ASH), a nonprofit organization representing more than 15,000 blood specialists, including scientists, practitioners, educators, and trainees from more than ninety countries. The mission of the ASH is to further the understanding, diagnosis, treatment, and prevention of
Salem Health: Cancer blood disorders by promoting research, clinical care, education, training, and advocacy in hematology. Services and procedures performed: Treatments provided by a hematologist may include therapeutic phlebotomy, bone marrow aspiration and biopsy, and chemotherapy. Therapeutic phlebotomy is the removal of blood from the circulatory system through an incision or puncture for analysis and diagnosis. Phlebotomy may be done as a treatment for certain blood disorders, such as polycythemia vera, a condition that causes increased red blood cell volume (hematocrit). It may also be performed to treat patients with disorders that highly elevate blood iron levels, such as hemochromatosis, hepatitis B, and hepatitis C. Bone marrow aspiration and core bone marrow biopsy are the removal of a sample of bone marrow and fluid for analysis. During the bone marrow biopsy procedure, a needle is inserted into the hip bone and a sample of fluid and bone marrow is withdrawn through the needle into an attached syringe. To accurately place the needle, ultrasound or computed tomography (CT) guidance may be used. Bone marrow aspiration can also be done to collect bone marrow for medical procedures such as stem cell transplantation or chromosomal analysis. Chemotherapy is the treatment of cancer with medications that have a certain toxic effect on cancer cells. Chemotherapy drugs are used to slow the growth of cancer cells, shrink tumors prior to other treatments such as surgery or radiation, or to cure a specific cancer. Related specialties and subspecialties: Hematologists work with a multidisciplinary team of cancer health care providers whose goals are to provide early detection; accurately diagnose the condition; offer prompt, appropriate state-of-the-art treatment to reduce morbidity and improve quality of life and survival; provide psychological guidance through complex treatment phases; reduce long-term effects of chemotherapy and radiation therapy; and provide long-term follow-up. Multidisciplinary team members include the primary care physician and other specialists such as medical oncologists, oncologist surgeons including urologic surgeons, orthopedic surgeons and neurosurgeons; diagnostic radiologists; radiation oncologists; infectious disease specialists; pathologists; oncology nurses; physical therapists; and oncology social workers and other allied health care professionals, such as educational specialists, registered dietitians, and pharmacologists. Medical oncologists determine the appropriate systemic or adjunctive drug regimen to treat the patient’s condition, and they supervise the dosage, schedule, and ad-
Hematologic oncology ministration of cancer drugs. They are trained and skilled in chemotherapy drug indications and toxicities so that they can safely administer these therapies while keeping side effects at a minimum and appropriately managing complications. To diagnose and treat cancers, oncologist surgeons use laparoscopy, thoracoscopy, and other surgical techniques. These doctors first obtain a four-year medical degree from an accredited program and board certification from the American Board of Surgery, then complete five years of residency training in an accredited general surgery program and at least two years of fellowship training in oncological surgery. Diagnostic radiologists obtain and interpret medical images to diagnose diseases. Besides having a four-year medical degree from an accredited program and board certification from the American Board of Radiology or the American Osteopathic Board of Radiology, radiologists must pass a licensing examination and complete at least four years of residency training in an accredited radiology program. Radiation oncologists, also known as clinical oncologists, treat cancers using radiation. In the United States, most of them have completed residency training in radiation oncology in a program approved by the American Council of Graduate Medical Education or the American Board of Radiology. Infectious disease specialists are physicians who are experts in the diagnosis and treatment of infectious diseases. They first obtain a four-year medical degree from an accredited program and board certification from the American Board of Pediatrics, then complete three or more years of residency training and two to three years of additional training in infectious diseases. Pathologists are physicians who are experts in the pathology of hematologic malignancies and solid tumors. They are skilled in immunochemistry and molecular techniques to assess malignancies. In addition to having a fouryear medical degree from an accredited program and board certification from the American Board of Internal Medicine, pathologists have completed three or more years of residency training and one to two years of additional training in pathology. Oncology nurses administer medications, provide medical care, and educate patients and family. Oncology clinical nurse specialists are registered nurses with a master’s degree in oncology nursing. They prepare and administer medications, including chemotherapy; understand treatment protocols; and have experience in managing treatment complications. Oncology nurse practitioners are registered nurses with a master’s or doctoral degree. The 563
Hematuria professional development of oncology nurses is facilitated by the Oncology Nurses Society. Angela M. Costello, B.S. u For Further Information Abeloff, M. D., et al. Clinical Oncology. 3d ed. Edinburgh, Scotland: Churchill Livingstone, 2004. Cavalli, F., et al., eds. Textbook of Medical Oncology. 3d ed. New York: Informa Healthcare, 2004. Kantarjian, H. M., et al. The M. D. Anderson Manual of Medical Oncology. New York: McGraw-Hill, 2006. u
Organizations and Professional Societies
American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 American Society of Hematology http://www.hematology.org 1900 M Street, NW, Suite 200 Washington, D.C. 20036 The Center for International Blood and Marrow Transplant Research http://www.cibmtr.org 9200 W. Wisconsin Avenue, Suite C5500 Milwaukee, WI 53226 National Comprehensive Cancer Network http://www.nccn.org 275 Commerce Drive, Suite 200 Fort Washington, PA 19034 Oncology Nurses Society http://www.ons.org 125 Enterprise Drive Pittsburgh, PA 15275 u
Other Resources
CancerCare http://www.cancercare.org Cancer.Net http://www.cancer.net/portal/site/patient Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org See also Anemia; Blood cancers; Bone marrow aspiration and biopsy; Cancer biology; Cytology; Leukemias; Lymphomas; Medical oncology; Multiple myeloma; Pediatric oncology and hematology. 564
Salem Health: Cancer
u Hematuria Category: Diseases, symptoms, and conditions Also known as: Blood in the urine Related conditions: Cancers of the bladder, kidney, prostate, or urethra Definition: The American Urological Association defines hematuria as three or more red blood cells per high-power field in two of three specimens. Hematuria can originate from any site along the urinary tract. Risk factors: The presence of heme or red blood cells in microscopic or gross amounts in the urine is a sign requiring interpretation within the context of the patient’s presenting symptoms to rule out kidney or urinary tract disease. Etiology and the disease process: The cause of hematuria may range from transitory and insignificant to increasingly serious diagnoses. The blood may be from excessive or strenuous exercise, menstrual bleeding, hemorrhoids, trauma, infection, stones or calculi, obstruction, drugs, poisoning, or tumors. Hematuria is among the most common and earliest indications of cancers of the bladder, kidney, prostate, or urethra. Incidence: The American Urological Association reports that the prevalence of asymptomatic microscopic hematuria varies from less than 1 to 21 percent. Symptoms: Hematuria manifests in urine that is smoky, pink, bright red, or dark red (although urine may appear clear and still result in a diagnosis of hematuria). Screening and diagnosis: Blood in urine is detected in the form of intact red blood cells under the microscope or as the heme subunit of the hemoglobin molecule in a routine chemical evaluation of urine. Screening involves a routine urinalysis in each of the three distinct testing phases: • Physical examination (the urine sample may appear in color and clarity from clear to smoky, pink, bright red, or dark red. • Microscopic examination (identifies and counts the blood cells per high-power field) • Biochemical examination (to determine the presence or absence of blood in the urine; relies on the peroxidase activity of the heme moiety, which leaks from the red blood cell or from muscle tissue in the form of myoglobin into the urine) Because hematuria can originate from a wide variety of causes, the presence of red blood cells in the urine is not a useful screening tool to detect tumors of the urinary tract.
Salem Health: Cancer Once hematuria has been detected, the clinician must find the cause. Often the diagnosis of cancer begins with ruling out all other possible sources of blood in the urine. Definitive diagnosis may require one or more exploratory and confirmatory procedures: urine cytology; intravenous urography (IVU), a radiology procedure that uses an injected dye to show the kidneys, ureters, and bladder; ultrasonography; computed tomography (CT); magnetic resonance imaging (MRI); or a cystoscopy with biopsy. Treatment and therapy: Treatment depends on the underlying cause. Prognosis, prevention, and outcomes: Hematuria requires evaluation within the context of the patient’s history and physical examination. Asymptomatic, microscopic hematuria may range from insignificant to life-threatening. Risk factors for significant disease in patients with microscopic hematuria include smoking, occupational exposure to chemicals, analgesic abuse, urinary tract infection, and a history of urologic disorders. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) See also 4-Aminobiphenyl; Bladder cancer; Cyclophosphamide; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Kidney cancer; Malignant rhabdoid tumor of the kidney; Transitional cell carcinomas; Urinalysis; Urinary system cancers.
u Hemochromatosis Category: Diseases, symptoms, and conditions Also known as: Hematochromatosis; bronze diabetes; hereditary, familial, or type 1 hemochromatosis; iron overload Related conditions: Liver cancer, heart disease, impotence, infertility, premature menopause, diabetes, arthritis, cirrhosis of the liver, bronze skin Definition: Hemochromatosis is a metabolic disorder in which iron accumulates in the liver, heart, skin, pancreas, and other organs. Once iron is absorbed, the only way the body can excrete the excess iron is through bleeding. Hemochromatosis may be either genetic or nongenetic in origin. Nongenetic sources include excess deposition of iron in the tissues due to multiple transfusions, chronic hepatitis, excessive iron intake, or megadoses of vitamin C, which promotes iron absorption. Genetic hemochromatosis is inherited in an autosomal recessive pattern, as
Hemochromatosis with homozygous mutations in the HFE gene region. The most common HFE gene mutation is C282Y, followed by H63D. Risk factors: Hereditary hemochromatosis is most prevalent among persons of European descent. Not everyone who demonstrates the HFE mutation will develop hemochromatosis. Etiology and the disease process: Normally the HFE gene codes for the intestinal transmembrane glycoprotein that regulates dietary iron absorption. Amutation causes the system to deposit more iron in the organs than is needed, leading to increased absorption and creating an overload of unbound iron molecules circulating within the system. Once the body exceeds its natural limit of iron storage of ferritin molecules, the excess unbound iron molecules promote free-radical formation, resulting in peroxidation of the lipid membrane and cellular injury. People who are predisposed to hemochromatosis may accumulate 0.5 to 1.0 gram of iron per year. Incidence: The Centers for Disease Control and Prevention estimate that 1 million people in the United States have hemochromatosis. Symptoms: Early symptoms of hemochromatosis include fatigue, weakness, weight loss, joint pain, or abdominal pain. These symptoms typically appear after the age of forty in men and after fifty in women. Screening and diagnosis: A series of fasting serum blood tests—ferritin, iron, total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), or transferring saturation (TS)—assist in the diagnosis of hemochromatosis. The TS may be calculated or measured directly by immunoassay. Genotyping may confirm if the HFE mutation is present. A liver biopsy may establish a prognosis of risk of advancing fibrosis. Treatment and therapy: Therapeutic phlebotomy to decrease the excess iron stores is especially effective before symptoms of complications appear. Prognosis, prevention, and outcomes: Early detection and therapeutic phlebotomy to maintain iron levels within established limits results in the prevention of tissue and organ complications associated with hemochromatosis. For individuals who have already experienced organ compromise, while earlier damage may not be reversed, further damage can be slowed with therapeutic phlebotomy. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) See also Genetic testing; Hematologic oncology; Hepatomegaly; Liver cancers. 565
Hemolytic anemia
u Hemolytic anemia Category: Diseases, symptoms, and conditions Also known as: Autoimmune hemolytic anemia Related conditions: Lymphoproliferative disorders such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, and thymoma. May be seen in patients with carcinoma of the breast or stomach as well as cancers of the colon, prostate, lung, cervix, and pancreas. Also seen in patients with hepatitis, cytomegalovirus, or streptococcus. Definition: Hemolytic anemia occurs when there are too few red blood cells in the body as a result of premature destruction of red blood cells. Destruction occurs more quickly than the bone marrow can produce new cells. Risk factors: Patients receiving chemotherapy or radiation for the treatment of a lymphoproliferative disease or solid tumors of the breast, stomach, colon, prostate, lung, cervix, or pancreas are at risk for developing hemolytic anemia. Also at risk are people suffering with an infection, such as hepatitis, cytomegalovirus, or streptococcus, or those taking penicillin, sulfa drugs, or large quantities of acetaminophen. People diagnosed with autoimmune disorders, lupus, rheumatoid arthritis, or ulcerative colitis can also be at risk. Etiology and the disease process: This destruction of red blood cells, or hemolysis, falls into two groups: intrinsic and extrinsic. Intrinsic refers to the destruction of the red blood cells due to a defect within the cells themselves. Intrinsic hemolysis is caused by an inherited condition such as sickle cell anemia or thalassemia, which cause red blood cells to have a shorter life span than normal. Extrinsic refers to red blood cells that develop in a healthful manner but then are destroyed by infection or drugs. Extrinsic hemolysis can be temporary and resolve over several months. Incidence: Some 20 percent of hemolytic anemias are caused by lymphocytic leukemia, 10 percent are the result of an autoimmune disease, and all others are related to medications. Women are twice as likely to contract hemolytic anemia as are men. One in 80,000 cases of anemia is hemolytic anemia. Symptoms: Symptoms of hemolytic anemia include pale skin, a yellowing of the skin or eyes, dark urine, fever, weakness, dizziness, confusion, inability to tolerate physical activity, an enlarged spleen and liver, rapid heart rate, or heart murmur. Screening and diagnosis: Hemolytic anemia is found when a patient visits the physician’s office with com566
Salem Health: Cancer plaints of tiring easily, dizziness, or paleness of the skin. The physician will order laboratory tests to monitor the patient’s red blood cell count. Laboratory tests include tests for hemoglobin levels, reticulocyte counts, liver function tests, and, in more serious conditions, a bone marrow aspiration and biopsy. A urine sample may be needed to evaluate for increased proteins or hemoglobin. Treatment and therapy: Treatment is based on the patient’s overall condition and type of anemia. The patient’s age, medical history, cause of disease, and ability to tolerate treatment are considered. Treatment includes blood transfusions, steroid medications, and infusions of immune globulins to strengthen the immune system. More severe cases are treated with surgical removal of the spleen or immunosuppressive therapy. Prognosis, prevention, and outcomes: There is no known prevention for intrinsic hemolytic anemia. Extrinsic hemolytic anemia can be prevented by avoiding the use of medications that may cause anemia. Mild cases may not need treatment, whereas severe cases can be life-threatening. An inherited form of anemia will require lifelong treatment. Katrina Green, R.N., B.S.N., O.C.N. See also Anemia; Transfusion therapy.
u Hemoptysis Category: Diseases, symptoms, and conditions Also known as: Coughing up of blood or blood-stained sputum Related conditions: Tuberculosis, bronchitis, bronchiectasis, aspergilloma, coccidioidomycosis, pulmonary embolism, pneumonia, pneumonic plague, lung cancer (especially bronchogenic carcinoma) Definition: Hemoptysis is the coughing up of blood or blood-stained sputum that originates in the bronchi, lungs, trachea, or some other part of the respiratory tract. Etiology and the disease process: There are many potential causes for hemoptysis, but it is most often caused by an underlying condition. The most common worldwide cause of hemoptysis is Mycobacterium tuberculosis infection. The most common causes of hemoptysis in industrialized nations are bronchitis, bronchiectasis, and bronchogenic carcinoma. Other pulmonary conditions, such as aspergilloma, coccidioidomycosis, pulmonary embolism, pneumonia, and pneumonic plague may also cause hemoptysis. Hemoptysis can also be caused by the presence of a for-
Salem Health: Cancer eign object in the respiratory tract, although this is much more common in children than in adults. Incidence: Some form of lung cancer causes hemoptysis in 23 percent of cases in the United States. One form in particular, bronchogenic carcinoma, causes hemoptysis in 5 to 44 percent of cancer-related cases. Symptoms: Hemoptysis, itself the symptom of an underlying disorder, is marked by the color of the blood in sputum, normally bright red and foamy as opposed to dark red.
Hemorrhoids See also Bronchial adenomas; Bronchoalveolar lung cancer; Bronchography; Coughing; Kaposi sarcoma; Lung cancers; Mediastinal tumors; Mustard gas; Superior vena cava syndrome.
u Hemorrhoids Category: Diseases, symptoms, and conditions Also known as: Piles Related conditions: Rectal itching, rectal canal blockage
Screening and diagnosis: In most cases, hemoptysis is diagnosed with a physical examination. One of the most important things in the examination is determining if the blood being coughed up is really hemoptysis. Blood that is coughed up can also originate from the gastrointestinal tract. The origin of blood can be determined by its color. Bright red, foamy blood originates from the respiratory tract, while dark red blood originates from the gastrointestinal tract. Sometimes a chest radiograph will be used to diagnose hemoptysis. In more complicated cases, advanced tests may be employed. The most common set of advanced tests includes fiber-optic bronchoscopy and high-resolution computed tomography. This set of tests is often used when the cause of hemoptysis is suspected to be a malignant cancer.
Definition: Hemorrhoids are swollen, often painful, veins in or around the anorectal area. External hemorrhoids protrude out of the anus. Internal hemorrhoids develop inside the body underneath the lining of the anus. Hemorrhoids do not turn into cancer.
Treatment and therapy: Goals in treating hemoptysis are stopping the bleeding, clearing the airways, and treating the underlying condition. Patients who are not high risk and have chest radiographs that appear to be normal may be treated as outpatients with close monitoring and antibiotics to treat any underlying infection that could be causing the hemoptysis. If the patient is diagnosed with life-threatening, massive hemoptysis, the situation becomes much more urgent. Massive hemoptysis is defined by the rate of bleeding rather than the volume of blood coughed up. The risk of death from massive hemoptysis is not from the loss of blood but from possible asphyxiation from blockage of the airways. Massive hemoptyis is defined as more than 200 milliliters of blood coughed up per day. Massive hemoptysis is a medical emergency and must be treated immediately. The most common treatments for massive hemoptysis are bronchial angiography with embolization or surgical removal of the bleeding site.
Incidence: Hemorrhoids are extremely common. The exact number of cases is difficult to determine because many people do not report hemorrhoids to their doctors.
Prognosis, prevention, and outcomes: Outcomes depend on the type of cancer or other disorder for which hemoptysis is a symptom. Jeremy W. Dugosh, Ph.D.
Risk factors: Anyone can develop hemorrhoids, although they are more common in older adults. Women who are pregnant or who have given birth in the past have an increased risk for hemorrhoids. Etiology and the disease process: Hemorrhoids are linked to increased pressure in the rectal area. Excess pressure, such as that produced when straining during a bowel movement, weakens the muscles that support area blood vessels.
Symptoms: The most common symptom is usually spots of bright red blood that appear on toilet paper following a bowel movement. Any rectal bleeding should be reported to a health care professional, since such bleeding may also occur with certain gastrointestinal diseases, including colon cancer. Hemorrhoids can cause rectal itching and may result in incomplete bowel movements if they block the rectal canal. External hemorrhoids may feel like a small lump around the anorectal area. Screening and diagnosis: A doctor may detect hemorrhoids during a rectal exam. A hollow, lighted tube called an anoscope is used to detect internal hemorrhoids. A similar instrument called a proctoscope allows a view of the entire rectum. Rectal bleeding may require closer examination with procedures such as a sigmoidoscopy or colonoscopy. Treatment and therapy: At-home therapies include taking warm baths, placing ice packs on the area, and wearing 567
Hepatic arterial infusion (HAI)
Salem Health: Cancer See also Anoscopy; Ascites; Colorectal cancer; Gastrointestinal cancers; Hematuria; Immunochemical fecal occult blood test (iFOBT).
u Hepatic arterial infusion (HAI) Category: Procedures Also known as: Regional chemotherapy, intra-arterial chemotherapy Definition: Hepatic arterial infusion (HAI) is the delivery of chemotherapy treatment directly to the liver by a catheter (thin tube) surgically implanted to the artery leading to the organ; the other end of the catheter is attached to a pump with a chemotherapy drug. Cancers treated: Tumors of the liver, including colon or rectal cancer that has spread to the liver Why performed: Liver tumors that cannot be operated on because of their size or location may be treated with HAI. An advantage of this procedure is the high concentrations of the drug sent directly to the liver; since the drug is broken down in the liver, the rest of the body does not suffer the side effects of the chemotherapy.
A large internal hemorrhoid. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
loose clothing. Over-the-counter hemorrhoid creams and ointments may relieve pain and swelling. Some hemorrhoids require more aggressive treatment. Such treatments may involve a chemical injection to reduce swelling, rubber band ligation to cut off the blood supply to the hemorrhoid, infrared or laser coagulation to shrink the hemorrhoid, or surgery to remove it. Prognosis, prevention, and outcomes: Most hemorrhoids go away on their own; however, they often recur. Regular exercise, drinking plenty of water, and increasing daily fiber intake may help prevent hemorrhoids, as can going to the bathroom as soon as the urge develops and avoiding rough toilet paper. Stool softeners or laxatives can help reduce constipation-related strain during bowel movements. Such medicines are intended for short-term, occasional use only, unless a physician instructs otherwise. Kelli Miller Stacy, ELS 568
Patient preparation: The selection of patients who would benefit from HAI is important, and evaluation includes a review of the disease history and a computed tomography (CT) scan looking for metastasized disease in the chest, abdomen, and pelvis. Patients also have a test called hepatic arteriography to look specifically at the arteries leading to the liver. Steps of the procedure: An incision is made under the right rib cage to place the catheter in the gastroduodenal artery, which joins the arteries to the liver. An incision is also made on the left side of the abdomen where the pump will be implanted. The pump is made of a circle of titanium about 3 inches wide. The pump storage reservoir is filled with sterile water and a blood thinner (heparin), and the pump is turned on. The pump is subsequently filled with the chemotherapy drug, and cycles of two weeks of chemotherapy followed by two weeks of water and heparin are started. The chemotherapy agents delivered by HAI include floxuridine, cisplatin, or doxorubicin. During the procedure, the surgeon also performs a cholecystectomy (removal of the gallbladder) to prevent chemotherapy from going to the gallbladder. After the procedure: The pump is refilled as needed with a needle through the skin to the pump reservoir. The pump does not interfere with normal activities.
Salem Health: Cancer
Hepatitis B virus (HBV)
Risks: There may be technical complications, including infection at the site of pump placement. Most of the systemic side effects of chemotherapy (such as nausea and vomiting) are bypassed with this treatment, but there may be side effects such as abdominal pain and diarrhea. Results: The use of HAI in inoperable liver tumors shows a higher response rate than does traditional systemic chemotherapy. Vicki Miskovsky, B.S., R.D. See also Cholecystectomy; Liver cancers.
u Hepatitis B virus (HBV) Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2004 Related cancer: Liver cancer Definition: The hepatitis B virus causes hepatitis B, a type of liver inflammation that is mainly spread through contact with blood and blood products and via sexual contact with an infected person, or carrier.
tion in adulthood in association with other risk factors such as coinfection with the hepatitis C virus (HCV) or chronic alcohol abuse. Etiology and symptoms of associated cancers: The hepatitis B virus causes hepatitis B, which can lead to chronic hepatitis B and cirrhosis, followed by liver cancer. The frequency of liver cancer can be correlated with the frequency of hepatitis B infection. It is believed that the inflammatory process involving chronic hepatitis B may be a crucial factor in the development of cancer. Most persons who are hepatitis B carriers and even those with early liver cancer may be asymptomatic. By the time symptoms do appear, liver cancer is usually inoperable. Symptoms may include jaundice, fatigue, abdominal pain and swelling, loss of appetite, nausea, vomiting, and joint pain. History: Although hepatitis has been long known, its etiology remained a mystery until a virus found in human blood became suspect; hepatitis B virus was isolated in 1963. Discovery of a specific antigen linked to the hepati-
Exposure routes: Mainly spread through intimate sexual contact (50 percent) and injection drug use (15 percent), but maternal transmission (common in Asia) can occur. Where found: About a million people in the United States have chronic hepatitis B virus (HBV) infection. Though the incidence of chronic hepatitis B is decreasing in the United States because of a vaccine, the incidence of HBV infection has increased to 1 in 10 Americans of Asian ancestry. At risk: Patients infected with the hepatitis B virus who are at greatest risk for liver cancer are those with cirrhosis (scarring of the liver) and a family history of liver cancer. In the United States, the highest incidence of liver cancer occurs in Asian immigrants; the frequency is lowest in whites, followed by Hispanics and African Americans. Closed environments such as prisons put people at risk. Across the globe, the vast majority of those who develop liver cancer have had the hepatitis B virus for most of their lives. However, in the United States, those with chronic hepatitis B infection mostly have contracted the infec-
A transmission electron micrograph of hepatitis virions. (Centers for Disease Control and Prevention)
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Hepatitis C virus (HCV)
Salem Health: Cancer
tis B virus led to development of a test to screen blood (1990), significantly reducing the incidence of post-transfusion hepatitis. A vaccine was then developed that protects against hepatitis B virus and, indirectly, against liver cancer. Cynthia Racer, M.A., M.P.H. See also Aflatoxins; Ascites; Asian Americans and cancer; Bile duct cancer; CA 15-3 test; CA 19-9 test; Hepatitis C virus (HCV); Hepatomegaly; Liver cancers; Vaccines, preventive; Viral oncology; Virus-related cancers.
u Hepatitis C virus (HCV) Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2004 Also known as: Parenterally transmitted non-A, non-B hepatitis Related cancers: Liver cancer and possibly non-Hodgkin lymphoma and multiple myeloma Definition: The hepatitis C virus (HCV), a flavivirus, is causally related to hepatitis C, a type of liver inflammation that is mainly spread via contact with infected blood. A causal relationship has been demonstrated between HCV and liver cancer, which is usually preceded by chronic hepatitis and cirrhosis. Being a ribonucleic acid (RNA) virus, the hepatitis C virus easily mutates, making vaccine development difficult. Exposure routes: HCV is transmitted by blood-to-blood contact with an infected individual or via blood transfusion with infected blood; rarely, maternal transmission may occur. Where found: From 150 million to 200 million people worldwide are infected with HCV. At risk: People who have a history of injected or inhaled drug use, have been exposed to blood via sexual contact, have received a transfusion of unscreened blood, or have been exposed to contaminated instruments during tattooing, ear and body piercing, and dental procedures are at risk. Health care workers are at risk from needlestick injuries. Coinfection with hepatitis B virus (HBV) or the human immunodeficiency virus (HIV) and alcohol abuse put people at risk for chronic hepatitis C, cirrhosis (scarring of the liver), and primary liver cancer, as does having a relative with liver cancer. Etiology and symptoms of associated cancers: The hepatitis C virus is the causative agent in primary liver cancer. 570
People who have a history of injected drug use are at risk for becoming infected with the hepatitis C virus. (PhotoDisc)
Moreover, liver cancer does not occur unless cirrhosis is present; 75 percent of those infected with the hepatitis C virus may become chronically infected, with 10 to 20 percent developing cirrhosis over a period of twenty to thirty years, and 1 to 5 percent of them will develop liver cancer. Specific symptoms of liver cancer are usually absent until cirrhosis has occurred. Signs and symptoms of adult primary liver cancer may include a hard lump below the right side of the rib cage; right side upper abdomen discomfort; right shoulder pain, nausea, and unusual fatigue. Signs and symptoms for multiple myeloma may include bone pain and skeletal and spinal fractures; for Burkitt lymphoma, symptoms may include swollen lymph nodes, abdominal pain, tumors, weight loss, and fatigue. History: Blood tests were first developed to identify the causative viruses of hepatitis B (1963) and hepatitis A (1973), but some post-transfusion blood samples proved negative for both. In the 1980’s scientists identified an-
Salem Health: Cancer
Hepatomegaly
other virus as the causative agent of “non-A, non-B hepatitis” and called it hepatitis C virus. In 1990 blood banks began screening donors for the hepatitis C virus, substantially lowering the risk of contracting post-transfusion hepatitis C. Cynthia Racer, M.A., M.P.H.
a protein deficiency, diabetes, obesity, starvation, endocrine disorders (Cushing syndrome), and many chronic diseases with nutrition or absorption problems. Other risk factors include corticosteroid use and exposure to aflatoxins, parasites, antibiotics (tetracyclines), contraceptive steroids, halothane, arsenic, thorium, and yellow phosphorus.
See also Aflatoxins; Bile duct cancer; CA 15-3 test; CA 19-9 test; Hepatitis B virus (HBV); Hepatomegaly; Liver cancers; Viral oncology; Virus-related cancers.
Etiology and the disease process: Liver cells perform some of the most important biochemical functions, such as detoxication of ammonia and foreign chemicals and degradation and synthesis of carbohydrates, proteins, amino acids, hormones, fatty acids, glycerides, cholesterol, bile salts, heme, and porphyrin. A problem with one or more of the metabolic functions can lead to both structural and functional abnormalities. Liver cells respond in various ways to etiologic agents to become enlarged. Pathophysiologic mechanisms include inflammation, excessive storage, infiltrations, congestion, and obstruction. Examples include dilated hepatic sinusoids (due to heart failure), persistently high venous pressure causing liver congestion (in chronic obstructive pancreatitis), dysfunction and enlargement of hepatocytes (during hepatitis), fatty infiltration of parenchymal cells causing fibrosis (in cirrhosis), distension of liver cells (in alcoholism), fatty degeneration and infiltration of hepatocytes (diabetes mellitus, alcoholism, amyloid or glycogen storage), hyperplasia (cirrhoses or hepatomas) leading to sarcoma (metastic carcinoma), and tenderness (congestive heart failure and infectious hepatitis).
u Hepatomegaly Category: Diseases, symptoms, and conditions Also known as: Fatty liver, enlarged liver Related conditions: Hepatitis, alcoholic cirrhosis, hepatocellular carcinoma (HCC) Definition: Hepatomegaly is a potentially reversible symptom of an underlying disease or condition in which the size of the liver (about 9 centimeters, or cm, in women and less than 12 cm in men) is abnormally increased as estimated by the amount of the liver’s edge below the lower edge of the ribs (coastal margin). Risk factors: Hepatomegaly, commonly known as an enlarged liver, can be caused by alcoholism (early stages), hepatocellular carcinoma (HCC, or primary liver cancer), nonalcoholic fatty liver disease, cirrhosis of the liver, chronic heart failure, infection with hepatitis (A, B, or C),
Incidence: The major causes of hepatomegaly depend on the age, geographical location, and metabolic-nutritional
Disorders That Can Lead to Hepatomegaly in Adults Type of Disorder
Disorder
Autoimmune
Autoimmune liver disease
Biliary
Extrahepatic obstruction, primary liver cirrhosis, primary sclerosing cholangitis
Cardiovascular
Congestive heart failure, right ventricular failure, constrictive pericarditis, Budd-Chiari syndrome
Drug-related
Alcoholic liver disease, acute alcoholic hepatitis, alcoholic fatty liver, hepatitis induced by statins, tetracyclines, phenylbutazone, vinyl chloride, carbon tetrachloride, arsenic, thorium, yellow phosphorus, macrolide, amiodarone, paracetamol
Hematological
Sickle cell disease, hemolytic anemia, myeloma, leukemia, lymphoma
Infectious
Viral hepatitis, Epstein-Barr virus (EBV), cytomegalovirus (CMV), malaria, pyrogenic abscess, amoebic abscess
Metabolic
Hemochromatosis, Wilson disease, glycogen storage diseases, porphyria, nonalcoholic fatty liver disease
Tumor-related
Metastatic carcinoma, hepatocellular carcinoma, granulomatous hepatitis, amyloidosis
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Hepatomegaly status of the patient. Hepatomegaly can be found in countries where there are hepatitis epidemics, children suffering from malnutrition, food contaminated with chlorinated hydrocarbons, and grains and oils contaminated with Aspergillus fungi. Some 15 to 20 percent of the general population in the United States are estimated to have fatty liver. An enlarged liver is caused primarily by alcoholism in the United States and Europe and by protein malnutrition in infancy and early childhood in tropical countries. Uncontrolled diabetes and obesity often cause people to have fatty livers. Symptoms: Hepatomegaly often produces no symptoms, although the liver may be tender to the touch and the patient may experience some abdominal pain or a feeling of fullness. Asymptomatic cases are usually related to congenital cystic disease, metastasis, or alcoholism. On palpitation, an alcoholic liver is enlarged and firm. In alcoholic hepatitis, hepatomegaly may be associated with jaundice, anorexia, and vomiting. In alcoholic cirrhosis, the enlarged liver is tender and may be associated with hepatitis, usually asymptomatic but occasionally with abdominal pain, jaundice, and gastrointestinal complaints and ascites. In cardiac cirrhosis, the liver may be slightly enlarged and tender. In nodular cirrhosis, the liver is palpable and firm with a blunt edge. Hepatomegaly with fever and tenderness may be due to acute viral hepatitis (A and B), mononucleosis, and ascending cholangitis (infection of the bile duct). In hepatocytic adenomas (in women age thirty to forty), typically there are solitary tumors of up to 10 centimeters in diameter in the right lobe, usually the result of the use of hormones and corticosteroids. Hepatomegaly with gross or occult blood in the stool would suggest metastatic neoplasm of the gastrointestinal tract. In hepatocellular carcinoma, symptoms may be vague and include loss of appetite and body weight, nausea, weakness, and sometimes fever with chills. If the tumor blocks the bile duct (cholangiocarcinoma), then symptoms may include jaundice, black-colored urine, pale stool, and ascites. Screening and diagnosis: The procedure for diagnosis depends on the suspected cause of hepatomegaly. The physician conducts a physical examination and takes the patient’s history. Through skillful palpitation, the physician can determine whether the mass or swelling in the liver area is indeed an enlarged liver. Then, the physician can use the symptoms reported by the patient to begin to distinguish between the many causes of hepatomegaly. Further diagnosis is aided by tests of liver function. The initial workup involves a complete blood count, urinaly572
Salem Health: Cancer sis, sedimentation rate study, chemistry panel, amylase and lipase level testing, and an X ray of the abdomen, followed by ultrasound, computed tomography (CT) scans, and magnetic resonance imaging (MRI). Additional tests are conducted based on the suspected condition. Patients who are likely to have hepatocellular carcinoma undergo a CT scan of the abdomen, followed by biopsy and histopathology to confirm the diagnosis. If chronic heart failure is suspected, a circulation time test and spirometry can confirm the diagnosis. A chest X ray and electroencephalograph (EEG) are also needed. If obstructive jaundice is suspected, endoscopic retrograde cholangiopancreatography may be done following a CT scan of the abdomen. The infectious diseases associated with hepatomegaly are diagnosed by antibody titers, blood smears, or skin tests. Treatment and therapy: Treatment for chronic enlarged liver depends on the underlying cause and the degree of liver damage, especially in the case of cancer. In nonalcoholic fatty liver cases, where any liver damage is minimal, the patient is directed to lose weight, exercise, and avoid alcohol. In advanced stages of hepatomegaly, the liver may undergo necrosis (due to hepatitis, alcoholism, or drug and toxin exposure) and fibrosis (due to alcoholic cirrhosis, chemical carcinogenesis, liver cancer). In patients with metastatic tumors, chemotherapy and nuclear medicine may prolong life. The treatments for hepatocellular carcinoma include liver transplant, chemotherapy, and radiation; however, death generally occurs within six to twenty months. Prognosis, prevention, and outcomes: Hepatomegaly is a symptom of liver diseases and other conditions. If the underlying condition causing the enlarged liver can be successfully treated, the prognosis is good. Ways to prevent hepatomegaly include exercising and eating healthfully, avoiding contact with others’ blood and bodily fluids to minimize the risk of hepatitis, limiting contact with toxins, drinking alcohol in moderation, not mixing medications such as acetaminophen with alcohol, and avoiding overuse of medications and supplements that can affect the liver. M. A. Q. Khan, M.D., Ph.D., and A. K. Khan, M.D., M.R.C.P. u
For Further Information Kasper, D. L., et al. Harrison’s Principles of Internal Medicine. 16th ed. New York: McGraw-Hill, 2005. Khan, M. A. Q., and R. H. Stanton. Toxicology of Halogenated Hydrocarbons. New York: Pergamon Press, 1980. Klaassen, C. D., M. O. Amdur, and J. Doull. Toxicology:
Salem Health: Cancer The Basic Science of Poisons. New York: Macmillan, 1986. Kumar, V., N. Fausto, and A. Abbas. Robbins and Cobran Pathological Basis of Disease. 7th ed. Philadelphia: Saunders, 2003. u
Other Resources
Liver Cancer Network http://www.livercancer.com MayoClinic.com Enlarged Liver http://www.mayoclinic.com/health/enlarged-liver/ DS00638 National Cancer Institute http://www.cancer.gov See also Aflatoxins; Alcohol, alcoholism, and cancer; Amyloidosis; Liver cancers.
u HER2/neu protein Category: Carcinogens and suspected carcinogens Also known as: Human epidermal growth factor receptor 2, ERBB2, ErbB2, HER-2, HER2 Related cancer: Breast cancer Definition: HER2/neu (human epidermal growth factor receptor 2) is one of four members of the epidermal growth factor receptor family. It is a receptor that is present normally on the outer membranes of cells. Certain growth factors are responsible for activation of these receptors, triggering them to send proliferation signals to the cell. However, HER2/neu is often overexpressed in various cancers such as breast cancer, typically because of a genetic alteration in the HER2/neu gene causing an increase in the number of HER2/neu receptors present on the cell surface. Overexpression of the receptor causes cells to divide more rapidly and increases their mobility and invasion potential. HER2/neu overexpressing cells are more likely to form aggressive cancers. Exposure routes: Overexpression is typically caused by a genetic alteration in the HER2/neu gene. Where found: The protein is found in normal cells of the human body, but overexpression is seen only in cancer cells. At risk: HER2/neu overexpression occurs in about 25 percent of breast cancers.
Herbs as antioxidants Etiology and symptoms of associated cancers: HER2/ neu-positive breast cancers are characteristically more aggressive, have poorer prognosis, and poor chemotherapy response. Herceptin, a targeted treatment developed for HER2/neu-positive tumors, has been shown to increase survival rates when combined with chemotherapy. It can also significantly reduce the risk of recurrence in women with HER2/neu-positive tumors. Symptoms of breast cancer include any change in the size or shape of the breast, change in the look or feel of the breast or nipple, or any lumps or thickening in or near the breast or underarm area. Other more obvious changes include nipple discharge, tenderness, inverted nipple, ridges, or pitting of the breast (when the skin looks like that of an orange). History: Epidermal growth factor receptors were first identified as potential oncogenes in the early 1980’s. A mutated form of the receptor was shown by researchers to link cell-growth signals to cancer. Discovery of similar oncogenes led to identification of HER2/neu, which was quickly found to be overexpressed in breast cancer patients and correlated with metastatic and aggressive forms of the disease. Testing for HER2/neu overexpression is standard for any newly diagnosed invasive carcinoma. The two tests are fluorescence in situ hybridization (FISH) to measure the number of genes that code for HER2/neu and immunohistochemistry (IHC) that measures the amount of HER2/neu protein expressed on the surfaces of cancer cells. Terry J. Shackleford, Ph.D. See also Breast cancers; Carcinomas; Endometrial cancer; Family history and risk assessment; Immune response to cancer; Monoclonal antibodies; Neuroendocrine tumors; Oncogenes; Pathology; Proto-oncogenes and carcinogenesis; Receptor analysis; Tubular carcinomas; Tumor markers.
u Herbs as antioxidants Category: Complementary and alternative therapies; lifestyle and prevention Definition: Herbs are roots, stems, leaves, flowers, or seeds of plants used for dietary (flavoring), health (preventive and therapeutic), and other purposes. The antioxidant properties of some compounds in herbs are being investigated for their ability to prevent or fight cancer. Subclasses of this group include oregano, milk thistle, thyme, rose hips, rosemary, garlic, saw palmetto, cat’s claw, and turmeric. 573
Hereditary cancer syndromes Cancers treated or prevented: Used in combination with standard chemotherapy for various cancers such as breast cancer, colon cancer, endometrial cancer, leukemia, and mutagenesis caused by smoking, exhaust fumes, and exposure to other carcinogens Delivery routes: Oral in the form of capsules or powders or as decoctions (extracts) or infusions; dietary in their naturally occurring forms, such as leaves, seeds, berries, and bark; topical as oils, ointments, and tinctures How these agents work: Studies indicate that a plantbased diet can reduce the risk of many types of cancers. Researchers have found that many of the common herbs used as natural flavor additives to food are a very rich source of antioxidants, a class of compounds that assist in neutralizing free radicals and thereby preventing damage to the cells in the body. Free radicals are species generated by normal cell metabolism and by the action of environmental pollutants such as cigarette smoke and pesticides that cause tissue damage. The damage caused by free radicals is thought to be a precursor to degenerative diseases such as cancer. It has been postulated that the therapeutic effect of herbs is mediated by the high concentration of antioxidants present in them. Many herbs are being tested in controlled studies for their anticancer properties and for supplementing standard chemotherapeutic regimens. Most of the antioxidant benefits of herbs are attributed to classes of compounds called isoflavones, polyphenols, flavonoids, lignans, and sulfurcontaining compounds. These compounds act in a synergistic fashion, conferring a composite benefit greater than that of any single component. Side effects: Using herbs in their natural form as flavor enhancers in the diet has the lowest risk of side effects. Although herbs have great potential health benefits, it is important to exercise caution when using them in a concentrated form for the treatment of serious illnesses. Patients should learn about these preventive therapies and consult with their physicians in order to avoid harmful interactions with standard chemotherapeutic drugs. Pregnant and lactating women should exercise special caution when using herbal remedies. Lalitha Krishnan, Ph.D. See also Angiogenesis; Angiogenesis inhibitors; Anthraquinones; Antioxidants; Beta-carotene; Bioflavonoids; Carotenoids; Complementary and alternative therapies; Curcumin; Dietary supplements; Essiac; Free radicals; Garlic and allicin; Green tea; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Phenolics; Phytoestrogens; Resveratrol; Sun’s soup. 574
Salem Health: Cancer
u Hereditary cancer syndromes Category: Social and personal issues Also known as: Familial cancer syndromes Definition: Hereditary cancer syndromes are a group of cancers that develop from an inherited defective or altered gene that can be passed on from parents to children and from generation to generation. Scientists have discovered familial genes that are responsible for hereditary cancers of the breast, ovaries, and colon. Researchers also believe that prostate and other types of cancer such as melanoma skin cancer may have a hereditary component. Incidence: Hereditary cancers account for only 5 to 10 percent of all cancers in the population. However, individuals with these syndromes are at higher risk—up to 90 percent— of developing cancer. Risk factors: When several cases of cancer occur in one family, heredity is not always the cause. Factors such as lifestyle (diet, exercise, tobacco use), exposure to carcinogens, or hormonal factors may be the cause. However, sometimes cancer is linked to heredity. Factors that indicate a risk for hereditary cancer include a family member who developed cancer at a young age (under the age of fifty for colon cancer, under forty-five for breast or ovarian cancer), more than one type of cancer in the family, more than two family members with the same type of cancer, a family member with more than one type of cancer, and a cancer in organs that occur in pairs (such as breasts, ovaries). Well-defined hereditary cancers include breast, ovarian, colon, and melanoma. Breast and ovarian cancers: Hereditary breast and ovarian cancers are a result of an alteration (mutation) in either of two genes: BRCA1 or BRCA2. Men who have the BRCA1 gene alteration are at increased risk for developing prostate cancer. Scientists also believe that those who carry the BRCA1 gene have an increased risk of developing colon cancer. The BRCA1 gene is believed to be responsible for as many as half of the cases of inherited breast cancer. In high-risk families, an individual may have up to a 50 percent chance of inheriting an altered or mutated copy of this gene. A person who does inherit the BRCA1 gene is at increased risk (up to 85 percent) of developing breast cancer. The BRCA2 gene is responsible for about 35 percent of inherited breast cancers in women. Women with an inherited BRCA1 gene also have up to an 85 percent chance of developing ovarian cancer by the age of eighty-five. However, it should also be noted that
Salem Health: Cancer genetically linked ovarian cancer usually occurs early in life, before the age of forty-five. Colon cancers: Colon cancers involving inherited gene mutations account for 5 percent of all colon cancers. There are several different forms of familial colon cancer, but the most common are hereditary nonpolyposis colon cancer (HNPCC) and familial adenomatous polyposis (FAP). There are four specific genes (MLH1, MSH2, PMS2, and MSH6) that have been identified in HNPCC. Individuals who carry one or more of these genes have an 80 percent risk of developing colon cancer. FAP—also known as familial polyposis coli or adenomatous polyposis coli—accounts for less than 1 percent of all colon cancers. A mutation of the APC gene is responsible for this syndrome. FAP can begin as early as age ten. More than 90 percent of people with FAP develop colon cancer by the age of fifty. Familial melanoma: In familial melanoma, there is a genetic mutation of the following genes: CDKN2, CDK4, and MCR1. In this cancer syndrome, at least two firstdegree relatives have a history of invasive melanoma skin cancer. The person at risk usually develops from ten to one hundred moles, usually on the upper trunk and arms. These moles, known as dysplastic nevi, are different in shape, color, and symmetry from normal moles and are present at a young age. Prevention, education, and screening: Researchers continue to study hereditary cancer syndromes to identify other gene alterations that may be responsible for certain types of cancers. These discoveries will lead to a reduction in cancer deaths because they will allow identification of those at risk, early diagnosis, and treatment. Many major hospitals, especially those that are university based, have cancer centers that include a program on hereditary cancers. Typically, such a program includes education, genetic testing, genetic counseling, research, and clinical management of high-risk individuals. It provides clinical services to families, including medical evaluations, consultations with a clinical geneticist, and cancer screenings. Advances in technology have already led to the discovery of defective genes that lead to breast, colon, ovarian, and other cancers. Education of the public as well as community physicians is important to help identify genetic mutation carriers and noncarriers within families. Genetic counseling involves a clinical geneticist and a genetic counselor. Their job is to review several generations of a family’s medical history, construct a medical
Hereditary cancer syndromes family tree, and conduct a clinical exam to evaluate a person’s current health status and look for any physical clues regarding that person’s expression of genetic disease. Genetic counselors also provide individuals with information needed to understand their potential risk for an inherited cancer and to help them decide whether to undergo genetic testing. Genetic testing normally involves a simple blood test or sample of cells taken from healthy individuals who are members of high-risk families. Described as predictive, the tests help determine an individual’s risk of developing cancer. Genetic testing is also used with people who have been diagnosed with cancer and have a strong family history of the disease. At this stage, genetic testing can help physicians and their patients learn if other cancers are likely to develop. For example, inherited genes that play a role in the development of colon or breast cancer also play a role in the development of stomach, uterine, and ovarian cancer. Patients and physicians can work together to plan a screening schedule that will enable detection of the cancer in its earliest, most treatable stage, when the chance of cure is highest. Perspectives and prospects: For those who are members of high-risk families, a negative result from genetic testing for hereditary cancer genes can be a relief. They can avoid undergoing unnecessary rigorous cancer screening and other tests. If the results of genetic testing are positive, this knowledge helps people in making their follow-up care decisions, determining preventive strategies, and making changes in
Uncommon Hereditary Cancer Syndromes These syndromes occur rarely in the population and are often discovered in childhood.
• • • • • • • • • • •
Chordoma Cowden syndrome Li-Fraumeni syndrome Multiple endocrine neoplasias Neurofibromatosis (type 2) Paraganglioma Peutz-Jeghers syndrome Retinoblastoma Tuberous sclerosis Von Hippel-Lindau disease Wilms’ tumor
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Hereditary diffuse gastric cancer lifestyle. Some people, after speaking with their physician and genetic counselor, may decide on a surgical intervention. For example, if a genetic test is positive for the hereditary gene for ovarian cancer, a woman may decide to have surgery to remove the ovaries and thereby minimize her risk. Some aspects of genetic testing involve ethical, legal, and social issues. Genetic testing, counseling, and screenings may be part of standard clinical protocol management for common hereditary cancers. However, health care insurance companies and other practitioners may not be willing to support testing for less common types. If the result of genetic testing is positive for having a hereditary cancer gene, people may fear that insurance companies will identify them as having a predisposing condition and will not cover their treatment if cancer develops. If a family is considered at risk for hereditary cancer syndromes, its members will need to make a decision about whether to have genetic testing. The decision to undergo genetic testing can be complex, and some family members may differ in their decisions. Privacy of test results for an individual family member and other members’ rights to know those results may be an issue as well. Jo Gambosi, M.A., B.S.N. u For Further Information Church, James. Hereditary Colorectal Cancer Syndromes. Malden, Mass.: Blackwell, 2006. Ellis, Neal C., ed. Inherited Cancer Syndromes: Current Clinical Management. New York: Springer, 2003. Sherbert, Gajanan, and M. Lakshmi. The Genetics of Cancer. New York: Elsevier, 1997. u
Other Resources
American Cancer Society Heredity and Cancer http://www.cancer.org/docroot/CRI/content/ CRI_2_6x_Heredity_and_Cancer .asp?sitearea=&level= FORCE: Facing Our Risk of Cancer Empowered http://www.facingourrisk.org National Cancer Institute Cancer Genetics http://www.cancer.gov/cancertopics/ prevention-genetics-causes/genetics See also Beckwith-Wiedemann syndrome (BWS); BirtHogg-Dubé syndrome (BHDS); Childhood cancers; Chromosomes and cancer; Cowden syndrome; Cushing syndrome and cancer; Cytogenetics; Denys-Drash syndrome 576
Salem Health: Cancer and cancer; Down syndrome and leukemia; Family history and risk assessment; 5Q minus syndrome; Gardner syndrome; Genetic testing; Genetics of cancer; Hereditary diffuse gastric cancer; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary mixed polyposis syndrome; Hereditary non-VHL clear cell renal cell carcinomas; Hereditary pancreatitis; Hereditary papillary renal cell carcinomas; Hereditary polyposis syndromes; Hodgkin disease; Horner syndrome; Juvenile polyposis syndrome; Klinefelter syndrome and cancer; Lambert-Eaton myasthenic syndrome (LEMS); Li-Fraumeni syndrome (LFS); Mitochondrial DNA mutations; Myelodysplastic syndromes; Nijmegen breakage syndrome; Non-Hodgkin lymphoma; Oncogenes; Paraneoplastic syndromes; PeutzJeghers syndrome (PJS); Proto-oncogenes and carcinogenesis; Richter syndrome; Rothmund-Thomson syndrome; Sézary syndrome; Sjögren syndrome; Turcot syndrome; Von Hippel-Lindau (VHL) disease; Waldenström macroglobulinemia (WM); Wilms’ tumor; Wilms’ tumor aniridiagenitourinary anomalies-mental retardation (WAGR) syndrome and cancer; Xeroderma pigmentosa; Yolk sac carcinomas; Young adult cancers; Zollinger-Ellison syndrome.
u Hereditary diffuse gastric
cancer Category: Diseases, symptoms, and conditions Also known as: HDGC syndrome Related conditions: Lobular breast cancer, colon cancer Definition: Hereditary diffuse gastric cancer is a rare cancer that affects many parts of the stomach simultaneously rather than forming localized tumors. Risk factors: Hereditary diffuse gastric cancer has a strong inherited component and is highly likely to occur in people who have a mutation on the CDH1 gene. However, other genes are also thought to be involved because 30 percent of people with hereditary diffuse gastric cancer do not have the CDH1 mutation. The average age at diagnosis is thirty-eight (the age range for diagnosis is fourteen to sixty-nine). Lifetime risk of having the syndrome is 67 percent for men and 83 percent for women. Etiology and the disease process: The CDH1 gene is an autosomal dominant gene, meaning that the individual needs to inherit a mutation in this gene from only one parent to be at risk for hereditary diffuse gastric cancer. Children who have one parent with the mutated gene have
Salem Health: Cancer
Hereditary leiomyomatosis and renal cell cancer (HLRCC)
a 50 percent chance of inheriting the condition. Cancer develops when individual cancer cells invade the stomach wall in many places, causing cancerous patches. This cancer does not form discrete tumors.
u Hereditary leiomyomatosis
Incidence: The rate of gastric cancers is highest in Japan, China, Russia, and other Southeast Asian countries (about 40 cases per 100,000 population). It is lowest in Western Europe and North America (about 4 cases per 100,000). Hereditary diffuse gastric cancer accounts for between 35 and 50 percent of all gastric cancers.
Category: Diseases, symptoms, and conditions Also known as: Hereditary renal carcinoma
Symptoms: Most people do not show symptoms until hereditary diffuse gastric cancer is advanced. Advanced cases of the disease cause stomach pain, nausea, vomiting, and bloating, often accompanied by weight loss. Screening and diagnosis: Although their value in screening remains statistically unproven, endoscopies are recommended for people who have a family history of hereditary diffuse gastric cancer. Colon cancer screening and breast cancer screening are also recommended, as these cancers commonly co-occur in people with hereditary diffuse gastric cancer. Genetic testing for the CDH1 mutation is available, and genetic counseling may be helpful. Diagnosis is most often made on a family history of hereditary diffuse gastric cancer or early gastric cancer and a biopsy. Treatment and therapy: Because cancer occurs throughout the stomach, complete surgical removal (gastrectomy) is the standard treatment. TNM (tumor/lymph node/ metastasis) staging of hereditary diffuse gastric cancer has not been standardized because of the nature of the cancer and its rarity. Prognosis, prevention, and outcomes: If diagnosed and treated with gastrectomy early (an uncommon event), the five-year survival rate is about 90 percent. When diagnosed in a late stage (most common), the five-year survival rate is less than 20 percent. Because of its strong inherited component, there is no known way to prevent hereditary diffuse gastric cancer. Martiscia Davidson, A.M. See also Colorectal cancer; Family history and risk assessment; Gastric polyps; Gastrinomas; Gastrointestinal cancers; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Stomach cancers.
and renal cell cancer (HLRCC)
Related conditions: Uterine fibroids, von Hippel-Lindau (VHL) disease, hereditary papillary renal carcinoma, BirtHogg-Dubé syndrome (BHDS) Definition: Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an inherited condition characterized by the development of one or more skin lesions called leiomyomas (tumors of smooth muscle tissue), uterine fibroids in women, and a form of renal cell carcinoma called papillary renal cancer. Risk factors: The only known risk factor for HLRCC is having a parent with the disease. If a parent has this condition, there is a 50 percent chance that it will be passed on to his or her children. Although this disease is hereditary, it can be caused by a genetic mutation. Etiology and the disease process: HLRCC is a dominant genetic trait. The affected gene is the one that produces the enzyme fumarate hydratase. This enzyme assists in the conversion of fumarate into L-malate in the Krebs cycle (involved in the metabolism of carbohydrates by the cells). As a result, fumarate accumulates in the cells. It is theorized that the high levels of fumarate interfere with the availability of oxygen for activation of several genes involved in angiogenesis (the formation of new blood vessels), cell metabolism, and cell growth and reproduction. This is called pseudohypoxia. It is thought that fumarate hydratase plays a role in the suppression of tumor formation in the body. Incidence: HLRCC is an extremely rare condition. Less than 1,000 cases have been documented. Symptoms: The major symptom of HLRCC is the presence of one or more leiomyomas on the skin. The leiomyomas are painful nodules that range from flesh colored to light brown. About 75 percent of persons with HLRCC develop leiomyomas. Almost all women with HLRCC will develop uterine fibroids. They cause pelvic pain and heavy menstrual periods. Patients with renal cell cancer may not exhibit any symptoms initially but later will exhibit hematuria (blood in the urine), lower back pain, and a palpable mass. Renal cell carcinoma develops in only 10 to 16 percent of persons with HLRCC. 577
Hereditary leiomyomatosis and renal cell cancer (HLRCC)
Salem Health: Cancer
Screening and diagnosis: There is no routine screening for HLRCC. If the patient has a family history of HLRCC, genetic testing is performed on all family members. Once HLRCC has been diagnosed, the patient should have annual skin examinations for leiomyomas and regular screenings for renal cell cancer. Female patients should have annual pelvic examinations or uterine or transvaginal ultrasounds to screen for uterine fibroids. HLRCC is suspected when a person seeks treatment for painful leiomyomas. A biopsy of a leiomyoma is taken, and the cells are examined for the activity of fumerate hydratase. In a person with HLRCC, there would be a significant reduction in activity of this Laser myomectomy is used to remove uterine fibroids. (LifeART© 2008 Wolters enzyme. Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.) Uterine fibroids are not accepted as an indicator of HLRCC because of the high prevalence of uterine fibroids in the general female releasing hormone agonists, antihormonal medications, population. While most uterine fibroids are benign, occaand pain relievers. sionally a leiomyosarcoma (cancer of the uterus) is disOnce a renal cell cancer is discovered in a person with covered in a woman with HLRCC. HLRCC, the tumor is surgically removed. The tumor can Once a diagnosis of HLRCC is made, the patient is be removed by direct surgical radical nephrectomy (rescreened for renal cell cancer, by abdominal computed moval of the kidney and adrenal gland), by a partial netomography (CT) scan or magnetic resonance imaging phrectomy, or by one of several laparoscopic nephrectomy (MRI). The renal cell cancer related to HLRCC is particuprocedures. larly aggressive and grows and spreads faster than other Prognosis, prevention, and outcomes: HLRCC is a chronic renal cell cancers. condition. However, with careful monitoring, a person Because HLRCC is not a cancer, there is no staging for with this disease can live a fairly normal life. Because the condition. If a person with HLRCC develops renal cell HLRCC is caused by a genetic mutation, there is no way cancer, then this cancer is staged like other renal cell to prevent it. An important part of the management of cancers. HLRCC is genetic testing of all related family members and genetic counseling. Even siblings of an affected perTreatment and therapy: There is no cure for HLRCC; it son should be screened for HLRCC because of the possican only be managed. The leiomyomas of the skin can be bility of their having additional unpaired genes. Should removed by surgical excision, cryoablation (freezing), or two persons with the gene for HLRCC wish to have a laser surgery. If there are many leiomyomas, removal may child, their child would possess both HLRCC genes. This not be possible. There are a number of medications that genetic combination is marked by severe encephalopathy are effective in treating the pain caused by the skin leiomy(brain damage). omas. They are calcium-channel blockers, alpha-blockers, Christine M. Carroll, R.N., B.S.N., M.B.A. nitroglycerine, antidepressants, and some antiepileptic (antiseizure) medications. Uterine fibroids can be removed surgically by myomectomy (removal of the fibroids) or hysterectomy. To preserve the uterus and shrink the fibroids, embolization of the arteries feeding the fibroids can be performed. Medications for treating uterine fibroids include gonadotropin578
u
For Further Information Kiuru, M., and V. Launonen. “Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC).” Current Molecular Medicine 4, no. 8 (December, 2004): 869-875. Sudarshan, Sunil, Peter A. Pinto, Len Neckers, and
Salem Health: Cancer W. Marston Linehan. “Mechanisms of Disease: Hereditary Leiomyomatosis and Renal Cell Cancer—A Distinct Form of Hereditary Kidney Cancer.” Nature Clinical Practice—Urology 4, no. 2 (February, 2007): 104-110. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Birt-Hogg-Dubé syndrome (BHDS); Family history and risk assessment; Hereditary non-VHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Hysterectomy; Kidney cancer; Leiomyomas; Renal pelvis tumors; Urinary system cancers; Von HippelLindau (VHL) disease.
u Hereditary mixed polyposis
syndrome Category: Diseases, symptoms, and conditions Also known as: Colorectal adenoma and carcinoma 1 (CRAC1), HMPS Related condition: Juvenile polyposis Definition: Hereditary mixed polyposis syndrome is a dominantly inherited condition that predisposes an individual to the development of polyps in the gastrointestinal tract. Patients with this syndrome exhibit multiple polyp types—including atypical juvenile polyps, hyperplastic polyps, colonic adenomas, and colonic adenocarcinomas— as well as polyps that show mixed or hybrid characteristics. The syndrome predisposes patients to developing colorectal cancer. Risk factors: Hereditary mixed polyposis syndrome is a genetic disorder that is transmitted in a dominant fashion. This means that only one of the two copies of a gene needs to be affected to develop the condition. Therefore, if one parent has the disease, then there is a 50 percent chance that his or her child will have it. Etiology and the disease process: Hereditary mixed polyposis syndrome is a genetic disorder. Although the specific gene that is mutated has not been identified, numerous genetic studies have shown that the disease is linked to regions on chromosome 6, chromosome 10, and chromo-
Hereditary mixed polyposis syndrome some 15. The disease begins by the formation of polyps, or growths of tissue originating from a mucous membrane. Although polyps are usually benign, they can develop into tumors if they are not removed. Symptoms: Symptoms of hereditary mixed polyposis syndrome are associated with polyp formation and can include anemia, blood loss, the passage of bright red, bloody stool, or bowel obstruction. Incidence: Hereditary mixed polyposis syndrome is a rare disease that has been described in only a few families. Screening and diagnosis: Patients with a family history of hereditary mixed polyposis syndrome should undergo frequent colonoscopies to screen for polyp formation because polyps that are left untreated can develop into cancer. Screening by colonoscopy should begin by age twentyfive and be repeated every two years. Patients with hereditary mixed polyposis syndrome usually have less than fifteen polyps during colonoscopy. Diagnosis is made based on the presence of multiple types of polyps or polyps with mixed characteristics in histological examination as well as a family history of the disease. Treatment and therapy: Colonoscopy with polyp removal is usually sufficient to control the symptoms. Prognosis, prevention, and outcomes: The median age of diagnosis for hereditary mixed polyposis syndrome is forty years. The median age of cancer diagnosis is fortyseven years. The lifetime risk for developing colorectal cancer is 30 percent. Prevention is based on identifying atrisk individuals based on a family history of hereditary mixed polyposis syndrome. Lindsay Lewellyn, B.S. See also Adenomatous polyps; APC gene testing; Ashkenazi Jews and cancer; Bethesda criteria; Colon polyps; Colorectal cancer; Colorectal cancer screening; Cyclooxygenase 2 (COX-2) inhibitors; Desmoid tumors; DPC4 gene testing; Duodenal carcinomas; Endometrial cancer; Endometrial hyperplasia; Enterostomal therapy; Ethnicity and cancer; Family history and risk assessment; Gardner syndrome; Gastric polyps; Gastrointestinal cancers; Genetics of cancer; Hereditary cancer syndromes; Hereditary polyposis syndromes; Juvenile polyposis syndrome; MLH1 gene; MSH genes; Pancreatic cancers; Peutz-Jeghers syndrome (PJS); PMS genes; Premalignancies; Sarcomas, soft-tissue; Small intestine cancer; Turcot syndrome. 579
Hereditary non-VHL clear cell renal cell carcinomas
u Hereditary non-VHL clear cell
renal cell carcinomas Category: Diseases, symptoms, and conditions Also known as: Hereditary non-VHL CCRCC Related condition: Clear cell renal cell cancer (CCRCC) Definition: Hereditary non-VHL clear cell renal cell carcinoma is a cancer that develops in the nephrons, the filtering parts of the kidney. Its cells are characterized by clear cytoplasm. The VHL (von Hippel-Lindau) gene, which is a more common cause of clear cell renal cell carcinoma, is absent. Risk factors: The primary risk factor is a family history of clear cell renal cell carcinoma in the absence of the VHL gene. Etiology and the disease process: Hereditary non-VHL clear cell renal cell carcinoma arises from a single cell of the tubular epithelium of the nephron. It spreads through the lymph nodes and the bloodstream. The most common sites of metastases are the other kidney, the lung, the adrenal gland, the bones, or the liver. Incidence: Hereditary non-VHL clear cell renal cell carcinoma is very rare. Symptoms: Typically, this type of kidney cancer appears as a single tumor. There are no symptoms until the tumor has become quite large or has metastasized. The symptoms are hematuria (blood in the urine), abdominal mass, back or flank pain, weight loss, recurrent fever, and fatigue. Screening and diagnosis: There is no routine screening for hereditary non-VHL clear cell renal cell carcinoma. However, if a person has a family member with the disease, that person and other family members would be screened annually. Both screening and diagnosis are performed by abdominal computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI). A biopsy is done to determine the type of cancer. It may be performed by inserting a core needle through the skin into the kidney or by ureteroscopy. Hereditary non-VHL clear cell renal cell carcinoma is staged in the same way as other kidney cancers, using numeric groupings from I to IV and the TNM (tumor/lymph node/metastasis) staging system. Treatment and therapy: Usually, the affected kidney is removed, although sometimes only part of the kidney is removed. Research is investigating the use of radioablation 580
Salem Health: Cancer (destroying the tumor with radiation), cryoablation (freezing), and arterial embolization. Kidney cancers, including hereditary non-VHL clear cell renal cell carcinoma, are not treated with chemotherapy or radiation therapy, unless they are Stages III or IV, as these therapies produce a low survival rate. Prognosis, prevention, and outcomes: The prognosis depends on the stage of the tumor. With Stages I and II, surgical intervention is likely to cure the cancer. With Stage III and IV kidney cancer, the prognosis is guarded and depends on the patient’s response to chemotherapy. Hereditary non-VHL clear cell renal cell carcinoma cannot be prevented. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Birt-Hogg-Dubé syndrome (BHDS); Family history and risk assessment; Giant cell tumors (GCTs); Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary papillary renal cell carcinomas; Kidney cancer; Ovarian epithelial cancer; Renal pelvis tumors; Salivary gland cancer; Urinary system cancers; Uterine cancer; Vaginal cancer; Von Hippel-Lindau (VHL) disease; Wilms’ tumor.
u Hereditary pancreatitis Category: Diseases, symptoms, and conditions Also known as: HP Related conditions: Diabetes mellitus, malabsorption, pancreatic cancer Definition: Hereditary pancreatitis is an inherited disease characterized by recurrent acute (short and severe) episodes of pancreatitis (inflammation of the pancreas) that often progress to chronic (persistent) pancreatitis. Most people develop symptoms before the age of twenty. A person with hereditary pancreatitis has a 40 percent chance of developing pancreatic cancer by the age of seventy. Risk factors: Because hereditary pancreatitis is inherited, the main risk factor is having a family history of this disease. Each child born to a person with hereditary pancreatitis has a 50 percent chance of inheriting the disease. Alcohol may worsen pain and other symptoms, and smoking increases the risk of developing pancreatic cancer. Etiology and the disease process: The underlying genetic cause of most cases of hereditary pancreatitis is a mutation, or a genetic change, in the PRSS1 gene. Normally, the protein made by PRSS1—called cationic trypsino-
Salem Health: Cancer
Hereditary papillary renal cell carcinomas
gen—is changed into trypsin, which is an enzyme that helps digest protein. In people with hereditary pancreatitis, an excess of trypsin damages the pancreas by autodigestion (the trypsin destroys cells of the pancreas). The process by which pancreatitis causes pancreatic cancer is not well understood. Usually, each person has two normal copies of the PRSS1 gene. A mutation in one copy of the gene is sufficient to cause hereditary pancreatitis. A person with hereditary pancreatitis has a PRSS1 gene mutation from the time of conception. About 20 percent of people with a PRSS1 mutation do not develop pancreatitis.
u Hereditary papillary renal cell
Incidence: It is estimated that at least 1,000 people in the United States are affected with hereditary pancreatitis.
Risk factors: The primary risk factor is a family history of hereditary papillary renal cell carcinoma.
Symptoms: Symptoms include abdominal pain, nausea, vomiting, malnutrition (not getting enough nutrients from food), and diabetes mellitus. Screening and diagnosis: Generally, imaging studies of the pancreas, a detailed family history, and blood tests help diagnose this disease. Because most cases of hereditary pancreatitis are caused by mutations in the PRSS1 gene, genetic testing may assist in confirming a suspected diagnosis. Treatment and therapy: The main focus of treatment is to reduce the symptoms by giving pancreatic enzyme supplements to treat malnutrition, insulin to treat diabetes, and medication to treat pain. Occasionally surgery removing part or all of the pancreas is performed to treat complications. Treatment for pancreatic cancer may include surgery, radiation therapy, and chemotherapy. Prognosis, prevention, and outcomes: Because hereditary pancreatitis is a genetic condition, it cannot be prevented. To reduce the risk of pancreatic cancer and to prevent the worsening of pancreatitis, the patient should avoid smoking and alcohol. Imaging of the pancreas may be done to detect cancer at an early stage. The medical team caring for the patient decides the age at which monitoring should start. Abbie L. Abboud, M.S., C.G.C. See also Antidiarrheal agents; Antiviral therapies; CA 199 test; Endoscopic retrograde cholangiopancreatography (ERCP); Family history and risk assessment; Hepatomegaly; Hypercalcemia; Pancreatic cancers; Pancreatitis; Paracentesis; Thoracentesis; Ultrasound tests.
carcinomas Category: Diseases, symptoms, and conditions Also known as: HPRCC Related condition: Papillary renal cell carcinomas Definition: Hereditary papillary renal cell carcinoma develops in the nephrons, the filtering parts of the kidney. Papillary tumors are characterized by fingerlike projections from the tumor. There are two types of papillary renal cell cancers, and HPRCC is type 1.
Etiology and the disease process: Hereditary papillary renal cell carcinoma is characterized by multifocal sites of papillary tumor development within one or both kidneys. These sites develop concurrently rather than spreading from an initial site. The sites often vary in size. Research demonstrates that hereditary papillary renal cell carcinoma is caused by a mutation in the MET gene. However, hereditary papillary renal cell carcinoma is less aggressive than other renal cell cancers and is less likely to metastasize. Incidence: Hereditary papillary renal cell carcinoma is quite rare. It is much more common in men and in African Americans than in the population as a whole. Symptoms: There are no symptoms until the tumors have become large enough to interfere with kidney function. The symptoms are hematuria (blood in the urine), abdominal mass, back or flank pain, weight loss, recurrent fever, and fatigue. Screening and diagnosis: There is no routine screening for hereditary papillary renal cell carcinoma, unless a person has a family member who develops it. In this case, family members would be screened annually. Both screening and diagnosis are performed by abdominal computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI). A biopsy is required to determine the type of cancer. It may be performed by inserting a core needle through the skin into the kidney or by ureteroscopy. Hereditary papillary renal cell carcinoma is staged in the same manner as other kidney cancers, using numeric groupings from I to IV, and the TNM (tumor/lymph node/ metastasis) staging system. Treatment and therapy: Hereditary papillary renal cell carcinoma is usually treated by partial nephrectomy or by 581
Hereditary polyposis syndromes destruction of the tumor sites only. This can be performed by radioablation (destroying the tumor with radiation), cryoablation (freezing), or arterial embolization. The presence of many sites of hereditary papillary renal cell carcinoma makes it likely that all stages of this cancer are treated with chemotherapy, immunotherapy, and radiation. Here, the goal is to maintain some kidney function. Prognosis, prevention, and outcomes: Hereditary papillary renal cell carcinoma is more likely to be a chronic condition because it rarely metastasizes. However, a patient with Stage III or IV hereditary papillary renal cell carcinoma could require dialysis because of a lack of kidney function. Hereditary papillary renal cell carcinoma cannot be prevented. Christine M. Carroll, R.N., B.S.N., M.B.A. See also African Americans and cancer; Family history and risk assessment; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Kidney cancer; Renal pelvis tumors; Urinary system cancers.
u Hereditary polyposis
syndromes Category: Diseases, symptoms, and conditions Also known as: Familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome, Gardner syndrome, hereditary mixed polyposis syndrome, harmatomas, adenomas, juvenile polyps Related conditions: Colorectal cancer, bowel obstruction, rectal bleeding desmoid tumors, osteomas, soft-tissue tumors, pigmented lesions, intestinal polyps Definition: Hereditary polyposis syndromes are several disorders caused by a genetic predisposition for the growth of large numbers of polyps in the small and large intestine: familial adenomatous polyposis, Gardner syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and hereditary mixed polyposis syndrome. Individuals diagnosed with familial adenomatous polyposis (FAP) have an APC gene alteration on chromosome 5q21 and are likely to grow large numbers (more than one hundred) of intestinal polyps. Gardner syndrome is a variant of FAP that causes intestinal polyps, skin and soft-tissue tumors, desmoid tumors, and multiple osteomas. The intestinal polyps have an almost 100 percent chance of becoming malignant. This 582
Salem Health: Cancer condition can begin in puberty, but the average age for diagnosis of malignancy is thirty-nine years. Nonmalignant soft-tissue growths and osteomas can appear earlier. Peutz-Jeghers syndrome is caused by an STK11/LKB1 mutation and produces multiple polyplike growths called hamartomas that grow in the small intestine rather than the large intestine. They have a low potential for becoming malignant but can become quite large and cause symptoms requiring surgery. Juvenile polyposis syndrome is a rare childhood-onset, autosomal dominant disease. It produces hamartomous polyposis rather than adenomatous polyposis. Hereditary mixed polyposis syndrome, a rare syndrome seen in families, causes a variety of colon polyp types. Polyps are initially benign but can easily become malignant because of the genetic abnormalities. The term “adenomatous polyp” refers to a nonmalignant polyp with a high predisposition to become malignant. Risk factors: The hereditary polyposis syndromes all involve some sort of genetic error that is autosomal dominant. That means that if one parent carries the genetic mutation, there is a 50 percent chance that his or her child will have the disease. The sex of the child does not matter. Although genetic alterations can occur for unknown reasons, people who do not carry the mutated gene have an extremely small chance of randomly developing one of these syndromes and cannot transfer it to their offspring. Familial adenomatous polyposis (FAP) and its variant, Gardner syndrome, involve an error in the gene APC on chromosome 5, which is autosomal dominant. The gene responsible for Peutz-Jeghers is STK11/LKB1. Two genes, BMPR1A and SMAD4, have been identified as causing juvenile polyposis syndrome. Hereditary mixed polyposis syndrome is believed to arise from a gene error on chromosome 15. Etiology and the disease process: Polyps can begin at any age; however, polyps caused by FAP rarely occur before age ten, and juvenile polyposis syndrome is a very rare disease. The chromosome abnormalities in hereditary polyposis syndromes are responsible for cellular changes in the mucosal lining of the intestine that initiate the formation of polyps. The chromosomal abnormality drastically increases the possibility of a polyp becoming malignant. Individuals with FAP and Gardner syndrome will develop multiple polyps, so many, in fact, that surgical removal of the colon is sometimes the only option. Surveillance and screening are the best methods for prevention and early detection of intestinal polyps. Nonfamilial causes of polyps are not well understood but seem to be responsible for isolated polyp formation.
Salem Health: Cancer Some of these polyps will become malignant if left untreated. Colorectal cancer screening without genetic predisposition for familial polyposis or cancer usually begins at age fifty. Incidence: FAP affects 1 in 30,000 people, with 800 to 1,000 new cases per year. It is more common in Western countries. A person with a family history of adenomatous polyps has between a 15 and 20 percent risk of developing polyps and is at a much higher risk of developing colorectal cancer than the general population. Without intervention, 90 percent of those with FAP will develop colorectal cancer by their fourth or fifth decade of life. Gardner syndrome occurs in 1 in 1 million people. There is an almost 100 percent chance that polyps due to this syndrome will become malignant. Peutz-Jeghers syndrome occurs in 1 in 7,000 live births. Symptoms: Patients with familial adenomatous polyposis initially do not exhibit symptoms. However, polyps can cause blood to be passed in the stool, which can be detected through a fecal occult blood test (FOBT). As polyps get larger, patients experience symptoms such as diarrhea, constipation, and abdominal pain. Gardner syndrome causes osteomas, or bone cysts, in the jaw, skull, and teeth. Epidermoid cysts can be present on the face, scalp, arms, and legs. Juvenile polyposis syndrome can cause diarrhea, constipation, gastrointestinal hemorrhage, and proteinlosing abnormalities. Screening and diagnosis: People with a family history of polyps should have genetic testing to see if they are carriers of hereditary polyposis syndromes. Also, all of their primary relatives (parents, siblings, and children) should receive genetic testing. Earlier colorectal cancer screening is indicated if genetic testing is positive. Symptoms of hereditary polyposis syndromes, such as fecal blood or gastrointestinal problems, indicate the need for diagnostic tests such as sigmoidoscopy, bariumcontrast X rays, or colonoscopy. All of these tests can find polyps, but only a colonoscopy allows a biopsy to be performed. Biopsies are taken to determine the type of tissue: adenomatous, harmatomous, or cancerous. In cases of familial adenomatous polyposis, more than one hundred polyps can be present, making total polyp removal impossible. In addition to the presence of polyps, Gardner syndrome can be diagnosed from the presence of osteomas, or bone tumors (usually in the jaw, skull, and teeth), and epidermoid cysts. Treatment and therapy: Patients with familial adenomatous polyposis often have so many polyps that individual polyp removal during colonoscopy is not an option. In
Hereditary polyposis syndromes these cases, surgical removal of part or all of the large intestine and the rectum is the main treatment. In a colectomy with ileorectal anastomosis (IRA), the entire colon is removed. The last part of the small intestine (ileum) is attached (anastomosed) to the top of the rectum. Total proctocolectomy with permanent ileostomy involves the removal of the entire colon, rectum, and anus. A small opening is made through the abdominal wall (ostomy), where a bag can be attached to collect fecal material. The rationale for these seemingly radical procedures is that there is no way to prevent the formation of numerous polyps that have a high probability of becoming malignant. Removing the colon prevents the formation of the adenomatous polyps, lowers the chance of developing colorectal cancer, and saves lives. Recovery from colectomy takes approximately six to eight weeks. Patients may have to avoid certain foods that upset the bowel, adapt to more frequent bowel movements, and find out what foods and drink work best for them. Adjusting to a colostomy can be difficult and lifealtering. Issues related to self-image, general well-being, and sexuality need to be addressed. Counseling and family support are important components of physical and mental health. Epidermoid cysts and osteomas from Gardner syndrome can be removed if painful or disfiguring, but they are unlikely to become malignant. In Peutz-Jeghers syndrome and juvenile polyposis syndrome, the polyps are harmatomas, which usually appear in the small intestine and are fewer in number. Individual polyps can be removed if the patient develops symptoms and there is the chance of obstruction. Prognosis, prevention, and outcomes: People who have the gene alteration that causes a hereditary polyposis syndrome will develop the disease. Therefore, it is important for these people to see specialists in gastroenterology and genetics who can manage routine health, screening, and illness when indicated. It is recommended that patients with Gardner syndrome have a fecal occult blood test (FOBT), sigmoidoscopy or colonoscopy, and upper gastrointestinal tract testing every one to two years until age fifty. There is some evidence that a class of drugs called COX-2 (cyclooxygenase 2) inhibitors can prevent the growth of some intestinal polyps and limit the size of the ones that do form. This does not mean, however, that COX-2 inhibitors are effective for those with hereditary polyposis syndromes. Surgical removal of the colon alters patients’ lifestyles but can be lifesaving. Routine medical visits are still nec583
Herpes simplex virus essary, but the surgery significantly reduces the risk of developing colorectal cancer. Janet R. Green, M.S.P.H. u For Further Information Fisher, Stephen. Colon Cancer and the Polyps Connection. Tuscon, Ariz.: Fisher Books, 1995. Gardner, E. J. “A Genetic and Clinical Study of Intestinal Polyposis, a Predisposing Factor for Carcinoma of the Colon and Rectum.” American Journal of Human Genetics 3, no. 2 (June, 1951): 167-176. Herrera, Lemuel, ed. Familial Adenomatous Polyposis. New York: A. R. Liss, 1990. u
Other Resources
American Cancer Society http://www.cancer.org American Gastroenterology Association http://www.gastro.org National Cancer Institute http://www.cancer.gov National Institute of Diabetes and Digestive and Kidney Diseases http://www2.niddk.nih.gov See also Adenomatous polyps; APC gene testing; Ashkenazi Jews and cancer; Bethesda criteria; Colon polyps; Colorectal cancer; Colorectal cancer screening; Cyclooxygenase 2 (COX-2) inhibitors; Desmoid tumors; DPC4 gene testing; Duodenal carcinomas; Endometrial cancer; Endometrial hyperplasia; Enterostomal therapy; Ethnicity and cancer; Family history and risk assessment; Gardner syndrome; Gastric polyps; Gastrointestinal cancers; Genetics of cancer; Hereditary cancer syndromes; Hereditary mixed polyposis syndrome; Juvenile polyposis syndrome; MLH1 gene; MSH genes; Pancreatic cancers; Peutz-Jeghers syndrome (PJS); PMS genes; Premalignancies; Sarcomas, soft-tissue; Small intestine cancer; Turcot syndrome.
u Herpes simplex virus Category: Diseases, symptoms, and conditions; carcinogens and suspected carcinogens Also known as: HSV, HSV1, HSV2 Related condition: Gingivostomatitis Definition: Herpes simplex virus is an enveloped, doublestranded, deoxyribonucleic acid (DNA) virus that causes skin ulcers in infected persons. Herpes simplex virus 1 584
Salem Health: Cancer (HSV1) commonly affects the lips, the face, and the skin above the waist. Herpes simplex virus 2 (HSV2), which is sexually transmitted, affects the genitalia and the skin below the waist. Complications of HSV infection include inflammation of the brain lining and eye infections. Pregnant women can pass the virus to their newborns, who can become very ill. Newborns infected with HSV may develop disease in the liver, lungs, central nervous system, or skin, eyes, and mouth. Risk factors: Sexually active adolescents and adults are at risk of infection with HSV2. People with weakened immune systems, such as cancer patients, are at an increased risk of recurring HSV infection and disease. Etiology and the disease process: Once a person is infected, the virus spreads to the nerve cells and remains in the body (in a latent form) for life. The lesions in the genital area first look like red bumps but then turn into watery blisters that may open up, ooze fluid, or bleed. The lesions usually heal in seven to ten days but sometimes take up to four weeks to heal. The lesions may reappear every now and then, usually after periods of stress, fever, or overexposure to sunlight. Cancer, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), and the use of medications (corticosteroids) that weaken the immune system may also trigger the reappearance of symptoms. Some studies have suggested that women infected with both herpes simplex virus and a high-risk type of human papillomavirus (HPV) have a greater likelihood of developing cervical cancer than women who have only the HPV infection. However, HSV infection need not be present for cervical cancer to develop. Incidence: Infections with herpes simplex virus are ubiquitous and are transmitted from person to person whether or not they have symptoms. Most children will acquire an HSV1 infection during their first few years of life, usually through contact with infected saliva. In the United States, up to 90 percent of adults have antibodies to HSV1 and up to 30 percent have antibodies to HSV2. Symptoms: HSV infections in children beyond the neonatal (newborn) period, adolescents, and adults usually have no symptoms. HSV1 may cause fever (especially during the first episode), mouth sores (fever blisters), and enlarged lymph nodes in the neck or groin. HSV2 may cause genital lesions with a burning and tingling sensation, muscle pain, vaginal discharge, and trouble urinating. Screening and diagnosis: HSV infections can be diagnosed by the physical appearance of the skin lesions. There
Salem Health: Cancer
Herpes simplex virus
are, however, laboratory tests available to diagnose herpes simplex virus infections, including blood and cell culture tests. Other available tests include the following: • Tzanck test: The sore on the skin is scraped and the sample stained for examination under a microscope. • Direct fluorescent antibody (DFA) test: This uses a fluorescent antibody to detect the presence of the virus. Treatment and therapy: Mild cases of the disease may not require treatment. For more severe cases, two types of therapies are usually recommended— episodic and suppressive. The episodic Herpes simplex ulcer on the lip. (Custom Medical Stock Photo) therapy consists of taking medication at the first sign of recurrence to accelerate u For Further Information the healing process of the lesions. The medication is taken American Academy of Pediatrics. “Herpes Simplex.” In for a few days until the lesions disappear. Suppressive Red Book: 2006 Report of the Committee on Infectherapy consists of taking a medication daily to eliminate tious Diseases, edited by L. K. Pickering, C. J. Baker, or reduce recurrence. Suppressive therapy is usually recS. S. Long, and J. A. McMillan. 27th ed. Elk Grove Vilommended for people who have six or more recurrences lage, Ill.: Author, 2006. per year. Ebel, Charles. Managing Herpes: How to Live and Love Cancer patients with severe cases and frequent inwith a Chronic STD. Research Triangle Park, N.C.: fections may be treated with antiviral drugs such as acyAmerican Social Health Association, 2002. clovir (Zovirax), famciclovir (Famvir), and valacyclovir Stanberry, Lawrence. Understanding Herpes. 2d ed. Jack(Valtrex). Acyclovir is available in ointment and pill son: University Press of Mississippi, 2006. forms. Valacyclovir uses acyclovir as its active ingredient but is adsorbed better by the body than acyclovir, thus requiring fewer daily doses. Famciclovir stops the virus u Other Resources from replicating, using the active ingredient penciclovir. Like valacyclovir, it is well adsorbed by the body. American Social Health Association Prognosis, prevention, and outcomes: Herpes has no cure. Recurrences, however, may be milder over time. HSV skin lesions usually heal on their own in seven to ten days, but they may take longer to heal in people with weakened immune systems. People with genital herpes may feel ashamed or guilty and may think that they can no longer have sex; however, herpes can be treated and transmission can be prevented. Genital HSV infection may be prevented by the use of condoms and by reducing the number of sexual partners. Condoms, however, do not always cover the whole infected area and infection may occur. There is no licensed vaccine against herpes simplex virus but several candidate vaccines have been studied. Diego Pineda, M.S.
Herpes Resource Center http://www.ashastd.org/herpes/ herpes_learn_treatment.cfm MedlinePlus Herpes Simplex http://www.nlm.nih.gov/medlineplus/ herpessimplex.html SexualityandU.ca Sexually Transmitted Infections http://www.sexualityandu.ca/adults/sti-1-3.aspx See also Antifungal therapies; Cervical cancer; Epidemiology of cancer; Epidermoid cancers of mucous membranes; Gene therapy; Infection and sepsis; Vulvar cancer. 585
Herpes zoster virus
u Herpes zoster virus Category: Diseases, symptoms, and conditions; carcinogens and suspected carcinogens Also known as: Varicella-zoster virus (VZV) Related condition: Shingles Definition: Herpes zoster is an infection caused by the same virus that causes chickenpox, the varicella-zoster virus (VZV). This virus remains in the nerve cells for life in people who had chickenpox or received the chickenpox vaccine. The virus reappears as herpes zoster (shingles) later in life—particularly in the elderly and immunocompromised persons. The virus is reactivated because the body loses its immunity to the varicella-zoster virus over time. Risk factors: People with certain types of cancers are at an increased risk of developing herpes zoster because of their altered immunity. People who had chickenpox or the chickenpox live-virus vaccine are at risk for developing herpes zoster. The risk increases as people get older— more than 50 percent of all people with herpes zoster are older than age sixty. Etiology and the disease process: Herpes zoster results when the latent VZV within the sensory ganglia is reactivated. The first signs of the disease are pain and a burning sensation on one side of the body. These symptoms may last several days. Then the skin reddens and blisters form on the skin on the affected side of the body for three to five days. The blisters will then ooze and crust, and begin to heal. The whole disease process takes between three and four weeks. The reactivation of VZV is higher in cancer patients because cell-mediated immunity in these patients is deficient as a result of chemotherapy or the disease itself. Also, a Russian case study found that the whole disease process is generally longer in cancer patients. Because the infection affects the nerves, herpes zoster can be painful. A common complication that occurs in half of older patients is postherpetic neuralgia (PHN). In postherpetic neuralgia patients, the rash and the pain are severe and last for months. Incidence: Each year, about 500,000 cases of herpes zoster are reported in the United States. One large study of primary care patients estimated that the annual incidence of herpes zoster was 2 per 1,000 persons. Symptoms: The appearance of herpes zoster is accompanied by pain in one side of the body along with tingling and 586
Salem Health: Cancer a burning sensation. The skin reddens and blisters appear. The small blisters are dense and deep and may ooze and crust. Other symptoms include headache, fever, chills, abdominal pain, joint pain, lymph node swelling, hearing loss, genital lesions, vision and taste problems, and a general feeling of malaise. Screening and diagnosis: The skin blisters and a prior history of varicella or shingles are the basis for diagnosis. Tests are rarely used; however, tests such as a viral culture of a blister can be used to identify the herpes zoster virus. Other tests include the following: • Tzanck test: The sore on the skin is scared, and the sample is stained for examination under a microscope. • Complete blood count (CBC): The blood is tested to look for nonspecific signs of infection such as an elevated number of white blood cells. • Immunoglobulin measurement: Blood is tested to measure the level of varicella antibodies. Treatment and therapy: Although the disease disappears on its own after a few weeks, treatment is usually necessary for pain. The antiviral medication acyclovir reduces pain and complications and protects immunocompromised individuals such as cancer patients. Other medicines that can be used are desciclovir, famciclovir, valacyclovir, and penciclovir. Treatment with these drugs should begin within twentyfour hours of the initial signs and, if possible, before blistering. Although these drugs are generally given as pills, some cancer patients may require intravenous acyclovir therapy if they are severely immunocompromised. Other suggestions for treatment are as follows: • Control the pain with analgesics and the itching with antihistamines. • Use a capsaicin-containing cream to prevent postherpetic neuralgia. • Keep the affected skin covered and dry. • Keep skin clean and do not reuse contaminated items. • Rest in bed and avoid contact with others. Prognosis, prevention, and outcomes: Usually herpes zoster lesions heal within two to three weeks after the first signs appear. Patients, especially the elderly, may experience a temporary or permanent weakness or paralysis or may develop a continued nerve pain that persists for years. If the eyes are affected, the person may become blind if not treated. In 2006, a live zoster vaccine was licensed and recommended for routine administration to adults over the age of sixty. However, the vaccine is not recommended for people taking immunosuppressive therapy, including high-
Salem Health: Cancer
Histamine 2 antagonists
Herpes zoster on a patient’s back. (Custom Medical Stock Photo)
dose corticosteroids, or for people with primary or acquired immunodeficiency states—including leukemia, lymphoma of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system—or acquired immunodeficiency (AIDS) or other clinical manifestations of infection with human immunodeficiency viruses. Diego Pineda, M.S. u
For Further Information American Academy of Pediatrics. “Varicella-Zoster Infections.” In Red Book: 2006 Report of the Committee on Infectious Diseases, edited by L. K. Pickering, C. J. Baker, S. S. Long, and J. A. McMillan. 27th ed. Elk Grove Village, Ill.: Author, 2006. Bogomolov, B. P., and E. G. Bakhur. “Herpes Zoster in Cancer Patients.” Ter Arkh 62, no. 1 (1990): 99-103. Gnann, John W., Jr., and Richard J. Whitley. “Herpes Zoster.” New England Journal of Medicine 347, no. 5 (August 1, 2002): 340-346. Oxman, M. N., et al. “A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults.” New England Journal of Medicine 352, no. 22 (2005): 22712284.
Siegel, Mary-Ellen, and Gray Williams. Shingles: New Hope for an Old Disease. Rev. ed. Lanham, Md.: M. Evans, 2008. u
Other Resources
MedicineNet.com Shingles (Herpes Zoster) http://www.medicinenet.com/shingles/article.htm National Institutes of Health Senior Health Shingles http://nihseniorhealth.gov/shingles/toc.html See also Paraneoplastic syndromes; Viral oncology; Virusrelated cancers.
u Histamine 2 antagonists Category: Chemotherapy and other drugs ATC code: A02BA Definition: Histamine 2 antagonists are drugs that block acid production in the stomach. 587
Histiocytosis X
Salem Health: Cancer
Side effects: Common side effects of histamine 2 antagonists include mild diarrhea, allergic reactions, flulike sympDelivery toms, and bruising or bleeding easily. Drug Brands Mode Cancers Treated Intravenous (IV) administration of histaCimetidine Tagamet Oral Multiple endocrine neoplasia (MEN), mine 2 antagonists has been associated Zollinger-Ellison syndrome, Barrett with rare cases of irregular heartbeat esophagus and elevated blood pressure. Histamine Famotidine Pepcid Oral MEN, Zollinger-Ellison syndrome, 2 antagonists may also reduce the body’s Barrett esophagus ability to absorb drugs that require an Nizatidine Axid Oral MEN, Zollinger-Ellison syndrome, acidic setting in the stomach in order to Barrett esophagus function. Ranitidine Zantac Oral, IV MEN, Zollinger-Ellison syndrome, Studies have shown that histamine Barrett esophagus can also promote the growth of certain colorectal cancer cell lines, with histamine 2 antagonists abrogating these effects and inducing tumor cell death. The Cancers treated: Multiple endocrine neoplasia (MEN), mechanism behind these observations, however, is not yet Zollinger-Ellison syndrome, Barrett esophagus understood. Elizabeth A. Manning, Ph.D. Delivery routes: These drugs are administered intravenously, or orally as tablets, capsules, chewable tablets, or See also Barrett esophagus; Endocrine cancers; Esophaliquids. geal cancer; Esophagectomy; Esophagitis; Gastrinomas; Gastrointestinal cancers; Human growth factors and tuHow these drugs work: Fluids in the stomach, composed mor growth; Hypercalcemia; Islet cell tumors; Multiple primarily of hydrochloric acid and enzymes that break endocrine neoplasia type 1 (MEN 1); Multiple endodown proteins, aid in the digestion of food. Hydrochloric crine neoplasia type 2 (MEN 2); Neuroendocrine tumors; acid secretion can be triggered when histamine binds to Pheochromocytomas; Pituitary tumors; Premalignancies; one of its receptors, the H2 receptor, located in the cells Thyroid cancer; Upper gastrointestinal (GI) endoscopy; lining the stomach (known as parietal cells). If the lower Zollinger-Ellison syndrome. esophogeal sphincter (the muscle between the stomach and the esophagus) is not working correctly, then stomach acids may flow into the esophagus, resulting in heartburn and esophageal cell damage. Prolonged exposure to stomu Histiocytosis X ach acid in the esophagus can lead to gastroesophageal reflux disease (GERD). Category: Diseases, symptoms, and conditions Histamine 2 antagonists are competitive and reversible Also known as: Langerhans cell histiocytosis, inhibitors of histamine, blocking its ability to bind to the eosinophilic granuloma, pulmonary histiocytosis X H2 receptor and therefore decreasing stomach acid pro(PHX), eosinophilic granulomatosis, pulmonary duction, reducing the risk of acid reflux, and helping preLangerhans cell histiocytosis X (PLCH), Langerhans vent ulcers in the stomach and small intestine. cell granulomatosis Histamine 2 antagonists may be used to treat multiple Related conditions: Non-Langerhans cell histiocytosis, endocrine neoplasia (MEN) and Zollinger-Ellison synT-cell lymphoma (malignant histiocytosis syndrome) drome, which are conditions in which tumors within the digestive tract stimulate excess stomach acid production. Definition: Histiocytosis X, now generally called LangBarrett esophagus, a precancerous condition in which norerhans cell granulomatosis (LCG) or Langerhans cell hismal cells lining the esophagus are damaged as a result of tiocytosis (LCH), is characterized by granulomatous leGERD and replaced with abnormal or cancerous cells, sions containing Langerhans cells. Histiocytosis X is a may also be treated with histamine 2 antagonists. Addigroup of diseases that exhibit an increase in histiocytes. tionally, histamine 2 antagonists may be administered Variants of the condition may be localized or systemic. prior to chemotherapy to help manage gastrointestinal side Once considered cancerous, these diseases are now classified as autoimmune diseases. effects.
Histamine 2 Antagonists
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Salem Health: Cancer Histiocytes are cells critical to the immune response and arise from the mononuclear phagocytic system in the bone marrow. These precursor cells have the potential to transform into macrophage or Langerhans cell lineages. Langerhans cells engulf antigens such as foreign microbes and then alert the immune system to their presence. Histiocytosis X now includes Letterer-Siwe disease and Hand-Schüller-Christian disease. These conditions, seen in children, were once considered separate diseases. When children are afflicted, the disease erupts in many organs, while in adults the condition affects primarily the lung and more rarely the bones (about 4 to 20 percent of cases) and, even less likely, the skin. Risk factors: Risk factors include smoking and possibly genetic factors, but the exact etiology is unknown. Etiology and the disease process: The defining pathology is an accumulation of Langerhans cells in epithelial cells lining the lung tissue. These lung-tissue cells first undergo an increase in their numbers (hyperplasia) following some chronic insult, such as persistent smoking, then begin an uncontrolled immune response. The result and hallmark of this disease are discrete granulomatous lesions scattered through the upper and middle portions of the lung. These lesions are composed, in the early stages, mostly of Langerhans cells surrounded by eosinophils, lymphocytes, macrophages, and plasma cells. Granulomatous lesions are similar in the pediatric version of the disease but are scattered through the viscera, skin, and bones. Although the disease process in children includes the classic lung pathology, it also results in skin and bone lesions and, typically, an enlarged liver and spleen. There are also severe dental consequences such as inflamed gums, loss of teeth, and mandibular hyperplasia. Incidence: In the United States, the condition afflicts 1 in 250,000 children and 1 in 1 million adults. Langerhans cell granulomatosis represents approximately 1 percent of all interstitial lung disease. Most adult patients are between twenty and forty years old and have a history of smoking, while the childhood disease is most prevalent between ages one and three. Most cases of the disease occur before age seventeen. Symptoms: Adults may first complain of a persistent cough, lethargy, and labored breathing. Less frequently there is an associated weight loss, fever, and a vague feeling of illness, but, surprisingly, about 25 percent of cases are symptom free. The classic finding is pneumothorax, a collection of air in the plural cavity, which may eventually
Histiocytosis X cause the lung to collapse. This occurs in as many as 10 to 20 percent of cases. Typical symptoms may include cough, chest pain, fever, weight loss, bone pain, and skin rash. In young children, symptoms may vary with the severity of organ compromise. In the form called Letterer-Siwe disease, there is a generalized involvement of the viscera with potentially fatal consequences. Skin lesions range from small papules to hemorrhagic nodules. Oral symptoms include ulcerations, bruising, gum inflammation, and tooth loss. Fetid breath odor is a conspicuous result. Other symptoms reflect organ and tissue damage in the liver, spleen, and bones. Typical symptoms may include weight loss, fever, abdominal pain, jaundice, dermatitis, mental deficits, short stature, abdominal pain, ear drainage, and enlarged lymph nodes. Another childhood variation, Hand-Schüller-Christian disease, manifests itself in three ways: diabetes insipidus, lytic bone lesions, and a bulging of the eyes called proptosis. This condition also results in a dental pathology similar to Letterer-Siwe disease. Screening and diagnosis: In the adult form of the disease, the symptoms are nonspecific and reflect interstitial lung disease, which may be common to other conditions. Chest imaging including high-resolution computed tomography (CT) scans is useful in revealing nodules, and pulmonary function tests may uncover obstructive irregularities. Additionally, the results of bronchoalveolar lavage and a history of smoking may prove useful indicators, but they are not definitive. Only lung tissue biopsy will confirm the diagnosis. In children, bone radiographs, tissue and bone marrow biopsy, and general laboratory work are instructive, but biopsies containing clusters of Langerhans cells are required for a diagnosis. Treatment and therapy: The cardinal treatment is smoking cessation in the adult. Corticosteroid therapy is case dependent and is used only in patients with notable lung function deficits. In the childhood form of the disease, there has been notable success using immune-signaling molecules such as interleukins, and research is investigating their potential in the adult form of the disease. Other treatment options are palliative, such as infection control, supplemental oxygen, and bronchodilator therapy. Asymptomatic patients having only mild impairment are treated conservatively. Prognosis, prevention, and outcomes: Smoking cessation may halt the progression of the disease and possibly 589
HIV/AIDS-related cancers initiate its reversal. For the very young and the elderly, the prognosis is poor. This is also the case for those who have been treated with corticosteroids over an extended period, in patients suffering from multiorgan involvement, and when there are an extensive number of cysts revealed radiographically. When the disease involves only the lung and smoking is stopped, 50 percent of patients will improve (or at least get no worse), while 50 percent will suffer permanent pulmonary function loss. The outcome in children ranges from poor to excellent depending on the extent of the disease. Richard S. Spira, D.V.M. u For Further Information Andersson, B. U., E. Tani, U. Andersson, and J. I. Henter. “Tumor Necrosis Factor, Interleukin 11, and Leukemia Inhibitory Factor Produced by Langerhans Cells in Langerhans Cell Histiocytosis.” Journal of Pediatric Hematology Oncology 26, no. 11 (2004): 706-711. Broadbent, V., H. Gadner, D. M. Komp, and S. Ladisch. “Histiocytosis Syndromes in Children: II. Approach to the Clinical and Laboratory Evaluation of Children with Langerhans Cell Histiocytosis.” Medical and Pediatric Oncology 17, no. (1989): 492-495. Friedman, P. J., A. A. Liebow, and J. Sokoloff. “Eosinophilic Granuloma of Lung: Clinical Aspects of Primary Pulmonary Histiocytosis in the Adult.” Medicine 60 (1981): 385. Travis, W. D., et al. “Pulmonary Langerhans Cell Granulomatosis (Histiocytosis X): A Clinicopathologic Study of Forty-eight Cases.” American Journal of Surgical Pathology 17 (1993): 971.
u
Other Resources
MedlinePlus Histiocytosis http://www.nlm.nih.gov/medlineplus/ency/article/ 000068.htm University of Maryland Medical Center Histiocytosis http://www.umm.edu/ency/article/000068.htm See also Fibrosarcomas, soft-tissue; Pediatric oncology and hematology; Primary central nervous system lymphomas.
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u HIV/AIDS-related cancers Category: Diseases, symptoms, and conditions; carcinogens and suspected carcinogens Also known as: AIDS-associated Kaposi sarcoma Related conditions: Kaposi sarcoma (KS), lymphoma, progressive multifocal leukoencephalopathy (PML) Definition: The immunodeficiency associated with advanced human immunodeficiency virus (HIV) disease can give rise to a variety of cancers. HIV infection does not appear to cause cancer directly, though some researchers have suggested HIV is capable of altering the regulation of certain types of oncogenes. The most common cancer related to acquired immunodeficiency syndrome (AIDS) is Kaposi sarcoma, a form of the disease that arises from cells of mucous membranes or tissues lining lymphatic vessels. Other types of cancers observed more frequently among HIV-positive individuals include progressive multifocal leukoencephalopathy (PML), which results from the activation of a human papovavirus; non-Hodgkin lymphoma; and squamous cell carcinomas. A variety of other forms of tissue-specific cancers, including those of the liver and lung, are also observed with greater frequency among AIDS patients. Risk factors: Intravenous drug users and hemophiliacs, as well as those who engage in unprotected sex (especially with multiple partners), are at high risk of contracting HIV. The form of cancer that is likely to develop as a result of HIV infection is a function of the means of transmission of the virus. Kaposi sarcoma is associated with transmission through sex and is found primarily in gay men. Other forms of AIDS-related cancers are the result of immunosuppression, in particular the reduced level of CD4+ Tlymphocyte helper cells, and are not limited to those who became infected with HIV through sexual means. Etiology and the disease process: Both Kaposi sarcoma and progressive multifocal leukoencephalopathy have a viral etiology. Since Kaposi sarcoma is most commonly found in gay men rather than among HIV-positive hemophiliacs or in populations of intravenous drug abusers, HIV researchers long suspected it was a sexually transmitted disease with a viral etiology. In 1994, a newly discovered agent, later termed human herpesvirus 8 (HHV-8), was determined to be the cause of HIV-related Kaposi sarcoma. While the virus is relatively common, it appears to replicate in the white cell population of immunosuppressed individuals, eventually triggering the development of Kaposi sarcoma. The increased diagnosis of Kaposi sarcoma
Salem Health: Cancer in people with an immune system weakened by mechanisms other than AIDS lends support to the hypothesis. The induction of Kaposi sarcoma in AIDS patients appears to result from an interaction between the two viruses, HIV and HHV-8. Among the gene products produced by HIV is a transactivation protein, TAT, which acts to induce endothelial cell growth. HHV-8 in turn encodes a number of cytokines that likewise stimulate cell division within the skin. At the same time, angiogenesis factors are produced that induce blood-vessel production within the developing tumor. The result is a substantial blood supply that produces the purplish lesions common in Kaposi sarcoma. The fact that Kaposi sarcoma is more common in men than in women suggests that hormonal factors may also play a role in the process. Several forms of lymphomas, either non-Hodgkin lymphomas (NHL) or, less commonly, Hodgkin disease, as a group represent the second most common type of AIDSrelated cancers. Although a viral etiology is suspected for some lymphomas, including Hodgkin disease, the actual cause of these illnesses has yet to be firmly established. In some cases, the underlying cause has been shown to be mutations of certain oncogenes. Progressive multifocal leukoencephalopathy is caused by a member of the human papovavirus family, the Jamestown Canyon virus, carried by many individuals within the central nervous system. Disease associated with the virus is rare, limited almost entirely to persons with a defective immune system. The means of activation of this virus is unclear. Incidence: Approximately 40 percent of persons with advanced HIV disease will develop cancer. The most common form is Kaposi sarcoma, developing in some 20 percent of HIV-infected persons. Before the onset of the AIDS epidemic in the 1970’s, the incidence of Kaposi sarcoma within the population of the United States was about 0.3 per 100,000 people. The incidence peaked nationally at 8.9 per 100,000 by the end of the 1980’s, with the incidence as high as 32 per 100,000 in cities such as San Francisco. Since then, Kaposi sarcoma numbers have decreased, the result of the introduction of antiretroviral therapy as well as in the decrease in numbers of individuals newly infected with HIV. In San Francisco, for example, the incidence of Kaposi sarcoma had dropped to a level of 2.8 per 100,000 by the year 2000. The number of people affected by Kaposi sarcoma remains high in areas of the world such as Africa and Asia, where HIV infection remains common and treatment is minimal. As with Kaposi sarcoma, the incidence of lymphomas showed a significant increase in the 1980’s as a result of
HIV/AIDS-related cancers the AIDS epidemic. The incidence of non-Hodgkin lymphomas rose from a level of 10.7 per 100,000 in the mid1970’s to a peak of 31.4 per 100,000 in the mid-1990’s. The introduction of antiretroviral therapy as well as a leveling and reduction in the numbers of new cases of HIV infection resulted in a decline of such lymphomas to 21.6 per 100,000 by the end of the twentieth century. About 5 percent of HIV-positive persons are estimated to develop progressive multifocal leukoencephalopathy. The actual incidence is unclear because diagnosis is often made during autopsy, resulting in a likely underreporting of the precise number. Symptoms: Kaposi sarcoma associated with AIDS is a particularly aggressive form of the disease. A spreading purplish lesion is often the first indication of Kaposi sarcoma, particularly if the individual has been determined to be HIV-positive. Lymphomas usually begin as lumps or tumors in lymph nodes, with confirmation based on biopsy. Evidence for progressive multifocal leukoencephalopathy is symptomatic, based on evidence of neurological deterioration: mental disturbances, ataxia, and loss of speech, sight, and other senses. Screening and diagnosis: A preliminary diagnosis of Kaposi sarcoma is most commonly based on the appearance of purplish lesions. A histological examination of biopsy material is used to confirm the diagnosis. The staging system for Kaposi sarcoma differs from that for other cancers that define a stage based on the size or metastasis of the cancer. Staging of Kaposi sarcoma attempts to take into
A Snapshot of AIDS Worldwide, 2007 HIV-Infected People Total Adults Women Children under age 15
33.2 million 30.8 million 15.4 million 2.5 million
Deaths Adults Children under age 15
1.7 million 330,000
New Cases Total Adults Children under age 15
2.5 million 2.1 million 420,000
Source: AIDS Epidemic Update, World Health Organization, December, 2007
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Skin plaques due to Kaposi sarcoma on the right arm and chest of a patient with AIDS. (Dr. M. A. Ansary/Photo Researchers, Inc.)
account the extent of immunosuppression as well as the characteristics of the sarcoma by using three criteria: the size or extent of the tumor (T), the level of CD4 cells (I), and the extent of illness (S). Each category has two subgroups, defined as 0 (good risk) or 1 (poor risk). Diagnosis of the type of non-Hodgkin lymphoma is based on identification of the “appropriate” cell from biopsy material. Staging is based on the Ann Arbor system: • Stage I: Cancer is limited to a single site or organ and has not spread. • Stage II: Cancer is limited to two lymph node groups or organ in the same region but has begun to spread. • Stage III: Cancer is in two lymph node groups with possible involvement of an organ. • Stage IV: Cancer has spread beyond the initial site. Treatment and therapy: Since development of AIDSrelated cancer is the result of the immunosuppression that 592
Salem Health: Cancer follows HIV infection, any form of chemical treatment is carried out in conjunction with reversal, even if temporary, of the immunosuppressive state. Treatment of the immunosuppressive state involves a combination of drug cocktails—highly active antiretroviral therapy (HAART)— that do not cure the disease but may inhibit replication of the virus for varying periods of time. Treatment of Kaposi sarcoma depends on the extent of the cancer, including whether metastasis has taken place. If the cancer is localized, radiation or surgery may be sufficient, such as Kaposi sarcoma localized to the skin or mouth. However, Kaposi sarcoma frequently develops at multiple sites or has already spread by the time of diagnosis, requiring the use of anticancer chemotherapeutic agents such as doxorubicin, daunorubicin, or paclitaxel. Among the more promising forms of chemotherapy are those that inhibit angiogenesis, the formation of blood vessels. Combinations of therapy that include drugs to enhance the immune response are also being tested. Treatment of non-Hodgkin lymphoma also depends on reducing the viral load and restoring a level of immune function. Following HAART, radiation or chemotherapy is the preferred treatment. Generally chemotherapy uses a combination of drugs—cyclophosphamide, hydroxydoxorubicin/doxorubicin, vincristine (Oncovin), and prednisone (CHOP protocol)—as well as selective combinations. Other treatments have adapted forms of immunotherapy in conjunction with chemotherapy, including the use of monoclonal antibodies. Treatment of progressive multifocal leukoencephalopathy is problematic and historically has involved the direct infusion of drugs into the brain. However, HAART treatment, if successful, frequently results in the spontaneous remission of the disease. Prognosis, prevention, and outcomes: The prognosis for AIDS-related Kaposi sarcoma patients is a function of the extent of spread. If the tumor has been caught early and immune function has improved, the recovery rate is high. Once the disease has spread, however, the chances for recovery become increasingly poor. The likely prognosis of non-Hodgkin lymphoma is based on the International Prognostic Index, which takes into account factors such as age, the stage of the disease, and the extent of overall general health, including the state of immunosuppression. If all factors are optimal, especially the level of immune function, approximately 75 percent of patients survive five years or more. Prognosis in progressive multifocal leukoencephalopathy patients remains poor. Before the development of HAART, 90 percent of patients died within three months
Salem Health: Cancer of diagnosis. Even in the presence of therapy, the mortality rate remains approximately 50 percent within several months of diagnosis. Richard Adler, Ph.D. u For Further Information Cockerell, Clay, and Alvin Friedman-Kien. Color Atlas of AIDS. Philadelphia: W. B. Saunders, 1996. Feigal, Ellen, et al., eds. AIDS-Related Cancers and Their Treatment. New York: Marcel Dekker, 2000. Pelengaris, Stella, and Michael Khan, eds. The Molecular Biology of Cancer. Malden, Mass.: Blackwell, 2006. Stine, Gerald. AIDS Update: 2007. New York: McGrawHill, 2007. u
Other Resources
The Body: The Complete HIV/AIDS Resource Cancer in the HIV-Infected Population http://www.thebody.com/content/art16834.html National Cancer Institute Kaposi Sarcoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ kaposis/patient National Organization for Rare Diseases Progressive Multifocal Leukoencephalopathy Http://www.rarediseases.org/search/rdbdetail_ abstract.html?disname=Progressive%20Multifocal %20Leukoencephalopathy See also Africans and cancer; Anal cancer; Anoscopy; Antiviral therapies; Blood cancers; Bone cancers; Castleman disease; Cervical cancer; Developing nations and cancer; Dry mouth; Epstein-Barr virus; Gastrointestinal cancers; Hepatitis C virus (HCV); Herpes simplex virus; Hodgkin disease; Immunoelectrophoresis (IEP); Infectious cancers; Kaposi sarcoma; Leiomyosarcomas; Leukoplakia; Lymphomas; Medical marijuana; Merkel cell carcinomas (MCC); Moles; Night sweats; Oncogenic viruses; Organ transplantation and cancer; Pneumonia; Poverty and cancer; Proteasome inhibitors; Proto-oncogenes and carcinogenesis; Risks for cancer; Squamous cell carcinomas; Statistics of cancer; Viral oncology; Virus-related cancers.
Hodgkin disease
u Hodgkin disease Category: Diseases, symptoms, and conditions Also known as: Hodgkin’s disease, Hodgkin lymphoma, HD Related condition: Mononucleosis Definition: Hodgkin disease is the malignant growth of abnormal immune cells called lymphocytes in the lymphatic system—a critical part of the body’s immune system. There are two main types of lymphocytes, B and T. The malignant cells in Hodgkin disease are usually (in 98 percent of the cases) the B lymphocytes. There are five types of Hodgkin disease: nodular lymphocyte-predominant Hodgkin lymphoma and four classic types: • Nodular sclerosing Hodgkin lymphoma • Mixed-cellularity Hodgkin lymphoma • Lymphocyte-depletion Hodgkin lymphoma • Lymphocyte-rich Hodgkin lymphoma These five types differ mostly in how they look under a microscope. However, nodular lymphocyte-predominant Hodgkin lymphoma also behaves differently from the classic types. Risk factors: The risk for Hodgkin disease depends on gender, age, race, medical condition, and family history. The disease is more common in men, and the difference is particularly evident in children younger than age ten, with the number of boys with the disease up to four times the number of girls with the disease. With the exception of nodular lymphocyte-predominant Hodgkin lymphoma, the risk of developing the disease is highest in young adulthood and in later life. The risk for nodular lymphocytepredominant Hodgkin lymphoma is highest in a person’s thirties and forties. Hodgkin disease is more common in whites, and infection with the Epstein-Barr virus (EBV), which causes infectious mononucleosis, increases a person’s risk of developing Hodgkin disease up to four times that of a person who has not had Epstein-Barr. Having a first-degree relative with Hodgkin disease increases the risk for the disease. The identical twin of a Hodgkin patient has one hundred times the risk of developing this cancer compared with the general population. Etiology and the disease process: The causes of Hodgkin disease are unclear. There are no known chemicals or environmental factors that increase the risk of Hodgkin. However, in some cases, a good argument can be made for a combination of genetics and infection with the EpsteinBarr virus as causing the disease. EBV infects the majority of the world’s population—estimates put the infection 593
Hodgkin disease
Salem Health: Cancer
Incidence of Hodgkin Disease per 100,000 People, by Gender 3.5 3.2
Women
Men
3.0
2.8
2.8
Hodgkin disease spreads through the lymphatic system and, in advanced disease, blood vessels. It invades the lungs, bones, bone marrow, and liver. The presence of Hodgkin anywhere else usually means the patient has an HIV infection, which makes Hodgkin disease behave differently.
2.6
Incidence: New cases of Hodgkin disease occur in roughly 8,000 people each year. The incidence rate has been decreasing slightly over the past several decades. Hodgkin disease makes up 5 percent of childhood cancers and approximately 1 percent of adult cancers.
2.5 2.1 2.0 1.7 1.5
1.4
Symptoms: Swollen lymph nodes are often the first sign of Hodgkin disease. 1.0 In most cases, the swollen nodes will be above the diaphragm, in the chest or neck. Sometimes there are no symp0.5 toms, but people may feel pain in the affected nodes after drinking alcohol. The 0.0 tumors in Hodgkin can get fairly large White Hispanic Black Asian/Pacific and may cause symptoms such as diffiIslander culty swallowing and breathing. Itching, sometimes severe, can precede the deSource: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 velopment of Hodgkin disease by sevNote: Based on cases diagnosed in 2000-2004 eral years. Systemic symptoms that indicate a disease that is more serious are as follows: rates at 90 percent of adults worldwide. Not all infected Persistent fever higher than 38 degrees Celsius (100.4 • people develop signs of EBV infection. The virus infects degrees Fahrenheit) B lymphocytes and is thought to cause other types of can• Weight loss of more than 10 percent of the total body cer as well, including Burkitt lymphoma, another type of weight in six months immune system cancer. Malignant cells of Hodgkin disease • Drenching night sweats patients often carry EBV deoxyribonucleic acid (DNA). At the heart of Hodgkin disease are two types of large, Screening and diagnosis: Diagnosing Hodgkin disease abnormal cells. One type is the Reed-Sternberg cell, and requires a complete medical history and a number of the other is the Hodgkin lymphoma cell. Hodgkin disease tests. These tests include a complete blood count (CBC) patients usually have tumors made up of these cells and into look at the different cells in the blood and their levels; flammatory immune cells that surround them. The excepan erythrocyte sedimentation rate (ESR) test to see how tion is nodular lymphocyte-predominant Hodgkin lymfast blood cells settle to the bottom of a test tube and phoma, in which there are hardly any Reed-Sternberg thereby detect possible infection, cancer, or a bone marcells. Instead, this type of Hodgkin disease has typical abrow problem; a bone marrow biopsy; a fine-needle or normal cells known as “L and H” or “popcorn cells.” surgical biopsy of the affected nodes; plus X-ray, comThe abnormal cells, surrounded by inflammatory cells, puted tomography (CT), and positron emission tomogcreate tumors that usually start in lymph nodes in the chest raphy (PET) scans. Though surgery to determine the stage or neck. These tumors cause the swollen glands that are of the cancer is no longer standard, some patients may usually the first sign of the disease. still need it if the affected areas are hard to reach or hard 1.0
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Salem Health: Cancer
Hodgkin disease
to see or sample with nonsurgical techniques. Staging of Hodgkin disease is done according to criteria established in Ann Arbor, Michigan, and modified in Cotswolds, England. The staging system is known as either the modified Ann Arbor system or the Cotswolds classification system. The stages are as follows: • Stage I: The cancer affects only one lymph node or one area of the body but no lymph nodes. If an area outside the lymph node is affected, with no lymph node involvement, the letter E is added to the stage designation. Stage I may also be the presence of cancer in one lymphatic organ, such as the spleen or thymus, without the involvement of lymph nodes or Lymphadenopathy in the groin of a man with Hodgkin disease caused this swelling in his lower legs (Dr. P. Marazzi/Photo Researchers, Inc.) other areas in the body. Stage II: The cancer is in two or more • lymph node areas on the same side of the Risk factors for early-stage (Stages I and II) adult Hodgdiaphragm (above or below). Alternatively, one lymph kin disease include the following: node area and the part of the body with which it is associated are affected (IIE). A subscript next to the stage num• The presence of a tumor larger than 10 centimeters (cm; 3.9 inches) in size ber indicates the number of lymph node regions involved (for example, Stage II3). • The presence of systemic symptoms Stage III: The cancer has invaded lymph node areas on • An ESR value greater than 50 • both sides of the diaphragm (above and below). In addi• Cancer outside the lymph nodes tion, the areas of the body connected to the affected nodes • Cancer in three or more lymph nodes For advanced disease in adults (Stage III and IV), the may also be affected (IIIE), the spleen may be affected risk factors are as follows: (IIIS), or both conditions may occur (IIIE + S). Two subdivisions of Stage III exist, denoting the extent of the disease • Age older than forty-five years in the abdominal area and the spleen. • Male gender Stage IV: There are several tumors in one or more ar• Serum albumin levels lower than 4 grams/deciliter (this • is a measure of the levels of the most important protein in eas of the body outside the lymph nodes. The associated the blood) lymph nodes may or may not have cancer in them. Alternatively, there may be cancer in one area of the body and a • Hemoglobin levels below 10.5 grams/deciliter nonrelated (distant) lymph node region. • High white cell count A designation of A or B is added to each stage; a B des• Low lymphocyte count ignation means the patient has systemic symptoms. • Stage IV disease Four categories determine treatment: Treatment and therapy: Oncologists decide on treat• Early-stage favorable: Stage I or II disease with no risk factors ment for Hodgkin disease according to the predicted behavior of the disease. This predicted behavior depends not • Early-stage unfavorable: Stage I or II with one or more early-stage risk factors only on the stage of the cancer but also on several risk factors. The presence of these risk factors usually means the • Advanced favorable: Stage III or IV with up to three advanced-stage risk factors disease will be harder to control, and patients are likely to relapse unless they receive more intense or longer treat• Advanced unfavorable: Stage III or IV with four or more advanced-stage risk factors ment. Therefore, even in early-stage Hodgkin, some paTreatment for early-stage favorable disease consists of tients may require treatments similar to those given to patients with advanced disease. short-duration chemotherapy with radiation to the affected 595
Hodgkin disease areas or a longer duration of chemotherapy without radiation. The current standard chemotherapy regimen, known as ABVD, uses a combination of four drugs: doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine. Another common regimen, though less effective and more likely to cause infertility, is MOPP: mechlorethamine, vincristine (Oncovin), procarbazine, and prednisone. Other combinations of chemotherapy drugs are also available. Treatment of early-stage unfavorable disease consists of radiation to the affected site and four to eight cycles of chemotherapy. Advanced disease is treated with chemotherapy combinations. Patients who do not respond to treatment, or respond and relapse, can still be cured by high-dose chemotherapy treatment followed by a transplant of their own stem cells. Harvesting of stem cells is done before beginning the highdose chemotherapy. The stem cells are then transplanted back to produce healthy red and white blood cells. Risk factors in children are the same as those of the adult early-stage risk factors. Treatments in children are different in intensity of radiation and the drug combinations used in chemotherapy. For example, in drug protocols for boys, etoposide is substituted for procarbazine because procarbazine induces sterility. Because Hodgkin disease often strikes during the childbearing years, the question of treatment during pregnancy may arise. Treatment decisions for pregnant patients are individualized and depend on the stage of the disease, the stage of the pregnancy, and the mother’s preferences. In many cases, treatment of Hodgkin can be delayed until the end of the pregnancy, unless life-threatening symptoms occur. Early labor might be induced to allow for earlier start of treatments. Case reports also show that women receiving radiation treatments to the upper body, with heavy shielding of the fetus, deliver healthy babies with no apparent abnormalities. However, there is possibly a danger of future cancer in the child, resulting from stray radiation that may have penetrated the shield. Chemotherapy treatments with vinblastine during the second part of the pregnancy are safe and effective, as is the ABVD combination treatment. The ABVD regimen during the first trimester may harm the fetus. Prognosis, prevention, and outcomes: Hodgkin disease has a high cure rate. The total cure rate is approximately 75 percent in adults, and nearly 95 percent in children. Because Hodgkin is highly curable, more and more patients find themselves facing late complications of treatment years after their disease had disappeared. Late com596
Salem Health: Cancer plications include infertility, hypothyroidism, and lowered immunity. A particularly worrisome late complication is the development of secondary cancers, including leukemia as well as breast, skin, and lung cancers. Death in the first fifteen years following a Hodgkin diagnosis is usually due to the primary cancer. After fifteen years, death is more often due to secondary cancers. Adi Ferrara, B.S. u
For Further Information Dores, G. M., T. R. Coté, and L. B. Travis. “New Malignancies Following Hodgkin Lymphoma, Non-Hodgkin Lymphoma, and Myeloma.” In New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000, edited by R. E. Curtis et al. NIH Publication 05-5302. Bethesda, Md.: National Cancer Institute, 2006. Holman, Peter, Jodi Garrett, and William Jansen. One Hundred Questions and Answers About Lymphoma. Sudbury, Mass.: Jones and Bartlett, 2004. Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Adult Hodgkin’s Disease: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002.
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Other Resources
American Cancer Society Learn About Hodgkin Disease http://www.cancer.org/docroot/lrn/lrn_0.asp National Cancer Institute Hodgkin Lymphoma http://www.cancer.gov/cancertopics/types/ hodgkinslymphoma See also Agent Orange; Blood cancers; Childhood cancers; Eye cancers; Fever; Hematologic oncology; HIV/ AIDS-related cancers; Imaging tests; Infertility and cancer; Lymphomas; Mantle cell lymphoma (MCL); Mediastinal tumors; Mediastinoscopy; Non-Hodgkin lymphoma; Oncogenic viruses; Pericardial effusion; Pheresis; Pregnancy and cancer; Protein electrophoresis; Splenectomy; Surgical biopsies; Thymus cancer; Viral oncology; Young adult cancers.
Salem Health: Cancer
u Home health services Category: Social and personal issues Definition: Home health services are skilled and support services delivered in the home or residence of the patient or caregiver that promote, maintain, or restore health or minimize the effects of disability and illness. History: At one time, the poor were sent to the hospital while the wealthy received health care services in the comfort of their homes. Physicians made house calls and nurses made home visits. Both provided health care services and education. These nurses became known as public health or visiting nurses. In the twenty-first century, home health services are still provided in the patient’s residence, but the technology, costs, and scope of services have changed. Coming home: Cancer patients are often discharged from hospitals while still recovering from illness or surgery. Supportive skilled services and treatments by the home health care team make it possible for cancer patients to heal in the comfort of their homes. Home health care agencies provide intermittent skilled and nonskilled home care services as indicated by the patient’s diagnosis, medical orders, and insurance reimbursement. The home care team usually includes a multidisciplinary group of professionals such as registered nurses, nursing assistants/home health aides, physical therapists, respiratory therapists, occupational therapists, speech therapists, and medical social workers. Sometimes agencies also include chaplains and volunteers. Staff members work together to provide holistic health services in the home, with the physician providing oversight through the medical care plan. Most home care agencies provide home health services for Medicare patients as well as private insurance and selfpay patients. To qualify for home health care services under Medicare, the patient must meet the following criteria: • Require a skilled service by a registered nurse, physical therapist, or occupational therapist. • Meet guidelines as a homebound patient due to illness or injury. The patient does not have to be bed-bound but must require considerable assistance or use a supportive device, such as a wheelchair or walker, to get around. The patient is able to leave the home only on a limited basis, usually for doctor office visits. • Be under the care of a qualified physician who provides written medical orders to the home care agency for skilled care services and treatments.
Home health services
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Receive home health services from a certified home care agency, subject to state and federal requirements and inspection. Types of home health services: The interdisciplinary team of professionals coordinates the skills and knowledge needed to provide a comprehensive approach to home health services. Services may vary based on the needs of the cancer patient and the reimbursement. Services are provided on an intermittent basis (usually several times a week) so the caregiver remains the person responsible for daily continuous care. Home health services are not meant to be custodial or long term. Skilled nursing services are provided by a registered nurse (R.N.). The nurse usually coordinates care and develops the patient’s plan of care. Nurses provide infusion therapy in the home for intravenous antibiotics, chemotherapy, or home parenteral nutrition (HPN). They support the patient and caregiver with teaching. They provide pain management and medication information. The R.N. supervises the home health aide who gives personal care to the patient in the home. Also, the nurse assesses ongoing problems and addresses these promptly. Home safety is important for effective home health services. Physical therapists provide physical therapy to homebound patients with the goal of restoring function, encouraging independence, and minimizing decline. Physical therapists teach patients and caregivers how to maintain gains in function and prevent further injury. Occupational therapists are key to enabling homebound patients to perform activities of daily living, such as bathing, dressing, feeding, or toileting. They may help redesign the placement of kitchen dishes and utensils to allow the patient with decreased functional ability to carry on daily chores. These professionals teach the patient how to use adaptive equipment such as a prosthesis. The goal is for the patient to attain the highest level of functioning possible. Speech therapists work with patients who have suffered strokes, are neurologically compromised, or are having trouble swallowing or communicating, as is common among patients with cancers of the lips, mouth, or throat. Again, the goal is optimal function of the patient in normal routines. Home health aides can make all the difference in the success of home health services. These caregivers are supervised and directed by the R.N. while providing personal hygiene care such as bathing, dressing, feeding, washing hair, or helping the patient walk. Sometimes they provide light housekeeping or a simple meal if these tasks are covered by the insurance provider. Many patients and 597
Home health services caregivers report that the home health aide is the most helpful of all home health service providers. Medical social workers assist cancer patients and caregivers to assess resources available in the community. Their skills are valuable as they facilitate referrals to other services, provide counseling and support, and act as patient advocates. Registered dietitians and nutritionists may provide education for the patient and caregiver. These professionals are especially important if the patient is receiving an infusion of home parenteral nutrition (nutrition introduced nonintestinally, such as intravenously). They also can teach patients and caregivers critical aspects of diet and nutrition related to their cancer. An infusion therapy company may provide infusion therapy products and equipment, becoming an important part of the home health care team. Once infusion therapy was provided only in a hospital setting, but now it is a part of home care services. Intravenous antibiotics, chemotherapy, or home parenteral nutrition is delivered through an infusion pump within the residence. Specimens for tests ordered by the physician can be
Salem Health: Cancer collected in the home. Samples can be taken by a registered nurse or phlebotomist. Lab tests can vary from routine blood counts to monitoring of medication/drug levels needed for the treatment plan. Home medical equipment providers play a critical role in home health services. Specialized equipment provided in the home can make care of the patient more efficient and ease the physical stress on the caregiver. Typical equipment needs in the home include special beds designed for home use, walkers, wheelchairs, wound and ostomy supplies, catheters, bed pads for incontinence, and oxygen therapy and supplies. Volunteers may be a part of the home health care service. They can provide a range of services such as cooking, cleaning, emotional support, providing transportation, making phone calls, or providing respite care while the caregiver rests or runs errands. These services are needed in the home but rarely are covered under the reimbursement insurance. Chaplains are sometimes a part of the home care team, especially in a specialized home health service called hospice for terminally ill patients. These professionals pro-
A home health care team makes it possible for cancer patients to manage their disease in the comfort of their homes. (Digital Stock)
598
Salem Health: Cancer vide spiritual support to the patient, caregiver, and home care staff. Skilled vs. custodial health care services: Some cancer patients may not need a skilled service provided by professionals but may require support services to continue to stay in their homes. These services are considered custodial services and are usually not covered by Medicare or private insurance. Community or private agencies may provide support services such as private duty nurses or sitters to stay with the patient for shifts of eight to twelve hours, live-in companions, or home-delivered meals. Some pharmacies provide delivery services for medications. Groceries can be delivered to the home. These types of services are generally considered out-of-pocket expenses and are paid for by the patient, caregiver, or both. These services, however, can help the patient stay in the home environment. Medical social workers from a home health care agency are available to assess patient needs and make necessary referrals to community agencies. Nontraditional therapy at home: Cancer patients may choose to pay for nontraditional care services delivered in their homes. Therapies and services that may be available to homebound patients include massage therapy, podiatrist services, and acupuncture services. Engaging in relaxation therapies such as yoga, meditation, tai chi, or guided imagery may be useful to reduce stress. Patients may choose to investigate or use herbal or vitamin supplements, but they should discuss any supplement with their health care provider before adding these to the mediations already prescribed; certain medication interactions can occur when supplements are taken with prescribed drugs. For their safety and optimal health outcome, patients are advised to discuss alternative therapies with their health care provider. Marylane Wade Koch, M.S.N., R.N. u
For Further Information Balinsky, Warren L. Home Care: Current Problems and Future Solutions. San Francisco: Jossey-Bass, 1994. Cannon, Geneva. Caring for Your Loved One Who Is Ill at Home: A Comprehensive Guide and Planner for Family Caregivers and Personal Home Care Assistants. Salisbury, Md.: Avenegg, 2006. Gingerich, Barbara Stover, and Deborah Anne Ondeck, eds. Clinical Pathways for the Multidisciplinary Home Care Team. Gaithersburg, Md.: Aspen, 1997. Meyer, Marie M., and Paula Derr. The Comfort of Home: A Complete Guide for Caregivers. Portland, Oreg.: CareTrust Publications, 2007.
Hormonal therapies u
Other Resources
Department of Health and Human Services Eldercare Locator http://www.eldercare.gov/eldercare/Public/Home.asp Medicare http://www.medicare.gov National Cancer Institute Home Care for Cancer Patients http://www.cancer.gov/cancertopics/factsheet/ Support/home-care See also Aids and devices for cancer patients; Cancer care team; Caregivers and caregiving; Case management; Counseling for cancer patients and survivors; Hospice care; Living with cancer; Long-distance caregiving; Palliative treatment; Psychosocial aspects of cancer; Rehabilitation; Relationships; Singlehood and cancer; Stress management; Support groups; Transitional care.
u Hormonal therapies Category: Chemotherapy and other drugs Also known as: Hormone therapy, endocrine therapy, antiestrogen therapy Definition: Hormonal therapy is the use of exogenous hormones or hormone antagonists in the medical treatment of cancer. It removes hormones or prevents their growth and survival-promoting action in hormone-responsive cancer cells. Hormonal therapy should not be confused with hormone replacement therapy. Cancers treated: Hormonal therapy most often refers to hormone-sensitive or hormone-receptor-positive breast cancer, but it also refers to several other types of cancers resulting from hormone-responsive tissues, including the prostate, endometrium, and adrenal cortex. Hormonal therapy may also be used to treat paraneoplastic syndromes, which arise from substances produced by tumors, or to alleviate certain chemotherapy-induced symptoms, such as anorexia (appetite loss). Delivery routes: Oral How these drugs work: Gonadal hormones, including estrogens and androgens, activate hormone receptors in hormone-responsive cells that, in turn, stimulate gene expression and may activate cell-signaling pathways to induce tumor growth. Hormone therapies prevent a specific hormone receptor from the activation of cell-signaling 599
Hormonal therapies pathways that would induce tumor growth. There are two main effective strategies for starving hormone-responsive tumor cells. One strategy is to block a particular hormone’s ability to activate cell-signaling pathways, and the other approach is to introduce drugs that inhibit the production of the specific hormones responsible for tumor-cell growth. In particular, 80 percent of breast cancer needs the hormone estrogen to grow. The metabolism of estrogen starts with the synthesis of cholesterol into androgens. Then androgens, such as testosterone, are converted into estrogens via the aromatase enzyme. Primarily, estrogen is produced in the ovaries, but other tissues, including the liver, adrenal glands, and breasts, also produce estrogens. Although estrogen production in the ovaries ceases during menopause, the adrenal glands and other tissues continue to produce estrogen via the enzyme aromatase. Every year, approximately 23,000 postmenopausal women are diagnosed with estrogen-receptor-positive early breast cancer. One type of hormonal therapy for breast cancer patients prevents estrogen from binding to estrogen receptors in order to halt the growth of cancerous cells. This strategy has led to the development of tamoxifen (Nolvadex), which is a selective estrogen-response modulator (SERM) and an estrogen receptor antagonist. Tamoxifen used to be the gold standard of hormonal medicine for patients with hormone-receptor-positive breast cancer; it is currently used for the treatment and chemoprevention of breast cancer. Tamoxifen binds to estrogen receptors to prevent their activation, therefore blocking a tumor’s ability to use estrogen. Raloxifene (Evista) is another SERM commonly used for chemoprevention of breast cancer in high-risk patients, and it also prevents osteoporosis, a common side effect of hormonal therapy. Toremifene (Fareston) and fulvestrant (Faslodex) are SERMs used for the treatment of metastatic breast cancer. In particular, fulvestrant is an estrogenreceptor downregulator (ERD) that is an option for postmenopausal women with metastatic breast cancer that has stopped responding to antiestrogen therapy. Similar to other hormone antagonists, tamoxifen is also a weak agonist, or weak estrogen. As a result, in patients who develop resistance to estrogen agonists, the best alternative treatments are the use of aromatase inhibitors, which prevent the production of estrogens. As a result, estrogen levels drop, which in turns induces apoptosis (cell death), thus halting the growth of hormone-responsive cancer cells. Several international clinical trials have shown evidence that aromatase inhibitors—Arimidex (anastrozole), Aromasin (exemestane), and Femara (letrozole)—work more effectively than tamoxifen in postmenopausal women in treating breast cancer. Therefore, aromatase inhibitors 600
Salem Health: Cancer have become the standard of care for postmenopausal women with hormone-receptor-positive breast cancer. For premenopausal women, however, tamoxifen remains the choice of hormonal treatment. Typically, tamoxifen is used as adjuvant therapy following primary treatment for early-stage breast cancer. In the case of breast cancers in postmenopausal women, the first line of breast cancer treatment tends to be the use of aromatase inhibitors, such as letrozole and anastrozole. Exemestane has been shown to be superior to megestrol in the treatment of tamoxifen-refractory breast cancer. Aminoglutethimide is a nonselective inhibitor that blocks aromatase and other enzymes that promote steroid hormone synthesis. Since it is nonselective to estrogen, it is not preferred to treat breast cancer; however, it may also be prescribed for the treatment of hyperadrenocortical syndromes, such as Cushing syndrome and adrenocortical carcinoma. One of the most common cancers among men in the United States is prostate cancer. Antiandrogens (antitestosterone-like drugs), such as flutamide, bicalutamide, nilutamide, and cyproterone acetate, block the growthand survival-promoting effects of testosterone and dihydrotestosterone in prostate cancer cells. Another form of hormonal therapy is orchidectomy and ovariectomy (oophorectomy), which are surgical removal of male or female endocrine organs, respectively. In particular, removal of the Fallopian tubes and ovaries reduces the risk for or prevents breast and ovarian cancer in women at high risk because of mutations in the BRCA1 or BRCA2 gene. As an alternative to surgical castration, gonadotropinreleasing hormone (GnRH) analogs, such as leuprolide and goserelin, are used for chemical castration. GnRH suppresses the production of estrogen and progesterone in the ovaries and the production of testosterone by the testes. While most hormonal therapies block hormone-induced signals to cancer cells, in some therapies the hormone supplementation has a cytotoxic effect on tumor cells. Progestins (progesterone-like drugs), androgens, and estrogens are among these hormones. Side effects: The side effects of hormonal therapy vary among treatments. Side effects may be brief, mild, and manageable, or they may be serious. In women, side effects of hormonal therapy that are common to all treatments are mood swings, depression, weight gain, hot flashes, vaginal dryness, early start of menopause, and, in metastatic cancer, burning pain in the bones. Tamoxifen promotes a less than 1 percent increased risk of uterine cancer, blood clots, cataracts, stroke, and fertility issues. Hormone therapy with tamoxifen or estrogens may in-
Salem Health: Cancer crease the chance of developing endometrial cancer; therefore, women taking tamoxifen should have a pelvic examination every year to look for any signs of cancer. In particular, abnormal vaginal bleeding (other than menstrual bleeding) while taking estrogen-like medication should be reported to a doctor as soon as possible. The benefits of tamoxifen, however, far outweigh the potential risks. Aromatase inhibitors may induce osteoporosis and cause upset stomach and sweating, and they can increase cholesterol levels and the risk of blood clotting. Unlike other aromatase inhibitors, exemestane does not appear to have osteoporosis-promoting side effects. Similar to aromatase inhibitors, ERDs may weaken bones and cause upset stomach. In addition, ERDs may also cause swelling at the injection site. Ovariectomy weakens the bones and results in infertility. Research has showed that tamoxifen used for earlystage breast cancer reduces the risk of recurrence of the primary cancer and the risk of developing new cancers in the other breast. Taking tamoxifen for longer than five years, however, is no more effective than five years of therapy. Many women develop resistance to the hormonal therapy over time, leading to cancer recurrence. After tamoxifen treatment, breast cancer recurs in about onequarter of patients after five years. In large-scale clinical trials, both steroidal and nonsteroidal aromatase inhibitors have been shown to be superior to tamoxifen in extending survival in postmenopausal women with metastatic disease and in preventing recurrence when used as primary adjuvant therapy. Anita Nagypál, Ph.D. u
For Further Information Adamo, V., et al. “Overview and New Strategies in Metastatic Breast Cancer (MBC) for Treatment of Tamoxifen-Resistant Patients.” Annals of Oncology 18, suppl. 6 (June, 2007): 53-57. “Adjuvant Therapy for Breast Cancer.” NIH Consensus Statement 17, no. 4 (November 1-3, 2000): 1-35. Arnal, J. F., et al. “Understanding the Controversy About Hormonal Replacement Therapy: Insights from Estrogen Effects on Experimental and Clinical Atherosclerosis.” Archives des maladies du coeur et des vaisseaux 100, nos. 6/7 (June/July, 2007): 554-562. Garrett, Andrea, and Michael A. Quinn. “Hormonal Therapies and Gynaecological Cancers.” Best Practice & Research Clinical Obstetrics & Gynaecology 22, no. 2 (April, 2008): 407-421. Hind, D., et al. “Hormonal Therapies for Early Breast Cancer: Systematic Review and Economic Evaluation.” Health Technology Assessment 11, no. 26 (July, 2007).
Hormone receptor tests Lethaby, Anne E., and Beverley J. Vollenhoven. “An Evidence-Based Approach to Hormonal Therapies for Premenopausal Women with Fibroids.” Best Practice & Research Clinical Obstetrics & Gynaecology 22, no. 2 (April, 2008): 307-331. u
Other Resources
American Cancer Society Detailed Guide: Breast Cancer—Hormone Therapy http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Hormone_Therapy_5.asp BreastCancer.org Hormonal Therapy http://www.breastcancer.org/treatment/hormonal/ National Cancer Institute Treatment Option Overview http://www.cancer.gov/cancertopics/pdq/treatment/ breast/Patient/page5#Keypoint17 See also Androgen drugs; Antiandrogens; Antiestrogens; Antimetabolites in chemotherapy; Antineoplastics in chemotherapy; Biological therapy; Cancer biology; Chemotherapy; Corticosteroids; Cytokines; Diethylstilbestrol (DES); Estrogen receptor downregulator (ERD); Immune response to cancer; Immunotherapy; Interferon; Interleukins; Vaccines, therapeutic.
u Hormone receptor tests Category: Procedures Definition: The hormone receptor test is used to determine if a breast tumor is hormone receptor positive. Hormone receptors, present on the surfaces of normal cells, bind to hormones such as estrogen and progesterone to regulate normal cell growth. Many tumors express more of these receptors, however, thus making them more responsive to hormone-dependent cell growth. This is one method the tumor uses to grow at a faster rate than normal. The hormone receptor test analyzes tissue from a breast biopsy for the number of receptors present and will classify the tumor as hormone receptor positive or negative. This information is used to decide the method of treatment for breast cancer. Cancer diagnosed: Breast cancer Why performed: If symptoms and screening tests, such as a mammogram, suggest the likelihood of breast cancer, then a biopsy will be performed to determine if the disease 601
Hormone receptor tests is present, the stage of the cancer, and whether the tumor is hormone receptor positive. If the cancer is estrogen receptor (ER) positive or progesterone receptor (PR) positive, it will typically respond well to hormonal therapy. Hormonal therapy will either reduce the levels of estrogen present in the body or prevent the binding of estrogen to the receptors. Patient preparation: Depending on the type of biopsy planned, the patient may be asked to refrain from eating or drinking the night before any type of surgical procedure. If a needle biopsy is done, then it is advisable to eat lightly prior to the procedure. Steps of the procedure: A biopsy of the suspicious lump will be further analyzed to determine whether the lump is benign or malignant, the stage of the tumor, and whether it is hormone receptor positive. Tissue samples can be obtained by fine needle biopsy, core (large-needle) biopsy, or open surgical biopsy. The procedure used depends on the size of the tumor, with more invasive methods providing the most conclusive diagnosis and the least invasive method providing more false negatives. A commonly used technique is fine needle aspiration, in which a thin hollow needle is used to take out a small portion of the tumor. Vacuum-assisted or large-gauge needles are used to remove multiple pieces of the tumor. The needle is guided to the tumor using ultrasound imaging, guaranteeing that tissue is removed only from the suspicious region. Needle biopsies are minimally invasive and can be performed in the physician’s office with local anesthesia. Surgical biopsies include incisional biopsies, which remove a small piece of tissue, and excisional biopsies, which remove the entire area of suspected cancer. Surgical biopsies provide the most conclusive diagnosis, with fewer false negatives, but are far more invasive and require a longer recovery time. Once the tissue is removed, it is sent to the laboratory for analysis, where the number of hormone receptors present will be determined. After the procedure: For a needle biopsy, the opening is very small and little care is needed. It is covered with a small bandage for one to two days, and usual activity can be resumed immediately. If a surgical biopsy was performed, then care of the incision will require coverage with a bandage that can be removed in one or two days. If general anesthesia was used, a friend or relative should drive the patient home. Normal activities can be resumed in one to three days and stitches removed in about one week. Risks: There is little risk involved in having a biopsy, but the main risk is infection in the area of biopsy, indicated by 602
Salem Health: Cancer redness or swelling. A hematoma (collection of blood) may also occur and requires drainage. Results: The laboratory test will take a few days, after which the physician will discuss whether the suspicious lump is benign or malignant, the stage of the tumor, and the hormone receptor status. About 80 percent of all biopsies in the United States are benign. The results of the hormone receptor test determine whether the tumor will be declared hormone receptor positive. In some practices, a number between 0 and 3 is also given, with 0+ being no receptors present and 3+ having a large number of receptors present. If the tumor has a large number of receptors present, then it is hormone dependent, and hormonal therapies such as antiestrogens will be used. Antiestrogen therapies include tamoxifen and aromatase inhibitors (Arimides, Aromasin, and Femara). Tamoxifen is generally given for premenopausal women, while aromatase inhibitors work better in postmenopausal women. Women whose tumors are hormone receptor positive generally respond very well to antiestrogen therapies and have a better prognosis than those whose tumors are not hormone dependent. Terry J. Shackleford, Ph.D. u
For Further Information Hunt, Kelly K., et al. Breast Cancer. New York: SpringerVerlag, 2001. Link, John. Breast Cancer Survival Manual: A Step-byStep Guide for the Woman with Newly Diagnosed Breast Cancer. 4th ed. New York: Holt, 2007. Miller, William R., and James N. Ingle. Endocrine Therapy in Breast Cancer. New York: Informa Healthcare, 2002.
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Other Resources
American Cancer Society http://www.cancer.org BreastCancer.org http://www.breastcancer.org M. D. Anderson Cancer Center http://www.mdanderson.org/diseases/breastcancer National Cancer Institute http://www.cancer.gov/cancertopics/types/breast Susan G. Komen Foundation http://www.komen.org See also Antiestrogens; Estrogen receptor downregulator (ERD); Estrogen-receptor-sensitive breast cancer; Hormonal therapies; Progesterone receptor assay; Receptor analysis.
Salem Health: Cancer
u Hormone replacement
therapy (HRT) Category: Carcinogens and suspected carcinogens RoC status: Some forms of estrogen have been known human carcinogens since 1985, while other forms have been known human carcinogens since 2002; progesterone has been a reasonably anticipated human carcinogen since 1985. Also known as: Menopausal hormone therapy, estrogen replacement therapy Related cancers: Breast and uterine cancers, possibly ovarian, testicular, and prostate gland cancers Definition: Hormone replacement therapy (HRT) involves administration of estrogen alone or estrogen in combination with progesterone. Estrogen is a general term for any number of sex hormones, including estradiol, the main estrogen produced by the body, and estriol and estrone, which are products of estradiol metabolism. Progesterone is another sex hormone, which often opposes estrogen in action. Progestin is a general term for progesterone or other substances that have the same effect as progesterone. Exposure routes: Estrogen and progesterone, whether naturally occurring in the body or inhaled, ingested, injected, or absorbed through the skin, travel through the bloodstream. They are then absorbed by estrogen-dependent cells or metabolized by the liver for final excretion in urine and stool. Where found: Estrogen and progesterone are found in many animal fluids and tissues, including milk and meat, as well as many plants, including palm kernel oil. The estrogen most often used in HRT is extracted from the urine of pregnant mares. Estrogens and progesterones are also used commercially in skin and hair products in low concentrations. The most likely route of excessive exposure is use of prescribed HRT in oral, dermal, or vaginal preparations. At risk: Women who use HRT are at greatest risk. Workers in facilities where prescription estrogen and progesterone products are made can be also exposed through inhalation or skin contact. Etiology and symptoms of associated cancers: Prolonged or excessive estrogen exposure causes estrogendependent cells to divide more rapidly than normal. Overexposure to estrogen can damage chromosomes or alter gene expression in estrogen receptor cells. Estrogen receptors are proteins within cells that bind to estrogen and stim-
Hormone replacement therapy (HRT) ulate production of certain tissue cells, including breast, ovarian, and uterine lining cells. Overexpression of estrogen receptors causes increased cell division and deoxyribonucleic acid (DNA) replication, which increases the chance for mutations and causes tumor growth. The mechanism by which progesterone is associated with cancer is not known, but many studies have shown that injection of progesterone in animals causes tissue overgrowth and tumor formation in the uterine lining, the breast, and other reproductive tissues. The cancers that are known to result from HRT include breast cancer (lobular more than ductal) and endometrial, or uterine, cancer. At least one study has shown a causal relationship between HRT and ovarian cancer, but other studies have had conflicting results. The most common symptom of breast cancer is a lump or mass in the breast. Some breast cancers present as calcifications in breast ducts, with no mass. These are usually discovered on mammography. Uterine cancer is slow growing and is often found on imaging studies of the abdomen ordered for vaginal bleeding in a postmenopausal woman or for other symptoms not related to the cancer. History: Estrogen is a hormone naturally produced by the ovaries, placenta, testes, and adrenal glands. It regulates development of secondary sex characteristics, such as breast development and body hair distribution, and is important in the growth and functioning of all reproductive organs as well as bones. It regulates brain processes associated with reproduction, including mood and interest in sex. One of its most important functions is maintaining the lining of the uterus and preparing the body for pregnancy. Progesterone is produced by the ovaries in adult women and by the placenta during pregnancy. It is also produced by the adrenal glands and, like estrogen, is found in many body tissues and fluids. Progesterone is essential in the thickening and vascularity of the uterine lining that allow the fertilized ovum to implant and grow during pregnancy. Both hormones are used in oral contraceptives. Estrogen, alone or with progestin, has been prescribed for menopausal women to relieve unpleasant side effects of menopause and was once thought to prevent heart attacks and retard aging. Progestins are prescribed, among other reasons, to regulate the menstrual cycle and prevent miscarriage. HRT use flourished in the 1960’s and 1970’s until researchers started noticing a marked increase in the incidence of endometrial, or uterine lining, cancer in women treated with estrogen replacement therapy. The results of one of the first studies to make the connection were published in 1975 in the New England Journal of Medicine by 603
Hormone replacement therapy (HRT) D. C. Smith and colleagues, who found a 4.5 times greater risk of endometrial adenocarcinoma in postmenopausal women being treated with estrogen alone. Many other studies followed, and conjugated estrogen, a mixture of naturally occurring estrogens, was listed as a known carcinogen in 1985. Other studies, including a Swedish study by I. Persson and colleagues published in the British Medical Journal in 1989, found that estrogen therapy in combination with progestins did not increase the risk of endometrial cancer, so combination therapy came into common use, with an estimated 40 million prescriptions in the United States in 1992. By 1999, studies were showing an increased risk for breast cancer in patients using estrogen alone or combination (estrogen-progestin) therapy. The definitive study for the association of breast cancer and HRT was the 1991 Women’s Health Initiative, a U.S. government-sponsored research study consisting of clinical trials and an observational study, which included trials on more than 16,000 postmenopausal women using estrogen alone or combination therapy. The combination therapy part of the study was stopped in 2002, after nearly six years of research, because the findings showed the risks of combined HRT to be greater than the benefits. The study found that the incidence of breast cancer increased and that the risk increased with the duration of HRT. The estrogenalone part of the study was stopped in 2004 because data indicated an increased risk of stroke in patients taking estrogen supplements. Estrogen-alone therapy did not increase the risk of breast cancer in the study population. Use of HRT dropped significantly after the Women’s Health Initiative results were published, as did the incidence of breast cancer. Some researchers thought the drop was a direct result of less use of HRT. Other studies concluded that the decrease in the incidence of breast cancer began four years before the Women’s Health Initiative results were announced and that the decrease in the incidence of breast cancer was more likely to be a result of fewer women getting mammograms. Mammograms were part of the required follow-up for women getting HRT, and it is ironic that many women may have stopped getting mammograms because of decreased medical care that resulted from stopping HRT. This could have delayed detection of breast cancers. Studies of HRT continue, but the consensus seems to be that women who need HRT for relief of menopausal symptoms should receive therapy in the lowest effective dose for the shortest period of time needed. Estrogen therapy was shown in the Women’s Health Initiative to be effective in treatment of osteoporosis, or thinning of bone tissue, but its use is recommended only for patients who are not candidates for other treatments. HRT is no longer rec604
Salem Health: Cancer ommended for prevention of coronary artery disease. The benefits of HRT include a decreased risk of colorectal cancer and osteoporosis and relief of troublesome menopausal symptoms. Patients in need of HRT should discuss options with their physicians, who will weigh the benefits and risks of treatment for each patient. Cathy Anderson, R.N., B.A. u
For Further Information Lacey, J. V., et al. “Menopausal Hormone Therapy and Ovarian Cancer Risk in the NIH-AARP Diet and Health Study Cohort.” Journal of the National Cancer Institute 98, no. 19 (2006): 1397-1405. Li, C. I., et al. “Changing Incidence Rate of Invasive Lobular Breast Carcinoma Among Older Women.” Cancer 88, no. 11 (2000): 2561-2569. Persson, I., et al. “Risk of Endometrial Cancer After Treatment with Oestrogens Alone or in Conjunction with Progestogens: Results of a Prospective Study.” British Medical Journal 298, no. 6667 (January 21, 1989): 147-151. Stefanick, M. L., et al. “Effects of Conjugated Equine Estrogens on Breast Cancer and Mammography Screening in Postmenopausal Women with Hysterectomy.” Journal of the American Medical Association 295, no. 14 (2006): 1647-1657. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005.
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Other Resources
American College of Obstetrics and Gynecology http://www.acog.org International Agency for Research on Cancer http://www.iarc.fr/index.html MayoClinic.com Hormone Therapy: Is It Right for You? http://www.mayoclinic.com/health/hormone-therapy/ WO00046 National Institutes of Health Menopausal Hormone Therapy Information http://www.nih.gov/PHTindex.htm See also Adjuvant therapy; Aging and cancer; Amenorrhea; Androgen drugs; Antiestrogens; Biological therapy; Birth control pills and cancer; Breast cancers; Diethylstilbestrol (DES); Endocrine cancers; Endometrial cancer; Estrogen receptor downregulator (ERD); Estrogen-
Salem Health: Cancer receptor-sensitive breast cancer; Fertility drugs and cancer; Gynecologic cancers; Hormonal therapies; Hormone receptor tests; Hot flashes; Hypercoagulation disorders; Hysterectomy; Ovarian cancers; Phytoestrogens; Pregnancy and cancer; Progesterone receptor assay; Receptor analysis; Tumor markers.
u Horner syndrome Category: Diseases, symptoms, and conditions Also known as: Horner’s syndrome Related conditions: Neuroblastoma, Pancoast tumor of the lung Definition: Horner syndrome is not a disease but a collection of symptoms that are caused by damage to a nerve that controls the muscles of the eye. Horner syndrome has many causes, some of which are related to tumor growth. Risk factors: Risk factors for developing Horner syndrome vary and are related to the risk factors for developing the underlying disease that causes Horner syndrome symptoms. Etiology and the disease process: Horner syndrome is a disorder of the eye named for William Edmonds Horner, a Virginia physician who developed an operation to correct some of the symptoms associated with the syndrome. To understand the syndrome and how it is related to cancer, it is necessary to understand some information about the nervous system. The nervous system has two divisions. The voluntary nervous system consists of nerves that are under conscious control. These nerves control actions such as turning the head or raising the arm. The involuntary, or autonomic, nervous system controls muscle movements that are not under conscious control. The autonomic nervous system regulates activities such as breathing, digesting food, and the contraction and dilation (expansion) of the pupil of the eye. The autonomic nervous system has two divisions, the sympathetic and the parasympathetic nervous systems. Stimulation of the sympathetic nerves prepares the body for action by doing things such as moving more blood to the skeletal muscles. Stimulation of the parasympathetic nervous system calms the body by doing things such as allowing muscles to relax. The eye contains both sympathetic and parasympathetic nerves. Normally these two nervous systems balance each other. In Horner syndrome, the sympathetic
Horner syndrome nerve to the eye is damaged. As a result, there is only parasympathetic stimulation; the upper eyelid droops and the lower eyelid swells, and the pupil remains small and does not dilate. These changes occur only in one eye. The sympathetic nerve that is damaged in people with Horner syndrome does not go directly from the brain to the eye. It has a three-step path, and in each stage, different events can cause Horner syndrome. In the first step, the nerve starts in the brain and goes down the spinal cord to the chest. Damage to this part of the pathway (called firstneuron Horner syndrome) can be caused by brain tumors, by a tumor of the pituitary gland (an organ at the base of the brain), or by brief interruption in blood flow to the brain (a transient ischemic attack, or TIA). The next part of the pathway takes the nerve from the chest over the top of the lungs and up along the carotid artery in the side of the neck. Damage to the nerve in this part of the pathway (called second-neuron Horner syndrome) can be caused by a tumor in the upper part of the lung (a Pancoast tumor) or a tumor in the chest cavity (thoracic tumor). Noncancerous causes include trauma to the chest cavity or neck (either from surgery or an accident), an enlarged thyroid gland, and spinal cord injury or disease. In the final part of the pathway, the nerve goes from the neck through the middle ear and into the eye. Damage to the nerve in this part of the pathway (called third-neuron Horner syndrome) has noncancerous causes such as injury to the skull, middle-ear infections, and migraine or cluster headaches. Symptoms similar to Horner syndrome can also be caused by various drugs, including some antipsychotics, anesthetics, and drugs used for treating Parkinson’s disease. Incidence: The incidence of Horner syndrome is not known, but the syndrome is uncommon. Symptoms: Symptoms include a drooping upper eyelid and a puffy lower eyelid. The eyeball may appear sunken. The pupil of the affected eye is smaller than the pupil of the healthy eye. Children with congenital Horner syndrome (caused by nerve-cell tumors) often have eyes that are different colors. People who have third-neuron Horner syndrome do not sweat from the affected side of the face. Screening and diagnosis: An ophthalmologist (eye specialist) usually diagnoses Horner syndrome. A few drops of a solution containing a small amount of cocaine are put in the affected eye. If the sympathetic nerve to the eye is undamaged, then the pupil will dilate (enlarge). If there is damage, pupil size remains unchanged. Other drugs such as apraclonidine or hydroxyamphetamine help confirm 605
Hospice care the diagnosis. Following diagnosis, imaging scans (magnetic resonance imaging, computed tomography, ultrasound) are done to locate tumors that may be the source of the damage. Treatment and therapy: Treatment varies depending on the underlying cause of the symptoms. Prognosis, prevention, and outcomes: Prognosis and outcome depend on the cause of the syndrome. Martiscia Davidson, A.M. u For Further Information Icon Health. Horner’s Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Lee, J. H., et al. “Neuroimaging Strategies for Three Types of Horner Syndrome with Emphasis on Anatomic Location.” American Journal of Roentgenology 188, no. 1 (January, 2007): W74-W81. Rabady, D. Z. “Pediatric Horner Syndrome: Etiologies and Roles of Imaging and Urine Studies to Detect Neuroblastoma and Other Responsible Mass Lesions.” American Journal of Ophthalmology 144, no. 3 (September, 2007): 481-482. u
Other Resources
MedlinePlus Horner Syndrome http://www.nlm.nih.gov/medlineplus/ency/article/ 000708.htm National Organization for Rare Diseases http://www.rarediseases.org See also Eye cancers; Lung cancers.
u Hospice care Category: Social and personal issues Definition: Hospice care is care intended for terminally ill individuals who are expected to live for six months or less. It is focused on allowing terminally ill patients to spend their last days with family and friends in the most meaningful way possible and to die with dignity. Hospice care focuses mainly on palliative care, or care intended to provide comfort and reduce pain rather than trying to cure the disease or prolong life. In addition to palliative care services for patients, hospice care provides spiritual and emotional support and counseling to the patients and their family members, friends, and caregivers. Services are most 606
Salem Health: Cancer frequently provided in the home but are also available at hospitals, in nursing homes, and in other long-term care facilities. Many hospice care providers have live-in facilities of their own that are available if desired. According to the National Center for Health Statistics, more than half of all people in hospice care have cancer, although hospice care is available for people with any disease. Hospice services: A wide range of hospice services are available and are provided based on the specific needs of the terminally ill person and his or her family and friends. The services provided may change during the course of the illness. Hospice services are intended not only to help the terminally ill person but also to provide support to the family during the difficult time and even afterward, during the bereavement process. Hospice care focuses on making the individual as comfortable as possible during the final weeks or months of life. Relief from pain and other symptoms that interfere with enjoyment of the time remaining is a primary focus. A doctor will prescribe medications as necessary to relieve pain or reduce other symptoms, and they may be administered by a nurse or trained family member. Many hospices have pharmacy services to fill prescriptions. If hospice care is provided in an outpatient setting, nurses will regularly visit the patient to check on progress and administer any necessary services. There are also nurses available twenty-four hours a day to answer any questions the primary caregiver may have and who can send someone out to help immediately if necessary. The emotional experience of those needing hospice care and their families can be devastating. Skilled therapists, bereavement counselors, and others are available to help the terminally ill person and family through the painful experience and to help set realistic goals for the remaining time. Hospices often offer ways for the primary caregiver to take a break from providing round-the-clock care, either to take care of necessary issues such as running errands or meeting with lawyers, or just to take a break and relax. Respite care is the care provided in an inpatient setting, such as at a hospice or in a hospital, in place of the care normally provided by the primary caregiver. This leaves the caregiver free to do things such as travel if necessary or desired, or just to take care of chores that have been piling up. Respite care can last for up to five days. The hospice team: The hospice care team may differ from situation to situation depending on the needs of patients and their families and the services provided by a specific hospice care provider. The main members of the hospice care team are always the terminally ill person and the fam-
Salem Health: Cancer
Hospice care
Hospice Admissions, 2005 Kidney Disease 3.1% Other 14.5% Lung Disease 7.1%
Cancer 45.9%
Debility 8.3% Heart Disease 12.2%
Dementia 8.9%
ily members or friends who are providing the primary care. The patient makes the decisions about what kind of care is desired and what services would be most helpful, usually by talking to a representative from the hospice care provider to set up services and define goals for the care. The family member that is the primary caregiver helps determine when services such as respite care will be desired and will be responsible for most of the day-to-day care of the patient for as long as possible. Some hospice care providers have training to help the primary care provider better care for the terminally ill individual. A doctor leads the medical members of the hospice care team and oversees the care received by the terminally ill person. The doctor can prescribe medications to alleviate pain or other symptoms that are reducing the patient’s quality of life. Typically this doctor is a doctor from the hospice provider. The patient’s personal physician also is involved in the patient’s hospice care and can work with a hospice-provided doctor to ensure that the patient is as comfortable as possible. One or many nurses are also an important part of the hospice care team. They provide services such as administering medications to the individual and also report needs or changes to the doctor providing care. Counselors or therapists with experience in providing support for terminally ill patients and their families are an integral part of the hospice care team. The amount and type of support provided depend on the needs and desires of the
individual and the family, but often helping family members talk about the way they are feeling and helping them through the bereavement process is the job of the hospice counselor or therapist. Spiritual counselors or religious leaders such as priests or rabbis are often available to help the individual or family and to provide assistance with any desired religious rites or ceremonies. Volunteers are often an important part of the hospice care team. Usually they have been specially screened and trained to provide support services to the terminally ill person and family. This may include activities such as housework, providing light meals, or helping the patient’s caregiver with other basic tasks. The volunteer may stay with the terminally ill person to give the primary caregiver an opportunity to rest or run errands. Even just reading to the patient or playing board games can be a valuable service provided by volunteers from the hospice care provider. Paying for hospice care: Hospice care, like other medical care and services, can be extremely expensive. However, Medicare covers hospice care for eligible individuals, and forty-seven states and the District of Columbia also have Medicaid benefits that cover hospice care. Most private health insurance plans will cover all or part of the cost of hospice care. Generally, to be eligible, a doctor must certify that the patient is expected to live six months or less if the disease continues as predicted. Many patients with late-stage cancer fit this description. Many hospice organizations provide benefits on a sliding scale for those individuals and their families who do not have insurance to cover the costs and cannot afford to pay very much out of pocket. Some offer free services for people who cannot afford to pay at all. When the hospice benefit is being paid, it usually means that insurance will not continue to cover treatments that are intended to provide a cure, just those treatments intended to reduce pain or improve quality of life. There generally is not a limit to the length of time that hospice benefits can be provided, although often a doctor must recertify that a patient is expected to live six months or less. If a patient improves such that life expectancy increases past six months, such as when the cancer unexpectedly goes into remission, the patient will be discharged from hospice care. Hospice care can be begin again if appropriate at a later time. Helen Davidson, B.A. u
For Further Information Barraclough, Jennifer, ed. Enhancing Cancer Care: Complementary Therapy and Support. New York: Oxford University Press, 2007. 607
Hot flashes
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Head, Barbara Anderson, ed. Study Guide for the Hospice and Palliative Nursing Assistant. Dubuque, Iowa: Kendall/Hunt, 2004. Moorhouse, Timothy. Hospice Design Manual: For InPatient Facilities. Machiasport, Maine: Hospice Education Institute, 2006. Turk, Dennis C., and Caryn S. Feldman, eds. Noninvasive Approaches to Pain Management in the Terminally Ill. New York: Haworth, 1992. Zerwekh, Joyce V. Nursing Care at the End of Life: Palliative Care for Patients and Families. Philadelphia: F. A. Davis, 2006.
ration, and likelihood of hot flashes rise with increased consumption of sugar or caffeine, obesity, vitamin or mineral deficiencies, unhealthful diet, thyroid disorders, emotionally embarrassing or stressful situations, being overdressed in a warm environment, and the consumption of foods or liquids containing nitrates. Eating snacks, drinking alcohol, and not voiding a full bladder before bedtime can create intense night sweats. Wearing makeup can block pores, causing the face to retain heat and increasing thermal intensity. Any substance—prescriptions, overthe-counter medications, illegal drugs, and herbal remedies—may increase hot flashes or night sweats.
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Etiology and the disease process: When ovaries malfunction, become diseased, die, or are surgically removed, hot flashes tend to occur. Hot flashes often occur when the levels of estrogen, progesterone, or testosterone fluctuate greatly. The follicle-stimulating hormone (FSH) that is secreted by the pituitary gland may also cause dilation of blood vessels, triggering hot flashes or night sweats.
Other Resources
American Cancer Society Hospice Care Http://www.cancer.org/docroot/ETO/eto_2_4_ hospicecare.asp?sitearea=MLT&level=1 Hospice and Palliative Nurses Association http://www.hpna.org International Association for Hospice and Palliative Care http://www.hospicecare.com See also Advance directives; Aging and cancer; Aids and devices for cancer patients; Brompton cocktail; Cancer care team; Caregivers and caregiving; Case management; Counseling for cancer patients and survivors; End-of-life care; Home health services; Living will; Living with cancer; Long-distance caregiving; Pain management medications; Palliative treatment; Psychosocial aspects of cancer; Relationships; Singlehood and cancer; Stress management; Support groups; Transitional care.
u Hot flashes Category: Diseases, symptoms, and conditions Also known as: Hot flushes Related conditions: Premenopause, perimenopause, menopause, postmenopause, hysterectomy, oophorectomy Definition: A hot flash is an intense feeling of warmth that floods the body, causing extreme perspiration. Risk factors: The primary reasons for hot flashes are menopause, hysterectomy, or oophorectomy. Some diseases that can cause hot flashes include cancer of the ovaries, pituitary gland, uterus, and thyroid. The intensity, du608
Incidence: Approximately 75 percent of women in the United States who have a complete hysterectomy, oophorectomy, or pass through menopause experience hot flashes or night sweats. Symptoms: A hot flash manifests as a quick, tingling sensation, followed by a rush of intense heat, and immediately followed by perfuse sweating. It lasts one to twelve minutes. Screening and diagnosis: Hot flashes and night sweats are typically addressed when patients complain of these symptoms during a medical exam. Physicians will ask questions to verify what their patients are experiencing. An FSH test may be taken to confirm or indicate menopausal status. Treatment and therapy: Hot flashes may be decreased by hormone replacement therapy (HRT), a combination of estrogen, progesterone, or testosterone; bio-identical hormone replacement therapy (BHRT); herbal remedies; and vitamin and mineral supplements. However, the risks and side effects of any of these treatments must be carefully considered before and during their use. Treatments should also include eating healthfully, exercising, getting adequate rest, and adding milk or soy milk to the diet. Prognosis, prevention, and outcomes: By following a healthy diet, exercising, wearing loose layered clothing, and taking medication if necessary, hot flashes and night sweats can be decreased by 50 to 75 percent. Suzette Buhr, R.T.R., C.D.A.
Salem Health: Cancer See also Acupuncture and acupressure for cancer patients; Adjuvant therapy; Amenorrhea; Antiandrogens; Antiestrogens; Estrogen receptor downregulator (ERD); Fever; Hormonal therapies; Hysterectomy; Orchiectomy; Weight loss.
u HRAS gene testing Category: Procedures Also known as: v-Ha-ras Harvey rat sarcoma viral oncogene homolog, Harvey murine sarcoma virus oncogene, c-H-ras, HRAS1 Definition: The HRAS gene encodes a protein that allows cells to translate extracellular signals into intracellular events that induce cellular growth and division. HRAS is overexpressed or mutated to an overactive form in cancer of the bladder and other organs. It is also mutated in individuals afflicted with Costello syndrome, a rare developmental disorder. Symptoms of Costello syndrome include delayed development; distinctive facial features; flexible joints; papilloma around the mouth, nose, and anus; heart abnormalities; and an increased susceptibility to several types of cancer, including rhabdomyosarcoma, neuroblastoma, and transitional cell carcinoma. Conditions diagnosed: Costello syndrome Why performed: Costello syndrome is difficult to distinguish from other developmental disorders. Testing for mutations in HRAS is a useful method to diagnose Costello syndrome because approximately 80 percent of patients with this disorder have mutations in HRAS, while other syndromes are caused by mutations in different genes. Prenatal screening is also available for parents who have children affected with Costello syndrome. Patient preparation: Patients considering genetic testing may meet with a genetic counselor who will discuss the benefits and risks of the test and the significance of negative, positive, and inconclusive results. Steps of the procedure: Material required for confirming a diagnosis of Costello syndrome is generally obtained from a blood sample. For prenatal screening, amniotic fluid or chorionic villus sampling is required. Samples are sent to a clinical laboratory that offers HRAS screening. Deoxyribonucleic acid (DNA) is purified from the sample, and the DNA that encodes HRAS is amplified by polymerase chain reaction (PCR) and sequenced using standard methods.
Human chorionic gonadotropin (HCG) After the procedure: The patient will consult with a physician and/or genetic counselor to discuss the implications of the test results. Risks: Complications from drawing blood are rare but may include excessive bleeding, hematoma, or infection. The risk of miscarriage due to chorionic villus sampling is estimated at 1 in 100 to 1 in 200. Because the information obtained from HRAS screening may have significant psychological effects, it is important that patients be offered genetic counseling. Results: Between 10 and 15 percent of individuals with Costello syndrome develop malignant tumors. Once diagnosed, patients should be monitored closely for rhabdomyosarcoma, neuroblastoma, and transitional cell carcinoma. Kyle J. McQuade, Ph.D. See also Gene therapy; Genetic testing; Rhabdomyosarcomas; Neuroblastomas; Transitional cell carcinomas.
u Human chorionic
gonadotropin (HCG) Category: Cancer biology Definition: The hormone human chorionic gonadotropin (HCG) is secreted by a specialized type of cell (syncytiotrophoblasts) in the developing placenta during embryonic development. HCG is composed of two subunits (alpha and beta) and is normally found in the blood and urine during a normal pregnancy. The alpha subunit of HCG is shared with the pituitary hormones: follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroidstimulating hormone (TSH). The beta subunit is unique to HCG and determines its functional properties. HCG is needed to maintain pregnancy until the placenta is fully developed. Detection of HCG in the urine is the basis for pregnancy detection kits. Gestational trophoblastic disease: Gestational trophoblastic disease (GTD) includes several types of tumors, including hydatidiform mole and choriocarcinoma. These tumors develop because of an anomaly in pregnancy when placental (trophoblastic) cells grow out of control. Hydatidiform moles can progress to choriocarcinomas, which are generally aggressive and, if left untreated, tend to metastasize widely. HCG is elevated in almost all patients with trophoblastic tumors and is a very useful diagnostic marker for monitoring treatment. Gestational trophoblastic 609
Human growth factors and tumor growth disease can be diagnosed and followed by measuring HCG hormone levels in the blood and urine. Ultrasound, computed tomography (CT), positron emission tomography (PET), or magnetic resonance imaging (MRI) scans can also be used to look for tumors. However, when scans show no evidence of tumor presence, HCG levels are often relied on to determine whether the disease may be present. HCG as a diagnostic marker: HCG is used as a diagnostic indicator of tumor formation in gestational trophoblastic disease because of an association between elevated HCG levels and trophoblastic tumors as well as nonseminomatous testicular tumors. Trophoblast-derived tumors often secrete only the free beta-HCG subunit. Diagnostic assays that are specific for the free beta-HCG subunit are most useful for monitoring tumor development and progression. A negative result is generally less than 5 milli international units/milliliter (mIU/ml) of betaHCG in the blood. Gestational trophoblastic disease is treatable, and HCG levels can be used to monitor the success of treatment, in that as the tumor decreases, so does the level of HCG. In some cases, elevated HCG levels may be due to factors other than gestational trophoblastic disease. Certain hormones and proteins in the blood may interfere with the blood test results; therefore, HCG tests should be performed on both the blood and the urine in the diagnosis of gestational trophoblastic disease. Thomas L. Brown, Ph.D. See also Choriocarcinomas; Cryptorchidism; Germ-cell tumors; Gestational trophoblastic tumors (GTTs); Gynecologic cancers; Hydatidiform mole; Malignant tumors; Testicular cancer.
u Human growth factors and
tumor growth Category: Carcinogens and suspected carcinogens Also known as: Mitogens, cytokines Definition: Growth factors are naturally occurring proteins that act as signaling molecules between cells and participate in the control of cell growth and cellular differentiation. Most growth factors stimulate proliferation of different cell types, but some are involved in inhibition of cell growth or even cause target cells to undergo apoptosis. Classification of growth factors and their receptors is as follows: • Platelet-derived growth factor family (PDGF, CSF-1, M-CSF, SCF) 610
Salem Health: Cancer
• • • •
Vascular endothelial growth factor family (VEGF) Epidermal growth factor family (EGF) Fibroblast growth factor family (FGF) Insulin family: Insulin-like growth factors (for example, IGF-I, IGF-II) • Hepatocyte growth factor (HGF) • Neurotrophin family (for example, NGF, TRK family) • Ephrin family (EPH): a subfamily of receptor tyrosine kinases, RTK • Agrin family • GDNF family • Angiopoietins • Discoidin domain receptors • Orphan receptors Related cancers: Multiple endocrine neoplasia type 2, leukemias, breast cancers, colon carcinoma Where found: Naturally in the body At risk: No specific risk group Etiology and symptoms of associated cancers: Binding of a growth factor to its cell-surface receptor triggers an intracellular signal transduction pathway leading to changes in gene expression. The receptors of many growth factors have intrinsic proteintyrosine kinases in their cytosolic domains, which transmit the growth signal by phosphorylating tyrosine residues on themselves or on one or more target proteins, thus initiating a cascade of events. Several types of mutations lead to overproduction of constitutively active receptors, which transmit growth signals in the absence of the normal ligands. Tumors need nourishment by blood vessels to continue growing. Many tumors produce growth factors, called “transforming” or “tumor” growth factors (TGFs), that stimulate the growth of blood vessels (angiogenesis). Basic FGF, TGFα, and VEGF have angiogenic properties and are secreted by many tumors. Growing of the tumor increases the probability of new harmful mutations. Availability of blood vessels also facilitates metastatic processes. Some growth factors like TGFβ have the ability to inhibit the growth of many cell types, including most epithelial and immune system cells. Loss of TGFβ-mediated growth inhibition contributes to the development and progression of a variety of tumors. The TGFβ signaling pathway is also connected to expression of extracellular matrix proteins, such as collagen, a lack of which may contribute to metastasis. History: NGF and EGF were the first growth factors to be discovered and characterized in the beginning of the
Salem Health: Cancer
Human papillomavirus (HPV)
1950’s by Rita Levi-Montalcini and Stanley Cohen through the testing of growth-promoting extracts of animal tissues. In the following decades, other growth factors were isolated and characterized. Nicola E. Wittekindt, Dr.Sc. (ETH Zürich) See also Angiogenesis; Angiogenesis inhibitors; Aplastic anemia; Beckwith-Wiedemann syndrome (BWS); Breast cancers; Cancer biology; Colonystimulating factors (CSFs); Craniosynostosis; Cytokines; Endometrial cancer; Gene therapy; HER2/ neu protein; Immune response to cancer; Interleukins; Myelofibrosis; Neuroendocrine tumors; Obesity-associated cancers; Oncogenes; Pituitary tumors; Receptor analysis.
u Human papillomavirus
(HPV) Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2004 Related cancers: Cervical cancer, anogenital cancers (anus, vulva, vagina) Definition: Human papillomaviruses (HPVs) are a group of more than 120 different viruses. They are called papillomaviruses because some types (1, 2, and 3) cause warts, or papillomas, which are benign (noncancerous) tumors. These types are spread by casual skin-to-skin contact with another person. About forty other HPV types are sexually transmitted and may lead to cancer. Types 16 and 18 are strongly associated with cervical cancer and types 31, 33, 35, 39, 45, 51, 52, 58, and 59 are also associated with cervical cancer. Every year, HPV causes about 470,000 cases of cervical cancer around the world. HPV is a very common virus. It has been estimated that by the age of fifty, 70 to 80 percent of women will have acquired a genital HPV infection. Although most infected women do not develop cancer (only about 1 to 3 percent), researchers have identified some risk factors that can increase an infection’s chances of progressing to precancerous changes and invasive cancer. These factors include cigarette smoking, long-term use of oral contraceptives, and coinfection with other sexually transmitted diseases. Exposure routes: Sexually transmitted (genital-genital contact, oral-genital contact, and sexual intercourse), skinto-skin contact
Human papillomavirus. (Kwangshin Kim/Photo Researchers, Inc.)
Where found: Human genitalia and skin At risk: Sexually active people, especially those with multiple sexual partners Etiology and symptoms of associated cancers: Most HPV infections cause no symptoms and clear on their own within weeks or months. Some people, however, may develop a persistent infection, which—depending on the type—may lead to genital warts or cancer. A woman with a persistent infection with high-risk types of HPV may show precancerous changes on Pap smears. These precancerous changes can lead to carcinoma in situ (localized cervical cancer), which may progress to invasive cervical cancer if not treated. History: In the 1990’s researchers discovered that virtually all women with cervical cancer in the world were infected with certain types of HPV. They found that all the cervical cancers and precancers contained one of these HPVs. In 2006 an HPV vaccine, Gardasil, was licensed in the United States; this vaccine protects against both infection 611
Human T-cell leukemia virus (HTLV) and, as a result, the cancer caused by HPV types 16 and 18. These two types cause 70 percent of the cases of cervical cancer. Diego Pineda, M.S. See also Anal cancer; Antiviral therapies; Birth control pills and cancer; Carcinoma of unknown primary origin (CUP); Cervical cancer; Developing nations and cancer; Epidemiology of cancer; Epidermoid cancers of mucous membranes; Gynecologic cancers; Head and neck cancers; Herpes simplex virus; Immune response to cancer; Infectious cancers; Lip cancers; Metastatic squamous neck cancer with occult primary; Oncogenes; Oncogenic viruses; Oral and oropharyngeal cancers; Pap test; Penile cancer; Pregnancy and cancer; Prevention; Throat cancer; Urethral cancer; Urinary system cancers; Vaccines, preventive; Vaginal cancer; Viral oncology; Virus-related cancers; Vulvar cancer.
u Human T-cell leukemia virus
(HTLV) Category: Carcinogens and suspected carcinogens Also known as: Human T-lymphotropic virus, adult T-cell lymphoma virus; HTLV-1 may also be called human T-cell lymphotropic virus type 1 or adult T-cell lymphoma virus type 1 Related cancers: T-cell leukemia, T-cell lymphoma Definition: Human T-lymphotropic virus is a retrovirus grouped into four separate species: Human T-lymphotropic virus 1, 2, 3, or 4. Although HTLV-2, 3, and 4 are found in humans, they have not yet been clearly identified as the causative agent for a specific disease. However, infection with the HTLV-1 virus may result in adult T-cell lymphoma, adult T-cell leukemia, loss of spinal nerve function, eye damage that may lead to blindness, infectious dermatitis, and other inflammatory disorders. Exposure routes: Sexual transmission, breast-feeding, blood transfusions, intravenous drug use
Salem Health: Cancer uncertain, but intravenous drug users are at special risk, with infection rates reaching an alarming 50 percent in some areas. Etiology and symptoms of associated cancers: T cells are central to cell-mediated immunity. Originating in the bone marrow, T cells mature in the thymus, where they acquire surface markers allowing them to distinguish self from nonself. The HTLV-1 virus takes up residence by infecting a subset of the T cells called CD4+ helper cells. Once there, they grow continuously, turn on specific genes, and evolve into leukemic cells that spread throughout the body. The resulting leukemia is classified as acute, lymphomatous, chronic, or smoldering. The acute and lymphomatous forms have a poor prognosis, with survival rates averaging less than one year. There is no standardized treatment. History: Following interspecies transmission, this virus diverged from its simian prototype about 50,000 years ago in Africa. Discovered in 1977 as the causative agent for adult T-cell leukemia, this virus was the first identified human retrovirus. In 1980 Robert C. Gallo and Bernard J. Poiesz confirmed the virus’s infectivity, resulting antibody response, and presence in a patient with T-cell cancer. Richard S. Spira, D.V.M. See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Antifungal therapies; Cutaneous T-cell lymphoma (CTCL); Cyclin-dependent kinase inhibitor-2A(CDKN2A); Genetics of cancer; Infectious cancers; Leukemias; Mycosis fungoides; Oncogenic viruses; Proto-oncogenes and carcinogenesis.
u Hydatidiform mole Category: Diseases, symptoms, and conditions Also known as: Molar pregnancy, gestational trophoblastic disease Related conditions: Choriocarcinoma
Where found: The HTLV-1 virus is endemic in Japan and central Africa, It is also present in South America, parts of the southeastern United States, Melanesia, Papua New Guinea, and the Caribbean basin.
Definition: A hydatidiform mole is a growth that forms in the uterus during early pregnancy. About 20 to 25 percent of hydatidiform moles form a choriocarcinoma, a rare type of uterine cancer.
At risk: Worldwide, approximately 15 million people are infected with the HTLV-1 virus. In Japan alone, more than 1 million people carry the virus, resulting in 800 leukemia cases each year. The prevalence rate in the United States is
Risk factors: Pregnancy in the early teen years or after age thirty-five increases the risk for a hydatidiform mole. A previous hydatidiform mole very slightly increases the chance of a future one.
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Salem Health: Cancer Etiology and the disease process: A hydatidiform mole arises from an abnormally fertilized egg. The early placental tissue grows into a mass containing cysts that look like a cluster of grapes. There is usually no embryo present; however, in about 1 percent of cases, a normal fetus and hydatidiform mole develop together. There are two types of hydatidiform moles: A complete mole does not contain tissue from the embryo, and a partial mole often contains embryonic tissue. If the abnormal tissue continues to grow after treatment, it is considered persistent gestational trophoblastic disease (GTD). Choriocarcinoma, a cancerous form of gestational trophoblastic disease, may develop in rare cases. Incidence: In the United States, a hydatidiform mole occurs in about 1 of every 1,000 to 1,500 pregnancies. The rate is higher in Asian countries. Symptoms: The most common symptom is vaginal bleeding around the tenth week of pregnancy. Other symptoms may include nausea, vomiting, and signs of an overactive thyroid, such as a rapid heartbeat, sweating, and tremor. The woman may have a larger-than-normal uterus and signs of preeclampsia, including high blood pressure, protein in the urine, and swelling of the lower legs and feet. Screening and diagnosis: Ultrasound allows most moles to be diagnosed in the first trimester, before symptoms develop. A blood test that shows higher-than-normal levels of human chorionic gonadotropin (HCG) may indicate a complete mole. Treatment and therapy: A hydatidiform mole is a medical emergency. Treatment involves a dilation and curettage (D&C), a surgical procedure that gently scrapes the lining of the uterus to remove all molar tissue, including a developing embryo, if present. Levels of HCG are checked for up to a year after surgery to make sure no molar tissue remains. If a woman has an HCG level of zero after surgery, no further treatment is needed. Prognosis, prevention, and outcomes: There is no known prevention. Women who have had a hydatidiform mole should avoid pregnancy for six to twelve months, as pregnancy can interfere with HCG monitoring. Untreated, a hydatidiform mole can cause significant bleeding and, in some cases, may progress to cancer. Kelli Miller Stacy, ELS See also Choriocarcinomas; Dilation and curettage (D&C); Gestational trophoblastic tumors (GTTs); Gynecologic oncology; Human chorionic gonadotropin (HCG); Moles; Pregnancy and cancer; Salpingectomy and salpingooophorectomy.
5-Hydroxyindoleacetic acid (5HIAA) test
u 5-Hydroxyindoleacetic acid
(5HIAA) test Category: Procedures Also known as: HIAA test, serotonin metabolite test Definition: 5-Hydroxyindoleacetic acid (5HIAA) is the compound that results when the body breaks down (metabolizes) the hormone serotonin. Cancers diagnosed: Carcinoid tumors Why performed: Carcinoid tumors release large amounts of serotonin, so doctors look for its metabolite, 5HIAA, in the urine. This test is used to help diagnose and monitor the treatment of these types of tumors. Patient preparation: Patients are instructed to avoid fruits and nuts in general and, specifically, avocados, bananas, eggplant, kiwis, pineapple and pineapple juice, plums, tomatoes and all tomato products, and walnuts for at least three days before and during this test. These foods can interfere with the test results. In addition, the drugs caffeine, nicotine, acetaminophen (Tylenol), aspirin, cough medicine, diazepam (Valium), ephedrine, heparin, imipramine, isoniazid, levodopa, MAO inhibitors, methyldopa, phenobarbitol, and tricylic antidepressants, as well as herbal and over-the-counter medicines, can interfere with test results. Steps of the procedure: Generally, a patient provides a twenty-four-hour urine sample, which involves collecting and refrigerating all urine excreted over a twenty-fourhour period. If it is not possible to collect all urine over a twenty-four-hour period, then random urine samples may be collected, but this type of test is not as accurate, because 5HIAA levels can vary throughout the day. After the procedure: If the test is used as a diagnostic tool and levels of 5HIAA are elevated, leading to a suspicion of a carcinoid tumor, then further tests, such as magnetic resonance imaging (MRI) or a computed tomography (CT) scan, may be performed to determine the existence and location of the tumor. If the test is used as a monitoring tool, then decreasing levels of 5HIAA will indicate that a tumor is responding to treatment, whereas increasing levels indicate that treatment has not been successful. Risks: 5HIAA levels may be normal even when carcinoid tumors are present; conversely, 5HIAA levels may be elevated though no tumors exist. Results: Because results vary widely and false negative and false positive results are common, this test does not 613
Hypercalcemia definitely diagnose carcinoid tumors. The results should be used along with symptoms to determine what further testing is necessary for a diagnosis. As a monitoring tool, the results of this test are used to determine the level of treatment success. Marianne M. Madsen, M.S. See also Carcinoid tumors and carcinoid syndrome; Tumor markers.
u Hypercalcemia Category: Diseases, symptoms, and conditions Also known as: High levels of calcium in the blood
Salem Health: Cancer
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Severe, generalized immobilization Other conditions: Addison disease, peptic ulcer disease, hypophosphatasia, familial hypercalcemia Primary hyperparathyroidism and malignancy account for nearly 90 percent of all cases of hypercalcemia. Incidence: The annual incidence of hypercalcemia is estimated to be 0.2 percent in patients over the age of sixty, with an estimated prevalence of greater than 1 percent of the general population. It is estimated to affect 10 to 20 percent of people with cancer. The condition may manifest in subtle ways and have a benign course for many years or for a lifetime. It is more common in women than men by a ratio of 3:1.
Risk factors: Two fundamental types of genetic defects have been identified in parathyroid gland tumors: the overactivity of oncogenes and the loss of function of tumor-suppressor genes.
Symptoms: In mild hypercalcemia, many patients do not exhibit symptoms. Patients with moderate hypercalcemia can complain of a constellation of symptoms involving the skeletal system (bones and muscles), the gastrointestinal tract, the kidneys, and the central nervous system. Severe symptoms (these associated with calcium levels of 13 to 15 mg/dl) include the following: • Nausea and vomiting • Anorexia • Polydipsia (excessive thirst) • Polyuria (frequent urination) • Recurrent nephrolithiasis (formation of kidney stones) • Profound muscle weakness (fatigue) • Severe abdominal pain (constipation, peptic ulcer disease, pancreatitis) • Muscle and joint ache • Depression • Delirium (mental confusion) and psychosis • Coma • Cardiac arrhythmias (irregular heartbeat leading to cardiac arrest)
Etiology and the disease process: Causes of hypercalcemia can include the following: • Primary hyperparathyroidism (excessive secretion of PTH) • Malignancy (with and without bony metastasis) • Cancers that produce blood dyscrasias: lymphoma, multiple myeloma, leukemia • Multiple endocrine neoplasias (MEN): hormoneproducing tumors • Granulomatous diseases: sarcoidosis, tuberculosis • Hyperthyroidism • Vitamin D and vitamin A intoxication • Medications: lithium therapy, corticosteroids, thiazide diuretics • Milk-alkali syndrome
Screening and diagnosis: The current consensus is that simple medical surveillance is appropriate for patients over fifty years of age when bone and renal statuses are satisfactory. Differential diagnosis of hypercalcemia is best achieved by using clinical criteria (assessment of symptoms, dietary history, the use of vitamin supplements, drugs, and physical examination), but the immunoassay for parathyroid hormone (PTH) is especially useful, reliable, and accurate in distinguishing major causes. Diagnostic tests to confirm a diagnosis of hypercalcemia include PTH immunoassays (checking circulating levels of parathyroid hormone); serum calcium and creatinine tests, along with a twenty-four-hour urinary calcium test; and creatinine clearance tests. Selective imaging may employ the evaluation of bone density (X ray, com-
Related conditions: Primary hyperparathyroidism, hyperthyroidism Definition: Hypercalcemia is a condition in which the calcium level in the blood is above normal limits (greater than 10.4 milligrams/deciliter, or mg/dl). Serum-ionized calcium and intracellular calcium concentrations play a major role in many biologic activities, including bone formation, hormone secretion, neurotransmitter release, muscle contraction, and enzyme activities. Two hormones serve as primary regulators of calcium: parathyroid hormone (PTH) and calcitonin. Parathyroid hormone stimulates the bones to release calcium into the blood, while the thyroid gland produces calcitonin, a hormone that slows the release of calcium. A condition of hypercalcemia reflects a significant disturbance in this delicate balance.
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Salem Health: Cancer puted tomography, or dual energy X-ray absorptiometry, or DEXA scans). Identification of soft-tissue masses is usually demonstrated by magnetic resonance imaging (MRI). Treatment and therapy: In cases of severe hypercalcemia, individuals may need to be hospitalized to reduce calcium to a safe level. Treatment protocols include the following: • Intravenous fluids • Loop diuretic medications (furosemide-lasix) to flush excess calcium from the body and keep the kidneys functioning • Intravenous bisphosphonates (drugs that inhibit bone breakdown) • Calcitonin, a hormone produced by the thyroid gland to reduce bone resorption and slow bone loss • Glucocorticoids to help counter the effects of vitamin D toxicity • Cinacalet, a drug used to lower blood calcium levels by reducing production of PTH • Mobilization to prevent bone resorption • Hemodialysis (filtering of the blood to remove excess calcium) • Surgery The critical management question is whether the disease should be treated surgically. A30 percent reduction in creatinine clearance, a twenty-four-hour urinary calcium of greater than 400 mg, and an elevated serum calcium level are persuasive factors. Traditionally, surgery (for hyperparathyroidism) has involved an extensive cervical incision and general anesthesia. A newer technique (radioguided parathyroidectomy) is now available. In this procedure, a radioisotope scan is performed preoperatively to locate the abnormal parathyroid gland. The operation is performed in less than an hour through a 1-inch incision. All surgery poses some risks. Asmall percentage of people undergoing this intervention can experience damage to the nerves controlling the vocal cords, and some develop a chronically low calcium level requiring lifelong supplements of calcium and vitamin D. Prognosis, prevention, and outcomes: Calcium metabolism is carefully and strictly regulated within a narrow range (8.5 to 10.2 mg/dl). Too much calcium, for whatever reason, can interfere with essential life processes. Conservative care is indicated for mild to moderate electrolyte disturbances, but surgery is a viable treatment option and should be considered in conditions related to hyperparathyroidism and malignancy. John L. Zeller, M.D., Ph.D.
Hypercoagulation disorders u
For Further Information Bilezikian, J. “Management of Acute Hypercalcemia.” New England Journal of Medicine 326 (1992): 11961203. Fauci, A., et al., eds. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill Health, 1998. Kovacs, C., S. MacDonald, C. Chik, and E. Bruera. “Hypercalcemia of Malignancy: A Treatment Strategy.” Journal of Pain and Symptom Management 10 (1995): 224232. Kumar, V., A. Abbas, N. Fausto, and R. Mitchell, eds. Robbins Basic Pathology. Philadelphia: Elsevier/ Saunders, 2007. Rankin, W., V. Grill, and T. Martin. “Parathyroid HormoneRelated Protein and Hypercalcemia.” Cancer 80, no. 8 (1997): 1564-1571.
u
Other Resources
American College of Physicians http://www.acponline.org American College of Surgeons http://www.facs.org National Cancer Institute Hypercalcemia http://www.cancer.gov/cancertopics/pdq/ supportivecare/hypercalcemia/patient See also Androgen drugs; Bisphosphonates; Calcium; Mediastinal tumors; Parathyroid cancer; Side effects; Zollinger-Ellison syndrome.
u Hypercoagulation disorders Category: Diseases, symptoms, and conditions Also known as: Hypercoagulable states, blood-clotting disorders, thrombophilia or thrombotic disorders Related conditions: Blood clots, deep vein thrombosis, pulmonary embolism Definition: Hypercoagulation disorders are inherited or acquired conditions that increase the tendency to develop excessive or abnormal blood clots in the arteries or veins. These disorders increase the risk of blood clots even in the absence of injury. A thrombus is a blood clot that forms and remains in a certain location, such as a blood vessel or the heart. An embolus is a blood clot that travels through the bloodstream to another location. People with hypercoagulation 615
Hypercoagulation disorders disorders have an increased risk of a deep vein thrombosis (blood clot in the deep leg vein) or a pulmonary embolism (blockage in a lung artery caused by a traveling blood clot), two conditions collectively termed “venous thromboembolism.” The majority of hypercoagulation disorders are acquired, with cancer as the primary cause. A malignancy is the underlying cause in about 10 percent of patients with venous thromboembolism. Factor V Leiden is the most common inherited hypercoagulation disorder. Other inherited disorders include prothrombin gene mutation, elevated or abnormal fibrinogen levels, antithrombin deficiency, and protein C and S deficiencies. Risk factors: Risk factors for acquired disorders include cancer, recent trauma or surgery, pregnancy, hormone replacement therapy, oral contraceptive use, heparin-induced thrombocytopenia, antiphospholipid antibody syndrome, deep vein thrombosis, pulmonary embolism, myeloproliferative disorders including polycythemia vera or essential thrombocytosis, elevated homocysteine levels (hyperhomocysteinemia), diabetes, prolonged bed rest with immobility or inactivity, and smoking. Risk factors for hereditary disorders include a family history of blood-clotting disorders or venous thromboembolism. Hereditary defects in one or more of the clotting factors may also increase a person’s risk. Etiology and the disease process: Hemostasis is the body’s natural mechanism to stop bleeding upon injury. Blood clot formation is part of this process and involves a variety of blood cells, platelets, blood proteins, and coagulation (clotting) factors. If there is an inherited or acquired imbalance or malfunction in any of these substances, the process of clot formation becomes abnormal. Certain chemotherapy drugs, such as asparaginase, can increase the risk of clotting. Estrogen in hormone replacement therapy or oral contraceptives can also increase the risk of excessive clot formation. Incidence: According to the Centers for Disease Control and Prevention, about 5 to 8 percent of the U.S. population have a hypercoagulation disorder, and more than 60,000 Americans die each year from a venous thromboembolism. Symptoms: There are no specific signs or symptoms of hypercoagulation disorders. Screening and diagnosis: Laboratory tests to measure blood-clotting time include the prothrombin time test to calculate the International Normalized Ratio (PT-INR), 616
Salem Health: Cancer activated partial thromboplastin (APTT) fibrogen level, and thrombin time. Genetic blood tests may be performed to identify certain gene mutations when an inherited hypercoagulation disorder is suspected. A complete medical history and physical—including a complete blood count; liver function test; urinalysis; chemistry panel including electrolytes, calcium, and creatine; and chest X ray—are used to diagnose these conditions. When an abnormality is indicated, further tests should be performed to determine the underlying cause of the disorder. In patients with recurrent venous thromboembolism, further screening to detect a malignancy is recommended. Treatment and therapy: Treatment for hypercoagulation disorders varies depending on the type of disorder. Generally, treatment includes anticoagulant medications to decrease the blood’s clotting ability and reduce the risk of clot formation. Anticoagulants, given in pill or injection form, include warfarin (Coumadin), heparin, low molecular-weight heparin, aspirin, ticlopidine (Ticlid), clopidogrel (Plavix), and fondaparinux sodium (Arixtra). Lepirudin (Refludan), bivalirudin (Angiomax), and argatroban (Novastan) are other anticoagulants that directly inhibit thrombin, a key protein that helps induce clotting. The use of anticoagulants in patients with a known malignancy increases the risk of complications, particularly when the malignancy is advanced. Therefore, the potential benefits of each anticoagulant therapy should be weighed against the risks. Some studies have suggested a reduced mortality risk with the use of heparin injections instead of oral anticoagulants. With the use of all anticoagulants, close monitoring is required to evaluate the patient’s response to the medication and to make dosage adjustments as needed. Thrombolytic (fibrinolytic) drugs, including streptokinase (Kabikinase, Streptase) and tissue plasminogen activator (tPA) agents such as alteplase (Activase), reteplase (Retavase), or tenecteplase (TNKase), are injections that may be given to dissolve a blood clot in select patients. These drugs are administered in a hospital setting and are effective only when given within six hours after the onset of a clot-induced stroke or heart attack. Prognosis, prevention, and outcomes: The outcomes of patients with hypercoagulation disorders depend on the rates of venous thromboembolism recurrence associated with the different disorders. Patients with inherited hypercoagulation disorders do not have a reduced survival rate, according to published data.
Salem Health: Cancer Patients with cancer and venous thromboembolism have an increased risk of recurrent thromboembolic events and major bleeding. Thrombosis can potentially complicate the course of cancer treatment by increasing the rate of hospital readmission as well as morbidity and mortality. Angela M. Costello, B.S. u For Further Information Deitcher, Steven R. “Hypercoagulable State Testing and Malignancy Screening Following Venous Thromboembolic Events.” Vascular Medicine 8, no. 1 (2003): 33-46. Johnson, C. M., L. Mureebe, and D. Silver. “Hypercoagulable States: A Review.” Vascular and Endovascular Surgery 39 (2005): 123-133. Prandoni P., A. Falanga, and A. Picciolli. “Cancer and Venous Thromboembolism.” Lancet Oncology 6 (2005): 401-410. u
Other Resources
Cleveland Clinic Disease Management Program Hypercoagulable States http://www.clevelandclinicmeded.com/ diseasemanagement/hematology/hyperco/ hyperco.htm National Alliance for Thrombosis and Thrombophilia http://www.nattinfo.org Society for Vascular Surgery VascularWeb.org http://vascularweb.org See also Amputation; Crohn disease; Disseminated intravascular coagulation (DIC); Fever; Hematemesis; Myeloproliferative disorders; Thrombocytopenia.
u Hyperthermia therapy Category: Procedures Also known as: Thermal ablation, radiofrequency ablation, RFA Definition: Hyperthermia is a treatment that uses high temperatures to destroy cancer cells directly. Hyperthermia therapy may also be used to raise the temperature of a region of the body to assist other types of cancer treatments, such as chemotherapy or radiation therapy, to be more effective.
Hyperthermia therapy Cancers treated: Under study in many cancers, such as breast, cervical, colorectal, kidney, ovarian, and prostate cancers Why performed: Heat has been shown to ablate (destroy) cancer cells. Hyperthermia therapy also seems to make cancer treatments such as radiation therapy and chemotherapy more effective. While the therapy has been available for years in an experimental mode, recent advances have made the treatment more practical. Patient preparation: Patient preparation depends on whether hyperthermia therapy is external or internal, such as during surgery; whether heating is local, regional, or whole body; or whether hyperthermia is used as a standalone treatment or to potentiate the actions of chemotherapy or radiation therapy. The level of heat is similar to a fever or a hot bath, but medications may be used to make treatments more comfortable for the patient. When hyperthermia is used during surgery, the patient is generally asleep (under anesthesia), depending on the site being treated. Steps of the procedure: Hyperthermia therapy may involve local thermal ablation of a tumor using radio waves, ultrasound, or microwaves with a machine from outside the body. Internal hyperthermia therapy uses a probe or needle inserted in the tumor, usually during surgery. Radiofrequency ablation (RFA) uses ultrasound or visualization during surgery to deliver high-energy radio waves to a tumor. Whole-body hyperthermia may use warming blankets or thermal chambers that heat the body. Procedures may be one time, such as during surgery, or daily, as when combined with radiation therapy. After the procedure: Patients may remain in the hospital if surgery and internal hyperthermia are used. If used in combination with radiation therapy or chemotherapy, hyperthermia treatments are generally outpatient in nature, and the patient may go home after each treatment. Risks: Side effects depend on the type of hyperthermia therapy but may include pain, infection, bleeding, damage to the skin, and nerve or muscle damage near the treatment site. Whole-body hyperthermia may cause symptoms such as nausea, vomiting and diarrhea, and, rarely, problems with other organs, such as the heart. Results: Heat may cause cellular changes that kill cancer cells or make cells more susceptible to the effects of chemotherapy and radiation. Patricia Stanfill Edens, R.N., Ph.D., FACHE 617
Hyperthermic perfusion See also Continuous hyperthermic peritoneal perfusion (CHPP); Fever; Hyperthermic perfusion; Lip cancers; Mayo Clinic Cancer Center; Microwave hyperthermia therapy; Radiation oncology.
u Hyperthermic perfusion Category: Procedures Also known as: Regional perfusion, isolated limb perfusion, hyperthermic isolated limb perfusion, continuous hyperthermic peritoneal perfusion, intraperitoneal hyperthermic chemotherapy Definition: Hyperthermic perfusion is a delivery system of anticancer drugs in which a warmed solution containing the drugs is directed to a cancerous organ or tissue by passing the solution through the blood vessels of the area or by bathing the tissue or organ in the solution. Cancers treated: Melanoma, soft-tissue sarcomas, colon cancer, peritoneal carcinomatosis, liver cancer, lung cancer Why performed: Hyperthermic perfusion is a technique that allows for maximum exposure of the tumor to anticancer drugs while limiting the toxic effects to the entire body. Heating the chemotherapy solution improves the effectiveness of the anticancer drugs. Patient preparation: To prepare an area for hyperthermic perfusion, it is necessary to temporarily isolate the circulation of the area from systemic circulation. Additionally, in certain types of tumors (such as peritoneal carcinomatosis), cytoreductive surgery is first performed to remove as much visible tumor as possible prior to isolating the area and proceeding with hyperthermic perfusion. Steps of the procedure: The arms and legs are frequently the regions exposed to hyperthermic perfusion for the treatment of melanoma or for the treatment of sarcoma of soft tissues. Isolating the circulation of an arm or leg is achieved by putting small tubes (cannulas) in the arteries that carry blood to that limb and in the veins that carry blood out from the limb; this process is called cannulating. In addition, a rubber tourniquet is put at the top of the arm or leg to aid in isolating the area. Thermometers are placed at several locations on the limb to monitor the temperature during the procedure. A perfusion circuit is established by attaching tubing between the artery and vein cannulas and a special type of pump. The pump apparatus includes an oxygenator (to in618
Salem Health: Cancer crease the concentration of oxygen in the blood) and a mechanism to heat and cool the perfusion solution. Heparin (a blood-thinning substance), a special dye, and electrolytes are mixed with the patient’s blood and circulated through the isolated area. Heparin is used to prevent blood clots from forming, and the dye is used to monitor the perfusion solution and ensure that it does not escape the intended treatment area. The temperature of the perfusion solution is increased (hyperthermia) as it circulates through the isolated area; the anticancer drugs are added when the solution reaches a prescribed temperature. The temperature of the arm or leg, the rate of flow, and the perfusion pressure are all carefully monitored during the procedure. The circulation of the hyperthermic solution lasts for about one hour, and then the anticancer drug is drained from the treated area and the area is washed out. The whole procedure lasts a maximum of two hours. Continuous hyperthermic peritoneal perfusion or intraperitoneal hyperthermic chemotherapy uses techniques similar to those used for isolated limb perfusion to deliver a chemotherapy solution to the peritoneal cavity (the space inside the abdomen that has a membrane covering all the organs in the abdomen). Cannulas in the arteries and veins are used with tubing and a pump, and the cavity is sewn shut to create a closed circuit. The entire peritoneal cavity is bathed (perfused) with the warmed chemotherapy solution. Delivering the anticancer drugs directly to the peritoneal cavity allows a much higher dosage of the drugs to be used. As with hyperthermic perfusion of an isolated limb, the procedure for continous hyperthermic peritoneal perfusion lasts about two hours and ends with draining the drug solution and washing out the peritoneal cavity. Other organs, such as the liver and the lungs, can also be isolated with similar methods. A variety of anticancer drugs are used in hyperthermic perfusion, including mitomycin C, oxaliplatin, melphalan, and tumor necrosis factors (TNFs). After the procedure: Patients are hospitalized after the procedure and are given low doses of heparin to prevent blood clots. If the procedure has been used for an arm or a leg, then that limb is kept elevated for a few days; the period of hospitalization is approximately three days. The hospitalization period for a more extensive procedure, such as cytoreduction surgery in the peritoneal cavity followed by hyperthermic peritoneal perfusion, is approximately ten days. Risks: Edema (an accumulation of fluid in tissue) is an expected risk or discomfort from the procedure, but it is most often easily treatable. Severe swelling of an arm or leg to
Salem Health: Cancer the extent that it interferes with circulation is called compartment syndrome; severe cases of compartment syndrome require amputation of the limb. Other expected risks include temporary toxicity to the bone marrow, inflammation of the veins, and an increased risk of bleeding because of the use of heparin. Results: Research studies have shown an increased diseasefree survival of patients for whom hyperthermic perfusion is used. Results of any therapy, however, are dependent upon many factors, chief among them the stage of the cancer at the time of the therapy. Vicki Miskovsky, B.S., R.D. u For Further Information Dollinger, Malin, et al. Everyone’s Guide to Cancer Therapy. 4th rev. ed. Kansas City, Mo.: Andrews & McMeel, 2002. Perry, Michael C., ed. The Chemotherapy Source Book. 4th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008. u
Other Resources
National Cancer Institute Clinical Trials http://www.cancer.gov/clinical_trials See also Continuous hyperthermic peritoneal perfusion (CHPP).
u Hypopharyngeal cancer Category: Diseases, symptoms, and conditions Also known as: Throat cancer Related conditions: Head and neck cancers Definition: Hypopharyngeal cancer is a cancer of the throat (pharynx). Risk factors: Tobacco use (smoking and chewing), heavy alcohol use, and eating a very poor diet increase the risk of developing hypopharyngeal cancer. In the United States, hypopharyngeal cancer is three times more common in men than in women. Etiology and the disease process: Hypopharyngeal cancer develops in squamous epithelial cells lining the throat. Primary tumors may occur in more than one area. This is an aggressive cancer that spreads quickly. Incidence: This cancer is uncommon, with only about 2,500 new cases diagnosed in the United States each year.
Hypopharyngeal cancer It is most often found in people from the ages of fifty to sixty and is rare in people under age thirty. Symptoms: Symptoms are general, making early diagnosis difficult. The most common symptoms are a sore throat (usually on one side only) that does not respond to antibiotics, a lump on the neck (swollen lymph node), hoarseness, difficulty swallowing, and ear pain. Screening and diagnosis: There is no routine screening for hypopharyngeal cancer. Diagnosis is made by a physical examination of the neck and throat, followed by imaging studies (X rays, magnetic resonance imaging, or computed tomography scans). An endoscopy (lighted tube passed down the throat) and biopsy (tissue sample) confirm the diagnosis. The same procedures used in diagnosis are used for staging the cancer: • Stage 0: Cancer is on only the lining of the throat (carcinoma in situ). • Stage I: One tumor smaller than 2 centimeters (cm) in diameter is present. • Stage II: The tumor is 2 to 4 cm in diameter and has not spread to the larynx (voice box) but may be in more than one area of the pharynx. • Stage III: The tumors are less than 4 cm in diameter, but cancer has spread to at least one lymph node. • Stage IV: The tumor has spread to surrounding tissues and lymph nodes or to other parts of the body. Treatment and therapy: The tumor and surrounding tissue are surgically removed. This may cause permanent voice loss. Radiation treatments usually follow surgery. Chemotherapy may be used in very aggressive or inoperative cases. Prognosis, prevention, and outcomes: Most hypopharyngeal cancer is diagnosed in Stage III or IV. The fiveyear survival rate for cancers found in Stages I and II is 50 to 60 percent, and for those found in Stages III and IV, it falls to 15 to 30 percent. Recurrence may occur, usually within the first two years following surgery. Eating a good diet, avoiding tobacco products, and restricting alcohol help prevent this cancer. Martiscia Davidson, A.M. See also Barium swallow; Chewing tobacco; Cigarettes and cigars; Epidermoid cancers of mucous membranes; Esophageal cancer; Head and neck cancers; Oral and oropharyngeal cancers; Throat cancer; Tobacco-related cancers. 619
Hysterectomy
u Hysterectomy Category: Procedures Also known as: Vaginal hysterectomy, abdominal hysterectomy, total or complete hysterectomy, total hysterectomy with salpingo-oophorectomy, laparoscopic-assisted vaginal hysterectomy, radical hysterectomy Definition: Hysterectomy is the removal of the female reproductive organs. There are seven different types of hysterectomy. Basic hysterectomy is the surgical removal of the uterus. Total or complete abdominal hysterectomy (TAH) involves the surgical removal of the uterus and cervix. Total hysterectomy with salpingo-oophorectomy is the surgical removal of the uterus, cervix, ovaries, and Fallopian tubes. Vaginal hysterectomy (VH) is the surgical removal of the uterus through the vaginal opening. Abdominal hysterectomy is the surgical removal of the uterus through an abdominal incision. In laparoscopic-assisted vaginal hysterectomy (LAH or LAVH), a laparoscope is inserted through several small incisions in the abdominalpelvic region, helping guide the surgeon, who then removes the organs through the vaginal opening. Radical hysterectomy is the surgical removal of the uterus, cervix, ovaries, Fallopian tubes, surrounding lymph nodes, surrounding muscles and ligaments, and the superior portion of the vagina. Cancers treated: Ovarian, uterine, abdominal, Fallopian tube, and cervical cancers; for certain types of breast cancer, a complete hysterectomy or oophorectomy may be required if the type of tumor is estrogen sensitive. Why performed: In addition to the treatment of cancer, hysterectomy may be performed for abnormal bleeding or hemorrhaging, endometriosis, pelvic pain, dysmenorrhea, ovarian cysts, ovarian tumors, fibroid tumors, prolapsed bladder, prolapsed uterus, bleeding cervical polyps, pelvic floor reconstruction, hyperplasia, abdominal mass, and pelvic inflammatory disease (PID). Hysterectomy may also be advised for patients with colon, bladder, or rectal cancers to help increase their long-term survival. Patient preparation: Many patients find that doing their own research and getting a second opinion give them valuable information. They may ask their health care professionals for informational pamphlets from Krames Communication or the American College of Obstetricians and Gynecologists. Prior to having a hysterectomy, most patients undergo some of the following procedures: a Pap test and other laboratory tests, pelvic examination, hormone therapy, biopsy, ultrasound, hysteroscopy, electro620
Salem Health: Cancer cardiography (EKG), computed tomography (CT), magnetic resonance imaging (MRI), colposcopy, laparoscopy, colonoscopy, dilation and curettage (D&C), and myomectomy. Some patients have tried Kegel exercises to help strengthen the pelvic muscles or have worn a pessary. Patients should stop smoking one week prior to surgery. They should bring a list of questions and a complete list of all medications, including vitamins, herbal remedies, and any over-the-counter medications, to the preoperative (pre-op) examination in order to find out which medications they can take or which ones they will need to stop taking prior to surgery. A pre-op evaluation by a doctor or surgeon includes a chest X ray and laboratory work. The results of the pre-op tests have the potential to postpone or cancel any surgery. The risks versus the benefits of the surgery are evaluated. Patients should follow their physician’s pre-op instructions to help ensure the best possible outcome for the surgery. The night before the surgery, they should have nothing to eat or drink after 6:00 p.m. and should take a shower and wash the hair with antibacterial soap. Steps of the procedure: The morning of the surgery, the patient is given a hospital gown to wear. No personal clothing will be allowed. All jewelry must be removed as to not interfere with heart monitors and other medical electrical devices. All makeup and nail polish must be removed for the observation process, helping to verify oxygen levels. The patient should not use any lotions, deodorants, or perfumes, as they make it difficult for surgical personnel to adhere EKG chest leads, attach monitors, and secure bandages onto the body. A bladder catheter may be inserted for urinary drainage purposes. General anesthesia is required for this surgery. The anesthesiologist will talk to the patient before surgery. Four incision styles may be used. Vertical incision involves a visible external incision for an abdominal hysterectomy, approximately 6 inches long, extending upward from the symphysis pubic bone to the navel. For horizontal incision (also known as transverse incision or bikini cut), a 6-inch-wide, visible, horizontal incision is placed approximately 1 inch above the pubic bone. Vaginal incision requires an incision through the superior portion of the vagina. LAVH requires approximately four small incisions in the abdominal/pelvic area and an incision in the superior portion of the vagina. Four main abdominal muscle layers are cut in order to remove the uterus: rectum abdominis, external oblique, internal oblique, and transverse abdominis. If the ovaries are removed, then the ovarian ligament, suspensory ligament, and broad ligament are also severed.
Salem Health: Cancer The number of internal dissolvable stitches and the number of external staples to close the incision depend on the complexity of the surgery. The physician may also change the staples to Steri-Strips around five to ten days after the surgery (post-op). After the procedure: The initial recovery time is six to eight weeks; however, the complete healing process takes six to twelve months. The patient should take showers, not baths, until the doctor approves of the latter. The patient should also take pain medication as directed, walk for exercise, and drink plenty of liquids. The body endures many physical, emotional, and hormonal changes after a hysterectomy. Weight-lifting restrictions, sexual relationship concerns, anemia, post-op bleeding, adhesions, and blood clots are issues that the doctor should discuss with the patient. The patient should understand the post-op instructions and call the medical facility if fever, nausea or vomiting, severe pain anywhere in the body, difficulty breathing, or hemorrhaging occurs. It is normal to have a slightly bloody vaginal discharge up to fourteen days post-op as a result of the healing process and sutures dissolving and falling out. Menopause is a life-altering stage. The patient will need to educate herself about hot flashes, night sweats, hormone replacement therapy (HRT), vitamin and mineral supplements, and herbal remedies. Risks: The risks of hysterectomy may include bleeding, blood transfusions, adhesions, pain, surgical and postsurgical complications, nausea or vomiting, blood clots (thrombosis), abscess, cellulitis, infections, nerve injury, bowel injury, intestinal injury, bladder injury, prolapsed bladder, prolapsed rectum, twisted bowel, gas pain, adverse reaction to anesthesia, and death. Results: Hysterectomy may result in the removal of cancers, the stopping of menstrual and irregular bleeding, a decrease or elimination of pain, and repair of the bladder or bowel. Menopause is the direct result of a hysterectomy, as menstrual flow will permanently cease. Hot flashes, night sweats, vaginal dryness, osteoporosis, cardiovascular (heart) disease, memory loss, dry skin, xerostomia (dry mouth), dry eyes, and decreased sexual libido can occur. Suzette Buhr, R.T.R., C.D.A. u
For Further Information Dennerstein, Lorraine, Carl Wood, and Ann Westmore. Hysterectomy: New Options and Advances. New York: Oxford University Press, 1995. Jones, Marcia L., Theresa Eichenwald, and Nancy W.
Hysterography Hall. Menopause for Dummies. 2d ed. New York: Wiley, 2006. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003. Porter, Robert S., ed. The Merck Manual of Women’s and Men’s Health. 2d ed. New York: Simon & Schuster, 2006. u
Other Resources
BestHealth, Wake Forest University Baptist Medical Center http://www.besthealth.com University of Michigan Comprehensive Cancer Center http://www.cancer.med.umich.edu See also Cervical cancer; Choriocarcinomas; Dilation and curettage (D&C); Endometrial cancer; Endometrial hyperplasia; Fallopian tube cancer; Fertility drugs and cancer; Gestational trophoblastic tumors (GTTs); Granulosa cell tumors; Gynecologic cancers; Gynecologic oncology; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hormone replacement therapy (HRT); Hot flashes; Hystero-oophorectomy; Laparoscopy and laparoscopic surgery; Leiomyomas; Leiomyosarcomas; Pap test; Salpingectomy and salpingo-oophorectomy; Sexuality and cancer; Uterine cancer; Vaginal cancer.
u Hysterography Category: Procedures Also known as: Hysterogram Definition: Hysterography is a diagnostic procedure that uses contrast dye to enhance X-ray images of the interior of the uterus. Cancers diagnosed: Uterine cancer, endometrial cancer Why performed: Hysterography is a diagnostic procedure that is used to help identify uterine and endometrial cancer. Hysterography allows a doctor to analyze the interior lining of the uterus to check for possible cancerous growths, such as uterine sarcoma or endometrial cancer. Patient preparation: The preferred time to receive a hysterography is after the last day of menstruation and prior to ovulation, to prevent interrupting a pregnancy. Routine laboratory tests for sexually transmitted diseases (STDs) and pregnancy are conducted before the procedure. 621
Hystero-oophorectomy Hysterography is an outpatient procedure performed at a radiology department. Patients may receive pain medication, a mild sedative, or antibiotics prior to the procedure. Patients don an examination gown and wear nothing below the waist. The procedure can usually be completed in about fifteen to forty-five minutes. Steps of the procedure: Patients lie on their backs on an examination table during the procedure. The patient’s knees are spread and the feet are placed in stirrups. A speculum is inserted into the vagina to separate the vaginal walls. The cervix is cleansed. A thin catheter is inserted through the cervical opening. Contrast dye is delivered to the uterus through the thin tube. The doctor views the contrast dye as it fills the uterus by watching images on a fluoroscopy screen. X rays are taken during the process. Patients may be repositioned to allow X rays to be taken from various angles. When the hysterography is complete, the catheter and speculum are gently removed. Patients are monitored for a short time for allergic reaction or bleeding. After the procedure: Patients may experience menstruallike cramps or light bleeding for a few days following the procedure. Patients should not use tampons and douches or participate in sexual intercourse for two days. Patients may receive pain medication or antibiotics. Patients should contact their doctor if they experience heavy bleeding, infection, allergic reaction, breathing problems, or increased pain. Risks: The risks of hysterography include allergic reaction to the contrast dye, infection, or prolonged bleeding. Results: A healthy uterus has no abnormal growths or tissues. Suspicious or cancerous-appearing growths are biopsied in a separate procedure to confirm a diagnosis of cancer. Mary Car-Blanchard, O.T.D., B.S.O.T. See also Endometrial cancer; Endoscopy; Gynecologic cancers; Gynecologic oncology; Hysterectomy; Hysterooophorectomy; Hysteroscopy; Oophorectomy; Pelvic examination; Salpingectomy and salpingo-oophorectomy; Uterine cancer.
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u Hystero-oophorectomy Category: Procedures Also known as: Total abdominal hysterectomy and bilateral salpingo-oophorectomy Definition: Hystero-oophorectomy is the surgical removal of the uterus and both the right and left Fallopian tubes and ovaries. Cancers treated: Invasive cervical carcinoma Stage I to IIA, endometrial carcinoma, uterine leiomyomas Why performed: Hystero-oophorectomy is the primary treatment and staging modality for malignant cancers amenable to resection arising from any of the three tissue layers of the uterus. Benign tumors of the uterus such as fibroids (leiomyomas) that do not regress with time, that degenerate, or that bleed excessively are also an indication. The ovaries are often removed simultaneously in postmenopausal women in order to prevent possible degeneration of cells into ovarian cancer. In premenopausal women undergoing hystero-oophorectomy, the ovaries are removed when they are at high risk for developing estrogen-stimulated cancers such as breast and endometrial cancers. Patient preparation: The patient undergoes preoperative evaluation for any coexisting diseases to determine her fitness to undergo surgery and general anesthesia. Patients are instructed to take nothing per mouth the night before the procedure. Steps of the procedure: After the patient is anesthetized, in the lithotomy position, surgically prepped and draped, a transverse or vertical incision is made above the pubic bone. The incision is taken down to the pelvic cavity. The uterine and ovarian vessels are identified, dissected, and separated from the ureters, and the bladder is separated from the uterus. The supporting ligaments and dissected vessels of the Fallopian tubes, ovaries, uterus, and cervix are then isolated, cut, and ligated, and the vaginal and cardinal ligament stumps are sutured together. Alaparoscopic approach may be similarly done, except that the uterus, Fallopian tubes, and ovaries are removed vaginally. After the procedure: The patient is monitored in the postanesthesia care unit until she is fully awake and vital signs are stable. Once the patient is stable in the unit, she may be discharged to the gynecologic ward for postoperative monitoring. Once the patient is stable, ambulatory, voiding, and eating, she may be discharged after a few days.
Salem Health: Cancer
Hysteroscopy
Risks: The most significant risks of the procedure are deep vein thrombosis, pulmonary embolism, perforation of the bladder or bowel, and accidental ligation of the ureters. Results: A gross and microscopic examination of large masses may reveal central necrosis and hemorrhage and increased growth of uterine cells but no elements of disordered growth of abnormal cells. Microscopic examinations that reveal disordered proliferation and abnormal uterine or cervical cells are suggestive of uterine cancer or invasive cervical cancer. Aldo C. Dumlao, M.D. See also BRCA1 and BRCA2 genes; Breast cancers; Fallopian tube cancer; Gynecologic oncology; Hormonal therapies; Hot flashes; Hysterectomy; Oophorectomy; Salpingectomy and salpingo-oophorectomy.
u Hysteroscopy Category: Procedures Also known as: Uterine endoscopy Definition: Hysteroscopy uses a type of endoscope to allow a doctor to see, examine, and biopsy abnormal tissues or growths inside the uterus, the part of the female reproductive system where a fertilized egg develops. The procedure is used to check for cancer cells and remove suspicious tissue, precancerous tissue, or cancerous growths. A hysteroscope is a thin tube with a viewing instrument and a light. There are different types of hysteroscopes, depending on whether the procedure is for diagnosis or treatment purposes. The tube may be flexible or rigid. It expands like a telescope. A hysteroscope can contain fiber optics that produce images on a video screen. It can also contain tubes for inserting gas or fluids and surgical instruments.
with thin surgical instruments that are inserted through the hysteroscope. The tissues are examined for cancer cells in a laboratory. For small cancers, removing the cells helps to treat the cancer. Patient preparation: The preferred time to receive a hysteroscopy is after the last day of menstruation and before ovulation, to prevent interrupting a pregnancy. Routine laboratory tests, including blood and urine tests, are conducted before the hysteroscopy. A pregnancy test, Pap smear, and sexually transmitted disease (STD) testing may be performed as well. A hysteroscopy is an outpatient procedure performed in a doctor’s office, outpatient surgical center, or hospital. Hysteroscopy uses local anesthesia, general anesthesia, paracervical nerve block, or mild sedation. It can be performed with no anesthesia in select individuals. Patients receiving general anesthesia should not eat or drink after midnight prior to the day of surgery. On the day of the hysteroscopy, patients are requested to empty their bladder before the procedure begins. Patients wear an examination gown with nothing on below the waist. Steps of the procedure: Patients lie on their backs with their knees spread and feet placed and secured in stirrups.
Cancers diagnosed or treated: Uterine cancer, uterine sarcoma, endometrial cancer, precancerous growths Why performed: Hysteroscopy is used as a diagnostic or a treatment procedure. It is used to view the inside of the uterus to detect possible cancerous growths, such as uterine sarcoma and endometrial cancer. Suspicious tissues are biopsied. A biopsy entails removing tissue, mucus, or fluid samples
A hysteroscope is used to check the inside of the uterus. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Hysteroscopy Patients receive anesthesia, and their vital signs are monitored during the procedure. A catheter may be inserted through the urethra and into the bladder to collect urine. A speculum is inserted into the vagina to separate the vaginal walls, allowing the doctor to see the cervix (opening to the uterus). The doctor may dilate the cervical opening with a device; some hysteroscopes are narrow enough to fit through the cervical opening without requiring dilation. The hysteroscope is inserted in the vagina, moved through the cervix, and advanced to the uterus. Gas or sterile fluid may be used to expand the uterus and provide the doctor with a good view. The gas or fluid is delivered through a tube in the hysteroscope. Fluid is preferred in some cases because it washes mucus from the uterine walls, allowing the mucus to be collected for biopsy and creating a clearer image. The doctor views the walls of the uterus, looking for any signs of abnormality, such as an irregular growth, fibroid, or polyp. A biopsy is taken of any abnormal or suspicious tissue or growths. At completion of the hysteroscopy, the gas, fluid, catheter, and hysteroscope are removed. After the procedure: Patients are monitored in the recovery area. Patients are discharged when they are awake and alert. Patients should have another person drive them home. Mild cramping or pain may occur for about eight hours after the procedure. Light bleeding may occur for a couple of days. Risks: Rare complications of hysteroscopy include infection; prolonged bleeding; uterine, bowel, or bladder perforation; and fluid absorption into the bloodstream. Patients should contact their doctor if they develop a fever, severe pain, unusual discharge, or heavy bleeding. Results: A healthy uterus has no abnormal growths or tissues. Suspicious growths are biopsied to determine whether cancer is present. Mary Car-Blanchard, O.T.D., B.S.O.T.
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For Further Information Bettocchi, S., et al. “What Does ‘Diagnostic Hysteroscopy’ Mean Today? The Role of the New Techniques.” Current Opinions in Obstetrics and Gynecology 15, no. 4 (August, 2003): 303-308. Donnez, Jacques, ed. Atlas of Operative Laparoscopy and Hysteroscopy. 3d ed. New York: Informa Healthcare, 2007. Fuller, Arlan F., Jr., Robert H. Young, and Michael V. Seiden. Uterine Cancer. Hamilton, Ont.: BC Decker, 2004. Luesly, David M., Frank Lawton, and Andrew Berchuck, eds. Uterine Cancer. New York: Informa Healthcare, 2005. Mayo Clinic. Mayo Clinic: Guide to Women’s Cancers. New York: Kensington, 2005. Pasic, Resad P., and Ronald Leon Levine. A Practical Manual of Hysteroscopy and Endometrial Ablation Techniques: A Clinical Cookbook. New York: Informa Healthcare, 2004. Valle, R. F. “Development of Hysteroscopy: From a Dream to a Reality, and Its Linkage to the Present and Future.” Journal of Minimally Invasive Gynecology 14, no. 4 (July/August, 2007): 407-418.
u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov National Women’s Health Information Center U.S. Department of Health and Human Services http://womenshealth.gov See also Endometrial cancer; Endoscopy; Gynecologic cancers; Gynecologic oncology; Hysterectomy; Hysterography; Hystero-oophorectomy; Oophorectomy; Pelvic examination; Salpingectomy and salpingo-oophorectomy; Uterine cancer.
Salem Health: Cancer
u Ileostomy Category: Procedures Also known as: End ileostomy, loop ileostomy, separated loop ileostomy, continent ileostomy Definition: An ileostomy is a procedure that creates an opening on the abdomen (stoma) from a segment of the latter portion of the small bowel (ileum). An ileostomy can be permanent (end ileostomy) or temporary (loop ileostomy). Cancers treated: Colorectal and small bowel cancer; metastatic pelvic cancer, including vaginal, cervical, ovarian, and prostate cancers Why performed: The ileum may sometimes become diseased and may cause symptoms of bowel obstruction, bleeding, or nutrient malabsorption. Potentially lifethreatening or premalignant conditions such as severe inflammatory bowel disease involving the ileum and colon (Crohn disease, ulcerative colitis) are also managed with the use of ileostomy. Because the ileum absorbs many essential nutrients relative to the rest of the small bowel, preservation of disease-free regions is paramount. An ileostomy is performed primarily in order to divert digested material for excretion in cases where the colon or rectum is diseased or otherwise unusable. It is also done in order to permit healing of the remaining, but usable, colon to be used later in reestablishing continuity between the small and large bowel. This is also done after two bowel ends are newly rejoined (anastomosis) to allow the bowel to rest and expedite healing. The ileostomy is located before the anastomosis to prevent digested material from stimulating the joined ends from unnecessary contractions. Patient preparation: Surgical risk assessment is conducted through a general physical examination, medication review and revision, electrocardiography (EKG) and chest X ray, and pulmonary function tests as needed. Other considerations include ensuring that the patient is adequately nourished and hydrated beforehand. Bowel preparation by a gradual decrease in food and liquid intake and enemas is carried out at least twenty-four hours prior to the procedure. The decision to undergo the procedure should be accompanied by active patient participation. The patient must be thoroughly briefed regarding the care of and implications of a permanent ileostomy in the event that reattachment to the distal bowel is not possible. If the procedure is agreeable to the patient, then the position of the stoma is discussed and marked on the patient’s abdomen prior to the procedure.
Ileostomy Steps of the procedure: After the patient is positioned and the surgical site is sterilized, a mid-abdominal incision is made and carried down to the abdominal cavity. The length of the small and large bowel is examined for viable and nonviable regions. Any diseased sections are excised, with the undiseased ends reattached. Any additional abdominal cavity procedure such as lymph node dissection and resection is carried out. The construction of the ileostomy will depend on the severity of disease (the presence of disease-free colon for reattachment in a separate procedure). A permanent end ileostomy is constructed by dividing the remaining ileum from the colon, preserving as much bowel as possible. Both ends are closed with staples or sutures. The thin membrane containing the bowel’s blood vessels (mesentery) at the proximal ileal end is cut to allow manipulation; the vessels directly supplying it are preserved. Another abdominal incision is made over the previously marked area, through which 6 centimeters of ileum is pulled. The stapled end is cut, and a spigot is fashioned by suturing the ileum onto the skin at three points. This prevents the fluid and electrolyte imbalance of ileostomy dysfunction caused by partial stoma obstruction. A temporary loop ileostomy is constructed in a similar manner as an end ileostomy except that both ends of the ileum are used, with the distal end nonfunctional in excretion. In addition, interruption of the mesentery is minimal because of the need for both ends to be supplied adequately with blood. After the procedure: The patient is allowed to recover consciousness in a postanesthesia care unit before going to the surgical ward. Recovery time can reach ten to twelve days, with resumption of normal activity by four to eight weeks. Maintenance of the ileostomy involves becoming familiar with frequent changing of the different parts of the ileostomy appliance, such as the skin barrier and the ileostomy bag. With the absence of the colon as a waterreabsorbing and storage apparatus for digested food, the patient must empty the collection bag frequently and be more aware of the amount and type of food and drink consumed, especially during exercise and hot weather. Risks: The risks of bleeding, impaired healing, and infections are always present. Meticulous adherence to surgical technique prevents most of these complications. Long-term risks for the duration of the ileostomy include obstruction from food particles or bowel adhesions, fistulas, infection, and dehydration from increased ileostomy fluid output. Results: An ileostomy is not directly curative for cancer, but it is a helpful procedure in restoring the patient’s conti625
Imaging tests nence and a semblance of normal bowel function at a later time through anastomosis of ileum to colon or rectum. While the position of an ileostomy allows for easy cleaning and draining of the ileostomy appliance and does not interfere greatly with daily routines and activities, one of the most important patient considerations to be made is that of self-image after ileostomy. Aldo C. Dumlao, M.D. u For Further Information Bernstein, Charles N. Inflammatory Bowel Disease Yearbook 2004. London: Remedica, 2004. Gislason, Stephen J. Food and Digestive Disorders: Irritable Bowel Syndrome, Crohn’s Disease, Celiac Disease, Ulcerative Colitis, Ulcers, Reflux and Motility Disorders. Sechelt, B.C.: Environmed Research, 2003. Williams, Simon J. Medicine and the Body. London: Sage Publications, 2003.
See also Coloanal anastomosis; Colorectal cancer; Enterostomal therapy; Gastrointestinal complications of cancer treatment; Hereditary polyposis syndromes.
u Imaging tests Category: Procedures Also known as: Radiology tests Definition: Imaging tests are procedures that use a source of energy to evaluate specific internal structures of the body and obtain a visual representation of such structures using special equipment. The energy sources used for these procedures may be magnetic fields, radio waves, radioactive particles, sound waves, or X rays. Imaging tests include computed tomography (CT) scans, magnetic resonance imaging (MRI), radiography (X rays) with and without contrast studies, mammography, radionuclide imaging, and ultrasonography. Imaging tests are distinguished based on the manner by which the bodily structure is viewed. CT scans use a concentrated beam of X rays to obtain multiple views of such structures; the images are then processed in a computer to provide a three-dimensional composite for easier analysis and interpretation. MRI uses magnetic force to align hydrogen atoms of the body in one direction. A burst of radiofrequency waves is then applied, causing a change in alignment. Signals are emitted by the hydrogen atoms as they return to their original orientation. A computerized scanner detects and converts these signals into two- or three-dimensional images for analysis and interpretation. 626
Salem Health: Cancer Radiography utilizes X rays, high-energy electromagnetic waves in small doses, to obtain images of body structures. Modified types of X-ray studies employ dyes as contrast agents to view structures that regular X-ray techniques do not visualize; the contrast agents can outline or fill in structures and can provide better radiographic imaging. These modified studies include upper gastrointestinal (GI) series (barium swallow), examining the lining of the esophagus, stomach, and upper part of the small intestines; lower GI series (barium enema), analyzing the colon and rectum linings; intravenous pyelography (IVP), viewing the urinary tract (kidney, ureters, and bladder); angiography inspecting arteries such as those in the heart and brain; and lymphangiography, investigating the lymph vessels and lymph nodes. Mammography employs X rays for examining the breasts to screen for breast disease in the absence of symptoms and for diagnosis when breast abnormalities are detected by screening. The images are available either on Xray photographic films or in digital form electronically stored in a computer. Radionuclide imaging (nuclear scan) uses radioactive tracers to obtain images from within the body; radioactive emissions are picked up by a computerized external detector, and the processing of these signals provides images of the internal body structures. Examples of radiopharmaceuticals include gallium 67, used to detect bone marrow, lung, and lymph node tumors; technetium 99, employed in whole-body scans to evaluate metastasis of various primary cancers; thallium 201, utilized in detecting breast cancers, thyroid tumors, and lymphomas; and iodine 123 and iodine 131, used to detect thyroid cancers and neuroendocrine tumors such as carcinoid tumors. Depending on the disease, the tissues affected absorb more or less of the radioactive tracers; the nuclear scans can locate tumors and identify cancer spread. Ultrasonography employs high-frequency sound waves to produce images of internal body structures. During the procedure, the sonographer uses a small handheld transducer that generates sound waves. Internal body organs reflect these sound waves back to the transducer, and a computer processes these signals into images. Ultrasound scans show the size and shape of organs as well as blood flow in some cases; abnormalities in the organ structures and blood flow can be observed if present. Cancers diagnosed or treated: Almost all types of solid cancers, including those of the breasts, brain and spinal cord, thyroid, bones, gastrointestinal organs (esophagus, stomach, pancreas, liver, colon, and rectum), reproductive organs (ovaries, prostate, and testes), soft tissues (mus-
Salem Health: Cancer
Imaging tests
Imaging tests include CT scans, MRI, X rays with and without contrast studies, mammography, radionuclide imaging, and ultrasonography. (©Lester Lefkowitz/Corbis)
cles, tendon, and fat), and urinary tract organs (bladder, ureters, and kidneys); hematological cancers such as Hodgkin disease and non-Hodgkin lymphoma Why performed: Imaging tests are performed in cancer management for many reasons, including screening for the presence or absence of cancer in people who have no symptoms, diagnosing cancer, obtaining image-guided biopsy, staging cancer or evaluating tumor spread, planning a cancer treatment (such as assessing the specific site of a tumor prior to radiation treatment), and evaluating cancer treatment to determine if it is working or whether a tumor has recurred. Patient preparation: The type of imaging test and use of contrast material will dictate the patient preparation. For example, patients may be instructed not to eat or drink several hours before a CT scan, radionuclide imaging, special X-ray procedures, or ultrasound is performed. If a contrast dye will be used, and depending on what part of the body will be evaluated, then the patient may need to drink the liquid contrast, may need an intravenous (IV) catheter for injection, or may use an enema. The radioactive material for nuclear scans is given by mouth or by injection through an IV line. Standard X rays and mammograms do not require special preparation. The best time for a mammogram is about one week following a menstrual period, when the breasts are least likely to be sensitive. For pediatric patients, the parents need to be counseled on proper preparations for the imaging tests so that the patients’ anxiety may be reduced. In emergency cases, preparation for imaging procedures may not be possible.
Steps of the procedure: Imaging tests are often done on an outpatient basis in a hospital or clinic radiology department. The type of radiology test and use of contrast material will dictate the procedure. Generally, the patient will be asked to use a medical examination gown or to undress to expose the body part that needs to be studied. Metallic objects that can interfere with imaging tests will be removed, if possible. The patient may be asked to sit, stand, or lie down depending on the body structure that needs to be evaluated. A certified radiology technologist will guide patients through the steps of the procedure. A radiologist may be present if there is a need to perform a biopsy or provide an intervention; the radiologist will provide the final radiological report with the evaluation and analysis of the images. Patients undergoing CT scans lie on a flat table attached to a CT scanner that looks like a large doughnut-shaped machine. The table can slide in and out of the hole in the scanner. The X-ray tube and detector are rotated around the patient while images are obtained. The detector takes numerous snapshots of the X-ray beam, and these image slices are processed by a computer to provide the threedimensional CT scan image. Patients undergoing MRI scans lie flat on a table that can slide back and forth in the opening of the cylindrical or tunnel-type MRI scanner. The cylinder encloses the patient, causing a feeling of claustrophobia in some patients. During the procedure, the machine makes loud thumping or banging noises that represent the magnetic fields turning on and off. Earplugs or headphones can be used during the procedure. Patients who have metallic implants such 627
Imaging tests as pacemakers, surgical clips or staples, and implanted pumps, IV catheters, or ports for medications should thoroughly discuss the risks and benefits of MRI scans with their physicians. Tattoos and cosmetics can affect MRI images; thus, it is important to inform the radiology technologist about them before the procedure. Standard radiographic studies are straightforward. The patient will be examined for the specific body structure that is being evaluated, such as the chest or abdomen. Modified X-ray studies using contrast agents such as barium swallow, barium enema, IVP, angiography, and lymphangiography will require provision of the contrast material via oral, injection, or rectal routes prior to the procedure. Angiography and lymphangiography will require diet restriction to only liquid oral intakes before the test; the contrast agent will be injected through an IV line just before the X-ray procedure. Restriction of food intake (no food or drink) for eight to twelve hours prior to barium swallow, barium enema, or IVP will be required; a series of X rays of the upper GI, lower GI, and urinary tract will be obtained during the procedure. Mammography screening requires exposure of the breasts (undressing from the waist up to the breasts) and removal of jewelry from the neck. Deodorants, ointments, creams, perfumes, and powders should not be used on the day of the mammogram, as these substances can interfere with the breast imaging. The breasts are placed one at a time on a flat surface and compressed during the X-ray imaging; the patient has to hold her breath during this procedure. Additional views of the breasts will be obtained if there is suspicion of breast disease. Radionuclide imaging requires a patient to lie on a table while the nuclear scanner moves back and forth examining the nuclear activity in the patient’s body. Prior to the procedure, a radioactive tracer will be provided to the patient through oral intake or IV injection (for example, two hours before a bone scan or a few days before a gallium scan). The radiopharmaceuticals emit gamma rays during the procedure; these signals are detected by a special gamma camera and transformed by a computer process into a twoor three- dimensional image showing where the tracers are absorbed by the body to a greater or lesser degree. Ultrasonography is a straightforward examination in which the patient lies flat on a table. The ultrasonographer passes a transducer over the body structure (such as the liver, kidneys, gallbladder, or uterus) that is being evaluated. A gel is applied to the surface of the body above the structure; the gel has a dual purpose—to lubricate the skin to prevent friction and discomfort as well as to improve the transmission of sound waves. In some cases, the transducer is shaped as a probe (as in vaginal ultrasound or 628
Salem Health: Cancer prostate evaluation through the rectum). The transducer will be covered with gel before its insertion into the vaginal tract or anorectal passage. These procedures are not painful, but they can cause discomfort and a feeling of pressure. After the procedure: Generally, no aftercare is required for the imaging tests discussed, and patients can return to normal activities immediately after the procedures. Patients who used contrast dyes may be monitored after the imaging tests to ensure that they have no adverse reactions to the agents used. Patients who ingested radioactive tracers should drink plenty of fluids to aid in their excretion; flushing of the toilet immediately after voiding can also decrease the risk of exposure to radioactivity. Removal of the gel used in ultrasonography is done by the ultrasound technician. Risks: Strict guidelines are practiced by radiology departments to decrease the risk of radiation exposure in imaging tests. The risk of exposure to X rays is generally exceeded by the benefits. The amount of radiation is low enough that adverse reactions are rare. Mammography also uses such low levels of X rays that any risk from radiation exposure is minimal. CT scan exposure to radiation is higher than that of a standard X ray, but the level of exposure is still low and should not cause adverse effects. The risks of nuclear medicine scans are also minimal. The amount of radiopharmaceuticals used exposes patients to an amount of radiation that is similar to or lower than that of a conventional X ray. The radiotracers are passed out of the body quickly (within a few hours or days); increased fluid intake can facilitate rapid excretion. Close proximity to children and sexual activity should be discussed with the patient’s health care team; depending on what radiotracer was used, these activities may be restricted for a short time. Ultrasound is considered free of risks. MRI also poses no risks and does not produce adverse physical effects; however, the effects of MRI on an unborn child are unknown. Although radiation exposure in imaging tests is minimal and should not produce adverse effects, pregnant patients and mothers who are breast-feeding should discuss the risks and benefits of the imaging tests with their physicians, especially patients who will require ingestion of contrast dyes and radioactive materials. The abdominal region of pregnant patients is protected with a radiation shield when imaging tests are performed during mammography and radiography. Patients who have renal failure or who are allergic to contrast agents and radiopharmaceuticals should also discuss the use of these substances and other imaging test options with their physicians. Patients who have surgically implanted devices such as cardiac
Salem Health: Cancer pacemakers, surgical aneurysm clips, and other metallic implants in the eyes or ears should inform their physicians about these devices. Because of the strong magnetic field involved, MRI is absolutely contraindicated when these metallic devices are present. If a biopsy or other invasive techniques are performed, then the risks will include infection and bleeding at the site of intervention. Results: Normal results will show no structural abnormalities in the imaging tests. Abnormal findings will include masses, tumors, abnormal presence of blood or fluids, enlarged organs, and structural anomalies (such as unusual shape, size, borders, or function). The radiologist determines whether the structures are normal or abnormal and will send a formal report to the physician about these findings. Alex B. Cantrell, B.A., and Miriam E. Schwartz, M.D., M.A., Ph.D. u For Further Information American Cancer Society. Imaging. Atlanta: Author, 2007. Beers, Mark H., et al., eds. The Merck Manual of Medical Information, Second Home Edition. Whitehouse Station, N.J.: Merck Research Laboratories, 2003. Brinton Wolbarst, Anthony. Looking Within: How X-Ray, CT, MRI, Ultrasound, and Other Medical Images Are Created and How They Help Physicians Save Lives. Berkeley: University of California Press, 1999. D’Amico, Anthony V., Jay S. Loeffler, and Jay R. Harris, eds. Image-Guided Diagnosis and Treatment of Cancer. Totowa, N.J.: Humana Press, 2003. Hayat, M. A., ed. Cancer Imaging, Volume 1: Lung and Breast Carcinomas. Oxford, England: Elsevier Academic Press, 2007. _______. Cancer Imaging, Volume 2: Instrumentation and Applications. Oxford, England: Elsevier Academic Press, 2007. Kevles, Bettyann. Naked to the Bone: Medical Imaging in the Twentieth Century. New Brunswick, N.J.: Rutgers University Press, 1997. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Angiography; Bone scan; Brain scan; Bronchography; Computed tomography (CT)-guided biopsy; Computed tomography (CT) scan; Cystography; Ductogram; Endoscopic retrograde cholangiopancreatography
Immune response to cancer (ECRP); Gallium scan; Hysterography; Lymphangiography; Magnetic resonance imaging (MRI); Mammography; Nuclear medicine scan; Percutaneous transhepatic cholangiography (PTHC); Positron emission tomography (PET); Radionuclide scan; Thermal imaging; Thyroid nuclear medicine scan; Urography; X-ray tests.
u Immune response to cancer Category: Cancer biology Also known as: T-cell or cellular immune response, B-cell or humoral immune response Definition: The body’s immune response to cancer, in which tumor cells are recognized and killed, relies on T cells (also known as the cellular immune response) and B cells (also known as the humoral immune response). T cells are a type of lymphocyte (white blood cell) that matures in the thymus gland in the neck, and B cells are lymphocytes produced in the bone marrow. To escape immune-mediated cell death, tumor cells use several strategies. However, because of the potential benefits of generating tumor-specific immunity, tumor immunotherapy is being studied as a treatment for cancer. Tumor-associated antigens: T cells and B cells recognize specific proteins, known as antigens, expressed on tumor cells. These immune cells can then become activated and develop antigen-specific immune responses that kill cells expressing these antigens. There are many types of tumor-associated antigens. They may be reactivated embryonic gene products that are generally not found in normal adult cells but are turned on in some types of tumors (such as the MAGE proteins expressed in melanoma, breast, esophageal, and gastric cancers). Viral gene products are another category, which includes components of the Epstein-Barr virus and the human papillomavirus present in nasopharyngeal and cervical cancers, respectively. Tumor antigens may also be mutated, overexpressed, or dysregulated self-proteins. Common mutations in self-proteins include KRAS and beta-catenin, both found in multiple tumor types. Examples of overexpressed and dysregulated self-proteins include prostate-specific antigen (expressed in prostate cancers) and HER2/neu (expressed in breast, ovarian, and colorectal cancers). By mutating or overexpressing proteins involved in cell-cycle regulation and growth control, tumors can divide more and survive longer. Cellular immunity: For a T cell to become activated, its T-cell receptor (TCR) must recognize antigen fragments 629
Immune response to cancer (also called peptides) that are bound to the major histocompatibility complex (MHC) expressed on antigenpresenting cells, such as dendritic cells. The interaction of the T-cell receptor and the major histocompatability complex/peptide complex is referred to as signal 1. T cells must also interact with costimulatory molecules on antigenpresenting cells, commonly referred to as signal 2. T cells can multiply and carry out their effector functions only when they receive both signals. Two major types of T cells are classified by whether they express the CD4 or CD8 protein. T cells expressing the CD4 protein recognize peptides bound to major histocompatability complex class II. Here, extracellular proteins are taken up by antigen-presenting cells and digested into twelve to twenty amino acid fragments that associate with major histocompatability complex class II as it traffics to the cell surface. CD4+ T cells are referred to as helper T cells because they secrete proteins called cytokines that provide survival factors to other immune cells, including interleukin (IL)-2, IL-12, and interferon (IFN)gamma. In contrast, CD8+ T cells recognize peptides bound to
Salem Health: Cancer major histocompatability complex class I. Here, intracellular proteins are broken down into eight to ten amino acid fragments. These fragments are transported into the endoplasmic reticulum via the transporter associated with antigen processing (TAP), loaded onto major histocompatability complex class I molecules, and exported to the cell surface. CD8+ T cells may also be activated by cross-presentation, in which extracellular antigens released from dying cells are taken up by antigen-presenting cells and associate with major histocompatability complex class I. CD8+ T cells are referred to as killer T cells or cytotoxic T lymphocytes. CD8+ T cells release factors such as perforin and granulysin, which poke holes in the plasma membrane of a target cell and allow water to rush in, ultimately leading to cell death in a process called osmotic lysis. CD8+ T cells also secrete granzyme, which can enter target cells and activate caspases (enzymes involved in apoptosis or programmed cell death). Humoral immunity: Whereas T cells recognize peptides bound to major histocompatability complex molecules,
An artist’s rendering of cancer cell surrounded by three T lymphocytes. (Francis Leroy, Biocosmos/Photo Researchers, Inc.)
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Salem Health: Cancer B cells recognize whole or unprocessed antigens on the surface of target cells. B cells can activate T cells by serving as antigen-processing cells because they express major histocompatability complex class II. When B cells interact with CD4+ helper T cells, the T cells can activate the B cells and mature them into plasma cells. Plasma cells produce proteins called antibodies, which are specific for an antigen. Antibodies can bind to antigens on a target cell and cause cell death via the complement pathway (which causes osmotic lysis) and antibody-dependent cellular cytotoxicity (which recruits natural killer cells that, similar to CD8+ killer T cells, can secrete perforin and granzyme to induce tumor cell death). Antibodies can also bind to antigens, such as growth factor receptors, and block their activity. Immune tolerance: There are mechanisms that control the body’s ability to recognize and respond to foreign, or non-self, antigens, while not responding to self antigens. However, since most cancers develop as uncontrolled growths within the body, tumor-associated antigens may be seen as self proteins. As a result, the immune response to cancer may be limited by immune tolerance. Central tolerance occurs in the thymus during T cell development and involves the deletion of T cells that would respond too well to self-proteins. A similar process of deletion occurs in the periphery (outside the thymus). Other mechanisms of peripheral tolerance include ignorance and anergy. Ignorance occurs when self-reactive T cells are present but not activated by the antigen because the antigen is at low concentrations or not easily accessible to the peripheral blood. T-cell anergy is a state of unresponsiveness and may occur when there is T-cell-receptor ligation (signal 1) in the absence of costimulation (signal 2). Tumors themselves also have mechanisms to escape immune recognition. They can downregulate antigenprocessing factors such as major histocompatability complex molecules, the TAP transporter, or tumor-specific antigens, which makes it harder for T cells to recognize the antigens on tumor cells. Tumors can also express proteins that provide negative costimulation, leading to reduced Tcell activity or cell death. Some tumors secrete inhibitory cytokines, such as interleukin (IL)-10 and tumor growth factor beta (TGF-β), which may inhibit antigen-presenting cells and recruit regulatory T cells. Regulatory T cells account for approximately 5 to 10 percent of CD4+ cells and are characterized by expression of the CD25 protein and the FOXP3 transcription factor. Regulatory T cells can suppress activation of other T cells and have been found to be more prevalent in human cancer patients compared with normal donors.
Immune response to cancer Therefore, mechanisms of immune tolerance and a tumor’s ability to produce an immunosuppressive environment may limit the activity of the immune cells, allowing cancer to grow within the body. Immunotherapy: Since T cells and antibodies can specifically target tumor-associated antigens, anticancer therapies that use the immune system may be more specific than traditional cancer therapies such as chemotherapy, which targets all dividing cells (both normal and cancerous). Therefore, tumor immunotherapy may be less toxic and could lead to the development of immunological memory responses. Tumor vaccines are one type of immune-based therapy, where tumor cells (or nontumor cells engineered to express tumor antigens) are modified to boost immune responses. These cells can be genetically modified to express major histocompatability complex molecules or costimulatory molecules and would serve as the antigen-presenting cell to activate T cells. Other types of tumor vaccines use cells that secrete cytokines to recruit and activate the body’s own antigen-presenting cells. Tumor vaccines are being tested in a variety of cancers including melanoma, breast cancer, and prostate cancer. The use of antibodies represents another immunebased platform. For example, rituximab is an antibody specific for the protein CD20. CD20 is expressed on both normal and cancerous B cells, such as those in B-cell nonHodgkin lymphoma and B-cell leukemia. Depletion of CD20-expressing B cells with rituximab rids the body of cancerous B cells and has been shown to be effective as a first-line therapy and in relapsed cancers. Similarly, HER2/ neu is overexpressed in about 30 percent of breast tumors and is associated with a more aggressive cancer. The HER2/neu-specific antibody trastuzumab has been shown to increase survival rates in metastatic breast cancer and reduce relapse rates in early breast cancers. Tumor immunotherapy represents a different type of cancer treatment and may have benefits over traditional cancer therapies, including higher specificity and better tolerability. Although the Food and Drug Administration has approved several tumor-specific antibodies, the use of tumor vaccines remains investigational, although promising. Elizabeth A. Manning, Ph.D. u
For Further Information Fazekas de St. Groth, B. “DCs and Peripheral T Cell Tolerance.” Seminars in Immunology 13, no. 5 (2001): 311322. Janeway, C. A., ed. Immunobiology. 5th ed. New York: Garland, 2001. 631
Immunochemical fecal occult blood test (iFOBT)
Salem Health: Cancer
Marincola, F. M., E. M. Jaffee, D. J. Hicklin, and S. Ferrone. “Escape of Human Solid Tumors from T-Cell Recognition: Molecular Mechanisms and Functional Significance.” Advances in Immunology 74 (2000): 181-273. Pardoll, D. M. “Therapeutic Vaccination for Cancer.” Clinical Immunology 95, no. 1, pt. 2 (2000): S44-S62. Stern, M., and R. Herrmann. “Overview of Monoclonal Antibodies in Cancer Therapy: Present and Promise.” Critical Reviews in Oncology/Hematology 54, no. 1 (2005): 11-29.
heme subunit of mammalian hemoglobin and requires the patient to adhere to dietary and medication restrictions three days prior to testing.
u
Steps of the procedure: Two collection procedures are available, depending on which manufacturer provides the diagnostic kit. Both require the patient to follow the instructions provided with the kit. One company provides a collection paper that is taped to the toilet seat and onto which the feces is deposited. The patient unscrews the sampling device from the collection tube and randomly pierces the specimen with the grooved end of the device in at least five different sites of the feces. The sampler is then screwed in the collection tube and tightened. The patient shakes the tube to mix the specimen with the buffer solution in the collection tube. The second manufacturer provides two sampling pads that are inoculated with a sampling of toilet water collected after a bowel movement and brushed on the test card provided. After collection, the sample from either kit is sent to the clinical lab and the results are reported to the ordering physician.
Other Resources
Immune Central Immune System http://www.immunecentral.com/immune/general.cfm Immunotherapy for Cancer http://www.meds.com/immunotherapy/index.html See also Biological therapy; Cytokines; Gene therapy; HIV/AIDS-related cancers; Immunotherapy; Lymphomas; Medical oncology; Neutropenia; Radiation therapies; Vaccines, preventive; Vaccines, therapeutic.
u Immunochemical fecal occult
blood test (iFOBT) Category: Procedures Also known as: Fecal immunochemical test (FIT) Definition: An immunochemical fecal occult blood test (iFOBT) is a method for the qualitative detection of a minute amount in the feces of otherwise invisible blood from the lower gastrointestinal tract. Cancers diagnosed: Colorectal cancers Why performed: The iFOBT is a screening test for bleeding associated with cancer of the colon and rectum. The bleeding may be attributable to conditions other than cancer such as polyps and adenomas, which when discovered and removed early can significantly reduce the risk of cancer. Although the incidence of colorectal cancer has decreased in the United States since the 1980’s, the colon is still the third most common site of all cancers. The decrease in cancer cases is attributed to screening for fecal occult blood. The immunochemical fecal occult blood test uses an antibody specific for human globins and is more specific than the traditional guaiac test, which detects the 632
Patient preparation: The patient collects the specimen at home. No dietary or medication restrictions are required prior to sample collection. Blood from hemorrhoids, menstrual blood, or open wounds may invalidate the screening for fecal occult blood. Because bleeding from polyps or other potential lesions is typically intermittent, the patient may be asked to perform collection on three consecutive days.
After the procedure: Positive results are often followed by an endoscopic evaluation such as a colonoscopy. Risks: One of the risks in iFOBT is a false result because of improper sample collection, as patients may have an understandable aversion to handling a fecal sample. However, an adequate and carefully collected sample is the first critical step in detecting colorectal bleeding, which may be the first sign that the individual is facing disease. Early detection and treatment is the key to the prevention of colorectal cancer. Results: The iFOBT is a screening test. Positive results must be evaluated and followed by a physician to determine the source of the bleeding. Gastrointestinal bleeding may be the result of diverticulitis, colitis, polyps, or colorectal cancer. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) See also Asian Americans and cancer; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer
Salem Health: Cancer screening; Digital rectal exam (DRE); Fecal occult blood test (FOBT); Gastrointestinal cancers; Hereditary polyposis syndromes; Medicare and cancer; Polyps; Premalignancies; Primary care physician; Screening for cancer; Small intestine cancer.
u Immunocytochemistry and
immunohistochemistry Category: Medical specialties; procedures Also known as: Immunostain, ICC, IHC Definition: Immunocytochemistry (ICC) refers to the use of antibody-based protocols on cells to identify and localize visually specific molecules (antigens). Immunohistochemistry (IHC) refers to similar procedures carried out on tissue sections. Cancers diagnosed: Undifferentiated or metastatic cancers, leukemias, lymphomas, breast cancers Why performed: IHC and ICC are used to identify specific antigens on or in tissues or cells. These procedures are valuable in several aspects of the evaluation of human cancers. In cases of undifferentiated malignant tumors, the presence of antigens (such as tyrosinase) can confirm the origin of the cells, identifying the tumor (in this example, as a melanoma). In cases of metastatic tumors of unknown origin, the presence of antigens with highly restricted specificity can identify the primary site, as in the case of prostate-specific antigen (PSA) expression by a skeletal lesion. On occasion, subclassification of histologically similar tumors has prognostic implications, as in the case of embryonal carcinomas, which are distinguished from seminomas by the presence of keratin. Leukemias and lymphomas are especially amenable to IHC-assisted diagnosis and classification because of the abundant and diverse surface antigens present on white blood cells, although flow cytometry is sometimes favored in this class of malignancies. Several antigens of therapeutic importance can be detected by IHC, including estrogen and progesterone receptors in breast cancer. Finally, IHC can identify antigens associated with tumor cells’ growth rate, such as Ki67. While mostly performed after completion of the sample collection procedure, immunostains can also be performed rapidly as part of intraoperative consultations. Patient preparation: Samples taken as part of larger surgeries (such as mastectomy) require general anesthesia preceded by an overnight fast on the part of the patient.
Immunocytochemistry and immunohistochemistry Simpler biopsy procedures (such as bone marrow biopsy) may require only local anesthesia with or without sedation. Steps of the procedure: The first task of the pathologist is to construct a differential diagnosis and decide whether immunostaining is necessary. If so, the antigen or antigens to be interrogated must be selected based on specific hypotheses. Sample acquisition, immunostaining, and diagnostic interpretation are the next steps. Individual cells for ICC can be scraped or brushed from surfaces, aspirated from cavities or compartments via a fine needle, or concentrated from body fluids by centrifugation. For IHC, tissue samples are usually obtained by standard biopsy or open procedures. Routine tissue processing involving formalin fixation, paraffin embedding, and sectioning is suitable for many antigen-antibody interactions, but in some cases the interaction requires special sample handling such as frozen sectioning (to preserve the antigen) or heating (to increase exposure or “retrieve” the antigen). Immunostaining itself requires exposure of the sample to a specific (primary) antibody under conditions that allow antigen-antibody binding to take place. Hundreds of primary antibodies against tumor-specific molecules are commercially available. In some cases, the primary antibody is conjugated to an enzyme such as horseradish peroxidase (HRP). This format is rapid, but this direct conjugate-labeled method has low sensitivity and requires high concentrations of antibody. A more typical procedure involves a different (secondary) antibody that binds to the constant (Fc) region of the primary antibody and is linked to HRP or another enzyme. Since multiple secondary antibodies can attach to a single primary antibody, sensitivity is improved. Other methods are possible, but all result in localization of a detectable “tag” molecule near the antigen(s) of interest. Typically used tags include enzymes such as HRP, alkaline phosphatase, glucose oxidase, and beta-galactosidase. Antibody-conjugated fluorescent molecules are sometimes used as tags, but visualization requires specialized light sources and filters, and fluorescent tags degrade quickly. If higher magnification is needed, then antibody-conjugated gold particles can also serve as tags and are visualized with the electron microscope. Gold particle sizes can be tightly controlled, facilitating double labeling in individual sections. Signal generation on samples with attached enzyme tags is achieved by incubation with a color-producing (chromogenic) substrate system that results in local production of insoluble precipitates. Diaminobenzidine or aminoethylcarbazole are popular substrates for HRP 633
Immunoelectrophoresis (IEP) because the catalysis products are stable and easily identified in the microscope as brown or red deposits, respectively. Glucose oxidase and its substrate tetrazolium are popular for double-labeling techniques, since the blue reaction product is easily distinguished from products of HRP. The final processing step is counterstaining and mounting slides. Counterstaining is necessary to visualize cells and structures around the immunostain. Hematoxylin, which stains nuclei blue, is a popular choice, since many immunostains identify cell surface antigens. Appropriate positive and negative controls should always be stained and evaluated in parallel with the patient sample. After the procedure: Samples collected as part of larger surgical procedures require standard postoperative care. Simpler biopsy collection procedures require that the biopsy site be kept clean and dry until fully healed. Patients and caregivers are instructed to monitor for signs of infections. Risks: Immunostaining itself poses no additional risks to the patient. Results: Meaningful results from the patient sample are impossible without appropriate staining of parallel positive and negative control samples. The most important attribute of an adequate positive control is heterogeneous distribution of the stain within a cell and among groups of cells. Results for patient samples are usually given semiquantitatively and include estimates of staining intensity, cellular distribution (membranous, cytoplasmic, or nuclear), and abundance of positively staining cells. The report includes an interpretation that is either favored or ruled out by the observed staining pattern. John B. Welsh, M.D., Ph.D. u
For Further Information Al-Nafussi, Awatif. Tumor Diagnosis: Practical Approach and Pattern Analysis. New York: Oxford University Press, 2005. Dabbs, David J., ed. Diagnostic Immunohistochemistry. 2d ed. Philadelphia: Elsevier Churchill Livingstone, 2006. Leong A. S.-Y., and T. Y.-M. Leong. “Newer Developments in Immunohistology.” Journal of Clinical Pathology 59 (2006): 1117-1126. Leong, Anthony S.-Y., Kumarasen Cooper, and F. Joel W.-M. Leong. Manual of Diagnostic Antibodies for Immunohistology. 2d ed. London: Greenwich Medical Media, 2002. 634
Salem Health: Cancer u
Other Resources
Immunoquery http://www.immunoquery.com See also Biological therapy; Carcinoembryonic antigen antibody (CEA) test; Cytokines; Cytology; Gene therapy; HER2/neu protein; Hormone receptor tests; Immunotherapy; Ki67 test; Lactate dehydrogenase (LDH) test; Myelodysplastic syndromes; Neuroectodermal tumors; Phyllodes tumors; Placental alkaline phosphatase (PALP); Receptor analysis; Tumor markers.
u Immunoelectrophoresis (IEP) Category: Procedures Also known as: Gamma globulin electrophoresis, immunoglobulin electrophoresis Definition: Immunoelectrophoresis (IEP) is a semiquantitative method used in clinical and research laboratories to determine the levels of three major immunoglobulins in the blood: immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin (IgA). This test is often replaced by the quantitative immunofixation (IFE) test in clinical laboratories for diagnostic purposes. Cancers diagnosed: Multiple myeloma, chronic lymphocytic leukemia, Waldenström macroglobulinemia Why performed: An IEP test is often performed when the immunoglobulins are increased in a serum protein electrophoresis test. Patient preparation: The IEP test may be performed on urine, cerebrospinal fluid (CSF), or the serum obtained from a blood specimen collected by routine venipuncture. Steps of the procedure: The specimen is placed in a well on a slide prepared with a semi-solid gel. An electric current is passed through the gel. The current causes the different serum proteins to separate according to their varying electric charges. An antiserum is placed in a trough alongside the separated immunoglobulins. The antibodies in the antisera attach to the specific immunoglobulins. This reaction is measured, and relative quantities of IgM, IgG, and IgA per deciliter of patient serum are reported to the ordering physician. After the procedure: The physician may order an immunofixation test to further quantify the IgM, IgG, and IgA. Risks: There are no risks to this procedure other than those associated with specimen collection. Because the IEP test
Salem Health: Cancer
Immunotherapy
results may be applied to a large number of conditions, follow-up tests are necessary for a differential diagnosis.
U.S. Food and Drug Administration (FDA) are constantly studied for use in additional diseases.
Results: While some cancer diagnoses are associated with elevated immunoglobulins, increased immunoglobulins can also suggest recent vaccinations or treatment with hydralazine, isoniazid, phenytoin (Dilantin), procainamide, oral contraceptives, methadone, steroids, therapeutic gamma globulin, or tetanus toxoid and antitoxin. Consequently, immunoelectrophoresis test results must be interpreted in the context of the patient’s history and clinician judgment. IEP test results demonstrating elevated or decreased IgM, IgG, or IgAlevels may indicate a wide variety of conditions. Increased IgM may point to Waldenström macroglobulinemia, an increased secretion of IgM caused by malignant lymphocytes, chronic infections such as hepatitis, mononucleosis, and autoimmune diseases such as rheumatoid arthritis. Decreased IgM may suggest acquired immunodeficiency (HIV/AIDS), immunosuppression caused by steroids, or leukemia. Increased IgG may indicate chronic liver disease, autoimmune diseases, hyperimmunization reactions, or chronic infections, such as tuberculosis or sarcoidosis. Decreased IgG can indicate Wiskott-Aldrich syndrome, HIV/AIDS, or leukemia. Increased IgA can point to chronic liver disease, chronic infections, or inflammatory bowel disease. Decreased IgA is seen in ataxia-telangiectasia, low blood protein (hypoproteinemia), and drug-induced immunosuppression. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP)
Cancers treated: Breast cancer, lung cancer, melanoma, cervical cancer, leukemias, lymphomas, myelomas, prostate cancer, colorectal cancer, and ovarian cancer; others under investigation
See also Chronic lymphocytic leukemia (CLL); Lactate dehydrogenase (LDH) test; Multiple myeloma; Protein electrophoresis; Waldenström macroglobulinemia (WM).
u Immunotherapy Category: Chemotherapy and other drugs ATC code: 101, 103 Also known as: Biological therapy, biotherapy Definition: Immunotherapy is a treatment that stimulates the immune system in the body to fight cancer and lessen related side effects of disease. Agents come from biological sources and may be given alone or combined with chemotherapy. Immunotherapies boost the patient’s immune system to fight cancer cells, while chemotherapy drugs attack the cancer cells directly. Because immunotherapy is fairly new, agents are under development and investigation, and those approved by the
Subclasses of this group: Cytokines, including interferons, interleukins, and hematopoietic growth factors; monoclonal antibodies, which can be developed from mouse antibodies (murine), a combination of mouse and human antibodies (chimeric), human antibodies combined with a small amount of mouse antibody (humanized) or only human antibodies (human), antibodies fused with a toxin or radioactive material, or cells; vaccines developed from cells, parts of cells, or antigens Delivery routes: Agents may be administered by mouth (orally), injection (subcutaneously or intramuscularly), or injection into a vein (intravenously). Some vaccines are given into the skin (intradermal) or may be placed into the bladder in a liquid form (instillation). Agents may be taken at home or may require a visit to the physician’s office or hospital. The schedule of administration varies with the agent. How these drugs work: Cancer develops when normal cells change their genetic makeup over some period of time. As these changes occur, protein substances are created on the cell surface that the body does not recognize. An antigen is any substance that causes the immune system of the body to produce antibodies. The body’s activation of the immune system against these unrecognized substances is called an immune response and is the principle of immunotherapy. Antibodies developed outside the body or substances given to encourage the body to develop antibodies against antigens are the foundation for immunotherapy. The immune system includes lymph nodes, the spleen, the tonsils, bone marrow, and white blood cells. Actions of immunotherapy may include increasing a cancer cell’s sensitivity so that the immune system can better attack and kill the cell, preventing the normal cell from becoming malignant, preventing the spread of cancer cells, encouraging the body to repair damaged cells, and changing the activity of normal cells around tumors. Cytokines are used more frequently than any other type of immunotherapy, as they are emplyed at some point in most cancers. Because cancer treatments can cause serious side effects and complications, an important part of therapy is side effect control. White blood cells fight infection (continued on page 637)
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Immunotherapy
Salem Health: Cancer
Common Immunotherapeutic Agents Agent
Brands
Subclass
Delivery Mode
Aldesleukin
IL-2, Proleukin
Cytokines/Interleukin
Subcutaneous, IV Renal cell or kidney cancer, metastatic melanoma
Alemtuzumab
Campath
Monoclonal antibody
Subcutaneous, IV B-cell chronic lymphocytic leukemia
BCG live
PACIS, TICE BCG
Vaccine
Intradermal, instillation
Bladder cancer
Bevacizumab
Avastin, anti-VEGF
Monoclonal antibody
IV
Metastatic cancer of the colon or rectum or nonsquamous, non-small-cell lung cancer, usually in combination with chemotherapy
Cetuximab
Erbitux
Monoclonal antibody
IV
Metastatic colorectal cancer
Darbepoetin
Aranesp
Cytokines/Hematopoietic Subcutaneous, IV Anemia from most cancers, growth factor chemotherapy, or renal failure
Erlotinib
Tarceva
Cytokines/HER1/EGFR tyrosine kinase inhibitor
Erythropoietin
Procrit, Epogen
Cytokines/Hematopoietic Subcutaneous, IV Anemia from most cancers or growth factor chemotherapy
Filgrastim, pegfilgrastim
Neupogen, Neulasta
Cytokines/Granulocyte Subcutaneous, IV Used in most cancers, for patients with colony-stimulating factor neutropenia or febrile neutropenia from chemotherapy
Oral
Cancers or Side Effects Treated
Non-small-cell lung cancer
Ibritumomab tiuxetan Zevalin
Monoclonal antibody
IV
Some forms of B-cell non-Hodgkin lymphoma
Interferon alfa-2a
Roferon-A
Cytokines/Interferon
Subcutaneous, intramuscular
Kaposi sarcoma related to AIDS, hairy cell leukemia, some forms of chronic myelogenous leukemia
Interferon alfa-2b
Intron-A
Cytokines/Interferon
Subcutaneous, Malignant melanoma, hairy cell intramuscular, IV leukemia, some lymphomas, Kaposi sarcoma related to AIDS
Quadrivalent human Gardasil papillomavirus (types 6, 11, 16, 18) recombinant vaccine
Vaccine
Intramuscular
Cervical cancer, precancerous lesions of the cervix, vulva, vagina
Rituximab
Rituxan, anti-CD20
Monoclonal antibody
IV
Relapsed CD20-positive non-Hodgkin lymphoma
Sargramostim
Leukine
Cytokines/Granulocyte macrophage colonystimulating factor
Subcutaneous, IV Acute myelogenous leukemia
Tositumomab I-131
Bexxar
Monoclonal antibody
IV
CD20-positive follicular non-Hodgkin lymphoma not sensitive to Rituxan
Trastuzumab
Herceptin, Monoclonal antibody anti-HER2/neu Herceptin
IV
Metastatic breast cancer with tumors that overexpress the HER2/ner protein
636
Salem Health: Cancer in the body and are decreased by chemotherapy drugs, leading to neutropenia. Anemia, which is a decrease in red blood cells responsible for carrying oxygen to cells, can be life-threatening in cancer patients. Erythropoietin stimulates the release of mature red blood cells and may be used as an important part of cancer therapy. Colony-stimulating factors encourage the bone marrow to convert immune cells into neutrophils, critical to fighting infection. Cytokines are naturally produced in the body but can be developed in the laboratory using a system called recombinant deoxyribonucleic acid (DNA) technology. Cytokines can be developed to interact with receptors on immune cells to stimulate, for example, red blood cells to be produced or inhibit or slow cancer cell growth. While some cytokines are not therapeutic for cancer, they are needed to allow patients to receive their full doses of both immunotherapy and chemotherapy. A group of cytokines called interleukins are therapeutic for cancer. In 1992, interleukin-2 (IL-2) was the first immunotherapy approved for use alone in treating cancer. IL-2 is used for advanced kidney cancer and melanoma, either alone or in combination with other chemotherapies or immunotherapies. Interleukin stimulates T cells and natural killer cells in the immune system. Interferons, also cytokines, are thought to work by slowing the growth of cancer cells and the blood vessels that supply the tumor. It is also thought that interferons may increase the production of antigens in the cancer cell, making it more visible to antibodies. Natural killer cells may also be boosted by the administration of interferon. Monoclonal antibodies generally interrupt signals in the cell that cause it to become cancerous. They can be developed to be attracted to the antigen secreted by the cell in order to block its function. Each monoclonal antibody is designed to bind to a specific antigen on the cell. Some monoclonal antibodies attracting significant interest are those that cause the immune system to attack the blood supply of the tumor, called antiangiogenesis. Monoclonal antibodies are known as passive immunotherapy because they use antibodies made outside the body in large numbers. Active immunotherapy is when the patient’s own body makes antibodies against antigens, such as seen in vaccine therapy. There are approximately ten monoclonal antibodies approved for use in cancer treatment. Vaccines are able to trigger the immune system to attack cancer cells with a specific antigen developed in the patient’s body. Most vaccines are experimental in nature and available only as part of a research study, but a few are currently FDA-approved for use in the United States. Some forms of active immunotherapy are not vaccines but may try to have an impact on specific locations within the
Immunotherapy immune system. Most of these therapies are not approved by the FDA and are available only in a clinical research study. Lymphokine activated killer cell (LAK) therapy involves T cells made in the laboratory and treated with IL-2, and researchers are testing ways to make the cells more active against cancer. Tumor infiltrating lymphocyte (TIL) vaccine is composed of cells found inside tumors removed with surgery, treated with IL-2 in the laboratory, and then injected back into the patient. TIL is being tested in a variety of cancers. Side effects: Immunotherapy may cause flulike symptoms, including fever, chills, nausea, vomiting, fatigue, headache, low blood count (anemia), inability to fight infection, bone pain, and muscle aches. If the agent is injected, then a rash or swelling may be noted at the site. Blood pressure can drop during administration. More serious but less common side effects include bleeding, difficulty breathing, edema leading to congestive heart failure, heart damage, and severe and potentially life-threatening reactions (such as anaphylaxis). Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Chabner, Bruce A., and Dan L. Longo, eds. Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia: Lippincott Williams & Wilkins, 2006. Gullatte, M. M. Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook. Philadelphia: Oncology Nursing Society, 2005. National Cancer Institute. Biological Therapy: Treatments That Use Your Immune System to Fight Cancer. NIH Publication 03-5406. Bethesda, Md.: National Institutes of Health, 2003. Also available at http://www .cancer.gov. Polovich, M., J. M. White, and L. O. Kelleher, eds. Chemotherapy and Biotherapy Guidelines. 2d ed. Pittsburgh: Oncology Nursing Society, 2005.
u
Other Resources
American Cancer Society Biologic Therapies http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Biologic_Therapies.asp?sitearea=CRI Medscape http://www.medscape.com National Cancer Institute Drug Dictionary http://www.cancer.gov/drugdictionary 637
Indoles See also Angiogenesis inhibitors; Biological therapy; Cytokines; Gene therapy; HIV/AIDS-related cancers; Immune response to cancer; Infectious cancers; Interferon; Interleukins; Lymphomas; Medical oncology; Monoclonal antibodies; Neutropenia; Radiation therapies; Vaccines, preventive; Vaccines, therapeutic.
u Indoles Category: Lifestyle and prevention Definition: Dietary indoles are a family of organic phytonutrients found in plants that work with natural nutrients to protect against disease. Cancers treated or prevented: May provide some protection from certain types of cancer, especially hormonerelated cancers such as prostate, breast, thyroid, and cervical cancer, as well as colon cancer Delivery routes: Oral ingestion through diet How these compounds work: Cruciferous vegetables (named for cross-shaped pattern on the underside of the stalk) contain the phytonutrients indole-2-carbonal (13C) and sulforaphane. The mechanism by which dietary indoles protect against cancer is unclear. One theory is that dietary indoles contain phytonutrients that work as estrogen blockers. Researchers believe that the positive effect of dietary indoles may be related to improving the estrogen ratio of harmful estrogen to good or helpful estrogen. Indoles seem to lessen the effects, or rid the body, of the estrogen hormone and positively affect the estrogen metabolite balance. Research studies have demonstrated that dietary indoles participate in many biochemical processes in the human body and may increase the production of anticancer enzymes to improve the body’s natural ability to fight off cancer. Dietary indoles can be found in Brassica or cruciferous vegetables such as cauliflower, brussels sprouts, cabbage, broccoli, bok choy, kale, and watercress, as well as collard, turnip, and mustard greens. These vegetables can be prepared in a variety of ways, including raw added to salads, boiled, steamed, stir-fried, braised, or fermented as in sauerkraut or pickled cabbage. Some people avoid cabbage, as the cooking process releases a strong and somewhat unpleasant odor as a result of the sulfur compounds. To minimize the odor, the cabbage can be shredded so that it cooks faster and a large pan can be used with the cabbage submerged in a large amount of water. The sulfur will dissolve into the water and minimize 638
Salem Health: Cancer release into the air. The cabbage should be cooked only until tender, as overcooking contributes to the odor, and covering it immediately contains the smell. While cooking cabbage in a large amount of water can diffuse its strong taste and smell, however, steaming or quick cooking in smaller amounts of water retains nutrients. Consuming naturally occurring dietary indoles is preferred, but cruciferous vegetable extract supplements may provide some benefit as well. They are available at reputable health food stores. Side effects: It is unclear whether indoles cause side effects when taken in higher doses. Marylane Wade Koch, M.S.N., R.N. See also Antimetabolites in chemotherapy; Carcinomas; Chemoprevention; Cruciferous vegetables; 5-Hydroxyindoleacetic acid (5HIAA) test; Mantle cell lymphoma (MCL); Mucosa-associated lymphoid tissue (MALT) lymphomas; Multiple myeloma; Non-Hodgkin lymphoma; Plant alkaloids and terpenoids in chemotherapy; Tumor markers; Watchful waiting.
u Infection and sepsis Category: Diseases, symptoms, and conditions Related conditions: Any type of infection is a risk for a cancer patient. Pneumonia is especially common in certain types of blood cancer. Definition: An infection is the growth of a parasitic organism in the body, and sepsis is a widespread infection resulting from the presence of infectious organisms in the bloodstream. Sepsis overwhelms many parts of the body at once. Cancer patients are at risk for sepsis and various more limited infections as a result of their disease and the treatments they receive. Bacteria cause most infections in cancer patients, but serious fungal and viral infections are also common. Infection and sepsis are common causes of death in cancer patients. Risk factors: All cancer patients are at risk for infection and sepsis. Their risk may be higher or lower depending on the type of cancer they have and their body’s reaction to treatment. Patients at highest risk are those receiving bone marrow or stem cell transplants and patients with acute leukemias. Cancer patients with certain preexisting conditions are also at higher risk for infection. Etiology and the disease process: Cancer can make the body more vulnerable to infection in several ways. The
Salem Health: Cancer
Infection and sepsis
Common Sources of Infections in People with Cancer Bacteria • Clostridium difficile • Enterococcus • Escherichia coli • Klebsiella pneumonia • Pneumococcus • Pseudomonas aeruginosa • Salmonella • Staphylococcus aureus • Staphylococcus epidemidis
Fungi Aspergillus Candida Coccidioides Cryptococcus Histoplasma Phycomycetes
• • • • • •
Protozoa Cryptosporidium Pneumocystis carinii Toxoplasma gondii
• • •
Viruses Cytomegalovirus (CMV) Herpes simplex virus (HSV) Varicella-zoster virus (VZV)
• • •
Source: American Cancer Society
destruction of tissues resulting from invading tumors may allow infectious organisms access to places they do not normally enter. An example would be Staphylococcus aureus, a type of bacteria that normally lives on the skin. A break in the skin as the result of a malignancy (such as squamous cell carcinoma) may allow S. aureus to invade the inside of the body, causing a dangerous infection. Tumors may block ducts or other structures in the body. The blockage may trap infectious organisms that the body might have otherwise cleared out. An example is a tumor that blocks a bile duct. Trapped bacteria in the duct can multiply and reach the bloodstream, the liver, or the abdominal cavity, causing infection. Immunity depends on the normal production and growth of white blood cells. The bone marrow produces these cells, and they mature and take on specialized immune functions in the bloodstream. Cancers that affect the blood or bone marrow—the leukemias, lymphomas, and multiple myeloma—severely cripple the immune system. Individuals with these types of cancer are at very high risk of death from infection or sepsis. Cancer treatments also increase the risk of infection and sepsis. Chemotherapy drugs, especially at high doses, cause a condition known as neutropenia, an abnormally low level of neutrophils. Neutrophils are the most common white blood cells, constituents of the immune system. A low neutrophil count (level) means low immunity. Catheters implanted in cancer patients—for the ease of medication delivery and blood draws—are a potential gateway through which infectious organisms can enter the body. Chemotherapy drugs often cause ulceration of the mucous membranes in the mouth and the digestive tract. These ulcerations are a gateway for infectious organisms that may invade areas not normally accessible to them.
Treatment of certain cancers, such as lymphoma, sometimes requires the removal of the patient’s spleen. The spleen is an extremely important part of the body’s immune system. Patients who have had their spleens removed are vulnerable to severe infections for up to twentyfive years following the surgery. Common sites of infection in cancer patients include the lungs, the skin, and the digestive tract, beginning with the mouth. Incidence: Incidence depends on the type of cancer or other condition. Symptoms: Symptoms of sepsis include fever, chills, skin rash, rapid breathing, rapid heart beat, decreased urination, and confusion, hallucination, or agitation. Many early symptoms of sepsis are similar to symptoms of more limited infections. Additional symptoms of nonseptic infection vary by the location of infection and may include any of the following: red streaks on the skin; diarrhea; abdominal pain; nausea or vomiting; ulcerations (open sores) on the skin or in the mouth; difficulty swallowing; sore throat; discharge from the wounds, nose, or any opening in the body (such as the vagina or penis); swelling and tenderness; headache; stiff neck; cough; and difficulty breathing. Screening and diagnosis: At times, it may be very hard to determine whether symptoms are the result of an infection or a side effect of cancer treatment. Tests that look for the type and cause of infection vary by the location of the suspected infection. Such tests may include biopsy (obtaining a sample of infected tissue and testing it in the laboratory); X rays; blood counts, especially a neutrophil count; liver function tests; and cultures (attempts to grow an infectious 639
Infection and sepsis organism) grown from samples from stool, sputum, blood, and any oozing from a sore. Treatment and therapy: Because the vast majority of cancer patients develop bacterial infections, when symptoms of infection develop, doctors immediately start treatment with a broad-spectrum antibiotic. This type of antibiotic is effective against many different bacteria. There are many broad-spectrum antibiotics available. There is no standard initial antibiotic treatment that shows more benefits than others do. If needed, treatment can be modified when tests determine which bacteria cause the patient’s infection. If antibiotic treatment fails to make the patient better, antifungal medicine is added to the treatment. The mostoften used antifungal medicines are amphotericin B and voriconazole. In cases where the infection centers around the catheter, it may be necessary to remove the catheter to eliminate the infection. Viral infections, especially with the human herpesvirus family, are also a major problem in cancer patients. The most common treatment is acyclovir, though newer antiviral medications are available. Patients with a history of herpes simplex infection may get acyclovir as a prophylaxis (preventative). Viral respiratory infections, especially the flu and respiratory syncytial virus (RSV), also present major risks for people with cancer. Treatments for these infections include oseltamivir and zanamivir against influenza, and ribavirin for RSV and hepatitis viruses. The American Society of Clinical Oncology now recommends the use of granulocyte colony-stimulating factor (G-CSF, filgrastim) for high-risk patients beginning chemotherapy. G-CSF accelerates the production of white blood cells. Studies that looked at a total of more than three thousand patients showed those receiving G-CSF before complications occurred were almost 50 percent less likely to develop neutropenia and infections. Prognosis, prevention, and outcomes: The outcome of infections in cancer patients varies. It depends on the type of infection, the patient’s overall condition, and the state of the patient’s immune system. Doctors sometimes give severely immune-compromised patients a prophylactic broad-spectrum antibiotic. Such patients may also get prophylactic antifungal medicine. This method is not recommended for all patients, because resistant bacteria or fungi can develop and cause worse infections. Doctors use prophylactic antibiotic and antifungal treatment in patients after bone marrow transplants 640
Salem Health: Cancer or in those whom the doctors expect to stay immune compromised for lengthy periods. Cancer patients should receive certain vaccinations: • Annual influenza (“flu”) vaccine • Pneumonia vaccine (known as a pneumococcal vaccine or 23-valent pneumococcal vaccine) • Bacterial meningitis vaccine (known as a meningococcal vaccine or 4-valent meningococcal vaccine) Doctors may recommend other vaccines depending on the patient’s particular disease, treatment, and overall health. People with cancer should never receive vaccination without consulting with their oncologist (cancer specialist). It is important to remember that while a person is immune compromised, even a mild cold can become lifethreatening. Children who receive vaccination with a live virus (for example, chicken pox or live polio vaccines) may pass the live virus to others. These viruses can cause a serious illness in the immune-compromised patient. People receiving treatments for cancer should avoid contact with those who have recently had a live-virus vaccine. Patients can prevent some infections through the use of certain precautions. These precautions include the following: • Frequent hand washing (on the part of patient, visitors, and other household members) • Avoiding undercooked or raw foods • Letting someone else clean up after pets, especially cat litter boxes and birdcages • Practicing good oral hygiene • Thoroughly cleaning any breaks in the skin • Keeping surgical and catheter sites clean • Avoiding people with contagious diseases • Avoiding sexual practices that can result in skin breaks • Avoiding contact with those who have recently had a live-virus vaccine Adi Ferrara, B.S. u
For Further Information Kelvin, Joanne F., and Leslie Tyson. One Hundred Questions and Answers About Cancer Symptoms and Cancer Treatment Side Effects. Sudbury, Mass.: Jones and Bartlett, 2005. Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. Thiboldeaux, Kim, and Mitch Golant. The Total Cancer Wellness Guide: Reclaiming Your Life After Diagnosis. Dallas: BenBella Books, 2007.
Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org Cancer.Net http://www.cancer.net/portal/site/patient See also Antifungal therapies; Antiviral therapies; Blood cancers; Candidiasis; Chemotherapy; Culdoscopy; Disseminated intravascular coagulation (DIC); Fever; Infectious cancers; Infusion therapies; Mucositis; Overtreatment; Penile cancer; Pneumonectomy; Thrombocytopenia.
u Infectious cancers Category: Diseases, symptoms, and conditions Also known as: Viral cancer, bacterial cancer, parasitic cancer Related conditions: Oncogenic infections (bacterial, viral, parasitic), hepatitis, herpes, infection with human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), mononucleosis, schistosomiasis Definition: Infectious cancers are malignant tumors that result from disruptions and diseases caused by invasion and multiplication of microorganisms and parasites in body tissues and cells and that therefore could be transmitted from person to person. Risk factors: Some human infections of ribonucleic acid (RNA) and deoxyribonucleic (DNA) viruses, bacteria, and parasitic worms cause diseases, inflammation, and suppression of the immune system, leading to a higher risk of mutations and cancer. Long-term infection with Helicobacter pylori (H. Pylori) bacteria increases the risk of developing stomach cancer and lymphoma, which is also influenced by diet and smoking. Two RNA viruses and the linked cancers are HIV, which induces sarcoma, and human T-cell lymphotropic virus (HTLV), which causes leukemia. HIV infection promotes viral cancers such as Kaposi sarcoma, cancers linked to human herpesvirus 8 (HHV-8) and human papillomavirus (HPV), invasive cervical cancer, lymphomas, invasive anal cancer, Hodgkin disease, lung cancer, cancer of the mouth and throat, cancer of the testicles, and skin cancers. DNA viruses cause cancers of the nasopharynx and Burkitt lymphoma (Epstein-Barr virus, or EBV), liver (hepatitis B virus, or HBV), and cervix (HPV). The risk of developing cancer is increased by certain tropical parasitic worm infections, such as infections with
Infectious cancers liver flukes and blood flukes (Schistosoma haematobium), which are linked to bile duct cancer. Etiology and the disease process: Infectious cancer is induced by three main mechanisms: agents that increase cancer risk indirectly by interfering with the immune system (HIV); infectious agents that create tissue destruction and chronic inflammation (H. pylori), and agents that act as direct triggers for the proliferation of infected cells (viruses and a few bacteria). Many oncogenic viruses remain latent in cells until activation by toxic chemicals, hormones, radiation, or other viruses. People infected with human T-cell lymphotropic virus type 1 (HTLV-1) develop adult T-cell leukemia/lymphoma (ATL) after a latent period of twenty years or more. Hepatitis C virus triggers long-term chronic infections, 5 percent of which result in liver cancer after several decades. HIV infection stimulates Kaposi sarcoma about two years after the virus is first detected. HIV infects and destroys white blood cells (helper T cells) and weakens the body’s immune system, allowing viruses such as HPV to attack and trigger cancer development. H. pylori bacterial infections secrete toxins that cause chronic inflammation followed by abnormal cells that become cancerous, especially in the lower part of the stomach. The Epstein-Barr virus causes infectious mononucleosis, cancers of the throat (nasopharyngeal carcinoma) and stomach, Hodgkin disease, and lymphomas (cancers in the lymphatic system including the spleen, tonsils, and thymus), particularly in people with organ transplants. The hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause chronic infections that lead to most liver cancers. Some human papillomaviruses (HPV) initiate cervical cancer, promoted by hormones in oral contraceptives and Chlamydia trachomatis infection of the reproductive system. HPVs also cause some cancers of the penis, anus, vagina, and vulva, and are possibly linked with mouth, throat, head, and neck cancers. Blood flukes create chronic inflammation in the blood vessels of the intestine or bladder, which occasionally causes bladder and bile duct cancers. Incidence: Roughly 15 percent of all cancers worldwide are linked to viral (11 percent), bacterial (4 percent), or parasitic infections (0.1 percent). In the United States and other developed countries, fewer than 10 percent of cancers are linked to infectious agents, but they account for 20 percent of cancers in developing countries. Cancers from Epstein-Barr virus infections are few but are more common in Africa and parts of Southeast Asia. HBV infections (causing liver cancer) are prevalent in China, Southeast Asia, northern Canada, Africa, Alaska, 641
Infectious cancers
Infectious Agents That Are Risk Factors for Cancer Viruses • Epstein-Barr virus (EBV) • Hepatitis B virus (HBV) • Hepatitis C virus (HCV) • Human herpesvirus 8 (HHV-8) • Human immunodeficiency virus (HIV) • Human papillomavirus (HPV) • Human T-lymphotropic virus type 1 (HTLV-I) Bacteria • Chlamydia trachomatis • Helicobacter pylori (H. pylori) Parasites • Clonorchis sinensiare (liver fluke) • Opisthorchi viverrini (liver fluke) • Schistosoma haematobium Source: American Cancer Society
and Amazonia. In the United States, 30 percent of liver cancers are related to hepatitis B or C virus infections. Kaposi sarcoma was the most common cancer among the 40 million worldwide HIV infections recorded in 2004. HPV causes 70 percent of cervical cancers and is the second most common cancer among women worldwide. HTLV-1 infections, mostly in southern Japan, the Caribbean, Central Africa, parts of South America, and among immigrants in the southeastern United States, create up to a 5 percent chance of developing adult T-cell leukemia/ lymphoma. More than half of the worldwide cases of stomach cancer (the fourth most common cancer) are linked to H. pylori infection. About 10,000 parasitic infection cancer cases are reported annually. Parasitic bile duct cancer is localized in East Asia, while blood-fluke-induced bladder cancer is localized in Africa and Asia. Symptoms: Patients with infectious cancers exhibit symptoms of the viral, bacterial, or parasitic worm diseases associated with the particular infectious cancer, plus other general cancer symptoms such as a swelling (indicating a tumor), incessant pain, fever, constipation, weakness, fatigue, loss of appetite, anemia, nausea, vomiting, bone fractures, weakness or numbness in legs, weight loss, repeated infections, and urination problems. For example, symptoms of infectious mononucleosis (caused by the Epstein-Barr virus) are fever, sore throat, 642
Salem Health: Cancer swollen lymph glands, and occasionally a swollen spleen or liver. Kaposi sarcoma (associated with HIV infection) appears as reddish-purple or blue-brown tumors just underneath the skin. Patients infected with the hepatitis B virus have symptoms such as a flulike illness and a yellowing of the eyes and skin (jaundice of the liver). The hepatitis C virus normally has no symptoms but causes chronic infections that lead to liver damage. Screening and diagnosis: Screening of all donated blood in the United States has greatly reduced the chance of infection through transfusion, which has helped to control the spread of HIV, HTLV-1, and many other forms of infection. Epidemiological studies, combined with molecular analysis, enhance the diagnosis, screening, and analysis of stages in carcinogenesis and development of infectious cancers. Such studies have shown, for example, that infections of H. pylori are present before the appearance of stomach cancer. Using modern technology, viral infections can be monitored by polymerase chain reaction methods. Biochemical markers are useful for carcinogen exposure determinations, such as urine biochemical studies confirming a synergism between aflatoxin fungal and hepatitis B viral infections. Treatment and therapy: Antibiotics and other medicines effectively destroy carcinogenic infectious microorganisms such as H. pylori. Immunotherapy is a modern method of treating infectious cancers. Antigens expressed by virusinduced cancers generate host antibodies capable of killing the cancer cells. Vaccines against the types of HPV that cause cancer have been developed: One vaccine (Cervarix) protects against infection from two types of HPV; the other (Gardasil, which has U.S. Food and Drug Administration approval) protects against four types. The vaccine is recommended for girls and young women from ages nine through twenty-six. Few drugs can treat hepatitis B or C, but a vaccine is available to prevent hepatitis B virus infection. In the United States, it is recommended for all children and for adults who are at risk, such as health care workers and intravenous drug users. Hepatitis C virus has no preventive vaccine at present. Anti-HIV drugs reduce the risk of Kaposi sarcoma and cervical cancer in those infected with HIV. Prognosis, prevention, and outcomes: Epidemiological studies plus descriptive and clinical studies provide information on carcinogenic microorganisms and the effectiveness of cancer prevention and treatment. Antimicrobial drugs that kill or suppress growth of infectious cancer-
Salem Health: Cancer causing agents can be administered as a preventive measure against infectious cancers or after surgery that removes suspected abnormal cells. Stomach cancers from H. pylori infection, for example, have been effectively eliminated with antibiotics after removal of superficial cancerous areas. Exposure to carcinogenic infectious agents can be avoided or reduced through lifestyle changes, including diet management and healthy sexual practices (avoiding multiple partners and regulating contraception). Condoms reduce the risk of viral infection but do not protect exposed areas. Pap tests detect precancerous cervical cells for treatment and prevention of HPV-induced cancer. Screening of donated blood greatly reduces the chance of infection through transfusion. The Kaposi sarcoma rate has dropped in the United States because of better treatment of HIV infections. Investigations of carcinogenic infections continue, alongside the exploration of novel cancer treatments with minimum side effects, such as gene therapy, immunotherapy, and proton radiotherapy. Samuel V. A. Kisseadoo, Ph.D. u For Further Information American Cancer Society. “Cancers Linked to Infectious Disease.” In Cancer Facts and Figures. Atlanta: Author, 2005. Armstrong, G. L., et al. “The Prevalence of Hepatitis C Virus Infection in the United States, 1999 Through 2002.” Annals of Internal Medicine 144 (2006): 705-714. Bonnet, F., et al. “Malignancy-Related Causes of Death in Human Immunodeficiency Virus-Infected Patients in the Era of Highly Active Antiretroviral Therapy.” Cancer 101 (July 15, 2004): 317-324. Kleinsmith, L. J. Principles of Cancer Biology. New York: Pearson, Benjamin Cummings, 2006. Lambert, P. F., and B. Sugden. “Viruses and Human Cancer.” In Clinical Oncology, edited by M. D. Abeloff et al. 3d ed. Philadelphia: Elsevier Churchill Livingstone, 2004. u
Other Resources
American Cancer Society Infectious Agents and Cancer http://www.cancer.org/docroot/PED/content/ PED_1_3X_Infectious_Agents_and_Cancer.asp Center for Immunotherapy of Cancer and Infectious Diseases http://immunotherapy.uchc.edu/
Infertility and cancer National Cancer Institute http://www.cancer.gov See also Aflatoxins; Bacteria as causes of cancer; Epidemiology of cancer; Epstein-Barr virus; Hepatitis B virus (HBV); Hepatitis C virus (HCV); Herpes simplex virus; Herpes zoster virus; HIV/AIDS-related cancers; Infection and sepsis; Vaccines, preventive; Viral oncology; Virusrelated cancers.
u Infertility and cancer Category: Diseases, symptoms, and conditions Also known as: Subfertility, subfecundity Related conditions: Sterility, premature menopause Definition: Infertility is the inability to achieve pregnancy after one year of intercourse without contraception. Infertility, as it relates to cancer, refers to the loss of fertility due to cancer or its treatment and can be temporary or permanent. Infertility in men is caused by an absence of or a decrease in sperm production; a deficiency in the sperm quality affected by changes in sperm morphology, motility, or DNA integrity; or an inability to deliver sperm through ejaculation. Female infertility is caused when an egg cannot be successfully fertilized, a fertilized egg cannot implant in the uterus, or a pregnancy cannot be maintained. Risk factors: The risk of infertility depends on the type of cancer and its location; the cancer treatment, including the type, dose, location, and method of administration; and the use of any fertility preservation or sparing procedures before or during treatment. The risk of infertility is also affected by the person’s age, general health, and pretreatment fertility status. Testicular cancer and Hodgkin disease are associated with both pretreatment and posttreatment infertility in men. Etiology and the disease process: Cancer-related infertility is usually caused by the effects of treatment rather than the actual disease. Chemotherapy can damage the stem cells that make sperm or immature eggs (oocytes) and mature eggs. The effects of chemotherapy are drug specific and dose dependent, with alkylating agents causing the most damage. The effect of radiation on fertility depends on the dose and the location. Patients receiving very high doses delivered through total body irradiation or radiation focused to the abdomen, pelvis, or cranium are at highest risk for infertility. Radiation can kill sperm stem cells or oocytes, damage reproductive structures, or alter the pituitary gland. 643
Infertility and cancer
Salem Health: Cancer to enable conception of a child biologically related to both parents. Men with low sperm count or low sperm motility may be able to father a child through intrauterine insemination (IUI), in vitro fertilization (IVF), or in vitro fertilization using intracytoplasmic sperm injection (IVF-ICSI). If there are no sperm in the ejaculate, surgical sperm extraction techniques may be used to retrieve sperm from the testicles or epididymis for use in IVF-ISCI. Anejaculation or retrograde ejaculation may be addressed through surgery, medications, or use of mechanical or electrical stimulators. Women are often given fertility medications to induce ovulation. The eggs can be fertilized through sexual intercourse, IUI, or IVF. Scarring or vascular changes affecting female reproductive structures may be treatable by surgery. A surrogate mother may be used in instances in which a woman’s eggs can be fertilized but the pregnancy cannot be maintained.
Techniques for Preserving Fertility Before or During Cancer Treatment For Women • Embryo freezing • Egg freezing • Ovarian tissue freezing • Ovarian transposition (moving ovaries to avoid radiation) • Radical trachlectomy (removing the cervix but not the uterus and ovaries) Fertility-sparing procedure (removing only the affected ovary • in cases of ovarian cancer) For Men • Sperm banking • Sperm extraction • Testicular tissue freezing • Radiation shielding Source: American Cancer Society
Surgery to remove reproductive structures may cause intractable infertility (sterility) or require the use of assisted reproductive technologies to assist in conception. Unintended side effects of surgery, such as nerve damage, scarring, or vascular changes, can also cause infertility. Incidence: The occurrence of infertility is highly variable based on patient- and cancer-related factors. Data quantifying infertility in all cancer patients are scant. Symptoms: Infertility is not often detected until a person attempts to conceive. After cancer treatment, men may be unable to ejaculate (anejaculation) or may experience retrograde ejaculation, in which little or no semen is produced. Women may have an absence or cessation of menstruation, have irregular menstrual cycles, or experience painful intercourse. Screening and diagnosis: Screening for infertility occurs if there is difficulty conceiving or high- to medium-risk cancer treatments were used. Male infertility is diagnosed primarily through semen analysis to assess the number and quality of the sperm. Infertility in women can be diagnosed by assessing hormone levels, an ultrasound examination for ovulation, or visualization of reproductive structures through an ultrasound, a hysterosalpingogram, or laparoscopic surgery. The cause of infertility is sometimes indeterminable. Treatment and therapy: The underlying cause of infertility often cannot be treated; however, many cancer survivors are candidates for assisted reproductive technologies 644
Prognosis, prevention, and outcomes: It is advised that cancer patients discuss options to preserve or spare fertility with their oncologists before treatment and consult a fertility specialist. Before treatment, sperm can be frozen for use at a later time in IUI, IVF, or IVF-ISCI procedures; however, this may not be an option for men with testicular cancer or Hodgkin disease, whose sperm is already compromised. Researchers are investigating whether sperm production can be restored by freezing testicular tissue and later grafting the tissue onto the testicle or using it to isolate stem cells. Women can have their eggs collected and fertilized with partner or donor sperm. The resulting embryos are frozen for future implantation. Unfertilized eggs or ovarian tissue may also be frozen for later use in IVF procedures or transplantation back into the body, respectively; however, these techniques are experimental. Patients may benefit from options sparing fertility during treatment. These include protecting or shielding reproductive organs from radiation, conservative surgery when possible, and experimental hormonal therapy. Amanda McQuade, Ph.D. u
For Further Information Lee, S. J., et al. “American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients.” Journal of Clinical Oncology 24, no. 18 (2006): 2917-2931. Oktay, K. H., L. Beck, and J. D. Reinecke. One Hundred Questions and Answers About Cancer and Fertility. Sudbury, Mass.: Jones and Bartlett, 2008.
Salem Health: Cancer Potter, D. A., and J. S. Hanin. What to Do When You Can’t Get Pregnant: The Complete Guide to All the Technologies for Couples Facing Fertility Problems. New York: Marlowe, 2005. u
Other Resources
Cancer.Net http://www.cancer.net/portal/site/patient Fertile Hope http://www.fertilehope.org InterNational Council on Infertility Information Dissemination http://www.inciid.org/ Lance Armstrong Foundation http://www.livestrong.org See also Amenorrhea; Antiestrogens; Birth control pills and cancer; Breast cancer in pregnant women; Childbirth and cancer; Diethylstilbestrol (DES); Endocrine cancers; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Fertility issues; Gynecologic cancers; Gynecologic oncology; Hormone replacement therapy (HRT); Hysterectomy; Ovarian cancers; Placental alkaline phosphatase (PALP); Pregnancy and cancer; Sterility; Uterine cancer; Vaginal cancer.
u Inflammatory bowel disease Category: Diseases, symptoms, and conditions Also known as: IBD, Crohn disease, ulcerative colitis Related conditions: Colon cancer, irritable bowel syndrome (IBS) Definition: Inflammatory bowel disease is a chronic inflammation of the intestinal tissue. The two main conditions are Crohn disease and ulcerative colitis. Risk factors: Inflammatory bowel disease may be at least partially inherited, as studies have shown that 20 to 25 percent of IBD patients have a close relative with the disease. Race and ethnicity may also be important determinants in the formation of inflammatory bowel disease, and American Jews of European descent are particularly prone to developing Crohn disease. For unknown reasons, higher socioeconomic status seems to predispose for IBD. Etiology and the disease process: The development of inflammatory bowel disease is still undetermined, but it is thought to be the result of an abnormal immune response
Inflammatory bowel disease to an unknown antigen. In genetically susceptible individuals, this immune activation is prolonged, resulting in an inflammatory response that leads to intestinal tissue damage. Incidence: Nearly 1 million Americans are estimated to be affected by inflammatory bowel disease, with an equal prevalence of ulcerative colitis and Crohn disease. Men and women are equally affected. Symptoms: The symptoms of inflammatory bowel disease depend on the severity of the disease. Ulcerative colitis and Crohn disease patients may both complain of diarrhea, although bloody diarrhea is more characteristic of ulcerative colitis. Weight loss, nausea, vomiting, and fever are also common symptoms. Screening and diagnosis: Because the symptoms associated with inflammatory bowel disease are common to many other gastrointestinal disorders, a colonoscopy is used both to confirm a diagnosis of inflammatory bowel disease and to differentiate between ulcerative colitis and Crohn disease. Treatment and therapy: Treatment of inflammatory bowel disease depends entirely on the severity of the disease. The chronic nature of inflammatory bowel disease causes patients to experience extended periods of symptomfree living, interrupted by inflammatory “flares.” These flares are treated with a variety of agents, including antiinflammatory drugs, steroids, and immunosuppressants. Some biological therapies have proven effective in inflammatory bowel disease. Most of these biological therapies are antibodies that inhibit proinflammatory molecules within the intestine. The goal of therapy is to induce and maintain remission. Prognosis, prevention, and outcomes: The quality of life of patients with inflammatory bowel disease depends on the severity of their disease. Severe gastrointestinal symptoms can cause patients to restrict their lifestyles. Patients with inflammatory bowel disease are at an increased risk for developing colon cancer, although more than 90 percent of inflammatory bowel disease patients never develop intestinal cancers. Inflammatory bowel disesase is rarely fatal, but death can occur if serious complications are not properly treated. Lisa M. Cockrell, B.S. See also Azathioprine; Coloanal anastomosis; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Crohn disease; Enterostomal therapy; Fecal occult blood test (FOBT); Ileostomy; Immunoelectrophoresis (IEP); Pancolitis; Premalignancies; Risks for cancer. 645
Informed consent
u Informed consent Category: Social and personal issues Also known as: Written consent Definition: Informed consent is the process whereby a patient decides whether to accept the risks of a medical procedure, such as a surgery or chemotherapy, and to undergo that procedure. Its purpose is to protect the rights and welfare of patients. This decision-making process involves receiving comprehensive information about a proposed medical treatment, procedure, surgery, or clinical drug or medical device trial and its possible risks; having all questions satisfactorily answered; and signing a consent form to undergo the proposed course of action or refusing to sign the consent form and thereby refusing to undergo the procedure. By signing this form, patients are providing legal documentation that they have received all necessary information to make an informed decision and are giving permission for a physician to proceed with the proposed course of action. A parent, legal guardian, or court-authorized person may complete the process if the patient is a child or is mentally or physically unable to participate in the process. Informing the patient: Patients receive information about the proposed medical course of action. It should be as nontechnical as possible to ensure that it is understandable. Explanations can be in the following forms: • Verbal, via the physician or other health care provider • Written, via patient information handouts or educational booklets • Short films on video or DVD • Computer-provided interactive tutorials After receiving comprehensive information, patients are to have all their questions answered in language that they are able to understand. Nonsurgical treatments: For treatments, the American Cancer Society recommends that patients include questions about the diagnosis that has prompted the procedure, including how serious the condition is; the recommended treatment methods and possible benefits and risks of having, or not having, the treatment, including the effect on normal functions and everyday activities and possible immediate, short-term, and long-term side effects; other treatment options, if available, and their possible benefits and risks; any potential discomforts associated with the treatments and the methods used to prevent or relieve those discomforts; the treatment’s duration; and the treatment’s cost. Surgical procedures: For surgical procedures, the American College of Surgeons recommends that patients pose 646
Salem Health: Cancer questions about the factors that indicate an operation is required, and the possible benefits and risks of having, or not having, the operation, including the impact on health or quality of life; the alternatives to the surgery, if available, and their possible benefits and risks; the basic procedures involved in the operation, including expected length of hospitalization, if necessary; and expectations during the recovery period, including length of time before resumption of normal activities. Giving consent: Once patients have had all questions satisfactorily answered, they are asked to decide whether they want to undergo the proposed medical course of action. An affirmative decision is indicated by signing and dating a written informed consent form, signaling voluntary willingness. This form may then be signed by a witness to confirm that the patient has received an accurate explanation of the information contained both in the form and in any other printed or orally delivered material, has understood the information, and has freely given consent. Clinical trials: For clinical trials, the informed consent process is more detailed than that for a nonexperimental medical course of action. Clinical trials for investigational drugs, medical procedures, or medical devices are to be conducted using Good Clinical Practices (GCPs), as mandated by the Code of Federal Regulations (CFR) of the U.S. Food and Drug Administration (FDA) and by guidelines of the International Conference on Harmonization (ICH). Before screening for possible participation, the potential study subjects must receive information on and have all their questions answered about the investigational drug or medical device being tested and the probability of being assigned to a treatment group or placebo (nonexperimental drug/device) group; the study procedures to be followed (including identification of any that are experimental) and tests to be administered; and the potential risks and benefits involved in study participation. Patients must also receive information about the expected length of participation, their responsibilities as study subjects, anticipated compensation for participation (if any), the possible circumstances under which participation may be discontinued (despite subjects’ consent), the possible compensation and treatments available should they have a trial-related injury, and the extent to which records that contain information about their identity will be kept confidential. Once patients have had all questions satisfactorily answered, they are required to sign an informed consent form that has been approved by an institutional review board (IRB) or independent ethics committee (IEC). By providing written informed consent, patients are indicating that
Salem Health: Cancer all their questions have been answered, their participation in the study is voluntary, and they understand that they have the right to withdraw this consent to participate at any time during the study. During the procedure or clinical trial: Although an informed consent form has been signed to indicate voluntary participation in a clinical trial, the study personnel— including sponsors, investigators, monitors, clinical research assistants, and anyone else involved with clinical trial procedures—are not released from liability for negligence. In addition, patients have the right to have their questions answered throughout the treatment process and to withdraw their consent at any time. In the case of clinical trials, subjects are to be informed if any significant results occur during the study that might affect their willingness to continue to participate in that study. Cynthia L. De Vine, B.A. u For Further Information Berg, J. W., P. S. Appelbaum, C. W. Lidz, and L. S. Parker. Informed Consent: Legal Theory and Clinical Practice. New York: Oxford University Press, 2001. Faden, R. R., and T. L. Beauchamp. A History and Theory of Informed Consent. New York: Oxford University Press, 1986. U.S. Food and Drug Administration. Guidance for Institutional Review Boards and Clinical Investigators: A Guide to Informed Consent. Rockville, Md.: Author, 1998. u
Other Resources
American Cancer Society Informed Consent http://www.cancer.org/docroot/eto/content/ eto_1_2x_informed_consent.asp American College of Surgeons Giving Your Informed Consent http://www.facs.org/public_info/operation/ consent.html American Hospital Association Patient Care Partnership http://www.aha.org/aha/issues/ Communicating-With-Patients/pt-carepartnership.html National Cancer Institute A Guide to Understanding Informed Consent http://www.cancer.gov/ClinicalTrials/ AGuidetoUnderstandingInformedConsent
Infusion therapies U.S. Food and Drug Administration Guidances, Information Sheets, and Important Notices on Good Clinical Practice in FDA-Regulated Clinical Trials http://www.fda.gov/oc/gcp/guidance.html See also Advance directives; Clinical trials; Counseling for cancer patients and survivors; Do-not-resuscitate (DNR) order; End-of-life care; Family history and risk assessment; Hospice care; Living will; Overtreatment; Palliative treatment; Second opinions; Surgical biopsies; Transfusion therapy.
u Infusion therapies Category: Procedures Also known as: Central line infusions, intravenous therapy, parenteral therapy Definition: Infusion therapy is a medical procedure for the insertion of fluid, medication (such as chemotherapy, pain medications, or antibiotics), and nutrients or vitamins into the body. Fluid can be inserted either through a vein (intravenously), into a muscle (intramuscularly), into the tissue of the spinal cord (intraspinally), or under the skin (subcutaneously). Infusion therapies for cancers are typically used for pain medications, chemotherapy, and antibiotics. Cancers treated: Cancers that require chemotherapy or pain management, as directed by a physician Why performed: Infusion therapy is performed to provide the rapid delivery of medication, fluid, or nutrients to a patient. Patient preparation: Patients are requested to remain hydrated before and after infusion therapy, particularly when administered chemotherapy. Sugar consumption should be limited during this time frame. Many patients are recommended to participate in a low-impact stress relief program while undergoing infusion therapy. Steps of the procedure: Infusions can be performed in a clinical setting or at home. A catheter (a thin plastic tube that covers a needle) is typically inserted into either the hand or the arm of the patient. Once the catheter has been inserted, the needle is removed and the tube remains. The fluid to be inserted is administered at a predefined rate (either “pushed” at intervals or steadily) from an infusion bag that contains the solution. The type of catheter used depends upon the length of infusion time. 647
Insurance An intravenous port can also be inserted into the patient’s chest to provide easy access for infusion therapy, if the therapy is required frequently. After the procedure: Infusion therapy is typically an outpatient procedure. Patients should pay close attention to the injection site to watch for possible infusion-related reactions. Any unexpected or serious reactions should be reported to a doctor immediately. Chemotherapy can cause a variety of side effects following administration, particularly nausea and fatigue. Risks: Infusion therapy can lead to skin reactions including rash, bruising, burns, and tenderness, as well as fluid leakage at the site of injection. Furthermore, infusion therapy has a risk of sepsis, infection, occlusion of the catheter (partial or complete obstruction), and overdose. Chemotherapy can cause hair loss, fatigue, nausea, diarrhea, and fever. Results: Infusion therapies provide an effective, direct administration of fluids into the vascular system of the body. Anna Perez, M.Sc. See also Antidiarrheal agents; Antifungal therapies; Antiviral therapies; Autologous blood transfusion; Biological therapy; Bone marrow transplantation (BMT); Chemotherapy; Colony-stimulating factors (CSFs); Gene therapy; Hemolytic anemia; Hepatic arterial infusion (HAI); Herbs as antioxidants; HIV/AIDS-related cancers; Home health services; Interleukins; Leukapharesis; Lymphangiography; Magnetic resonance imaging (MRI); Monoclonal antibodies; Neurologic oncology; Pneumonectomy; Prevention; Stem cell transplantation; Topoisomerase inhibitors; Transfusion therapy; Transitional care; Tyrosine kinase inhibitors.
u Insurance Category: Social and personal issues Definition: Insurance is protection against financial loss incurred due to certain events. Benefits under an insurance policy are available only if a person has insurance before the event occurs. There are four types of insurance that may be particularly relevant to persons with cancer: life, disability, long-term care, and health insurance. Life, disability, and long-term care insurance: Life insurance is protection against loss due to death. It is available on the private, commercial market and sometimes through an employer as an employee benefit. Life insur648
Salem Health: Cancer ance is available in two major types: term and whole. Term life insurance pays a certain dollar amount if a person covered under the policy (a covered person) dies during the term of the policy, usually between one and thirty years. Whole life health insurance pays a benefit whenever death of the covered person occurs. Private disability insurance pays a certain percentage of income if a covered person is unable to work because of an accident or illness. Short-term or long-term disability insurance is available. Short-term replaces income for a period of less than two years, and long-term insurance usually replaces 60 percent of income for a period lasting a few years to a lifetime. Disability insurance can be purchased on the commercial market or can be obtained through an employer. Long-term care insurance pays for services of nursing homes, assisted living facilities, or in-home caregivers if a covered person is unable to perform activities of daily living. Neither private health insurance nor the public health insurance Medicare pays for long-term care expenses. Medicaid, another public health insurance program, pays for long-term care only for those persons who qualify financially (those who meet Medicaid’s definition of need). Long-term care insurance is usually purchased on the commercial market, although some employers offer it as an employee benefit. Health insurance: Health insurance is protection against loss due to illness or bodily injury. Health insurance plans cover the costs of medical services, equipment, and supplies provided by health care providers such as physicians, hospitals, and outpatient facilities. Health insurance is important for people with cancer. It can pay for preventive care and cancer screenings and for cancer treatments, which can be very expensive. In 2004, cancer was the second most costly condition in the United States, behind heart disease, accounting for $62.2 billion in direct medical costs for the civilian, noninstitutionalized population. Public and private health insurance paid for 89.5 percent of those costs. Public health insurance is provided to certain qualified individuals through Medicare, Medicaid, the State Children’s Health Insurance Program, the Federal Employees Health Benefits Plan, military health care, or the Indian Health Service. Private health insurance is provided to the general public through insured plans or self-funded plans. Insured plans are sold on the commercial market by insurance companies, mutual insurance companies, and health maintenance organizations. In exchange for a set fee called a premium, the insurer covers specified medical expenses for the length of the contract or policy, usually one year,
Salem Health: Cancer with the insurer bearing a specified portion of the financial risk. Insured plans cover groups of people or just individuals. Employers often purchase group insurance plans on behalf of their employees and pay the whole premium or share the costs with their employees. Individuals pay the entire premium for an individual insurance plan. Insured plans are regulated under state and federal laws. Self-funded plans are plans in which an employer or an employee group, such as a union, acts as an insurer and pays for employees’ health care costs directly. The employer or employee group bears a specified portion of the financial liability for paying for health costs. It can be difficult to determine if group health insurance is provided through a self-funded plan because many self-funded plans are administered by a commercial insurer. Self-funded plans are primarily regulated under federal law, regardless of whether a commercial insurer administers the plan, and many state laws do not apply to self-funded plans. Indemnity plans and managed care plans are two basic types of health insurance plans offered by public and private insurers. An indemnity plan is often called a fee-forservice plan because the insurer reimburses the covered person or the health care provider as expenses are incurred. Covered persons can use any health care provider they choose. In exchange for this flexibility, the covered person often bears more of the cost of the services by paying coinsurance, which is the amount expressed as a percentage and/or a fixed amount that a covered person is required to pay after meeting the deductible. The deductible is the amount a covered person must pay over the term of the policy before the insurer starts paying for services. Coinsurance is often split, with insurers typically paying 80 percent of the cost for medical services, (or what the insurer deems to be “usual and customary” charges) and covered persons typically paying 20 percent. These percentages may, however, vary with the type of care provided; for example, copayments for mental health services, if covered at all, usually are higher. The covered person might also have to pay for any difference between the usual and customary charges paid by the insurer and the actual amount charged by the health care provider. Unless health care providers agree to submit claims on behalf of their patients, persons covered under an indemnity plan may have to pay providers up front for services and submit a claim to the insurer for reimbursement. Many indemnity plans do not cover the costs of preventive care or screenings, unless coverage is required under state or federal law. Managed care plans are those that use financial incentives to manage the cost, quality, and delivery of care. Persons covered under a managed care plan typically have
Insurance fewer choices of health care providers, but out-of-pocket expenses are more predictable and lower than for indemnity plans, and the covered person manages less paperwork. Most managed care plans cover preventative care and screenings. There are three common types of managed care plans: health maintenance organization plans (HMOs), point-of-service plans (POS’s), and preferred provider organization plans (PPOs). Health insurance coverage: Health insurance plans vary in the health benefits they offer. Catastrophic plans pay for catastrophic events, such as treatment of cancer, but do not cover preventive or routine medical care. Catastrophic plans often have high deductibles but low premiums. Basic plans cover minimal services, including hospitalization, surgery, and some doctor visits. Major medical plans cover expanded services, such as preventive care and screenings, specialist care, physical therapy and rehabilitation, and care for chronic diseases, which includes treatment of cancer. Basic and major medical plans together are called comprehensive plans. Many states require comprehensive plans to cover screening for breast, colorectal, prostate, cervical, and ovarian cancers. These requirements are called mandated benefits and apply only to insured plans regulated by states. Federal law mandates the coverage of breast reconstruction after a mastectomy by all insured and self-funded plans that provide medical and surgical benefits for mastectomy. Riders to existing health plans or supplemental plans can be purchased to cover gaps in coverage of a health insurance plan. Riders to cover specific services are purchased from the same insurer that issues the health plan, while supplemental plans are separate health insurance policies. Common riders and supplemental plans include private prescription drug plans, Medicare supplement insurance (Medigap) policies, and disease-specific policies that cover only expenses related to diagnosis of a specific disease such as cancer, heart disease, or stroke. Cancer-specific supplemental policies vary widely in the health benefits covered. Some policies cover all medical expenses related to cancer treatment, while others may pay hospitalization costs only, a fixed dollar amount for services, or a lump sum on diagnosis of cancer. Some policies may cover home care or nonmedical expenses such as transportation and lodging when connected to cancer treatment. Cancer-specific policies may exclude coverage of certain types of cancers or put limits on how long benefits can be drawn, and most policies do not cover cancerrelated illness such as infection or pneumonia. Cancer patients may find that some of their medical services are not covered under their health insurance plan. 649
Insurance Some health insurance plans exclude coverage of certain treatments, such as alternative care, infertility treatments, or experimental treatments. However, some medical expenses incurred in experimental treatments are covered under Medicare plans and under insured plans in several states. Some patients’ care may be so expensive that it exceeds the plan’s maximum plan dollar limit. A maximum plan limit is the amount payable by the insurer for covered expenses over the plan year or over the entire lifetime of the plan. Lifetime maximums are often set at $1 million. Health insurers may deny coverage of services based on their assessment that coverage is not provided for under the policy, the proper procedures in obtaining the services were not followed, or the services were not appropriate or medically necessary. Health insurers must follow state and federal rules for internally reviewing covered persons’ complaints and appeals concerning denial of coverage. Most states have enacted procedures for external or independent reviews, especially when denial of coverage was based on a determination by the insurer that the services were not appropriate or medically necessary. Statemandated dispute resolution procedures usually apply only to insured plans. Many states have established an ombudsman office to act on behalf of covered persons during denial-of-coverage disputes with insurers. Health insurance accessibility: A person whose cancer was diagnosed before becoming insured may have a difficult time getting private health insurance. Only a few states require insurers to issue an individual plan to any person able to pay the premiums, regardless of prior insured history or health status. If a person is able to work for an employer who offers insurance, federal law protects a person’s ability to get group insurance. Federal law prohibits insured group plans and self-insured group plans from discriminating against a group member based on health status. Health status cannot be used to determine a person’s eligibility for coverage or the premium contributions made by that person. Federal law also requires insurers to issue insured plans to small employers with two to fifty employees regardless of health status of employees. If a person successfully obtains coverage, preexisting condition exclusions may apply. Persons with conditions diagnosed or apparent before insurance coverage began may be subject to a waiting period or exclusion period before an insurance plan covers medical services for those conditions. Federal law limits the exclusion period for preexisting conditions to twelve months for persons who switch from public or private insurance to private group insurance (insured or self-insured). Any exclusion period must be reduced by the number of months that a newly 650
Salem Health: Cancer covered person was previously covered under a private or public insurance plan; however, the gap between previous coverage and enrolling in the new plan can be no longer than sixty-three days. Individual plans may not have the same protections. Many states allow individual plans to be issued to persons with exclusionary riders that exclude coverage of preexisting medical conditions for the life of the insurance plan. Given these various difficulties, it is important for people with cancer to hold onto coverage as long as they can. Federal law allows certain persons who lose coverage under a group insurance plan to continue coverage for a period of eighteen months to three years, if the person pays the premium. These rights are referred to as COBRA continuation of health coverage. If a person exhausts coverage under COBRA, federal law requires insurers to issue an individual plan to the person regardless of health status and without any waiting periods for treatment. Amanda McQuade, Ph.D. u
For Further Information Cooper, Laura D. Insurance Solutions: Plan Well, Live Better—A Workbook for People with Chronic Illnesses or Disabilities. New York: Demos Medical, 2002. Garner, John C. Health Insurance Answer Book. 7th ed. New York: Aspen, 2006. Landay, David S. Be Prepared: The Complete Financial, Legal, and Practical Guide for Living with a LifeChallenging Condition. New York: St. Martin’s Press, 1998. Northrop, Dorothy E., Stephen E. Cooper, and Kimberly Calder. Health Insurance Resources: A Guide for People with Chronic Disease and Disability. 2d ed. New York: Demos Medical, 2007.
u
Other Resources
Kaiser Family Foundation http://www.statehealthfacts.org National Association of Insurance Commissioners http://www.naic.org U.S. Department of Health and Human Services Agency for Healthcare Research and Quality http://www.ahrq.gov Centers for Medicare and Medicaid Services http://www.cms.hhs.gov See also Advance directives; Aging and cancer; Aids and devices for cancer patients; Cancer care team; Case management; End-of-life care; Financial issues; Genetic counseling; Health maintenance organizations (HMOs); Home
Salem Health: Cancer health services; Long-distance caregiving; Managed care; Medicare and cancer; Palliative treatment; Preferred provider organizations (PPOs); Prevention; Screening for cancer; Second opinions; Social Security Disability Insurance (SSDI); Survivorship issues; Transitional care.
u Integrative oncology Category: Complementary and alternative therapies Also known as: Complementary medicine Definition: Integrative oncology combines mainstream or traditional cancer care with other approaches to manage symptoms, improve quality of life, enhance wellness, and improve the efficacy of treatment. It integrates the best of traditional cancer care with care that emphasizes the mindbody-spirit connection to provide a multidisciplinary approach to managing disease. Alternative medicine, by definition, is used to replace traditional treatment and should not be confused with complementary medicine. The patient population: Patients receiving cancer therapy encounter a challenging treatment period that lasts for an extended period of time, often years. Side effects of therapy are significant and can include nausea, vomiting, pain, limits on mobility, fatigue, and other symptoms often difficult to manage with traditional medicine. Recent surveys report that at least 20 to almost 100 percent of cancer patients use some type of complementary therapy, with or without their physicians’ knowledge, in an attempt to manage the side effects of their treatment and symptoms of their disease. Perceived benefits: Multiple studies report that complementary and alternative medicine (CAM) can provide benefits to the well-being of the patient. There are some scientific reports that document the benefits of complementary and alternative medicine, but anecdotal reports of benefits are often accepted when complementary medicine is used in conjunction with traditional medicine. The barrier of proof with alternative therapies is higher although some have been used for many years in nonWestern societies. Psychosocial interventions are an integral part of any cancer patient’s care. Mind-body-spirit therapies enhance mood, reduce anxiety, decrease depression, and improve coping skills, as reported in multiple studies. Pain reduction, managing conditioned nausea and vomiting, and control of other physical symptoms are also attributed to mind-body-spirit techniques practiced by the patient on a routine basis.
Integrative oncology Types of CAM therapies: The Office of Cancer Complementary and Alternative Medicine of the National Cancer Institute spends time and resources exploring the scientific validity and impact of complementary and alternative medicine in cancer care. Alternative medicine techniques are often based on theories generated apart from and earlier than conventional Western medicine. Some of the techniques come from Asia, including acupuncture, ayurveda, and traditional Chinese and Tibetan medicines; others are of Western origin, including homeopathy and naturopathy. Energy therapies are based on the use of energy fields purported to surround and penetrate the human body, but to date there is no scientific evidence that these fields exist. Reiki therapy, therapeutic touch, and qi gong are examples of energy therapies. Electromagnetic therapies include pulsed electromagnetic fields and magnet therapy. Exercise therapies such as tai chi, yoga, walking, and gentle workouts all contribute to the feeling of wellbeing in cancer patients and are often recommended. Massage therapy, reflexology, osteopathy, and chiropractic medicine are based on manipulating body parts. All manipulation must be appropriate to the physical condition of the patient, but gentle massage and reflexology often create a feeling similar to that created by exercise if that option is limited by the patient’s condition. The most common mind-body-spirit interventions are related to learned techniques that are practiced by the patient to provide benefits related to the control of side effects of care. Meditation, relaxation therapy, guided imagery, self-hypnosis, and biofeedback, when routinely practiced, may control pain, nausea, vomiting, anxiety, and other symptoms. Participation in support groups, art therapy classes, music therapy, dance therapy, journaling, and aromatherapy programs provides, both potential symptom management and social interaction that contribute to a feeling of well-being. Spiritual therapies are receiving greater attention, with spiritual healing and intercessory prayer as central components. Nutritional, pharmacological, and biologic treatments have varying levels of scientific support but are frequently used by patients. Nutritional counseling, macrobiotic and vegetarian diets, dietary supplements, vitamins, and minerals are routinely accepted in complementary medicine. Off-label drug use and natural products, such as shark cartilage and Laetrile (an amygdalin compound), have had varying levels of success in symptom management and are scientifically unproven as primary treatments. Future of integrative oncology: Integrative oncology is rapidly becoming an important part of cancer therapy, but complementary and alternative medicine therapies, like 651
Intensity-modulated radiation therapy (IMRT) other therapies, must be scientifically evaluated for safety and efficacy. Although many complementary therapies do not interfere with traditional therapies, there is still the threat of an inappropriate interaction with prescribed therapies. An increasing number of physicians and facilities are offering complementary and alternative medicine therapies as a part of their patients’ care, but patients should still inform their health care practitioner of any complementary and alternative medicine therapies used at the same time that they are undergoing therapy. Patricia Stanfill Edens, R.N., Ph.D., FACHE u For Further Information Cassileth, B., et al. PDQ Integrative Oncology. Hamilton, Ont.: BC Decker, 2005. Davies, A. A., et al. “Nutritional Interventions and Outcome in Patients with Cancer or Preinvasive Lesions: Systematic Review.” Journal of the National Cancer Institute 98 (2006): 961-963. Vickers, A. J., et al. “Acupuncture for Dyspnea in Advanced Cancer: A Randomized, Placebo-Controlled Pilot Trial.” BMC Palliative Care 4 (2005): 5. u
Other Resources
American Cancer Society Guidelines for Using Complementary and Alternative Methods http://www.cancer.org/docroot/ETO/content/ ETO_5_3x_Guidelines_For_Using_Complementary_ and_Alternative_Methods.asp National Cancer Institute Thinking About Complementary and Alternative Medicine http://www.cancer.gov/cancertopics/ thinking-about-CAM/allpages National Center for Complementary and Alternative Medicine Massage Therapy as CAM http://nccam.nih.gov/health/massage See also Aids and devices for cancer patients; Cancer care team; Caregivers and caregiving; Case management; Complementary and alternative therapies; Counseling for cancer patients and survivors; Dietary supplements; Duke Comprehensive Cancer Center; Home health services; Hospice care; Living with cancer; Occupational therapy; Oncology social worker; Palliative treatment; Personality and cancer; Psychosocial aspects of cancer; Stress management; Support groups. 652
Salem Health: Cancer
u Intensity-modulated radiation
therapy (IMRT) Category: Procedures Definition: Intensity-modulated radiation therapy (IMRT) is a cancer treatment that allows the precise delivery of higher doses of radiation to the cancer while protecting the normal tissue surrounding the tumor. Cancers treated: Cancers of the breast, head and neck, lung, prostate, liver, female reproductive system, and brain; lymphomas Why performed: IMRT enables radiation oncologists to deliver radiation to areas of the body that may be difficult to treat, or to reach tumors that may be located near vital organs and that cannot be treated surgically. Since IMRT allows higher doses of radiation to be given directly to the tumor and avoids normal tissue, there are fewer side effects than with traditional external radiation therapy. IMRT provides a more precise, conformed radiation dose to be delivered to the tumor area by controlling the intensity of the radiation beam within a given area. Radiation beams can be turned on or off or can be blocked during treatment, varying the beam intensity across the targeted field. The radiation beam or beams may be moved hundreds of times, with each beam having a different intensity. Using IMRT allows for lower doses of radiation to be delivered to one area of the tumor while higher doses may be delivered to another area. Patient preparation: There are no special preparations prior to IMRT treatment. Steps of the procedure: Approximately one to two weeks prior to treatment, a radiation oncologist evaluates the patient. A staging computed tomography (CT) scan is done to identify the three-dimensional shape of the tumor. This information is used to plan the dose and shape of the radiation beam(s) for treatment. Other tests may also be needed. The radiation oncologist works with a dosimetrist, who calculates the dosage, and a medical physicist to ensure that the radiation is delivered to the exact tumor area location. The area where the beam will be directed is usually temporarily tattooed on the patient’s skin with ink, which will help the radiologist each time the IMRT is given to the patient. IMRT usually takes fifteen to thirty minutes. After the procedure: IMRT is given on an outpatient basis. Patients can usually drive themselves to and from treatment. After IMRT, the patient may experience some
Salem Health: Cancer
Interferon
fatigue and, depending on the area of treatment, may have some redness on the skin over the area being treated. These effects are temporary and will subside a few weeks after treatment ends. Patients may also want to discuss taking vitamin supplements with their physician. Risks: The risks of IMRT affecting normal tissue and arteries adjacent to the tumor are minimal. Results: The goal of IMRT is to reduce tumor size and alleviate symptoms. IMRT involves multiple treatment sessions over a number of weeks or months, depending on the success of the results. Jo Gambosi, M.A., B.S.N. See also Mayo Clinic Cancer Center; Medulloblastomas; Memorial Sloan-Kettering Cancer Center; Radiation therapies.
u Interferon Category: Chemotherapy and other drugs ATC code: 103AB (interferons); LO3AB01 (interferon alfa natural, Alferon-N, Roferon-A); LO3AB02 (interferon beta natural); LO3AB03 (interferon gamma, Actimmune); LO3AB04 (interferon alfa-2a, Roferon-A, Pegasys); LO3AB05 (interferon alfa-2b, Rebetron, Pegintron, Intron-A); LO3AB06 (interferon alfa-n1); LO3AB07 (interferon beta-1a, Avonex, Rebif); LO3AB08 (interferon beta-1b, Betaseron); LO3AB09 (interferon alfacon-1, Infergen); SO1AD05 (interferons) Definition: Interferons are cytokines, naturally occurring proteins produced by leukocytes or fibroblasts. When a foreign agent such as a virus or cancer enters the cell, interferon is released into the body fluids to induce healthy
An intensity-modulated radiation therapy scanner. (Custom Medical Stock Photo)
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Interleukins
Salem Health: Cancer
cells to manufacture an enzyme to counter the invasion. The interferons are described as alpha, beta, and gamma according to their amino acid sequence and structure. The naturally occurring interferons were first described in the 1950’s. Then in 1980 scientists inserted the interferon gene into the bacteria Esherichia coli (E. coli) using recombinant DNA technology. The resulting bacterial culture allowed the recovery and purification of a quantity of interferon sufficient for therapeutic use. Today, interferon is used to fight viral infections and in conjunction with chemotherapy as an anticancer drug. Cancers treated or prevented: Kidney cancer, malignant melanoma, multiple myeloma, carcinoid tumors, some types of lymphoma and leukemia Delivery routes: Intramuscular, subcutaneous, or intravenous injection; also available as a nasal spray to protect against rhinoviruses How this substance works: Interferons, both naturally and therapeutically, work by stimulating the body’s own immune system by slowing, blocking, or changing the growth or function of the replication of foreign invaders such as viruses, bacteria, parasites, or tumor cells. • Alpha interferons: Various alpha interferons have been approved to treat approximately twenty cancers and more than ten infections—interferon alfa natural for treating kidney cancer, malignant melanoma, multiple myeloma, carcinoid tumors, some types of lymphoma and leukemia, and genital warts; and interferon alfa-2a for treating viral hepatitis B and C. • Beta interferons: Interferon beta-1a and -1b are being investigated for treating multiple sclerosis. • Gamma interferons: Interferon gamma-1b treats granulomatous disease. Side effects: Flulike symptoms such as fever, chills, headache, muscle aches and pains, and malaise are expected with all interferons. Life-threatening neuropsychiatric disorders such as depression and suicide have been reported, but the link between interferon and these psychiatric developments remains unclear. Fatigue, diarrhea, nausea, vomiting, abdominal pain, joint aches, back pain, and dizziness have been reported. Other possible side effects include anorexia, congestion, increased heart rate, confusion, low white blood cell count, low platelet count, low red blood cell count, increase in liver enzymes, increase in 654
Interferon. (National Cancer Institute)
triglycerides, temporary skin rashes, hair loss or thinning, swelling, cough, and difficulty breathing. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) See also Biological therapy; Bone cancers; Carcinoid tumors and carcinoid syndrome; Cardiomyopathy in cancer patients; Cytokines; Eosinophilic leukemia; Exercise and cancer; Fever; Gene therapy; Hairy cell leukemia; Immune response to cancer; Immunotherapy; Kaposi sarcoma; Kidney cancer; Liver cancers; Mantle cell lymphoma (MCL); Mesothelioma; Mycosis fungoides; Myelofibrosis; Myeloproliferative disorders; Non-Hodgkin lymphoma; Polycythemia vera; Waldenström macroglobulinemia (WM).
u Interleukins Category: Chemotherapy and other drugs ATC code: 103AC Definition: Interleukins are cytokines, or hormones of the immune system that are produced naturally in the body. Interleukins are an important part of the body’s response to infection and disease, and they help the immune system fight cancer. They can be made in the laboratory for use in therapeutic applications. Cancers treated: Melanoma, renal cell cancer, colorectal cancer Subclasses of this group: Biological response modifiers, immunostimulants, growth factors, colony-stimulating factors
Salem Health: Cancer
Invasive cancer
Common Therapeutic Interleukins Drug
Brands
Interleukin-2 (IL-2)
Proleukin, Aldesleukin Immunostimulant
Interleukin-11 (IL-11) Oprelvekin, Neumega
Subclass
Delivery Mode
IV, subcutaneous Melanoma, renal cell cancer, colorectal cancer
Growth factor, Subcutaneous colony-stimulating factor
Delivery routes: These drugs are administered through intravenous (IV) infusion or subcutaneous injection. How these drugs work: Interleukins and other biological response modifiers use the body’s immune defenses to enhance or restore immune function. Interleukins can directly target tumor cells, enhance the immune response to cancer cells, or reduce side effects from other cancer treatments. Interleukins can be used alone or in combination with cancer chemotherapeutic agents. Several interleukins are in various phases of clinical trial, but interleukin-2 (IL-2) and interleukin-11 (IL-11) have been the most widely studied and utilized. IL-2 stimulates the growth and activity of many immune cells, such as lymphocytes, which function in destroying tumor cells. IL-2 also directly interferes with cancer cell growth. Other interleukins, such as IL-11, function as support medications by reducing side effects that result from cancer treatment, such as low platelet count or low levels of other blood components. These interleukins, also called growth factors or colony-stimulating factors, stimulate bone marrow cells to divide and develop into white blood cells, platelets, or red blood cells. Specifically, IL-11 stimulates the production of platelets to increase their numbers to normal levels and thus reduce the need for platelet transfusions. Side effects: Side effects resulting from the use of interleukins vary widely depending on interleukin type, dosage, and the patient. Common side effects include flulike symptoms such as fever, chills, weakness, muscle and joint aches, diarrhea, nausea, and vomiting. Treatment can also result in increased heart rate, skin rash, low white blood cell count, low platelet count, anemia, and appetite loss. Swelling, primarily in the hands, feet, and ankles, can also occur. An uncommon side effect is capillary leak syndrome, which results in low blood pressure and poor blood flow. Catherine J. Walsh, Ph.D. See also Angiogenesis; Appetite loss; Biological therapy; Castleman disease; Colony-stimulating factors (CSFs); Cyclosporin A; Cytokines; Fever; 5Q minus syndrome;
Conditions Treated
Low platelets
Gene therapy; Helicobacter pylori; Hemangiosarcomas; Histiocytosis X; Immune response to cancer; Immunotherapy; Liver cancers; Melanomas; Mistletoe; Myelosuppression; Thrombocytopenia; Urinary system cancers.
u Invasive cancer Category: Diseases, symptoms, and conditions Related conditions: Cancer in situ, metastatic cancer Definition: Invasive cancer describes the dispersion and invasion of cancer cells into surrounding normal cells and tissues. It is preceded by cancer in situ (CIS) and precedes metastasis. Risk factors: Once cancer in situ has developed, the risk of invasive cancer increases with increasing tumor vascularity, loss of cell adhesion molecules, and expression of proteolytic enzymes. Etiology and the disease process: Invasiveness is a stage of cancer development that is preceded by dysplasia and then by cancer in situ (CIS). Several related changes occur for the transition from CIS to invasive cancer. Normal cell adhesion molecules must be disrupted, and invasive tumor cells show alterations in the integrin and cell adhesion families of proteins. In addition, invasive tumor cells secrete proteolytic enzymes that digest the surrounding extracellular matrix. Invasive tumor cells also secrete motility factors that prompt migration into adjacent tissues. Invasion can be into adjacent organs, blood vessels, or lymphatic vessels. Even though the efficiency with which invasive cancer cells establish metastatic lesions is low, about 60 percent of patients with invasive cancer have overt or occult metastases at diagnosis. Incidence: At diagnosis, the ratio of localized (preinvasive) cancer to invasive cancer varies from organ to organ. In prostate cancer, for example, 83 percent of new cases are confined to the prostate, but only 8 percent of pancreatic cancers are localized at diagnosis. 655
Invasive ductal carcinomas Symptoms: Symptoms of invasive cancer are usually nonspecific and related to infiltration of adjacent structures. They depend highly on the identity, vascularization, and innervation of the invaded structures. Screening and staging: Determination of a tumor’s invasiveness is done in the operating room and the laboratory. At surgery, invasiveness may be present as grossly apparent tumor growth into and around surrounding structures. Microscopic invasiveness is less apparent but contributes to the adherence of tumor cells to surrounding tissue. Diagnosis of invasiveness can also be made by screening blood for the presence of circulating tumor cells. Treatment and therapy: Therapeutic options directed at inhibiting tumor invasiveness include biologic agents that block growth factor receptors and antibodies that target the integrin family of extracellular adhesion molecules. For example, blockade of the vitronectin receptor (an integrin) reduces the vascularization of tumor masses and may improve patient outcomes. Prognosis, prevention, and outcomes: Tumor invasion complicates complete surgical removal of a tumor and is a precondition for metastases, significantly worsening prognosis. Prevention of invasive cancer requires early detection and removal of cancerous in situ lesions. John B. Welsh, M.D., Ph.D. See also Breast cancer in men; Cancer biology; Carcinomatosis; Gestational trophoblastic tumors (GTTs); Invasive ductal carcinomas; Invasive lobular carcinomas; Malignant tumors; Metastasis.
u Invasive ductal carcinomas Category: Diseases, symptoms, and conditions Also known as: Breast cancer, infiltrating ductal carcinomas Related conditions: Inflammatory breast cancer Definition: Invasive ductal carcinoma originates in the ducts of the milk-secreting glands and has invaded to other tissues of the breast. Risk factors: Risk factors include never having a fullterm pregnancy, first becoming pregnant after age thirty, starting menarche early, and entering menopause late. Risk increases with age, family history, carrying the breast cancer susceptibility genes BRCA1 and BRCA2, and the use of synthetic hormones. 656
Salem Health: Cancer Etiology and the disease process: Invasive ductal carcinoma invades the surrounding breast tissue and lymph nodes and can spread throughout the body. Incidence: About 12.7 percent of women will be diagnosed with breast cancer, making it the most common type of cancer in women other than skin cancer. Some 80 percent of breast cancers are invasive ductal carcinomas. Symptoms: Any change in the size or shape of the breast or in the look or feel of the breast or nipple, or any lumps or thickening in or near the breast or underarm area, may be a symptom of breast cancer. Other more obvious changes include nipple discharge, tenderness, an inverted nipple, and ridges or pitting of the breast (when the skin looks like that of an orange). Screening and diagnosis: Monthly breast self-exams after the age of twenty, yearly checkups, and regular mammograms after the age of forty are crucial to early detection. Biopsies of a suspicious lesion are taken to obtain a diagnosis. Staging of breast cancer is based on the TNM (tumor/ lymph node/metastasis) system: • Stage I: Has not spread beyond the breast • Stage II: May or may not have spread to lymph nodes under the arm • Stage III: Has spread to nearby lymph nodes but not spread beyond the breast • Stage IV: Has spread to other parts of the body Treatment and therapy: Treatments, which vary from case to case, include surgery, radiation treatment, and chemotherapy. A lumpectomy or mastectomy followed by radiation is the standard treatment and is followed by whole-body treatments, including hormonal therapies, chemotherapies, and biological therapies. Prognosis, prevention, and outcomes: Early detection and treatment increase overall survival rates. Invasive ductal carcinoma has a five-year disease-free survival rate of 83.5 percent. Physical activity, multiple pregnancies, breast-feeding, and early removal of both ovaries may lower the risk of getting this disease. Terry J. Shackleford, Ph.D. See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Ductal lavage; Ductogram; Lobular carcinoma in situ (LCIS); Medullary carcinoma of the breast; Mucinous carcinomas; Progesterone receptor assay; Tubular carcinomas.
Salem Health: Cancer
u Invasive lobular carcinomas Category: Diseases, symptoms, and conditions Also known as: Stage I-IV breast cancer, infiltrating lobular carcinomas Related conditions: Breast cancer Definition: Invasive lobular carcinoma originates in the lobules (milk-producing glands) and has invaded other tissues of the breast. Risk factors: Risk factors include reproductive factors such as never having had a full-term pregnancy, first becoming pregnant after age thirty, starting menstruation early, and entering menopause late. Using synthetic hormones, having a family history of breast cancer, carrying the breast cancer susceptibility genes BRCA1 and BRCA2, and advancing age also increase a woman’s risk. Etiology and the disease process: In invasive lobular carcinoma, the cancer starts in the lobules, invades the surrounding breast tissue and lymph nodes, and can spread throughout the body. Incidence: About 12.7 percent of women will be diagnosed with breast cancer, making it the most common type of cancer in women other than skin cancer. Only 10 to 15 percent of breast cancer cases are diagnosed as invasive lobular carcinoma. Symptoms: Any change in the look, size, or shape of the breast, and any lumps or thickening in or near the breast or underarm area, may be a symptom of breast cancer. Symptoms also include any change in the feel of the breast or nipple, such as nipple discharge, tenderness, a nipple turned in toward the breast, and ridges or pitting of the breast (when the skin looks like the skin of an orange). Screening and diagnosis: Women should undergo monthly self-exams after the age of twenty, yearly checkups, and regular mammograms after the age of forty. Once breast cancer is detected, biopsies of the tumor are taken to obtain a diagnosis. Staging of breast cancer is based on the TNM (tumor/ lymph node/metastasis) system: • Stage I: Has not spread beyond the breast • Stage II: May or may not have spread to lymph nodes under the arm • Stage III: Has spread to nearby lymph nodes but has not spread beyond the breast • Stage IV: Has spread to other parts of the body
Ionizing radiation Treatment and therapy: Treatments include surgery, radiation treatment, and chemotherapy, with the extent of treatment depending on the stage and hormone-receptor status. Surgery followed by radiation is the standard treatment and may involve a lumpectomy or mastectomy. Other treatments include hormonal therapies, chemotherapy, and biological therapies. Prognosis, prevention, and outcomes: Invasive lobular carcinoma has a five-year disease-free survival rate of 85.7 percent. Factors that reduce the risk of breast cancer include physical activity, multiple pregnancies, breastfeeding, and early removal of both ovaries. Terry J. Shackleford, Ph.D. See also Breast cancers; Lobular carcinoma in situ (LCIS); Tubular carcinomas.
u Ionizing radiation Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogens include X radiation and gamma radiation (since 2004), neutrons (since 2004), radon (since 1994), and thorium dioxide (since 1981) Also known as: Gamma radiation, X radiation Related cancers: Lung, bone, bone marrow (leukemia), thyroid, breast, liver, skin Definition: Ionizing radiation is energy released from the disintegration of unstable atomic nuclei during radioactive decay. This type of radiation may originate from X radiation or the emission of various subatomic particles from both natural and artificial sources. Some substances decay at faster rates than others and are more or less stable than others. Exposure routes: Inhalation, ingestion, direct external exposure Where found: Ionizing radiation is both naturally occurring and artificially produced. It is found in radon (55 percent) and in the earth. Nonnatural sources include military weapons, nuclear reactors, and electronic products. Technologically enhanced naturally occurring radioactive materials (TENORMs) concentrate ionizing radiation in solid sludge, water treatment facilities, aluminum oxide reactions, fertilizers, coal ash, concrete aggregates, diagnostic medical procedures, cable insulation, security screening equipment, and equipment used to kill microorganisms in food. 657
Iridium seeds At risk: Children, pregnant women, industry workers, medical personnel, military personnel, residents in high background radiation areas Etiology and symptoms of associated cancers: Ionizing radiation, regardless of the source, damages deoxyribonucleic acid (DNA, the genetic material) inside cells. The damage can be chromosomal breaks, cell mutations, and actual cell transformation. The consequences of this damage range from immediate cell death to transformation into cells that become malignant over time. The ability of ionizing radiation to kill cells explains its use to treat many cancers. Cancer cells divide more rapidly and are more vulnerable to radiation. Thus, ionizing radiation has the ability, when the trajectory of the beam is focused on a tumor, to shrink tumors by killing cells. Immediate symptoms of exposure vary according to the type of particle, the dose, the length of exposure, and the route of exposure. Radiation sickness, or acute radiation syndrome, results from immediate excessive high-dose exposure. Whole body penetration damages the cardiovascular and central nervous systems. The blood pressure will drop (hypotension), and the brain will swell. Nausea, vomiting, convulsions, and confusion will follow. Death is inevitable when exposure is greater than 3,000 rads. History: In 1896 Henri Becquerel presented his discovery of radioactivity in Paris at the Academy of Sciences. During the 1900’s scientists Marie and Pierre Curie, Dmitry Mendeleyev, and Wilhelm Conrad Röntgen defined the properties of ionizing radiation. Many of the scientists working with ionizing radiation died as a result of their exposures. In 1970 the Environmental Protection Agency started regulating ionizing radiation. Janet R. Green, M.S.P.H. See also Acoustic neuromas; Afterloading radiation therapy; Astrocytomas; Ataxia telangiectasia (AT); Blood cancers; Bone cancers; Bone scan; Brain and central nervous system cancers; Brain scan; Carcinomas; Carcinomatosis; Electromagnetic radiation; Endotheliomas; Hemangiopericytomas; Hemangiosarcomas; Imaging tests; Leukemias; Magnetic resonance imaging (MRI); Malignant tumors; Meningiomas; Mesenchymomas, malignant; Mutagenesis and cancer; Myelodysplastic syndromes; Myelofibrosis; Nijmegen breakage syndrome; Nuclear medicine scan; Radiation oncology; Radionuclide scan; Radiopharmaceuticals; Radon; X-ray tests.
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Salem Health: Cancer
u Iridium seeds Category: Procedures Also known as: Iridium 192, high-dose-rate (HDR) or temporary brachytherapy Definition: Iridium seeds are high-dose radiation sources temporarily placed into a tumor site in order to stop the growth of cancer cells or to relieve symptoms without damaging normal tissue. Cancers treated: Breast, prostate, gynecologic, head and neck, esophageal, lung, rectal, and other cancers Why performed: Internal radiation used to kill cancer cells at the site of a tumor provides effective local cell death and discourages regrowth. Using iridium seeds delivers a higher dose of radiation directly to the tumor, protects normal tissue, and allows outpatient care with shorter, more comfortable treatments and fewer side effects. Patient preparation: Before the procedure, patients will have imaging studies such as X rays, a computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI) to decide where the iridium seeds should be placed to work best. Patients may have other tests such as blood work or electrocardiography (EKG). If seeds are to be placed in the prostate, then an enema and bowel cleansing routine is used. Some sites require only local anesthesia, while others may require general anesthesia and surgery. Patients should receive clear directions from a doctor or nurse based on the site of treatment before the procedure. Steps of the procedure: A treatment plan is developed by the doctor and the radiation therapy staff. A needle, catheter, or balloon catheter is placed in the site when patients are either asleep or the area has been numbed to ensure that there is no pain. An iridium seed is sent through the catheter by a computerized machine called a high dose remote afterloader; it is left in the tumor for a few minutes and then removed. Treatments can be once or twice a day and the number varies by site. After the procedure: Once all treatments are complete, the catheters will be removed gently, usually without difficulty or discomfort. It is safe for patients to be around others, including children and pregnant women, because no radiation remains in the body. Risks: The side effects depend on the site treated but may include urinary symptoms, rectal symptoms, fatigue, eating problems, shortness of breath, pain, redness, and swelling.
Salem Health: Cancer
Islet cell tumors
Irradiated rice-sized pellets used for prostate cancer treatment. (©Dan Lamont/Corbis)
Results: Iridium seeds for high-dose brachytherapy appear to be as effective as other methods of prostate cancer treatments. Their use in the treatment of breast cancer is newer, but early data show control of cancer cells at the local site equal to that of other treatments. Other diseases report equally effective results with good local control as compared to other treatments. Patricia Stanfill Edens, R.N., Ph.D., FACHE See also Afterloading radiation therapy; Brachytherapy; Neurologic oncology; Radiation oncology.
u Islet cell tumors Category: Diseases, symptoms, and conditions Also known as: Neuroendocrine tumors of the pancreas Related conditions: Multiple endocrine neoplasms, von Hippel-Lindau disease, Zollinger-Ellison syndrome Definition: Islet cell tumors are abnormal cell masses that develop in the islet cells (islets of Langerhans) of the pan-
creas. These tumors can be either malignant (cancerous) or benign. Risk factors: About 15 to 25 percent of islet cell tumors are associated with the inherited disorder multiple endocrine neoplasia type 1 (MEN 1), but most arise spontaneously with no known risk factors. Etiology and the disease process: The pancreas is a digestive organ located on the right side of the abdomen near where the stomach joins the small intestine. It is composed of two cell types. About 95 percent of pancreas cells (the exocrine pancreas) secrete digestive juices that flow into ducts that empty into the small intestine. The remaining cells (the endocrine pancreas) release hormones, mostly insulin and glucagon, directly into the bloodstream. These hormones regulate the use of glucose (sugar) in the body. When islet cell tumors develop, about 75 percent of the tumors produce excess amounts of hormones. These are called functioning tumors. The remaining 25 percent do not produce excess hormones and are called nonfunctioning tumors. Either type of tumor can be malignant or 659
Islet cell tumors
Salem Health: Cancer
benign. Nonfunctioning tumors are more likely to be malignant than functioning tumors. Islet cell tumors arise from different types of islet cells and are named for the main hormone that they secrete. Insulinomas produce insulin, which decreases the amount of glucose in the blood and increases the amount of glucose stored in the body. Insulinomas make up about threequarters of all islet cell tumors. Glucagonomas produce glucagon, which releases stored glucose and increases the level of glucose in the blood, causing high blood sugar (hyperglycemia). Vasoactive intestinal peptide tumors (VIPomas) produce vasoactive intestinal peptide, which relaxes smooth muscles in the digestive system and increases the amount of water in stool, causing severe diarrhea. Gastrinomas produce gastrin, which causes the stomach to secrete acid. Excess acid leads to stomach and intestinal ulcers. Somatostatinomas produce somatostatin, which helps regulate the production of other hormones. Although islet cell tumors can occur in people of any age, most are diagnosed in young to middle-aged individuals. In most, especially those who do not have MEN 1, these tumors tend to develop slowly.
nausea. Glucagonomas cause high blood sugar or mild diabetes accompanied by severe skin inflammation (dermatitis). Gastronomas cause stomach pain and ulcers. VIPomas cause severe watery diarrhea. Somatostatinomas cause weight loss and diarrhea.
Incidence: Tumors of the islet cells are rare. Only about 2,500 cases are diagnosed in the United States each year, although autopsies of people dying from other causes find much higher rates of these tumors. Islet cell cancers constitute less than 2 percent of all pancreatic cancers.
Treatment and therapy: Treatment involves removing the tumor and sometimes the surrounding tissue. This is often followed by chemotherapy. When surgery is not an option, chemotherapy is often given, followed by hormone therapy to slow the growth of the cancer. Clinical trials are under way to develop better ways to treat islet cell cancer.
Symptoms: Nonfunctioning tumors produce few symptoms. Symptoms of functioning tumors depend on the type of hormone secreted. Insulinomas cause low blood sugar (hypoglycemia), hunger, weight gain, sweating, and
Relative Survival Rates of Islet Cell Carcinoma Patients Among Adults, 1988-2001 Years 1 2 3 5 8 10
Survival Rate (%) 80.7 70.0 59.3 47.7 37.8 32.5
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
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Screening and diagnosis: Diagnosis of a suspected islet cell tumor is difficult. Various blood and urine tests are used to determine the level of specific hormones in the body. Once a tumor is suspected, an array of imaging studies, including magnetic resonance imaging (MRI), computed tomography (CT) scans, ultrasound, and arteriography, are used to locate the tumor. Certain biochemical tests are being developed to pinpoint the type of islet cells involved. Staging for islet cell cancers is still under development, but the cancer is currently assigned one of three categories. • Cancer occurs at only one site in the pancreas. • Cancer occurs in multiple sites within the pancreas. • Cancer has spread beyond the pancreas to lymph nodes or distant sites.
Prognosis, prevention, and outcomes: The prognosis and outcome of islet cell cancer are highly variable because of the different tumors involved. Large, nonfunctioning tumors produce the worst outcome. In functioning tumors, tumor size is not related to outcome. Many tumors grow slowly and people survive for years. Islet cell cancer most often metastasizes to the liver and lymph nodes. If metastasis occurs, the outcome is poor. There is no known way to prevent this cancer. Martiscia Davidson, A.M. u
For Further Information Nakakura, E. K., and E. K. Bergsland. “Islet Cell Carcinoma: Neuroendocrine Tumors of the Pancreas and Periampullary Region.” Hematology/Oncology Clinics of North America 21, no. 3 (June, 2007): 457-473. Riess, H., A. Goerke, and H. Oettle, eds. Pancreatic Cancer. New York: Springer, 2007. Tamm, E. P., E. E. Kim, and C. S. Ng. “Imaging of Neuroendocrine Tumors.” Hematology/Oncology Clin-
Salem Health: Cancer ics of North America 21, no. 3 (June, 2007): 409-432. Von Hoff, Daniel D., Douglas Evans, and Ralph H. Hruban, eds. Pancreatic Cancer. Sudbury, Mass.: Jones and Bartlett, 2005. u
Other Resources
eMedicine.com Pancreas, Islet Cell Tumors http://www.emedicine.com/radio/topic363.htm National Cancer Institute Islet Cell Carcinoma (Endocrine Pancreas) Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ isletcell/patient See also Endocrine cancers; Endocrinology oncology; Gastrinomas; Histiocytosis X; Multiple endocrine neoplasia (MEN) type 1; Neuroendocrine tumors; Pancreatic cancers; Von Hippel-Lindau (VHL) disease; ZollingerEllison syndrome.
u Isoflavones Category: Lifestyle and prevention Also known as: Phytoestrogens Definition: Isoflavones are a subclass of plant chemicals known as flavonoids (also referred to as bioflavonoids in the media). The beneficial effects attributed to isoflavones have encouraged nutritional supplement manufacturers to purify and market isoflavones derived from soybeans. Most of these purported benefits, however, are based on epidemiological or laboratory animal studies. More definitive conclusions with regard to human health await the results of long-term clinical trials. Cancers treated or prevented: Breast, prostate, and endometrial cancers, although no conclusive evidence exists Delivery routes: Oral by diet, pill, or capsule How these compounds work: Isoflavones occur in foods bound to sugar in the form of glycosides. After ingestion, the glycosides are digested in the small intestine with the help of bacteria, releasing the active isoflavones. The isoflavones are absorbed and bound to plasma proteins for transport in the blood. There are two forms of estrogen receptors. Alpha receptors are predominantly found in reproductive tissue (uterus, breast, and ovaries), while beta receptors are predominant in other tissues. Isoflavones bind with greatest affinity to beta receptors, while the estrogen hormone principally targets the alpha receptor.
Itching When isoflavones bind to estrogen receptors in the breast, endometrium, or prostate (in place of estrogen), they may help prevent cancer by inhibiting activation of the receptor and the resultant growth-signaling process. Isoflavones are found naturally in legume plants. Soybeans contain the isoflavones genistein and daidzein, which are the most common active isoflavones in human foods. They are also known as phytoestrogens, since they are similar in structure to estrogen hormones produced in the human body and demonstrate weak estrogenic activity. Many claims have been made regarding beneficial actions of isoflavones. This may be attributable to the binding of isoflavones to beta receptors in various tissues to enhance the estrogen effect. One study evaluated the results of nineteen clinical trials with isoflavones and found that isoflavones had a negligible effect on cardiovascular risk factors. Likewise, isoflavones did not appear to be beneficial in reducing flushing or bone loss in postmenopausal women. Epidemiological (population) studies indicate that Asians, who consume a traditional diet high in soy products, have a much lower incidence of breast and prostate cancer than do Western peoples. Studies have suggested that long-term exposure to high levels of estrogen may increase the risk of women developing breast or endometrial cancer. The lifetime consumption of isoflavones may provide protection for Asian women. Very few clinical trials, however, have been conducted to support this idea. Side effects: Some studies have indicated that the protective effect of hormone therapies for cancer, such as tamoxifen or other antiestrogenic drugs, may be abrogated by use of isoflavones. Those undergoing hormone therapies should consult their physician about the use of isoflavones. David A. Olle, M.S. See also Antioxidants; Bioflavonoids; Chemoprevention; Dietary supplements; Fruits; Herbs as antioxidants; Nutrition and cancer prevention; Phytoestrogens; Soy foods.
u Itching Category: Diseases, symptoms, and conditions Also known as: Pruritus Related conditions: Cancers treated with chemotherapy drugs, other medications, or radiation Definition: Itching is the overwhelming feeling of the need to scratch the skin. It can be caused by many cancer treatments and some cancers, and it can lead to frustration, 661
Itching anxiety, and sleeplessness as well as tearing of the skin and infection. Risk factors: Many cancer treatment options are associated with an increased risk of itching. These include radiation therapy, chemotherapy, and many medications. Individuals who are undergoing both chemotherapy and radiation therapy at the same time are at an especially increased risk for itching. Some cancers also may cause itching, including lymphoma, leukemia, invasive squamous cell carcinoma, and Kaposi sarcoma. Individuals with cancers of the lung, breast, colon, stomach, and prostate may be at an increased risk of itching, as may individuals with tumors occurring on the spinal cord or brain. Etiology and the disease process: A sensation of itching is caused when the receptors in the skin called purireceptors are stimulated. This stimulation can occur due to skin dryness, an excess of dead skin cells, an inflammation of the area, or other skin problems. The receptors can also be stimulated by things that are not on or around the skin, such as an allergic reaction to an ingested chemical. Once these purireceptors are stimulated, they send signals along specialized nerve fibers similar to the fibers that carry information about pain. The signals travel along the nerves to the brain, where the signals are interpreted by the brain to produce the feeling of itching. The biologic reasons that scratching can relieve the feeling of itching are not completely clear. There are many theories on the interaction of scratching and itching, including that scratching activates pain receptors, causing the brain to release chemicals to reduce the sensation of pain, which may decrease the feeling of itching. Another theory is that the scratching is also an irritation at the same site as the itching and causes the brain to become distracted from the original sensation. Although scratching the itch can lead to a temporary feeling of relief, it can also begin a negative cycle in which every scratch makes the itch worse. This may be because scratching the skin, especially with sharp nails, can irritate the skin, worsening the original problem. Incidence: It is not certain how many cancer patients experience itching at some time during treatment. In many cases, it is not severe enough for patients to report it as a specific problem to their cancer care team. Symptoms: The main symptom of itching is a sensation that causes a desire or need to scratch the affected area. Screening and diagnosis: When patients report a problem with itching, their doctor will try to find an underlying cause. In some cases, the cause may become obvious 662
Salem Health: Cancer through visual inspection. In other cases, no obvious cause may be found. The doctor may perform tests to determine if the itching is caused by an undetected underlying disease, such as leukemia or Hodgkin disease. The doctor may also order blood tests to check for diseases other than cancer that can cause itching, such as liver or kidney disease. Treatment and therapy: The primary treatment for itching is to treat the underlying disease or condition that is causing the itching. However, while the underlying problem is being treated, or if no cause can be found, there are other ways to provide some relief. Using lotions or creams to provide moisture to dry skin may help relieve itching. Reducing irritants by not using perfumes, traditional razors, or deodorants may be helpful. Washing sheets and clothes in mild detergents or using an extra rinse cycle can help avoid irritating detergent residues. Tight, confining clothes can irritate the skin. Choosing loose clothing made of cotton may help reduce itching. Very hot water can dry skin out, so taking short, warm baths, especially with oatmeal or bath oils added to the water, may be helpful. Hot, dry weather can increase skin irritation, so keeping rooms cool and humid may provide relief. Scratching can make the itch worse and can lead to tears in the skin, which can become infected. Instead of scratching, it may be helpful to put ice or a cool washcloth on the area, or to use vibration to dull the itching sensation. Prognosis, prevention, and outcomes: The prognosis of itching is usually good. Itching caused by cancer generally clears up after the cancer has been treated. When itching is caused by chemotherapy, the itching usually stops between 30 and 90 minutes after the treatment ends. Itching caused by radiation therapy usually clears up when the skin at the site of the radiation heals. Itching that is a side effect of a medication generally ends when the individual has been off the medication for a short time. The best way to prevent itching is for patients to take good care of their skin. Drinking plenty of fluids can help keep the body hydrated, which can prevent dry skin. Eating a healthy diet with a variety of fruits, vegetables, whole grains, and lean proteins may also help improve overall skin health. Robert Bockstiegel, B.S. u
For Further Information Egan, Tracie. Skin Cancer: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Fleischer, Alan B., Jr. The Clinical Management of Itching. New York: Informa Healthcare, 2000.
Salem Health: Cancer Yosipovitch, Gil, et al., eds. Itch: Basic Mechanisms and Therapy. New York: Marcel Dekker, 2004. Zylicz, Zbigniew, Robert Twycross, and E. Anthony Jones, eds. Pruritus in Advanced Disease. New York: Oxford University Press, 2004. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Pruritus http://www.cancer.gov/cancertopics/pdq/ supportivecare/pruritus/patient
Itching See also Anal cancer; Antidiarrheal agents; Antifungal therapies; Azathioprine; Benign tumors; Bile duct cancer; Candidiasis; Computed tomography (CT) scan; Cutaneous T-cell lymphoma (CTCL); Epstein-Barr virus; Gallbladder cancer; Gynecologic cancers; Hemorrhoids; Herpes zoster virus; Hodgkin disease; Lymphomas; Mantle cell lymphoma (MCL); Mastectomy; Moles; Mustard gas; Myeloproliferative disorders; Non-Hodgkin lymphoma; Nonsteroidal anti-inflammatory drugs (NSAIDs); Pancreatic cancers; Paraneoplastic syndromes; Polycythemia vera; Sézary syndrome; Side effects; Sjögren syndrome; Squamous cell carcinomas; Symptoms and cancer; Urethral cancer; Vulvar cancer; Young adult cancers.
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Jonsson Comprehensive Cancer Center (JCCC)
u Jonsson Comprehensive
Cancer Center (JCCC) Category: Organizations Definition: The Jonsson Comprehensive Cancer Care Center (JCCC) is a cancer research and cancer patient treatment facility at the University of California at Los Angeles Medical Center. Founded in 1960, it is one of the largest comprehensive cancer centers in the United States. Research: At the Jonsson Comprehensive Cancer Care Center, research into the prevention, diagnosis, and treatment of cancer is divided into three program areas, which are subdivided into particular research programs. The basic research program area includes the Cancer Cell Biology Program Area, the Gene Regulation Program Area, the Signal Transduction and Therapeutics Program Area, the Tumor Immunology Program Area, and the Cancer Molecular Imaging Program Area. The clinical and translational research program area includes the Genitourinary Oncology Program Area, the Hematopoietic Malignancies Program Area, the Thoracic Oncology Program Area, the Women’s Cancers Program Area, and (again) the Signal Transduction and Therapeutics Program Area. The cancer prevention and control program area includes the Healthy and At-Risk Populations Program Area, the Patients and Survivors Program Area, and the Molecular Epidemiology Program Area. The JCCC also operates a specialized Sarcoma Program. The directors of the JCCC believe that collaborative research can provide more helpful insights into the prevention and treatment of cancer than research done by scientists who work alone. By having a great variety of programs in a single cancer center, the JCCC seeks to utilize the advantage of such collaborative efforts. In 1996, the center formed the Interdisciplinary Seed Grant Program. This program helps bring together researchers from disparate fields who might not otherwise collaborate. For example, an investigator working on lung cancer might collaborate with an investigator working on skin cancer because of a similarity that another researcher discovered while working on molecular imaging. This is one of the advantages of a comprehensive research center, and it can lead to innovative research that might otherwise have taken much longer or never have happened at all. Education and outreach: To help patients and family members deal with the emotional and physical difficulties of cancer and cancer treatment, the JCCC designed the Ted Mann Family Resource Center. At the center, support groups and counselors help people deal with the strain of 664
Salem Health: Cancer the entire ordeal. Some examples of support groups include the Healing Through Art Group, which uses painting, drawing, and crafts to help women express their issues with cancer, and the Journal Writing Group, in which an experienced psychotherapist helps patients use writing as a therapeutic release. Education programs are also offered through the center so that patients and families can learn more about the effects of cancer and the details of particular treatment programs. Clinical trials: Cancer research studies that involve actual patients are known as clinical trials. These clinical trials are usually conducted to test a new cancer treatment option and determine whether it can or should be used in a larger context. Before a clinical trial is attempted, the treatment in question is carefully studied in a laboratory setting, often involving studies on animals, but there is no replacement for clinical trials. For a treatment to be proven effective, it must first be tested on human subjects. To maintain safety standards, all clinical studies at the JCCC must first be approved by an internal review board. Researchers at the JCCC recognize the vital importance of clinical trials in the fight against cancer. Hundreds of clinical trials take place at the center every year. In 2007, more than two hundred trials were actively recruiting participants. Some of the trials conducted involve the microwave ablation of malignant liver tumors, lung cancer chemoprevention with celecoxib in former smokers, and the mechanisms of radiation-induced fatigue in cancer. Accomplishments: As one of the largest cancer research centers in the nation, the JCCC has achieved many noteworthy accomplishments. In 2007, it was named the best cancer center in California for the seventh year in a row, by U.S. News and World Report. The JCCC is a National Cancer Institute-designated comprehensive cancer center. Of the sixty-three cancer centers recognized by the National Cancer Institute, only thirty-nine have received the designation “comprehensive”, which means that the center’s research activities achieve a high level of breadth, depth, and interaction. The JCCC has more than 230 physicians and scientist members, and it serves more than 20,000 patients each year. Robert Bockstiegel, B.S. u
For Further Information Jeffries, Lee P., ed. Leading Topics in Cancer Research. New York: Nova Science, 2007. Martakis, Ignatius K., ed. Cancer Research at the Leading Edge. New York: Nova Science, 2007. Pereira, Larissa S., ed. Cancer Research Perspectives. New York: Nova Science, 2008.
Salem Health: Cancer u
Other Resources
American Society of Clinical Oncology http://www.asco.org Association of American Cancer Institutes http://www.aaci-cancer.org/ National Comprehensive Cancer Network http://www.nccn.org/ UCLA Jonsson Comprehensive Cancer Center http://www.cancer.ucla.edu See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Journaling Category: Social and personal issues Also known as: Writing, blogging, keeping a diary Definition: Journaling is writing one’s thoughts and recording one’s activities on a regular basis. Why performed: Knowledge that one has a serious illness, such as cancer, is stressful because of the uncertainty it may bring. Additionally, the gravity of medical procedures and physical and emotional experiences one may endure to treat the illness may also be inherently stressful. Journaling may allow individuals to experience decreased stress via feelings of relief through connecting with others or their own experience, increased insight, increased private expression, or feelings of personal cohesion or wholeness resulting from writing about their experience. Stress management approaches such as journaling are especially useful for individuals who may not be able to participate in other stress-relieving activities or to take stress-relieving medications. It is also a low-cost technique that can be implemented almost anywhere. Patient preparation: Clients using a simple paper diary or computer to write a journal need little preparation. Clients are instructed to write at a regular time or when experiencing any symptoms, reactions, behaviors, thoughts, or
Juvenile polyposis syndrome feelings that may be important to their condition and treatment. They may also need instruction about how long to spend writing, how to do free writing (writing whatever comes to mind without self-censorship), or how to handle emotional responses that may arise while writing. For those wishing to develop blogs, they may need instruction about how to create a blog, as well as information about privacy limitations. Steps of the procedure: Clients are given tools to write (such as paper and pencil or a computer). They are then told to write on a regular basis or when having certain experiences. The writing is then kept for a period decided by the client, provider, or both. After the procedure: Clients generally experience stress relief. They may review what they have written on one or more occasions to gain personal insights. They may also share this information with a therapist or significant others for discussion or share it with individuals who have similar conditions in order to foster a sense of group support. Risks: Journaling does not contain any inherent risks beyond what may come from frequent writing; increased personal awareness of one’s thoughts, feelings, and behaviors; or from publicly sharing personal information with others. Results: Clients may experience a sense of stress relief, well-being, or personal cohesion; they may also experience greater social support if what they write is shared and stimulates responses in others. Nancy A. Piotrowski, Ph.D. See also Integrative oncology; Living will; Living with cancer; Personality and cancer; Prayer and cancer support; Psychosocial aspects of cancer; Relationships; Stress management.
u Juvenile polyposis syndrome Category: Diseases, symptoms, and conditions Also known as: JPS, multiple polyposis coli Related conditions: Hereditary colon cancer syndromes, colorectal carcinoma Definition: Juvenile polyposis syndrome is a hereditary disease in which patches of overproliferative inner intestinal tissue (polyps) occur, which can progress to colon cancer. Risk factors: A family history is an important risk factor in juvenile polyposis syndrome, particularly the diffuse 665
Juvenile polyposis syndrome type. Risk factors for subsequent development of colon cancer include increasing age and duration of disease. Etiology and the disease process: Juvenile polyposis syndrome is an autosomal dominant disease caused by mutations in two genes: SMAD4/DPC4 on chromosome 18q21 and BMPR1A on chromosome 10q21-22. These mutations predispose proliferating intestinal glandular tissue to developing into cancerous cells. Incidence: Juvenile polyposis syndrome is rare compared with other causes of colon cancer in spite of its inheritance pattern. The name “juvenile” is a misnomer; the incidental discovery of a polyp can occur as early as infancy. In addition, juvenile polyposis syndrome peaks during two age groups: late childhood (average age of nine years) and young adulthood (average age of twenty-five). The incidence of detected colon cancer peaks at around age sixty. Symptoms: The first symptom in a child is usually bleeding from the rectum, owing to spontaneous amputation of a polyp. The bleeding often stops without further intervention. However, several instance of bleeding over time may predispose the patient to iron deficiency anemia in more extreme cases, seen as slowing growth, fatigue, and pallor. Persistent, intermittent abdominal pain can result from telescoping of the intestine into itself (intussusception), with a polyp as the lead point. In adults, similar symptoms may be observed.
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Salem Health: Cancer Screening and diagnosis: The diagnosis of juvenile polyposis syndrome is suggested by a patient with three to five polyps or a family history in conjunction with the physical finding of a polyp. Isolated polyps that are removed or that avulse (tear away) and bleed spontaneously require no further intervention, and once they have been removed, they no longer put the patient at risk for colon cancer later in life. Screening colonoscopies are done earlier in individuals with afflicted first-degree relatives, starting at the age of twelve and performed every three years. Treatment and therapy: Removal of polyps (polypectomy), whether through colonoscopy or surgical removal of the entire colon, is warranted. There are no effective chemotherapies in use at present. Prognosis, prevention, and outcomes: Prognosis generally improves with removal of all polyps that are detected by regular colonic surveillance. Patients who have this done also have a significant decrease in the risk of developing colon cancer. Aldo C. Dumlao, M.D. See also Adenomatous polyps; Colon polyps; Colorectal cancer; Colorectal cancer screening; DPC4 gene testing; Family history and risk assessment; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Premalignancies; Turcot syndrome; Young adult cancers.
Salem Health: Cancer
Kaposi sarcoma
u Kaposi sarcoma Category: Diseases, symptoms, and conditions Also known as: KS, classic Kaposi sarcoma, AIDSrelated or epidemic Kaposi sarcoma, endemic Kaposi sarcoma, acquired Kaposi sarcoma Related conditions: Human herpesvirus 8 (HHV-8), acquired immunodeficiency syndrome (AIDS), organ transplant Definition: Kaposi sarcoma is a cancer of connective tissue named for dermatologist Moritz Kaposi, who first described endothelial raised lesions that develop in connective tissues and mucosal membranes. Four types of Kaposi sarcoma affect varying populations: Classic Kaposi sarcoma afflicts Eastern European Jewish or Mediterranean Italian men from the ages of fifty to seventy years; endemic Kaposi sarcoma develops in people of equatorial Africa; acquired Kaposi sarcoma develops in posttransplant patients; and AIDS-related or epidemic Kaposi sarcoma afflicts people with human immunodeficiency virus (HIV) and AIDS. Epidemic Kaposi sarcoma is the most
clinically aggressive and most prevalent form of the disease. Risk factors: Risk factors differ for each type of Kaposi sarcoma but include ethnicity, age, and disease state; HIV is a distinct risk factor for epidemic Kaposi sarcoma. Human herpesvirus 8 (HHV-8), a deoxyribonucleic (DNA) virus, is a risk factor for all types of Kaposi sarcoma. Etiology and the disease process: Kaposi sarcoma develops from excessive spindle cell proliferation. HHV-8 is likely causative. Exact mechanisms are unclear; abnormal cytokine development that incites cell proliferation may contribute. HHV-8 DNA seroconversion typically precedes lesion development, and antibodies in blood and saliva indicate Kaposi sarcoma even before lesions appear. Neutralizing antibodies appear to prevent clinical Kaposi sarcoma. Lesions initially develop as raised, colored blotches under the skin or mucous membranes. Swelling may impair nearby organ function, especially in the lungs, liver, and gastrointestinal (GI) tract. Classic, endemic, and transplant-associated Kaposi sar-
Kaposi sarcoma lesions on the back of a patient. (National Institutes of Health)
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Kaposi sarcoma
Salem Health: Cancer
Stages of HIV-Related Kaposi Sarcoma Stage
Tumor
Immune System
Systemic Illness
Prognosis
0, Early
Skin, lymph, minimal oral involvement
CD4 count greater than 200 cells/cubic millimeter
No opportunistic infections, thrush, or other infections; weight loss not greater than 10 percent
Good
1, Late
Pulmonary or gastrointestinal involvement, extensive oral involvement, edema, or ulceration
CD4 count is less than 200 cells/cubic millimeter
History of opportunistic infection, thrush, or other disease; weight loss greater than 10 percent
Poor
coma lesions usually occur on the skin and only occasionally spread into the lymph or gastrointestinal systems. However, aggressive endemic Kaposi sarcoma tumors do penetrate bone or manifest in lymph nodes and organs. AIDS-related Kaposi sarcoma lesions are nodular, widespread, and rapidly multiplying. They develop in the skin, mouth, lymph, and organs, especially in the gastrointestinal tract, lung, liver, and spleen. Untreated, AIDS-related Kaposi sarcoma spreads extensively through organs. Incidence: Classic Kaposi sarcoma is rare but has increased in women, although it still occurs in a 4:1 ratio of men to women. Endemic Kaposi sarcoma accounts for 9 percent of cancers in Ugandan men and occurs in prepubescent boys three times more often than in girls. People who have received organ transplants are 150 to 200 times more likely to develop Kaposi sarcoma than the general population. Epidemic Kaposi sarcoma occurs as the AIDS-defining illness in 10 to 15 percent of homosexual, HIV-infected men and is the most common AIDS-related cancer in the United States. The overall incidence of HIV-related Kaposi sarcoma once was as high as 20 percent, but it has decreased steadily with the use of antiretroviral regimens. Symptoms: Lesions are often disfiguring, palpable, and painful when swollen. Tumors bleed easily, causing ulceration, necrosis, and tissue discoloration. Symptoms are directly related to lesion location; for example, speech and feeding problems occur with palate tumors. Common symptoms of lesions in organs include bleeding from gastrointestinal lesions, nausea, vomiting, bowel obstruction, cough, dyspnea, and hemoptysis. Symptoms unique to AIDS-related Kaposi sarcoma are swollen lymph nodes, fever, and weight loss. Screening and diagnosis: Much of Kaposi sarcoma evaluation focuses on epidemic Kaposi sarcoma. Although 668
HHV-8 is directly associated with Kaposi sarcoma, routine screening is not recommended. Ultrasounds, endoscopies, and chest X rays may be used to screen for KS lesions but are unspecific. Identifiable diagnostic features are purple nodules along skin tension lines, green-yellow discoloration secondary to hemorrhage, surrounding edema, and lesion dissemination. Diagnostic histology shows an intact epidermis, new blood vessel formation with extravasated red blood cells, hemosiderin deposits, infiltrates of spindle-shaped cells, and lymphocytic inflammatory infiltrate. Lesion biopsies are definitive but carry a bleeding risk. Detection of HHV-8 in tumor tissue can confirm an uncertain diagnosis. Kaposi sarcoma lesions are hard to measure and cannot be staged by traditional cancer classification methods. However, the AIDS Clinical Trials Group has developed staging for HIV-related Kaposi sarcoma that accounts for lesion size and presence and for HIV stability. Treatment and therapy: Kaposi sarcoma treatment involves local, systemic, and antiretroviral treatments or any combination of these. Surgical treatment is limited to diagnostic biopsies and often requires concomitant radiation to prevent spreading. Local treatment with radiation, cryotherapy, or topical retinoids is best for palliation, for cosmetically unacceptable lesions, or for refractory disease. Radiation, the primary method, has a response rate of 80 to 90 percent. Systemic treatment for progressive disease includes interferon (INF)-alpha, liposomal anthracyclines or paclitaxel, and investigational signal transduction or cytokine inhibitors. INF-alpha is an immunomodulatory agent associated with 45 to 70 percent remission rates. Palliative chemotherapeutics may eradicate some lesions and decrease morbidity. Ganciclovir, foscarnet, and cidofovir antivirals are active against HHV-8 and are being studied to reduce lesion size or progression.
Salem Health: Cancer First-line treatment of HIV-related Kaposi sarcoma is highly active antiretroviral therapy (HAART), which decreases HIV replication and thereby decreases the frequency of Kaposi sarcoma lesion development. In addition, protease inhibitors such as saquinavir, indinavir, and ritonavir have direct antitumor and antiproliferative effects that can improve Kaposi sarcoma even without an observed increase in the CD4 count. Additional treatments are reserved for visceral disease progression despite HAART. Prognosis, prevention, and outcomes: Kaposi sarcoma may resolve spontaneously or with treatment. However, prepubescent patients with aggressive endemic Kaposi sarcoma face mortality within three years, and approximately 30 percent of patients with classic Kaposi sarcoma risk development of secondary tumors. Although AIDSrelated Kaposi sarcoma with respiratory failure was once associated with fatality within weeks, HIV-suppressive therapy has made stabilization, complete remission, and prevention of new lesions possible. Nicole M. Van Hoey, Pharm.D. u For Further Information Boshoff, C., and R. A. Weiss, eds. “Kaposi Sarcoma Herpesvirus: New Perspectives.” Current Topics in Microbiology and Immunology 312 (2007). Clayton, G., A. Omasta-Martin, and M. Bower. “The Effects of HAART on AIDS-Related Kaposi’s Sarcoma and Non-Hodgkin’s Lymphoma.” Journal of HIV Therapy 11, no. 3 (September, 2006): 51-53. Di Lorenzo, G., et al. “Management of AIDS-Related Kaposi’s Sarcoma.” Lancet Oncology 8, no. 2 (February, 2007): 167-176. Konstantinopoulos, P. A., R. J. Sullivan, M. V. Karamouzis, and B. J. Dezube. “Investigational Agents for Treatment of AIDS-Related Kaposi’s Sarcoma.” Expert Opinion on Investigational Drugs 16, no. 4 (April, 2007): 495-504. u
Other Resources
American Cancer Society Detailed Guide: Kaposi Sarcoma http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_Kaposis_Sarcoma_21.asp The Body Kaposi’s Sarcoma http://www.thebody.com/index/treat/kaposis.html See also African Americans and cancer; Africans and cancer; Biological therapy; Carcinoma of unknown primary origin (CUP); Cytokines; Dermatology oncology; De-
Karnofsky performance status (KPS) veloping nations and cancer; Electroporation therapy; Fibrosarcomas, soft-tissue; HIV/AIDS-related cancers; Infectious cancers; Itching; Lymphangiosarcomas; Oncogenic viruses; Organ transplantation and cancer; Sarcomas, soft-tissue; Viral oncology; Virus-related cancers; Young adult cancers.
u Karnofsky performance status
(KPS) Category: Social and personal issues Definition: The Karnofsky performance status (KPS) scale is a tool used to measure cancer patients’ ability to function and carry out the normal activities of daily living. The KPS first appeared in the scientific literature in 1948 in a study of patients’ responses to palliative treatment for inoperable lung cancer and was widely adapted thereafter for use in other types of cancers and terminal illness. The KPS remains commonly used in the twenty-first century in both research and clinical applications. Description: The Karnofsky performance status scale uses an 11-point scale to describe functional status. The scoring on each point ranges from 0 (dead) to 100 (normal, no complaints, no evidence of disease) in 10-point intervals that represent percentages of “normal” functioning. Each score is associated with a brief definition to aid in scoring. Scores below 50 indicate significant impairment and inability to care for oneself. Administration and scoring: The KPS score is determined by a trained interviewer or a clinician. The person scoring the KPS observes the patient and gathers information on the patient’s symptoms, limitations, and dependence on others. Examples of abilities and activities that the scorer might take into account include independence in dressing, bathing, toileting, and mobility in and around the home. At higher levels of functioning, scores reflect the degree of effort required to carry out work and other activities, or the degree to which symptoms interfere with normal activities. At the lowest levels of functioning, scores reflect needs for acute medical care and institutional services. Clinical use: It is useful to health providers to know not only the clinical status of a patient’s disease but also the extent to which the disease has impaired the patient’s ability to function. Broadly, a patient’s functional status can be thought to represent the overall physical and psychological toll of the disease on the ability to carry out day-to-day 669
Keratosis activities. The KPS score provides a concise summary that can help health care providers make determinations about a patient’s need for hospitalization, nursing care, and other services. In several studies, the KPS has proven useful in predicting longevity among patients with advanced disease, and decline in the KPS score is a sensitive indicator of late-stage disease progression. The KPS is primarily a measurement of functional impairment and disability and does not necessarily reflect broader aspects of quality of life such as emotional distress or life satisfaction. Andrea Bradford, M.A. See also Aging and cancer; Aids and devices for cancer patients; Caregivers and caregiving; Case management; Cognitive effects of cancer and chemotherapy; Counseling for cancer patients and survivors; Elderly and cancer; End-of-life care; Home health services; Living with cancer; Occupational exposures and cancer; Psychosocial aspects of cancer; Relationships; Singlehood and cancer.
u Keratosis Category: Diseases, symptoms, and conditions Also known as: Actinic (solar) keratosis, seborrheic keratosis, keratosis pilaris (chicken skin) Related conditions: Actinic keratosis, seborrheic keratosis, keratosis pilaris Definition: Keratosis is a benign growth of keratin on the skin. There are three main kinds of keratosis: actinic keratosis, seborrheic keratosis, and keratosis pilaris. Risk factors: Risk factors are sun exposure, fair skin, and genetic factors.
Salem Health: Cancer estimated 50 to 80 percent of adolescents and 40 to 50 percent of the adult population. It is more common in women than in men. Symptoms: In actinic keratosis, the affected area of the skin may be the same color, darker, or lighter than the skin. It is often accompanied by solar damage on consistently sun-exposed areas. Seborrheic keratosis growths resemble warts and may exhibit a variety of colors, from yellow through black. Keratosis pilaris is excess keratin in the skin that accumulates within the hair follicles. Keratosis pilaris appears as rough bumps on the skin, most often on the backs and outer sides of the upper arms. It may also appear on the lower arms or on the thighs, or any body part except on glabrous (hairless) skin. Screening and diagnosis: People with mild keratosis pilaris often are not aware of the condition. Diagnosis is generally made by visually examining the skin. Skin biopsies are sometimes done in seborrheic and actinic keratosis. Treatment and therapy: Actinic keratosis is often treated with cryosurgery. Other therapies involve the application of 5-fluorouracil, a chemotherapy agent, photodynamic therapy, electrocautery (burning off the area with electricity), and topical immunotherapy. Prognosis, prevention, and outcomes: Preventive measures for actinic keratosis are similar to those for skin cancer, such as limiting sun exposure and applying sunscreens. Because seborrheic keratosis tumors are a benign and not painful condition, treatment is often not necessary. There is no cure for keratosis pilaris, but there are treatments to alleviate symptoms. Anita Nagypál, Ph.D. See also Aplastic anemia; Leukoplakia; Moles; Premalignancies; Skin cancers.
Etiology and the disease process: Actinic keratosis is a premalignant condition of the skin, presenting as thick, scaly, or crusty patches. Frequent sun exposure and fair skin may increase the risk of developing actinic keratosis. A seborrheic keratosis is a benign skin growth on the top layers of the epidermis. It has been associated with a mutation in the growth factor receptor (FGFR3) gene. Keratosis pilaris is a follicular condition that runs in families. It is often worse in winter than in the summer, but it often improves with age. There are several different types of keratosis pilaris, including keratosis pilaris rubra (inflamed and red bumps), alba (bumpy skin without irritation), and rubra faceii (reddish rash on the cheeks).
Definition: The Ki67 protein is present in actively dividing cells. It is expressed during all phases of the cell cycle, except for G0 (known as the resting phase). The Ki67 test detects Ki67 in tumors using an immune-based assay, which identifies the dividing cells.
Incidence: Seborrheic keratosis is most common among people over forty years of age. Keratosis pilaris affects an
Cancers diagnosed or treated: Primarily breast and prostate cancers
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u Ki67 test Category: Procedures Also known as: Ki67 proliferation index
Salem Health: Cancer Why performed: High Ki67 levels correlate with more aggressive tumors. Characterizing the proliferation rates of tumors via Ki67 expression can help determine what kind of treatment a patient should receive. The Ki67 test can also be used to examine whether a patient has responded to therapy by evaluating changes in cellular proliferation. Patient preparation: A biopsy is performed to obtain tumor tissue for the Ki67 test. Biopsies can be done either with a needle or through surgery, depending on the size and location of the tumor. If general anesthesia is required for surgery, then the patient must fast prior to the biopsy. Steps of the procedure: Tumor tissue collected from the biopsy will be sliced very thin and then fixed to a microscope slide. Ki67 will be detected by a method called immunohistochemistry, in which antibodies are used to bind to tumor cells expressing Ki67, and then the cells are stained with a colored reagent to identify Ki67+ cells. The tumor sample is examined under a microscope, where cells are counted using an eyepiece grid. Approximately five hundred to two thousand cells are counted and marked as either Ki67+ or Ki67−. After the procedure: After a needle biopsy, pressure will be applied at the injection site to stop bleeding. For an open biopsy requiring general anesthesia, the patient will have blood pressure and pulse monitored prior to discharge from the hospital. Transport home must be provided. Open biopsies may also require bed rest for up to twenty-four hours after the procedure, and heavy lifting should be avoided for at least two weeks to allow the incision to heal. Risks: Because the Ki67 test is an ex vivo assay (meaning “outside of the body”), the only risks are those associated with the biopsy, which include bleeding and infection. Open biopsies may also have risks associated with the surgery (such as scarring) and the anesthesia (such as allergic reactions and changes in blood pressure or heart rate). Results: Results are reported as a percentage using this equation: ([number of Ki67 + cells / total number of tumor cells] × 100). There is no established cutoff to define a high Ki67 proliferation index, but approximately 20 to 30 percent is a common result to be deemed positive. Elizabeth A. Manning, PhD. See also Biopsy; Immunocytochemistry and immunohistochemistry; Tumor markers.
Kidney cancer
u Kidney cancer Category: Diseases, symptoms, and conditions Also known as: Renal cancer, renal cell cancer, transitional cell cancer, clear cell renal cancer, papillary renal cancer, chromophil renal cancer, chromophobe renal cancer, renal oncocytoma, collecting duct renal cancer, medullary renal cancer, sarcomatoid renal cancer, Wilms’ tumor Related conditions: Kidney cysts Definition: The two main types of kidney cancer are renal cell cancer, which arises from the filtering part of the kidney, the nephrons, and transitional cell cancer, which arises from the renal pelvis, where the urine passes from the nephrons to the ureter and then to the bladder. It more closely resembles bladder cancer than renal cell cancer. Renal cell cancer falls into these subtypes: clear cell, papillary, chromophobe, renal oncocytoma, collecting duct, medullary, sarcomatoid, Wilms’ tumor, and unclassified. Clear cell cancer is the most common type and represents 66 to 75 percent of all cases of kidney cancer. Its name derives from the clear cytoplasm within its cells. A majority of clear cell renal cancer cases have the von Hippel-Lindau (VHL) genetic mutation. The two types of papillary renal cancer (characterized by fingerlike projections) are differentiated by the type of cells found in the tumor. Type I tends to be more common in African Americans and to involve both kidneys. Type II is associated with hereditary leiomyomatosis and can be difficult to treat once it has metastasized (spread to other organs). It is the second most common renal cell cancer and represents about 10 to 15 percent of cases. Sometimes papillary renal cancer is called chromophil renal cancer. About 5 percent of renal cell cancers are chromophobe. The cells of this type of cancer are similar to those in renal oncocytoma, but they are resistant to some stains used to analyze cancer cells. Chromophobe renal cancer is often related to BirtHogg-Dubé syndrome, a dominant hereditary trait that is marked by renal tumors, lung cysts, fibrofolliculomas (benign tumors of hair follicles), and spontaneous pneumothorax (collapse of the lung). It is the third most common type of kidney cancer. Renal oncocytoma is a benign kidney tumor that is also related to Birt-Hogg-Dubé syndrome. This type of tumor does not metastasize, although it can grow quite large. Its cells are similar to those of chromophobe renal cancer. Collecting duct renal cancer is rare but quite aggressive. Often it has metastasized before being discovered. Its name comes from the fact that the tumor cells often form a tube. Medullary renal cancer is also rare and quite aggres671
Kidney cancer
Salem Health: Cancer
sive. It is related to the sickle cell trait. Sarcomatoid renal cancer is thought to arise from the blood vessels of the kidney. It also is quite rare and quite aggressive. Its name comes from the fact that its cells appear like those of a sarcoma (cancer of the soft tissues). Wilms’ tumor is found predominantly in infants and young children, under the age of five. It is relatively rare and tends to spread locally into the lymph nodes, renal vein, and vena cava. Wilms’ tumor is an embryonal adenomyosarcoma. Unclassified renal cell cancer has cells that do not appear like those of other types of kidney cancer. Risk factors: The most common risk factor for kidney cancer is smoking cigarettes. Kidney cancer also appears to be more common in persons who are obese or who have high blood pressure. There are three hereditary syndromes that put a person at a higher risk of developing kidney cancer. They are von Hippel-Lindau disease, hereditary leiomyomatosis, and Birt-Hogg-Dubé syndrome. These syndromes may be caused by spontaneous mutations. Some occupations put a person at higher risk for develop-
ing kidney cancer. These include occupations in which a person is exposed to certain toxic chemicals or substances, such as petroleum-based products, asbestos, lead, or cadmium. Also, persons who are on long-term dialysis therapy for kidney failure are at higher risk of developing kidney cancer. Etiology and the disease process: Kidney cancer arises from a single cell that grows wildly. For renal cell cancer, this is a cell of the tubular epithelium of the nephron, the part of the kidney that filters the blood of waste products and produces urine for excreting these wastes. Transitional cell renal cancer manifests itself in the renal pelvis, where urine is delivered by the nephrons. The types of renal cancer vary in their aggressiveness and in how quickly they metastasize. Some will metastasize from a small tumor in the kidney, and other types do not metastasize until they have engulfed the kidney. Kidney cancer spreads through the lymph nodes and the bloodstream. Common sites for metastases are the other kidney, the lung, the adrenal gland, the bones, and the liver.
A tumor in a polycystic kidney. (©Lester V. Bergman/Corbis)
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Salem Health: Cancer
Kidney cancer
Incidence: Kidney cancer strikes about 51,000 people a year in the United States. It is twice as common in men as in women. However, kidney cancer is actually relatively rare compared with other cancers. It represents about 3 percent of all cases of cancer in the United States. About 12,000 people die of kidney cancer each year.
Stage at Diagnosis and Five-Year Relative Survival Rates for Cancer of the Kidney and Renal Pelvis, 1996-2004 Stage
Symptoms: The symptoms of kidney cancer do not appear until the tumor is fairly large or has metastasized. The symptoms are blood in the urine (hematuria), abdominal mass, back or flank pain, weight loss, recurrent fever, and fatigue. Blood tests may demonstrate a high serum calcium and either anemia or high red blood cell counts. A urine analysis test may show microscopic hematuria that is not visible to the eye. Kidney cancer can also cause hypertension, although this symptom is not particularly helpful in diagnosing kidney cancer because it is so common. Screening and diagnosis: There is no routine screening performed for kidney cancer. However, kidney cancer may be found incidentally on a chest, abdominal, or pelvic ultrasound; computed tomography (CT) scan; or magnetic resonance imaging (MRI) performed for another reason. Kidney cancer is usually diagnosed by a renal ultrasound, an abdominal CT scan, an MRI, or a positron emission tomography (PET) scan. Occasionally, an intravenous pyelogram (IVP) is performed, although this diagnostic test has largely been replaced by ultrasounds, CT scans, and MRIs. Once a kidney tumor is discovered, it needs to be biopsied to identify the type of cells in the tumor. Kidney cancers may be biopsied by fine needle through the skin below the rib cage on the back or by ureteroscopy (the passing of a ureteroscope through the urethra, the bladder, one of the ureters, and the renal pelvis, and then into the body of the kidney). Both procedures require fluoroscopy to localize the tumor. Kidney cancer is usually staged with a combination of the American Joint Committee on Cancer (AJCC) TNM staging system and a numeric grouping. “T” refers to the size of the tumor, “N” refers to lymph node involvement, and “M” refers to whether there are metastases. The stages are as follows: • Stage I, T1a-T1b, N0, M0: The tumor is less than 7 centimeters (cm) with no lymph node involvement and no metastases. • Stage II, T2, N0, M0: The tumor is greater than 7 cm with no spread outside the kidney. • Stage III, T1a-T3b, N1, M0 or T3a-3c, N0, M0: The tumor has spread to a single lymph node but not metastasized, or has spread to adjacent tissue or structures, such as the adrenal glands, to fatty tissue around the kidney, or into the vena cava.
Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
55 19 20 5
89.6 60.8 9.5 35.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
•
Stage IV, T4, N0-N1, M0; any T, N2, M0; or any T, any N, M1: The tumor extends beyond the kidney locally and has spread into the lymph system. It is present in more than one lymph node. There may also be metastases to other organs. Treatment and therapy: For many years, the only treatment for kidney cancer was to remove the affected kidney. This was done unless the cancer was so far advanced that there was little hope for the patient. Kidney cancer did not respond well to either radiation therapy or chemotherapy. Consequently, these treatments were used only to treat metastatic kidney cancer, to relieve the symptoms, and to prolong the patient’s life. However, in the mid-2000’s, the treatment options for kidney cancer proliferated. Research to develop additional new drugs that are effective for treating kidney cancer is ongoing. Kidney cancer surgery includes a total radical nephrectomy, laparoscopic radical nephrectomy, partial nephrectomy, radioablation (destroying the tumor with radiation therapy), cryoablation (freezing), and arterial embolization (blocking the artery feeding the tumor with material). The original total radical nephrectomy procedure, in which an 18-inch incision is made from below the mediastinum (breast bone) to the middle of the back, is no longer the sole surgical option. Several laparoscopic radical nephrectomy procedures are available. These laparoscopic procedures require a 3- to 4-inch incision and 3.5-inch incisions. Recovery time for the patient is four weeks rather than the twelve weeks of recovery required for the original procedure. 673
Klinefelter syndrome and cancer Kidney cancer still does not respond well to radiation therapy. Advances in the development of chemotherapy drugs have benefited the treatment of kidney cancer. However, it is still not routine to prevent the recurrence of a kidney cancer with chemotherapy, as is done with other cancers. The focus of chemotherapy treatment for kidney cancer is to prolong the life of the patient. As a result, chemotherapy is reserved for treating advanced renal cancers with metastases. Kidney cancer may be treated with angiogenesis inhibitors (drugs that inhibit the growth of blood vessels feeding the tumors), such as sorafenib tosylate (Nexavar) and sunitinib malate (Sutent). In May of 2007, the drug temsirolimus (Torisel) was approved by the Food and Drug Administration for treating kidney cancer. Temsirolimus is an enzyme inhibitor that interferes with cell growth, development, and survival. Other drugs now being used to treat advanced kidney cancer are bevacizumab, interleukin-2, and interferon. Avastin is a monoclonal antibody that interferes with the growth and development of new blood vessels within a tumor. Interleukin-2 and interferon are referred to as biological therapy, because these substances are normally produced by the body in small amounts. Their role in kidney cancer treatment is to stimulate the body’s normal immune defenses. Like other chemotherapy drugs, these drugs have many severe side effects. Prognosis, prevention, and outcomes: With kidney cancer, the prognosis depends on the stage of the cancer at diagnosis. With Stages I and II, surgical intervention is likely to cure the kidney cancer. With Stages III and IV, the prognosis is guarded and depends on the patient’s response to treatments, particularly drug therapy. In Stages III and IV, treatment may be aimed at extending the patient’s life and providing a reasonable quality of life. It is not possible to prevent kidney cancer. Certainly, not smoking cigarettes will decrease a person’s likelihood of developing kidney cancer. Other lifestyle choices, such as occupation, might also decrease the likelihood of developing kidney cancer, but many of the substances thought to cause kidney cancer are fairly pervasive in the environment. Some kidney cancers develop in people with no apparent risk factors for the disease. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Diaz, José I., Linda B. Mora, and Ardeshir Hakam. “The Mainz Classification of Renal Cell Tumors.” Cancer Control: Journal of the Moffitt Cancer Center 6 (November/December, 1999): 571-579. Nuñez, Kevin R., ed. Trends in Kidney Cancer Research. New York: Nova Biomedical Books, 2006. 674
Salem Health: Cancer Patel, Uday, ed. Carcinoma of the Kidney. New York: Cambridge University Press, 2008. Rodriquez, Alejandro, and Wade J. Sexton. “Management of Locally Advanced Renal Cell Carcinoma.” Cancer Control: Journal of the Moffitt Cancer Center 13 (July, 2006): 199-210. u
Other Resources
American Cancer Society Detailed Guide: Kidney Cancer http://www.cancer.org/docroot/cri/content/ cri_2_4_1x_what_is_kidney_cancer_22.asp Kidney Cancer Association http://www.kidneycancer.org National Cancer Institute http://www.cancer.gov/cancertopics/types/kidney National Kidney Foundation http://www.kidney.org See also Adenocarcinomas; Adrenal gland cancers; Angiogenesis inhibitors; Biological therapy; Birt-Hogg-Dubé syndrome (BHDS); Bladder cancer; Denys-Drash syndrome and cancer; Diethanolamine (DEA); Endocrine cancers; Fanconi anemia; Hematuria; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary nonVHL clear cell renal cell carcinomas; Hereditary papillary renal cell carcinomas; Malignant rhabdoid tumor of the kidney; Nephroblastomas; Nephrostomy; Organ transplantation and cancer; Renal pelvis tumors; Syndrome of inappropriate antidiuretic hormone production (SIADH); Transitional cell carcinomas; Urinalysis; Urinary system cancers; Urography; Urologic oncology; Von Hippel-Lindau (VHL) disease; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Klinefelter syndrome and
cancer Category: Diseases, symptoms, and conditions Also known as: Klinefelter’s syndrome, XXY syndrome, 47,XXY syndrome Related conditions: Breast, prostate, and lung cancer; non-Hodgkin lymphoma; extragonadal (often mediastinal) germ-cell tumors; testicular tumors (such as germinoma)
Salem Health: Cancer Definition: Klinefelter syndrome is a condition caused by an extra sex chromosome (usually 47,XXY) that results in a phenotypic man with several characteristic manifestations. Risk factors: The risks of certain cancers are increased in Klinefelter syndrome. Klinefelter patients given testosterone hormone replacement therapy increase their risk of prostate cancer. Etiology and the disease process: The XXY chromosome arrangement disrupts normal testicular development, leading to impaired sex hormone production. This is the etiology of many symptoms of Klinefelter syndrome. Klinefelter patients are sterile because of seminiferous tubule dysgenesis. Genes not related to sex on the X chromosome may cause other manifestations. Incidence: Klinefelter syndrome occurs in 1 in 500 to 1 in 1,000 newborn male children. The overall incidence of all malignancies in patients with Klinefelter syndrome is not significantly different from the incidence among men with normal male chromosomes. However, certain types of cancer are more common among Klinefelter patients than 46,XY (so-called normal) men. These include male breast cancer, non-Hodgkin lymphoma, extragonadal (often mediastinal) teratomas, germ-cell tumors of the testes, and possibly lung cancer, gallbladder cancer, and extrahepatic bile duct tumors. Prostate cancer risk is very low unless hormone therapy with testosterone is initiated; then, the risk for adenocarcinoma of the prostate is increased. Symptoms: Klinefelter patients typically have small, atrophic testes (microorchidism), infertility, a small penis, gynecomastia (enlarged breasts), tall stature, truncal obesity, autoimmune disorders, diabetes, and an increased risk of behavioral, emotional, and intellectual difficulties. Life expectancy is normal. Hypogonadism results from abnormally low male sex hormone production and abnormally high female hormone levels. Precocious puberty may result from germ-cell tumor production of male sex hormones in children with Klinefelter. Screening and diagnosis: Cytogenetic analysis is necessary to diagnose Klinefelter syndrome. Klinefelter is often discovered coincidentally during cytogenetic testing for cancer, infertility, or prenatal birth defects (amniocentesis). Doctors may notice clinical signs of Klinefelter syndrome and request cytogenetic testing. Treatment and therapy: Hormone replacement therapy is given to some patients to reduce symptoms and improve masculinization; however, testosterone therapy will in-
Krukenberg tumors crease the risk of prostate cancer. It is not necessary to treat Klinefelter syndrome. Assisted reproductive technologies have been used to overcome sterility. Prognosis, prevention, and outcomes: The long-term prognosis for Klinefelter syndrome is good because the condition is not life-threatening. Surveillance for cancers that are more common in men with Klinefelter syndrome should be instituted. Christopher Pung, B.S., C.L.Sp. (CG) See also Breast cancer in men; Childhood cancers; Cryptorchidism; Germ-cell tumors; Prostate cancer; Teratocarcinomas; Testicular cancer; Testicular self-examination (TSE).
u Krukenberg tumors Category: Diseases, symptoms, and conditions Also known as: Metastatic stomach cancer Related conditions: Stomach cancer Definition: Krukenberg tumors are bilateral ovarian tumors resulting from the spread of primary stomach cancer. Other possible sources of primary malignancy include the breast, colon, and biliary tract. Friedrich Ernst Krukenberg of Germany first described this tumor in 1896. Risk factors: Women between the ages of forty and fifty are most frequently affected. The tumor occurs more in Asian women because stomach cancer is a common malignancy of adult women in this geographic region. A history of stomach cancer in a middle-aged female patient should alert the physician to the possible risk of developing a Krukenberg tumor. Etiology and the disease process: The mechanism of tumor spread to the ovaries has not yet been determined. Blood and lymph fluid flow may be responsible for stomach tumor cell metastasis to the ovaries. Incidence: Krukenberg tumors make up 5 to 6 percent of all malignant ovarian tumors. Japan, China, and Korea have a particularly high incidence of Krukenberg tumors. Symptoms: Most patients complain of pain and abdominal distension, ascribed to both ovarian enlargement and ascites (fluid accumulation in the abdominal cavity). Abnormal menstruation, pain during sexual intercourse, and vaginal bleeding are other notable symptoms. A small number of patients remain asymptomatic or complain of gastrointestinal symptoms related to the primary cancer. 675
Krukenberg tumors Screening and diagnosis: A laparotomy (a surgical incision of the abdominal wall) is important in diagnosing a Krukenberg tumor. Chest X rays, abdominal computed tomography (CT) scans, and pelvic ultrasound are useful in determining the extent of tissue involvement. A biopsy of the ovary will confirm the diagnosis: Microscopically, Krukenberg tumors are characterized by cancer cells with a “signet-ring” appearance, that is, identical to tumor cells in stomach cancer tissue. The presence of a Krukenberg tumor signifies that the primary stomach cancer is in an advanced stage (Stage IV, distant metastasis). Treatment and therapy: In cases in which the tumor is confined to the ovaries and the stomach, surgical removal of both the ovarian tumor and the primary cancer is recom-
676
Salem Health: Cancer mended. Chemotherapy and radiotherapy may be required in cases in which cancer has spread beyond the ovaries and the stomach. Prognosis, prevention, and outcomes: The prognosis is poor for patients diagnosed with a Krukenberg tumor. Prophylactic surgical removal of both ovaries during gastric cancer surgery may be the only way of preventing tumor growth. Because the tumor is a sign of advanced gastric cancer, the outcome is poor for patients with Krukenberg tumors. Ophelia Panganiban, B.S. See also Asian Americans and cancer; Ovarian cancers; Ovarian cysts; Stomach cancers.
Salem Health: Cancer
u Lacrimal gland tumors Category: Diseases, symptoms, and conditions Also known as: Orbital tumors Related conditions: Lymphomas Definition: Lacrimal gland tumors are rare neoplasms of tear-secreting glands located above the outer corner of each eye. The most common benign and malignant lacrimal gland tumors are called pleomorphic adenomas and adenoid cystic carcinomas, respectively. Risk factors: Benign tumors are commonly diagnosed in adults between the ages of forty and fifty years, while malignant neoplasms typically occur during the third decade and the teenage years. Individuals previously diagnosed with lymphoma are at risk for developing orbital lymphoma. Etiology and the disease process: The etiology of lacrimal gland tumors is unknown. Benign tumors arise from epithelial or mesenchymal cells, while malignant lesions originate from duct cells.
Lacrimal gland tumors Incidence: In the United States, 2 percent of orbital tumors are malignant epithelial tumors of the lacrimal gland. There are only a few reports of this tumor in the literature because of its rarity. Symptoms: Some patients may be asymptomatic, while some may complain of a mild fullness in the affected eyelid. Occasionally, patients may have gross bulging of the affected eye (proptosis), blurry or double vision, and a visible mass on the eyelid. Eye pain may or may not be present. Screening and diagnosis: A tissue biopsy is the definitive tool for diagnosing lacrimal gland tumors. Imaging tests such as a computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scans, and positron emission tomography (PET) scanning are useful for determining adjacent tissue involvement. The TNM (tumor/lymph node/metastasis) system is used for staging lacrimal gland tumors. Tumor size and location are described as Tx (primary tumor not evaluable), T0 (no tumor), T1 (tumor is 2.5 centimeters, or cm, or less and limited to the lacrimal gland), T2 (tumor is 2.5 to 5 cm and limited to the lacrimal gland),
A man with lacrimal sac carcinoma. (©Bart’s Medical Library/Phototake—All rights reserved)
677
Lactate dehydrogenase (LDH) test T3a (tumor extends to periosteum but is 5 cm or less), T3b (tumor extends to periosteum and is greater than 5 cm), and T4 (tumor invasion of surrounding structures such as the orbital structures or brain). Node involvement is classified as Nx (regional lymph nodes not evaluable), N0 (no metastasis to regional nodes), and N1 (metastasis to regional nodes). Metastasis is assessed as Mx (distant metastasis not evaluable), M0 (no distant metastasis), or M1 (distant metastasis present). Treatment and therapy: Treatment depends on the type of tumor. Benign lacrimal gland tumors are treated by complete excisional biopsy. Adenoid cystic carcinoma is treated by surgically removing all orbital structures and bone (exenteration). Prognosis, prevention, and outcomes: An incompletely excised benign tumor of the lacrimal gland has a 10 to 20 percent chance of becoming malignant. Because of bone and nerve involvement, malignant lacrimal gland tumors have a poor prognosis. Ophelia Panganiban, B.S. See also Adenoid cystic carcinoma (ACC); Eye cancers; Eyelid cancer; Orbit tumors; Rhabdomyosarcomas.
u Lactate dehydrogenase (LDH)
test Category: Procedures Also known as: Lactic acid dehydrogenase, Llactate:NAD+ oxidoreductase Definition: Lactate dehydrogenase (LDH) is a ubiquitous intracellular enzyme that catalyzes the interconversion of pyruvate and lactate. In oncology it is used as a serum marker of cell damage or turnover. The enzyme is a tetramer of H (heart) and/or M (muscle) subunits, allowing five possible isoenzyme forms: LDH-1 (H4), LDH-2 (H3M1), LDH-3 (H2M2), LDH-4 (H1M3), and LDH-5 (M4). Cancers diagnosed: Malignancies causing effusions, germcell tumors, and other tumors with high cell turnover Why performed: Serum LDH is elevated in many nonneoplastic diseases. In oncology, its concentration may be determined to estimate the stage of disease and prognosis in several cancers, such as non-Hodgkin lymphoma, myeloma, disseminated melanoma, and metastatic prostate carcinoma. The ratio of serum LDH to LDH concentration in pleural, peritoneal, or pericardial effusions can help distinguish benign from malignant processes; high 678
Salem Health: Cancer LDH concentrations in effusion fluid suggest the presence of cancer. Because the five isoenzymes have characteristic relative abundances in different tissues, determination can assist in the diagnosis of several tumors. Patient preparation: No fasting or other special preparation on the part of the patient is necessary for this simple blood test. Steps of the procedure: After the blood sample is collected, serum is isolated by centrifugation and the activity of the enzyme is measured in either the forward direction (oxidation of lactate and NAD+ to pyruvate, NADH, and H+) or the reverse direction. In the forward reaction, the rate of appearance of NADH can be followed spectrophotometrically because it strongly absorbs ultraviolet (UV) light at 340 nM; NAD+ does not. The enzyme activity is calculated by comparing the rate of NADH appearance in the patient sample to rates obtained from standard preparations. If the cause of elevated LDH cannot be determined by other means, then the isoenzymes can be separated by electrophoresis, with LDH-1 (all H subunits) migrating fastest, followed in order by LDH-2 through LDH-5. LDH can also be visualized in tissue sections by immunohistochemistry. After the procedure: No special aftercare is required other than monitoring the blood collection site for signs of infection until healed. Risks: There are no risks to the patient. High false positive rates are seen in patients with other systemic illnesses. Results: Abnormally high LDH values and abnormal isoenzyme patterns are seen in many different diseases and must be interpreted in the light of the clinical history and other laboratory results. Results for enzyme activity obtained with different methods are not interchangeable. In oncology, abrupt increases in LDH indicate an unfavorable prognosis in terminally ill patients. The LDH-1 isoenzyme is reliably elevated in germ-cell tumors (teratoma, seminoma, or ovarian dysgerminoma) and can serve as a tumor marker. In leukemia, lymphoma, and multiple myeloma, LDH-3 and LDH-4 are often elevated. Elevated LDH-5 in colorectal cancer is strongly associated with poor survival. John B. Welsh, M.D., Ph.D. See also Germ-cell tumors; Multiple myeloma; NonHodgkin lymphoma; Paracentesis; Testicular cancer; Tumor markers.
Salem Health: Cancer
u Laetrile Category: Complementary and alternative therapies Also known as: Amygdalin, mandelonitrile beta-Dgentiobioside, mandelonitrile-beta-glucuronide, vitamin B17, amigdalina B-17 Definition: Laetrile is the purified form of amygdalin, a cyanide derivative, which is extracted from almonds and the pits of apricots and peaches. The cyanogenic glucoside is a sugar and produces cyanide. There are two other byproducts of amygdalin: prusanin and benzaldehyde. Cancers treated or prevented: None Delivery routes: Injection, intravenously, pill, enema How this substance works: Amygdalin was first extracted in 1830 and used as an anticancer drug in Russia in 1845. The popularity of laetrile reemerged in the 1970’s, and a court challenge succeeded in legalizing its use. Twenty states legalized laetrile as a result of the challenge. Laetrile is currently not approved by the Food and Drug Administration (FDA) to treat cancer or any other disease. It is, however, manufactured and used for cancer treatment in Mexico and sold in the United States as a dietary supplement. The FDA does not test supplements for effectiveness. This supplement can be toxic and fatal because of the risk of cyanide poisoning. In fact, there are known deaths directly attributable to laetrile use and the resulting cyanide poisoning. Proponents believe that cyanide has anticancer effects. Laboratory and clinical studies have yielded no data supporting the effectiveness of laetrile as an anticancer drug. Human studies have yielded inconclusive results. In some studies, patients were given traditional cancer treatment along with laetrile. Thus, it was not possible to study the laetrile independently. A study published in 1982, however, followed 175 patients with different types of cancer who took laetrile. Cancer returned in all patients by eight months. No patient was cured of cancer by laetrile. The primary mechanism of the most widely held belief in laetrile’s effectiveness is that cyanide has a direct toxic effect on cells by preventing oxygen from being effectively used by the cancer cells, causing them to die. The second main theory is that cancer is caused by a vitamin deficiency and that laetrile (termed vitamin B17) treats the deficiency. Neither of these theories has been shown to be valid. Side effects: Cyanide poisoning is the main side effect. It causes nausea and vomiting and can be fatal in high doses.
Lambert-Eaton myasthenic syndrome (LEMS) Laetrile as a supplement is particularly hazardous to children and pregnant women. Taking raw amygdalin while on laetrile can induce toxic cyanide levels in the blood. Janet R. Green, M.S.P.H. See also Complementary and alternative therapies; Integrative oncology.
u Lambert-Eaton myasthenic
syndrome (LEMS) Category: Diseases, symptoms, and conditions Also known as: Lambert-Eaton syndrome, EatonLambert syndrome Related conditions: Small-cell lung cancer (SCLC), nonHodgkin lymphoma, thymoma, carcinoma of the breast and colon, autoimmune disorders Definition: Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder of the neuromuscular junction, the point where nerve endings meet muscle fibers. LEMS affects muscles and nerves, causing progressive muscle weakness and decreased reflexes. Commonly, the first symptom noticed by an individual with the syndrome is an exceptionally dry mouth, which stems from the disorder’s effect on the autonomic nervous system. LEMS is frequently an early indication of cancer, allowing for early detection and treatment of the disease. It most often is associated with small-cell lung cancer (SCLC) and also has been linked to non-Hodgkin lymphoma, thymoma, and carcinoma of the breast and colon. Risk factors: People with various types of cancer, especially small-cell lung cancer, are at increased risk for developing Lambert-Eaton myasthenic syndrome. Additional risk factors include advanced age and smoking. Etiology and the disease process: Lambert-Eaton myasthenic syndrome is an autoimmune disease caused by antibodies acting at the neuromuscular junction. These antibodies target the area of the nerve fiber responsible for releasing acetylcholine, a chemical needed to stimulate normal muscle contraction. The antibodies cause too little acetylcholine to be released, and muscle contractions are weakened. When patients have cancer (about half of LEMS cases), antibodies are thought to be released in response to cancer cell growth, affecting the muscles and autonomic nervous system as secondary reactions. When patients do not have cancer, what triggers the antibody release is unknown. 679
Lambert-Eaton myasthenic syndrome (LEMS) Typically, patients seek care well before the cancer is diagnosed because antibody release occurs at a very early stage in a tumor’s development. Symptoms of LEMS may begin two or more years before detection of a tumor. Because LEMS is a progressive disease, increasing weakness usually limits patients’ ability to perform normal daily activities. Although LEMS can cause respiratory difficulties, successful cancer treatment or death usually occurs before LEMS progresses to a life-threatening stage. Incidence: The exact incidence rate of Lambert-Eaton myasthenic syndrome is unknown because it is not common; however, it is estimated to occur at a rate of 1 per 100,000 people in the United States. The highest incidence occurs in people who are middle-aged and older, but it has also occurred in children. Between 50 and 70 percent of cases of LEMS are associated with small-cell lung cancer, but only about 3 percent of people with small-cell lung cancer develop LEMS. All patients with LEMS and smallcell lung cancer have a long-term history of smoking. Symptoms: The symptoms of Lambert-Eaton myasthenic syndrome usually begin slowly, developing over a period of months or years. The most common symptom is progressive weakness of the arms and legs that typically occurs in the muscles closest to the body, with the thighs and hips being the most frequently affected. Reflexes in the affected extremities are usually absent or reduced. People with LEMS often have trouble climbing stairs, getting up from a seated or reclining position, and walking. As the disorder affects the autonomic nervous system, patients may complain of mouth dryness, dizziness after standing up, and impotence. Additional symptoms found in people with LEMS include double vision, constipation, excessive sweating, and difficulty talking, chewing, and swallowing. Screening and diagnosis: There are no screening tests for Lambert-Eaton myasthenic syndrome. The disorder is typically diagnosed by clinical history, physical examination, and laboratory testing. If it is advanced and related to a malignancy, symptoms of the underlying cancer may be present; however, LEMS is usually diagnosed before the cancer produces discernible symptoms. Diagnostic tests include basic blood tests, such as complete blood count and chemistry; testing for voltage-gated calcium channel antibodies, which are present in 50 to 100 percent of patients with LEMS; chest X rays and a computed tomography (CT) scan if malignancy is suspected; electromyography and nerve conduction studies; bronchoscopy; and positron emission tomography (PET) scanning. A Tensilon (edrophonium chloride) test, which is commonly used to differentiate LEMS from myasthenia gravis, may pro680
Salem Health: Cancer duce a noticeable short-term increase in strength. Staging would be determined by the associated cancer. Treatment and therapy: When Lambert-Eaton myasthenic syndrome has been diagnosed with an underlying cancer, successful treatment of the cancer usually results in improvement of LEMS. When no cancer has been diagnosed, continued monitoring and testing are recommended because the typical time interval between the onset of LEMS and the diagnosis of cancer can be prolonged. Immunosuppression therapy with corticosteroids or gamma globulin has proven to provide short-term relief of LEMS but should be used only if symptoms do not resolve after effective treatment of an underlying cancer or if no cancer is present, as it may reduce immunologic suppression of tumor growth. Several drugs, including guanidine and 3,4-diaminopyridine, increase the release of acetylcholine and have been shown to significantly decrease symptoms. Physical therapy and a regular exercise routine can help patients maintain muscle tone and strength. Prognosis, prevention, and outcomes: The prognosis of Lambert-Eaton myasthenic syndrome varies and is dependent on the prognosis for the associated cancer. There is no known prevention for LEMS; however, patients should be made aware that certain medications, such as neuromuscular blocking agents, aminoglycosides, magnesium, and calcium channel blockers, can make their condition worse. Patients should also be advised that exposure to hot environments and fever during illness can increase the weakness in their extremities. Dorothy P. Terry, R.N. u
For Further Information Pascuzzi, Robert M. “Myasthenia Gravis and LambertEaton Syndrome.” Therapeutic Apheresis and Dialysis 6, no. 1 (February, 2002): 57-68. Schiff, David, and Patrick Y. Wen, eds. Cancer Neurology in Clinical Practice. Totowa, N.J.: Humana Press, 2002. Verschuuren, J. J., et al. “Available Treatment Options for the Management of Lambert-Eaton Myasthenic Syndrome.” Expert Opinion on Pharmacotherapy 7, no. 10 (July, 2006): 1323-1336.
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Other Resources
Merck Manuals Neuromuscular Junction Disorders http://www.merck.com/mmhe/sec06/ch095/ ch095c.html
Salem Health: Cancer
Laparoscopy and laparoscopic surgery
WebMd Lambert-Eaton Myasthenic Syndrome http://www.webmd.com/cancer/ lambert-eaton-myasthenic-syndrome See also Dry mouth; Lung cancers; Paraneoplastic syndromes; Side effects.
u Laparoscopy and laparoscopic
surgery Category: Procedures Also known as: Keyhole surgery, minimally invasive surgery (MIS), pinhole surgery Definition: Laparoscopy is a procedure that allows doctors to look inside the abdominal or pelvic cavities using a small tube attached to a camera and video monitor. This procedure has been used since 1973 to diagnose and to treat various conditions, including certain types of cancer. Cancers diagnosed or treated: Cervical, colorectal, gallbladder, kidney, liver, ovarian, pancreatic, prostate, stomach, and uterine cancers Why performed: There is some evidence that laparoscopy may involve less risk than open abdominal surgery because it uses only a small incision in the abdomen. Although the procedure can take longer than conventional surgery, some studies report that patients recover more quickly from laparoscopy and have a lower risk of infections.
gina into the uterus of a female patient to help doctors move the uterus and ovaries and obtain a better view of other organs. Then a short incision (0.5 to 1.0 inch) is made, usually in the navel area. Ahollow needle is inserted into this incision, and gas (either carbon dioxide or nitrous oxide) is slowly pumped through the needle. The gas inflates the abdominal cavity, lifting it away from the organs, to allow doctors to see the organs clearly. Next, a thin tube (a laparoscope) is inserted through the incision into the abdominal cavity. A camera located on the eyepiece of this tube transmits images to a video monitor, enabling the surgeon to see into the abdominal and pelvic areas. Other small incisions may be made in the abdomen to insert instruments used to remove organs or collect tissue samples. In some cases, the surgeon also may be assisted by a robotic arm. When the procedure is finished, the scope is removed and the gas is released from the abdominal cavity. The incision is closed, usually with stitches that dissolve within several days. New hand-access devices can now enable surgeons to place a hand into the abdomen during laparoscopy and use it for different functions, which used to be possible only with open abdominal surgery. After the procedure: Depending on the procedures performed and their outcomes, patients either return home or remain in the hospital. Patients may feel some abdominal bloating or shoulder pain, caused by the effects of the gas
Patient preparation: No food or liquids are allowed for twelve hours before the procedure, and medical staff will ensure that the patient’s bladder and colon are empty. The hospital may provide specific instructions to help patients prepare for the procedure. Steps of the procedure: Patients usually are given general anesthesia, but sometimes other types of anesthesia may be used. Following anesthesia, when the patient is unconscious, the abdominal area is cleaned and shaved. A small tube (catheter) may be inserted through the urethra into the bladder to collect urine that may be discharged during the procedure. A cannula may be inserted through the va-
Laparoscopy. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Laryngeal cancer on the diaphragm. Patients should contact their doctor if they experience bleeding, redness, swelling, or discharge at the incision site or if they develop a fever, hoarseness that lasts more than a few days, or severe abdominal pain. Risks: The risks and benefits of this procedure are still being studied. The laparoscopic procedure is technically complex for the surgeon because it involves restricted vision, a limited working area, and hand-eye coordination when working with the instruments. The risks for the patient may include infection in the abdominal cavity, damage to internal organs, failure to remove the cancerous tissue or organs completely, or damage to blood vessels that causes internal bleeding. Patients with existing lung problems may not be able to tolerate the increased carbon dioxide in the abdominal cavity. Deciding whether to use laparoscopy rather than open abdominal surgery to diagnose and treat certain cancers (for example, ovarian cancer) should be made according to the patient’s overall risk factors as determined by additional tests, such as ultrasound. Open abdominal surgery allows the doctor to look inside organs for tumors and to remove cancerous organs or tissue during the same procedure. There are concerns that laparoscopy may limit doctors’ ability to completely detect and or remove such tissue, and it is important that patients discuss these concerns with their doctors. Research shows that the length of hospital stay and risk for infection are reduced with laparoscopy, but also that the success of the procedure is dependent upon the training and skill of the surgeon. Results: The results of laparoscopy vary according to the procedures performed and the type and stage of cancer. The scar from the incision is very small and should heal quickly, depending on the patient’s general health. Amy J. Neil, M.S., M.A.P. u
For Further Information Hamad, G. G., M. T. Brown, and J. A. Clavijo-Alvarez. “Postoperative Video Debriefing Reduces Technical Errors in Laparoscopic Surgery.” American Journal of Surgery 194 (2007): 110-114. Huscher, C. G., et al. “Laparoscopic Versus Open Subtotal Gastrectomy for Distal Gastric Cancer: Five-Year Results of a Randomized Prospective Trial.” Annals of Surgery 241, no. 2 (2005): 232-237. Meadows, Michelle. “Robots Lend a Helping Hand to Surgeons.” FDA Consumer 36 (2002). Shehzad, K., et al. “Current Status of Minimal Access Surgery for Gastric Cancer.” Surgical Oncology 16, no. 2 (June 6, 2007): 85-98. 682
Salem Health: Cancer u
Other Resources
WebMD Laparoscopic Abdominoperineal Resection Laparoscopic Proctosigmoidectomy Prostate Cancer: Laparoscopic Prostate Surgery Risks of Hysterectomy Surgery to Treat Colorectal Cancer http://www.webmd.com See also Abdominoperineal resection (APR); Biopsy; Cholecystectomy; Colectomy; Colorectal cancer; Colostomy; Culdoscopy; Endoscopy; Exenteration; Fallopian tube cancer; Gastrointestinal oncology; Hematologic oncology; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hysterectomy; Hystero-oophorectomy; Hysteroscopy; Infertility and cancer; Kidney cancer; Liver biopsy; Liver cancers; Mediastinal tumors; Medical oncology; Mesothelioma; Oophorectomy; Ovarian cancers; Ovarian cysts; Pancreatic cancers; Pediatric oncology and hematology; Pheochromocytomas; Pleural biopsy; Prostatectomy; Salpingectomy and salpingo-oophorectomy; Splenectomy; Surgical biopsies; Urinary system cancers.
u Laryngeal cancer Category: Diseases, symptoms, and conditions Also known as: Cancer of the larynx, voice box cancer Related conditions: Cancer of the lymph nodes, throat cancer, lung cancer, bone cancer, liver cancer Definition: Laryngeal cancer is a cancer of the larynx, or voice box. The larynx is situated between the pharynx, the passage that connects the back of the mouth and nose to the esophagus, and the trachea. It is a muscular passage through which food passes from the back of the mouth toward the stomach. The larynx has three divisions. The first, called the supraglottic larynx, contains the false vocal cords, the epiglottis or small flap that keeps food from entering the lungs, and other structures high in the throat toward the base of the tongue. The glottis, situated below the supraglottic larynx, contains the true vocal cords. The subglottis lies below the glottis and continues down the throat to the first ring of cartilage that surrounds the trachea. Risk factors: The major risk factors in laryngeal cancer are heavy tobacco smoking and the regular consumption, over an extended period, of excessive quantities of alcoholic beverages, generally construed as being more than
Salem Health: Cancer
Laryngeal cancer
Age at Diagnosis for Laryngeal Cancer, 2001-2005 Age Group
Cases Diagnosed (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
0.0 0.5 3.9 15.6 28.5 29.7 17.8 4.0
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of diagnosis from 2001 to 2005 was sixty-five, with an age-adjusted incidence rate of 3.6 per 100,000 men and women per year.
three ounces a day. This cancer affects men, especially those over the age of sixty, more often than it does women. In the late 1990’s, ten men were afflicted by this disease for every woman who suffered from it, although an increase in the number of women with the disease has been observed since then, correlating with an increase in the number of women smokers. No convincing link has been made between this form of cancer and a family’s medical history. Only an inconsequential number of people suffering from the disease have a familial history of laryngeal cancer. However, a link has been detected between laryngeal cancer and longterm occupational exposure to certain carcinogens, notably asbestos, nickel, mustard gas, and fumes from sulfuric acid. Etiology and the disease process: Laryngeal cancer can form in any part of the larynx, although it usually starts in the glottis. Almost all cancers of the larynx start in the squamous cells that line its inner walls, and these cancers are known as squamous cell carcinomas. The cancer can spread (metastasize) to the lymph nodes in the neck, the back of the tongue, and other parts of the throat and neck. It also can reach the lungs, the liver, and other parts of the body. Incidence: Laryngeal cancer is a relatively rare form of cancer, accounting for about 2 percent of all cancers in the United States. The American Cancer Society has estimated that there would be 2,400 new cases of the cancer, 12,250 people with the disease, and 2,670 deaths from it in
2008. There has been a notable overall decrease in laryngeal cancer since 2000 as increasing restrictions on smoking have been imposed and as heavy and sustained drinking has become less prevalent. Symptoms: Cancer of the supraglottic larynx may result in a persistent sore throat. Sometimes swallowing is difficult and choking frequent. Changes in the quality of the voice may be detected. Some people suffering from the disease suffer from pain in the ears. If the cancer develops in the glottis, some of these symptoms are present, including significant hoarseness caused by tumors on the vocal cords. Cancer in the subglottis, which involves the true vocal cords and may continue to the first cartilaginous ring that surrounds the trachea, is quite rare, although some cases have been reported. In subglottic laryngeal cancer, besides hoarseness, patients may experience shortness of breath. Their breathing may be labored and noisy. Symptoms of the disease that cannot be ignored and that require immediate medical attention are hoarseness that persists for two weeks or longer, a sore throat that lingers, difficulty in swallowing accompanied by frequent choking, swelling in the neck, and in some cases, pain in the ears. Screening and diagnosis: When a small tumor grows in the glottis, it can cause pronounced and prolonged hoarseness, which often will lead patients to their physicians while the cancer is still at in an early stage and is most susceptible to elimination and cure. However, the symptoms often develop gradually and may be ignored until they become quite pronounced. When symptoms appear, a laryngoscopy is indicated. This procedure can be performed either by using a mirror and light to examine the endangered area or through the use of an endoscope inserted into the affected area for a more extensive examination. Usually tissue is taken from the vocal cord and is biopsied to determine whether it is cancerous. Such techniques work well if the area involved is the supraglottis or glottis. If the subglottis is involved, however, endoscopic examination is essential and even it is not wholly reliable because the vocal cords often obscure the area that requires examination. Other tests may include computed tomography (CT), magnetic resonance imaging (MRI), and a barium swallow. The staging system for laryngeal cancer looks at the size of the tumor and whether it has spread to the lymph nodes or distant parts of the body. The stages range from Stage 0, carcinoma in situ, to Stage IV, with spread of the cancer to distant organs. Stage definitions differ depending on whether the cancer is in the supraglottis, glottis, or subglottis. 683
Laryngeal cancer
Salem Health: Cancer Cancers that develop below the vocal cords are particularly problematic because the vocal cords can prevent these cancers from being seen. Also, subglottal tumors and their lesions do not produce symptoms early in the course of the disease; therefore, by the time symptoms occur, the cancer may be well advanced. Prognosis, prevention, and outcomes: Most laryngeal cancers are 90 percent curable as long as they are detected early and treated aggressively. The five-year survival rate for Stage I throat cancers is between 75 and 95 percent, whereas the three-year survival rate of those with Stage IV throat cancers sinks to between 15 and 30 percent. Prevention offers the best hope for controlling laryngeal cancers. The two most identifiable causes of such cancers are smoking and heavy drinking. Although abstinence from tobacco products and alcohol cannot guarantee that someone will not develop laryngeal cancer, it is clear that most of those suffering from this disease have abused tobacco, alcohol, or both. Once symptoms appear, those who smoke or drink should stop doing so immediately. R. Baird Shuman, Ph.D. u
Stage IV laryngeal carcinoma in the glottic and supraglottic regions of the larynx. (John M. Daugherty/Photo Researchers, Inc.)
Treatment and therapy: If a small cancerous growth is discovered early, it is usually treated with radiation, although in some cases, surgery is indicated. Usually surgery is avoided if possible because it can damage the vocal cords and lead to problems in speaking. Biopsies must be done on any tissue that is removed. If the biopsy indicates a malignancy, further investigation is required to determine whether the malignancy has spread to such sites as the lymph nodes, the throat, the lungs, the throat, the tongue, the liver, and the bones. Advanced cancers that produce large tumors may require a laryngectomy, the surgical removal of the voice box. This treatment is usually a treatment of last resort because it robs the patient of the ability to speak normally, although extensive speech therapy can teach people to produce speech through an artificial larynx or through such means as esophageal speech. In Stage III and IV laryngeal cancer, surgery is usually followed by both radiation and chemotherapy. 684
For Further Information Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003. Lydiatt, William, and Perry Johnson. Cancers of the Mouth and Throat: A Patient’s Guide to Treatment. Omaha, Nebr.: Addicus Books, 2000. National Cancer Institute. What You Need to Know About Cancer of the Larynx. Bethesda, Md.: National Institutes of Health, 1995. Silverman, Sol. Oral Cancer. Lewiston, N.Y.: BC Decker, 2003. Stasney, C. Richard. Atlas of Dynamic Laryngeal Pathology. San Diego, Calif.: Singular, 1996. Teeley, Peter, and Philip Bashe. The Complete Cancer Survival Guide. New York: Broadway Books, 2005.
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Other Resources
American Cancer Society http://www.cancer.org Cancer Links http://www.cancerlinks.com
Salem Health: Cancer National Cancer Institute Throat (Laryngeal and Pharyngeal) Cancer http://www.cancer.gov/cancertopics/types/throat/ See also Asbestos; Barium swallow; Bronchography; Chewing tobacco; Cigarettes and cigars; Coal tars and coal tar pitches; Cordectomy; Electrolarynx; Endoscopy; Epidermoid cancers of mucous membranes; Esophageal speech; Head and neck cancers; Laryngeal nerve palsy; Laryngectomy; Laryngoscopy; Mustard gas; Occupational exposures and cancer; Oral and oropharyngeal cancers; Salivary gland cancer; Throat cancer; TNM staging; Tobacco-related cancers; Tracheostomy; Upper gastrointestinal (GI) series.
u Laryngeal nerve palsy Category: Diseases, symptoms, and conditions Also known as: Recurrent laryngeal nerve damage, paralysis of the laryngeal nerve, paralysis of the larnyx Related conditions: Intrathoracic diseases, neurolaryngological lesion Definition: Laryngeal nerve palsy is the paralysis of the laryngeal nerve. Risk factors: Damage to the laryngeal nerve can result from tumors in the neck and chest or from intrathoracic diseases such as tumor or aneurysm of the arch of the aorta or of the left atrium of the heart. Tumors and aneurysms may press on the nerve, causing nerve damage. Damage to the recurrent laryngeal nerve may also occur during surgery on the thyroid gland. Etiology and the disease process: The vagus nerve is one of twelve cranial nerves. It originates in the brain stem and reaches to the large intestine. In the neck, the vagus nerve branches off a paired nerve called the recurrent laryngeal nerve. When the laryngeal nerve separates from the vagus nerve, it reaches into the chest and loops back up to the voice box (larynx). The recurrent laryngeal nerves extend along either side of the trachea (windpipe) between the trachea and the thyroid gland, and they control movement of the larynx. The larynx is located where the throat divides into the esophagus and the trachea. The larynx is where the voice is produced, and it controls the flow of air into the lungs. It houses the vocal cords and the muscles and ligaments that move the vocal cords. Damage to the laryngeal nerve itself causes laryngeal palsy on the affected side.
Laryngeal nerve palsy Less commonly, laryngeal palsy, or paralysis of the larynx, can be the result of damage to the vagus nerve before the recurrent laryngeal nerve branches off. A damaged laryngeal nerve results in reduced movements of the larynx, causing voice weakness, hoarseness, or the complete loss of voice. Although rare, life-threatening cases may occur if the larynx is paralyzed to the extent that air cannot enter the lungs. Damage can occur to either one or both branches of the nerve, and paralysis of the laryngeal nerve may be temporary or permanent. Incidence: Recurrent laryngeal nerve injury, without injury to the superior laryngeal nerve, is the most common traumatic neurolaryngological lesion. Laryngeal nerve palsy is an uncommon side effect of thyroidectomy. It occurs in 1 to 2 percent of complete thyroidectomies performed to treat cancer, and less often when only part of the thyroid is removed. Most often patients experience only transient laryngeal nerve palsy and within a few weeks spontaneously recover their normal voice. Symptoms: The effects of laryngeal nerve damage are flaccidity of the ipsilateral vocal fold, loss of adduction (movement of a limb), severe dysphonia or laryngeal dystonia, (involuntary movements of the muscles of the larynx) complete paralytic aphonia (inability to speak), and frequently aspiration of food and drink into the trachea. Screening and diagnosis: Diagnosis and treatment of the immobile or hypomobile vocal fold are challenging. True paralysis and paresis (impaired movement) result from vocal fold denervation secondary to injury to the laryngeal or vagus nerve. Location of the vocal fold paralysis and paresis may be unilateral or bilateral and central or peripheral. Paralysis may involve the recurrent laryngeal nerve, the superior laryngeal nerve, or both. It is important to confirm that the laryngeal impairment is not caused by arytenoid cartilage subluxation (dislocation of small cartilages in the back of the larynx), cricoarytenoid arthritis or ankylosis (stiffness of a joint), neoplasm, or other mechanical causes. Most common diagnostic tools are strobovideolaryngoscopy, endoscopy, radiologic and laboratory studies, and electromyography (EMG). Treatment and therapy: Once the recurrent laryngeal nerve is damaged, there is no specific treatment to heal it. Common treatments for laryngeal nerve damage are polytetrafluoroethylene (trademark Teflon) injection, a surgical procedure in which an implant is inserted into the paralyzed vocal cord (medialization thyroplasty); arytenoid adduction procedures; or reinnervation by nerve trans685
Laryngectomy fer. With time, most cases of recurrent laryngeal palsy improve spontaneously. In some cases, the larynx may be paralyzed so that air cannot flow past it into the lungs, and an emergency tracheotomy needs to be performed. A tracheotomy is a surgical procedure to make an artificial opening in the trachea, which allows air to bypass the larynx and to enter the lungs. If the paralysis is temporary, the tracheotomy hole can be surgically closed. There are no alternative or complementary therapies to heal laryngeal nerve palsy. When loss of speech is permanent, artificial speech devices exist to produce tone. Prognosis, prevention, and outcomes: Muscle function can be assessed by observing the movements of the structures or by recording the electrical activity of the muscles via electromyography. Although electromyography is an invasive technique, it may be helpful in patients with voice problems of suspected neurological or neuromuscular etiology. Electromyography recordings are helpful in differentiating vocal fold paralysis from arytenoid dislocation. Electromyography is useful for the diagnosis to establish a reliable prognosis and treatment plan and to monitor muscle denervation and reinnervation. Following acute denervation, the subsequent progression is either chronic denervation or laryngeal nerve regeneration. Anita Nagypál, Ph.D. u For Further Information Crumley, R. L. “Unilateral Recurrent Laryngeal Nerve Paralysis.” Journal of Voice 8, no. 1 (March, 1994): 79-83. Harti, D. M., and D. F. Brasnu. “Recurrent Laryngeal Nerve Paralysis: Current Concepts and Treatment.” Ear, Nose and Throat Journal 79, no. 12 (December, 2000): 918. Rubin, A. D., and R. T. Sataloff. “Vocal Fold Paresis and Paralysis.” Otolaryngolic Clinic of North America 40, no. 5 (October, 2007): 1109-1231. Woodson, G. “Evolving Concepts of Laryngeal Paralysis.” The Journal of Laryngology and Otology 122, no. 5 (May, 2008): 437-441. Ysunza, A., et al. “The Role of Laryngeal Electromyography in the Diagnosis of Vocal Fold Immobility in Children.” International Journal of Pediatric Otorhinolaryngology 71, no. 6 (June, 2007): 949-958. u
Other Resources
MayoClinic.com Vocal Cord Paralysis http://www.mayoclinic.com/health/ vocal-cord-paralysis/DS00670 686
Salem Health: Cancer National Cancer Institute Thyroid Cancer http://www.cancer.gov/cancertopics/types/Thyroid See also Electrolarynx; Esophageal speech; Head and neck cancers; Laryngeal cancer; Laryngectomy; Laryngoscopy; Oral and oropharyngeal cancers; Salivary gland cancer; Throat cancer; Tracheostomy.
u Laryngectomy Category: Procedures Also known as: Hemilaryngectomy, vertical partial laryngectomy, total laryngectomy Definition: Laryngectomy is the surgical removal of some or all of the larynx (voice box). Total laryngectomy removes the entire structure, whereas partial laryngectomy involves removal of only sections of the larynx. Cancers treated: Primary or recurrent cancer of the larynx, tumors metastasized to the larynx from other parts of the body Why performed: Laryngectomy is performed when tumors and cancers prevent normal larynx function and threaten to invade other tissues of the head and neck. Partial laryngectomy is performed for early-stage cancers (T1 and T2 stages). Total laryngectomy is performed for advanced cancers (stages T3 and T4) and when cancer recurs after radiation therapy or more conservative surgical treatments. Patient preparation: Apart from the usual presurgery blood and heart tests, patients may undergo a battery of other tests. To determine the extent of spread and permit staging of the cancer, patients will undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans. They may have chest X rays to rule out the spread of cancer in the lungs and barium swallows to determine if the cancer has invaded the esophagus. Patients will also have tests to determine if they have sufficient lung function to cough; coughing is necessary to remove secretions from the airway and prevent aspiration of food and liquids into the lungs. Patients undergoing total laryngectomy will meet with a speech therapist before the surgery to discuss options for artificial voice restoration. Some patients may undergo radiation therapy prior to surgery. Steps of the procedure: Following anesthesia, the surgeon will make an incision into the trachea at the base of the throat and insert a tracheostomy tube to deliver air into
Salem Health: Cancer the lungs. An extensive incision is created in the neck, and the cancerous region of the larynx is excised. In total laryngectomy, the entire larynx is removed and the end of the trachea is sewn to the hole at the base of the throat. The opening into the throat is sewn shut, which means that the esophagus no longer has any connection to the airway. Depending on the extent of the cancer, patients undergoing partial or total laryngectomy may also require removal of portions of the esophagus, thyroid gland, or lymph nodes. After the procedure: Patients will stay in the intensive care unit (ICU) for one to two days after surgery. Tubes will be inserted in the neck to drain fluid from the surgical site, which will prevent blood clots from forming that can impair healing. Patients will still have the tracheostomy tube in place to help them breathe. In partial laryngectomy, once swelling in the airway has subsided, the tube is removed and the hole at the base of the throat is sealed. In total laryngectomy, this hole, called a stoma, remains permanently open after tube removal. Patients who have undergone total laryngectomy breathe through the stoma for the rest of their lives. For several days after surgery, patients will also have a tube threaded through a nostril and down the esophagus to permit the delivery of liquids and nourishment into the stomach. This tube will stay in place until the swelling in the throat subsides and the patient is able to swallow without aspirating. Patients usually spend seven to ten days in the hospital, although convalescence continues at home and may take many weeks. During the hospital stay, partial laryngectomy patients will learn new swallowing techniques to prevent aspiration. Total laryngectomy patients will begin working with a speech therapist on an alternative method of voicing. Risks: Laryngectomy patients are at risk for pulmonary embolism, heart attack, and stroke. Risks related to the surgery include infection, impaired wound healing, tissue necrosis, and respiratory problems as a result of aspiration or narrowing of the airway. Aspiration pneumonia is a common postsurgical complication of partial laryngectomy until the patient relearns how to swallow. Total laryngectomy patients are not at risk for aspiration because the throat is no longer connected to the airway; however, they may still experience problems swallowing because of impaired motility or narrowing of the esophagus. A common complication of total laryngectomy is development of a pharyngocutaneous fistula, which is an opening that causes saliva to drain from the throat into the neck. Fistulas increase the risk of infection and hemorrhage from carotid artery rupture.
Laryngoscopy Results: The primary goal of laryngectomy is to eliminate the cancer, with secondary goals of retaining voice function and swallowing capability. Cure rates after laryngectomy depend on the cancer location and stage and whether metastasis to the neck has occurred. Generally, cancers detected at the T1 and T2 stages have cure rates of 80 to 95 percent. For advanced cancers, cure rates are 25 to 50 percent. Cure rates at any stage are lower if laryngectomy must be performed because cancer has recurred. Partial laryngectomy patients who experience ongoing difficulties with aspiration may require either total laryngectomy or placement of a gastrotomy feeding tube. When one or both vocal cords are preserved, the voice will be functional but altered. Total laryngectomy patients must undergo postsurgery therapy to learn new ways of voicing. These patients must also learn to how care for their stomas to prevent infection and entry of foreign materials into the lungs. Pamela S. Cooper, Ph.D. u
For Further Information Casper, Janina K., and Raymond H. Colton. Clinical Manual for Laryngectomy and Head/Neck Cancer Rehabilitation. 2d ed. San Diego, Calif.: Singular, 1998. Lawson, Glenda. “Upper Airway Problems.” In MedicalSurgical Nursing, edited by Wilma J. Phipps et al. 7th ed. St. Louis: Mosby, 2003. National Cancer Institute. Laryngeal Cancer (PDQ) Treatment. Washington, D.C.: Author. Available online at http://www.cancer.gov.
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Other Resources
American Cancer Society http://www.cancer.org International Association of Laryngectomees http://www.larynxlink.com See also Cordectomy; Electrolarynx; Esophageal speech; Laryngeal cancer; Oral and maxillofacial surgery; Throat cancer.
u Laryngoscopy Category: Procedures Also known as: Autoscopy, laryngeal endoscopy Definition: Laryngoscopy is the visual examination of the voice box (larynx) using a long-handled mirror or rigid or flexible tube (indirect) or a laryngoscope (direct). 687
Laser therapies
Salem Health: Cancer fore the physician threads the tube through a nostril and into the throat. In direct laryngoscopy, the patient is anesthetized lying face up to allow insertion of laryngoscope into the throat. Anesthesia is delivered via a line inserted into a vein. The throat and larynx are sprayed with topical anesthetic prior to insertion of a small breathing tube followed by the laryngoscope. After the procedure: Laryngoscopy is usually performed on an outpatient basis. If extensive surgery is also performed, however, then an overnight hospital stay may be necessary. Patients who have biopsy or surgery with laryngoscopy may experience hoarseness, and slight bleeding is normal. After surgery, patients may be advised not to smoke, to rest the voice, and to avoid coughing or throat clearing. Risks: Laryngoscopy is a generally safe procedure. Rare complications of direct laryngoscopy are excessive swelling or spasm of the larynx, which are medical emergencies if breathing is hindered. The most common side effects caused by laryngoscope insertion are sore throat, gums, lips, or tongue. Tongue numbness may occur, but feeling usually returns in a few weeks. Rarely, introduction of the laryngoscope may chip a tooth. Results: Normal vocal cords are symmetrical and move freely. If cancer is present, then cord movement may be reduced or absent on one side or cords may appear asymmetrical. Normal tissues appear pink and smooth. Raised, irregular white or red lesions or ulcerated, bleeding masses are suspicious. Biopsy and pathology are necessary to determine whether lesions are cancerous. Pamela S. Cooper, Ph.D.
Direct laryngoscopy using a curved instrument is performed on an adolescent. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Cancers diagnosed or treated: Cancer of the larynx Why performed: Indirect and direct laryngoscopy are both diagnostic. Direct laryngoscopy is used for close-up, comprehensive examination, biopsy, and surgery. Patient preparation: Indirect laryngoscopy is performed in the doctor’s office and requires no advance preparation. Patients must remove dentures just prior to the examination. Direct laryngoscopy is performed under anesthesia, so the patient must not eat or drink several hours beforehand. Blood tests may be required several days before the procedure to confirm that anesthesia poses no risk. Steps of the procedure: For indirect laryngoscopy, the patient sits facing the physician. The physician sprays a topical anesthetic on the patient’s tongue and throat prior to inserting the mirror or rigid telescope into the mouth. If a flexible fiber-optic tube is used for viewing, then the nose is sprayed with topical anesthetic/decongestant be688
See also Cordectomy; Endoscopy; Gastrointestinal cancers; Laryngeal cancer; Laryngeal nerve palsy; Otolaryngology; Throat cancer.
u Laser therapies Category: Procedures Definition: Laser therapies use light amplification by the stimulated emission of radiation (LASER) instead of or in addition to other treatment options. Some laser therapies are widely accepted, while many are still considered experimental.
Salem Health: Cancer Cancers treated: Many types of cancers, including skin, eye, colon, lung, esophageal, vaginal, and liver cancers Why performed: There are many reasons that laser therapy may be performed on a cancer patient. Some laser therapies are done in place of surgery, with the goal of destroying some or all of a tumor. In other cases, laser therapy may be used to shrink a tumor to provide relief from symptoms and improve quality of life. Laser therapy may also be done to activate photosensitizing chemicals in cancer cells to start a chemical reaction that kills the cells. Patient preparation: The patient preparation required for laser therapy varies depending on the procedure being performed. The patient may be required to avoid eating or drinking fluids for a certain amount of time or may be given antibiotics to help prevent infection. A patient undergoing photodynamic laser therapy will be given a photosensitizing chemical a specified number of hours or days before the procedure is scheduled to be performed. The photosensitizing chemical is usually injected but can be applied topically in some cases. Steps of the procedure: The actual steps differ depending on the type of procedure; the type of laser used; the size, type, and extent of the cancer; and the preferences of the surgeon performing the procedure. The first step of photodynamic therapy is usually to expose, or mostly expose, the tumor or area of cancerous cells, or to introduce the laser to the area using an endoscope. This is necessary because many of the lasers used to activate photosensitizing chemicals cannot travel safely through thick amounts of skin, tissue, or membrane. Therefore the laser must be very near the cells that it is going to activate. The laser is then directed toward the tumor or cancerous area and turned on for a short period of time. The endoscope or other instrument is then removed. This procedure can be repeated as necessary. When the laser is being used to shrink a tumor, the laser light must also be able to reach the tumor without having to travel through normal, healthy cells that would be damaged. This is often achieved using an endoscope. The endoscope is introduced to the area of the tumor, and the laser is directed. The beam from the laser heats up the tumor cells to a point hot enough to kill them. After the desired amount of cancer cells have been killed, or it is no longer feasible to treat additional cells without harming surrounding healthy tissue, the endoscope is removed. Laser surgery is generally done in much the same way as traditional surgery; however, instead of a scalpel, the surgeon uses a laser to make cuts. Lasers are preferable to
Laser therapies scalpels in some cases because of their ability to make very thin, fine cuts, allowing the surgeon to work with increased precision. The laser beam also tends to seal and sterilize blood vessels as it cuts, reducing the chances of infection and minimizing bleeding. Laser surgery requires extremely specialized, often very costly equipment, and it requires that the surgeon have significant training to perform it. After the procedure: After a patient has received photosensitive chemicals to treat the cancer, it is necessary for the patient to stay out of the sun. Although the photosensitizing chemicals are generally left mainly in the cancer cells after a few days, enough residual chemicals may be present in the rest of the body to make the skin extremely sensitive to sunlight. In some cases, the patient may be required to avoid sunlight for as long thirty days or more. Aftercare for other forms of laser therapy varies depending on the way in which the therapy was performed and the area that was treated. Aftercare for many procedures will be similar to aftercare for similar surgical procedures performed to the same area. Risks: The risks associated with laser therapy vary. Procedures in which a laser is used to shrink or destroy a tumor, as well as those in which a laser is used to cut out all of or a portion of the tumor, have the risks normally associated with surgical procedures, which can include swelling, bleeding, infection, pain, and some risk of damage to surrounding tissue. Specific risks are also associated with the use of a laser to activate photosensitive chemicals; however, they are usually considered mild and vary depending on the type of laser and chemical used. Results: The result expected from laser therapies varies depending on the type of laser treatment performed, the type and extent of the cancer being treated, and the goals of the treatment. When laser therapy is done instead of surgical procedures, patients often experience less swelling and bleeding and are less likely to develop an infection. Laser procedures, however, may not last as long as other types of treatments and may need to be repeated. Helen Davidson, B.A. u
For Further Information Lyons, Lyman. Diagnosis and Treatment of Cancer. New York: Chelsea House, 2007. Vij, D. F., and K. Mahesh, eds. Medical Applications of Lasers. Boston: Kluwer Academic, 2002. Watson, Tim, ed. Electrotherapy: Evidence-Based Practice. 12th ed. New York: Churchill Livingstone, 2008. 689
Latinos/Hispanics and cancer Waynant, Ronald W. Lasers in Medicine. Boca Raton, Fla.: CRC Press, 2002. See also Colorectal cancer; Coughing; Electroporation therapy; Electrosurgery; Endotheliomas; Esophageal cancer; Eye cancers; Liver cancers; Lung cancers; Ophthalmic oncology; Penile cancer; Rothmund-Thomson syndrome; Skin cancers; Vaginal cancer.
u Latinos/Hispanics and cancer Category: Social and personal issues Definition: Cancer is the second leading cause of death among Latinos/Hispanics, who include people of any Spanish, Mexican, Puerto Rican, Cuban, or Central or South American (Latin America) origin. The term “Hispanic” has been abandoned by many members of this population because of its erroneous use as an umbrella term for those whose heritage may not necessarily be Spanish (European). “Hispanic,” however, has been used by the U.S. Census Bureau in its population surveys. Description of the population: The United States Census Bureau, 2004, defined about 14 percent of the population as Latino/Hispanic. Of these 42 million Americans, 60 percent were born in the United States. Hispanics have been described as a mosaic of cultures as their origins are diverse: 60 percent are from Mexico, 9.7 percent from Puerto Rico, 5.1 percent from Central America, 4 percent from South America, 3.5 percent from Cuba, 3 percent from Spain, 2.3 percent from the Dominican Republic, and the remainder from various other areas. Mexican Americans mostly live in the western United States, while Cubans are likely to reside in the southern states and Puerto Ricans in the northeastern states and Puerto Rico. Incidence, death, and survival statistics: Cancer affects all racial and ethnic groups. However, some groups have a higher incidence of cancer (cancer burden) than other groups. This is known as a health disparity. The burden of cancer is often greater for ethnic groups with lower incomes, no or minimal health insurance, and limited access to health care services. The goal is that everyone in the United States receive cancer screening for early detection, diagnosis, and treatment. Understanding how cancer affects Hispanics can assist health care providers with identification, diagnosis, and treatment. Cancer is the second leading cause of death in Hispanics, causing 20 percent of all Hispanic deaths. The average age for Hispanics to receive a diagnosis is sixty690
Salem Health: Cancer two. A little less than 1 in 2 Hispanic men will have cancer in his lifetime, and 1 in 5 will die from it. About 1 in 3 Hispanic women will face cancer in her lifetime, with about 1 in 6 dying from the disease. For Hispanic men, prostate cancer is the most common cancer; for Latino women, breast cancer is the most common. Colon and rectal cancer holds the second highest incidence for both Hispanic men and women, followed by lung cancer. The most common forms of cancer (prostate or breast, colorectal, and lung) account for 50 percent of all cancer diagnoses in Hispanics. The leading cause of cancer deaths for Hispanic women is breast cancer, compared with non-Hispanic women, whose chief cause of cancer death is lung cancer. Among Hispanic men with cancer, lung cancer is the primary cause of death, with colon and rectum next, followed by prostate cancer. In reviewing the ten-year span (19942003) of cancer statistics in Hispanics, the American Cancer Society reports that the incidence of cancer for Hispanic men has declined about 1.1 percent each year, while the corresponding incidence for non-Hispanic men has declined only 0.5 percent each year. Hispanic and nonHispanic women have not seen a decline in the incidence of cancer in this same period. When comparing incidence and death rates for all cancers, Hispanics score lower than non-Hispanics. Hispanics tend to have statistics similar to those found in their country of origin. However, some studies demonstrate that these statistics are changing because as the time that immigrants (40 percent of the Latino/Hispanic group per the Census Bureau) have spent in the United States grows, they tend to adopt many American values, customs, and behaviors. Behaviors that could negatively affect Hispanics are eating processed and fast foods, drinking alcohol, smoking, decreasing exercise, and becoming obese. Survival rates can be expressed in several ways. Relative survival, the most common expression, is a ratio of observed survival within a specific group of cancer patients to the expected survival in a similar group of cancer-free patients. For Hispanics, the data are not available to calculate this ratio, so the measurement cause-specific survival is used in comparisons. Hispanics have lower causespecific survival rates than non-Hispanics for most cancers. Some researchers attribute this to delayed access to quality health care services for diagnosis and treatment. Risk factors and statistics: Some sources believe that at least half of all cancers are preventable. One way to prevent cancer is by adopting healthy behaviors. A primary behavioral risk factor for cancer is smoking and tobacco use, accounting for about 30 percent of all cancer deaths.
Salem Health: Cancer Lung cancer is directly linked to smoking, but other cancers are also related to tobacco use. These include cancer of the lip and mouth, throat, larynx (voice box), pharynx (windpipe), cervix, bladder, kidney, and pancreas. Fewer Hispanics smoke than non-Hispanics, and the rate of cancer related to tobacco use is lower in Hispanics. Hispanic youths are less likely to smoke than non-Hispanic youths. However, rates for Hispanics have begun to increase in American-born Hispanics as compared with those born elsewhere. Also, as more Latinos smoke, the danger of secondhand smoke for families will increase and expose nonsmokers to the harmful substances in tobacco. Another risk factor for cancer is alcohol consumption. Excessive alcohol intake is linked to cirrhosis and liver cancer. Drinking alcohol is also associated with increased risk of cancers of the oral cavity, pharynx, larynx, esophagus, large bowel, and breast. Although Hispanics drink less alcohol than non-Hispanics, they have a higher rate of liver cancer. Hispanic men and women are encouraged to abstain or drink moderately. Hispanic youths consume slightly less alcohol than non-Hispanic youths, with young Hispanic women drinking more than young Hispanic men. This could occur because Hispanic youths are adopting American culture norms. A third risk factor for cancer is obesity. Cancers associated with obesity are breast, colon, uterus, and prostate. Rates of obesity in Hispanics remain higher than those for non-Hispanics. The percentage of Mexican Americans with obesity has increased significantly since the late 1970’s. A study from 1976 through 1980 found obesity in 26.6 percent of Mexican American women and 15.7 percent of Mexican American men; a study in 2003-2004 found obesity had risen to 42.3 percent in these women and to 31.6 percent in these men. This study also documented that about 80 percent of all Mexican Americans were overweight, while 58 percent of non-Hispanic women and 71 percent of non-Hispanic men were overweight. Socioeconomic factors such as education and income influence both the occurrence of cancer and the survival of the person with cancer. These factors can influence whether a person has access to health insurance for preventive care, early detection, and treatment. Hispanics are less likely to have health insurance than non-Hispanic whites because many members of this group cannot afford it or are employed in jobs that do not offer health insurance. Hispanics in America are less educated than nonHispanic whites; many lack a high school education and live in poverty. Hispanics who immigrated to the United States typically are nonnative English speakers, making it difficult to communicate and secure better jobs.
Latinos/Hispanics and cancer Prevention: Measures to prevent cancer benefit both Hispanics and non-Hispanics. When a Hispanic stops smoking or never starts smoking, the risk of tobacco and smoking-related cancers decreases. Access to health care providers or treatments that assist with smoking cessation are sometimes not available to Hispanics. These therapies include counseling, medications, and behavioral modifications. Lack of health insurance can be a factor as well. Alcohol consumption is a behavior that a person can modify. The American Cancer Society guidelines suggest that alcohol intake should be limited to no more than two drinks per day for men and one drink per day for women. Health education should highlight the risks and dangers of alcohol for both Hispanic men and women. As the rate of Hispanic youths who drink alcohol rises, Hispanic parents should teach their children the dangers of alcohol consumption and its relationship to cancer. Obesity in Hispanics is related to changes in cultural behaviors. As Hispanics increasingly follow American cultural practices, they increase their consumption of fast food and eat fewer fruits and vegetables. Foods in the United States tend to be more processed with fewer nutrients and more calories than those foods typical of the ancestral countries of most Hispanics. Less healthy food combined with decreased physical activity at work or leisure is an equation for obesity. Socioeconomic status also plays a part, as this affects food choice and availability as well as access to physical recreation (safe parks, recreation centers, and backyards). Lower socioeconomic groups such as Hispanics underutilize cancer screening and tend to be diagnosed when cancer is in later stages. Screening and early detection are critical to saving lives. Education on available options and referral to public services can encourage Hispanics to embrace prevention as a way to fight cancer. Robert W. Koch, D.N.S., R.N. u
For Further Information American Cancer Society. Facts and Figures for Hispanics/Latinos, 2003-2005. Atlanta: Author, 2003. Bellenir, Karen, ed. Tobacco Information for Teens. Detroit: Omnigraphics, 2007. National Institutes of Health. Proceedings from Enhancing Interactions to Reduce Cancer Health Disparities, an NCI Workshop. Bethesda, Md.: Author, 2006. Schulz, Amy J., and Leith Mullings, eds. Gender, Race, Class, and Health: Intersectional Approaches. San Francisco: Jossey-Bass, 2006,
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American Lung Association Lung Cancer and Hispanics/Latinos http://www.lungusa.org/site/ pp.asp?c=dvLUK9O0E&b=326641 CancerCare http://www.cancercare.org National Alliance for Hispanic Health http://www.hispanichealth.org National Cancer Institute Cancer Health Disparities http://www.cancer.gov/cancertopics/types/disparities Redes en Acción/National Latino Cancer Research Network http://www.redesenaccion.org/ See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Ethnicity and cancer; Family history and risk assessment; Geography and cancer; Native North Americans and cancer; Occupational exposures and cancer; Statistics of cancer.
u Laxatives Category: Chemotherapy and other drugs Also known as: Bowel stimulants Definition: Laxatives are drugs, food, or compounds that promote a bowel movement. They can be used to prepare the bowel for diagnostic examination or to prevent or treat constipation.
Salem Health: Cancer have an impact on the body’s ability to empty waste material. How these agents work: Laxatives work in diverse ways. Bulk-producing agents combine with water to increase the mass of the stool and stimulate the intestinal muscles. Common bulk-producing laxatives include psyllium husk, dietary fiber, and apples. These gentle agents enhance peristalsis within twelve to seventy-two hours. Stool softeners or surfactants also produce bowel movements in twelve to seventy-two hours. By drawing water into the stool, these laxatives soften the stool, which is useful for cancer patients who experience pain when passing a firm stool. Stool softeners can build a tolerance, however, making the laxative ineffective for some cancer patients. Docusate (Colace) is a stool softener. Lubricants or emollients make the stool slippery and act in the colon within six to eight hours. They work by making the stool slide more easily through the colon. An example of a lubricant laxative is mineral oil. One concern is that mineral oil can cause decreased absorption of the fat-soluble vitamins, such as A, D, E, and K. Hydrating agents or osmotics are laxatives that draw water into the colon to soften the stool. These laxatives produce desired results within thirty minutes to six hours. Examples of hyperosmotic laxatives include milk of magnesia (magnesium hydroxide), Epsom salts (magnesium sulfate), and glycerin suppositories. GoLYTELY, a solution of polyethylene glycol (PEG) 3350 and electrolytes, is often used as a preparatory agent for colon procedures such as colonoscopy. Another form of laxative is a stimulant or irritant, such as cascara, senna, aloe vera, biscodyl (Ducolax), or castor oil. These agents stimulate movement in the colon and are the most severe of all laxatives; they should not be the cancer patient’s laxative of choice.
Cancers treated: All Subclasses of this group: Bulk-producing agents, stool softeners, lubricants and emollients, hydrating agents, stimulants Delivery routes: Laxatives are taken orally or in a suppository form. Description: Cancer patients experience constipation for various reasons. Cancer treatments may render patients less active or mobile, which increases the risk of constipation. Depression or anxiety as a result of cancer treatments or pain can result in constipation. Repeated use of pain medications, decreased intake of fluids, or chemotherapy may lead to constipation in cancer patients. Intestinal tumors or scar tissue from intestinal surgeries for cancer can 692
Side effects: The side effects of laxatives may include diarrhea and dependency. Overuse can result in the inability to have a bowel movement and lead to constipation or impaction. Because laxatives can lessen the effectiveness of some medications, a health care provider should be consulted before their use. Marylane Wade Koch, M.S.N., R.N. See also Antidiarrheal agents; Antinausea medications; Chemotherapy; Crohn disease; Diarrhea; Diverticulosis and diverticulitis; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Hemorrhoids; Inflammatory bowel disease; Rectal cancer; Side effects; Symptoms and cancer; Weight loss.
Salem Health: Cancer
Leiomyomas
u Leiomyomas Category: Diseases, symptoms, and conditions Also known as: Myomas, fibroids, uterine fibroids, genital leiomyomas, angioleiomyomas, piloleiomyomas Related conditions: Leiomyosarcomas Definition: Leiomyomas are benign tumors that arise from smooth muscle of the digestive tract, piloerector muscle in hair (piloleiomyoma), blood vessels (angioleiomyoma), nipples, and the genital tract (genital leiomyoma). While any organ possessing smooth muscle may become involved, the myometrium (the muscular layer of the uterus) is the most common site. Leiomyomas may arise at any location in the myometrium as a single mass, as a cluster, or as diffuse disease. Risk factors: One risk factor is a family history of leiomyomas, especially of a tumor involving the skin and uterus called Reed syndrome (familial leiomyomatosis cutis et uteri), which is inherited in an autosomal dominant fashion but expressed variably. The responsible gene, MCU11, is located on the long arm of chromosome 1(1q42.3-q43). Women are at risk of developing a uterine leiomyoma during their reproductive years. Etiology and the disease process: The development of extrauterine leiomyomas is still obscure. The unusual manifestation of pain has been postulated to arise when these tumors stimulate the sympathetic nervous system, causing muscle contraction, but remains poorly understood. Uterine leiomyomas occur only in the presence of estrogen and progesterone stimulation and arise as a result of overproliferation of smooth muscle and connective tissue cells within the myometrium. They have been linked with a specific mutation (G354R) of a tumor-suppressor gene encoding for fumarate hydratase in MCU11. Estrogen and progesterone receptor stimulation on these cells accelerate or decrease proliferation, suggesting that leiomyomas depend on estrogen and progesterone. Incidence: Leiomyomas outside the uterus are rare. In contrast, around 50 percent of women in their reproductive years will develop a uterine leiomyoma in their lifetime, with a peak age of thirty. Leiomyomas ac-
count for half of esophageal masses found. Less than 1 percent of uterine leiomyoma cases will experience malignant transformation (leiomyosarcoma). Symptoms: Patients with most extrauterine tumors experience pain induced by cold, pressure, menses, or pregnancy. On examination, these tumors may appear as flat lesions or skin nodules. A woman of reproductive age who has a leiomyoma proximal to the vascular endometrium will experience bleeding and may exhibit fatigue and pallor. A uterine leiomyoma may be felt through the abdominal wall and mistaken for pregnancy. However, a pregnancy test would be negative. Subtler symptoms may include menometrorrhagia (increased, frequent, and irregular bleeding from the vagina), infertility and pressure symptoms causing difficulty in swallowing, and compression of the bladder and ureter (urine duct from the kidney to the bladder). A blood test may reveal significant anemia when the woman is experiencing frequent and substantial blood loss. Screening and diagnosis: A diagnosis of an extrauterine leiomyoma may be confirmed by an excisional biopsy, where excision of the entire mass is also therapeutic. A
Fibroid polyp pedunculated submucous
Subserous
Submucous
Interstitial or intramural
Pedunculated subserous
Broad ligament
Cervical
Common types of uterine fibroids. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Leiomyosarcomas barium contrast study may show a “punched-out” defect in the esophagus. Ultrasound and magnetic resonance imaging (MRI) are not as helpful. A pelvic ultrasound may reveal a vague mass darker than the surrounding normal tissue within the myometrium. A distortion in the uterine contour may be the only hint of a leiomyoma. An endometrial biopsy is also performed to rule out endometrial cancer. Specific screening tests other than regular pelvic examinations are not available for leiomyomas. Treatment and therapy: Apart from excisional biopsy, pain from extrauterine leiomyomas may be alleviated with calcium channel blockers (nifedipine), alpha-receptor blockers (phenoxybenzamine), or gamma-aminobutyric acid (GABA) analogs (gabapentin). Enucleation with repair may be sufficient in esophageal masses. Treatment of uterine leiomyomas may be conservative or curative. If the patient is symptomatic (for example, anemic from chronic bleeding), no longer desires to bear children, wishes to be pain free, and is amenable to a hysterectomy (surgical removal of the uterus), a curative approach is adapted. If the patient is relatively young and desires to bear children, a conservative approach is preferred. Conservative treatment consists of options from watchful waiting and myomectomy to newer procedures such as uterine arterial embolization (UAE). UAE involves injecting polyvinyl alcohol foam particles into the uterine arteries, which occludes the leiomyoma’s blood supply, inducing tumor involution. As only 10 to 20 percent of patients require definitive treatment, with most leiomyomas shrinking after menopause and pregnancy, monitoring with serial pelvic ultrasound may be done. A myomectomy, in which the leiomyomas are surgically removed, seeks to preserve as much of the muscular integrity of the uterus as possible. Excessive blood loss during an operation may be prevented by chemotherapy with a gonadotropin-releasing hormone (GnRH) analog such as nafarelin or leuprolide acetate. A fertility workup including Fallopian tube patency with a hysterosalpingogram and semen analysis should also be carried out. Curative options include an abdominal or vaginal hysterectomy to remove the uterus along with the mass. Prognosis, prevention, and outcomes: The overall prognosis of uncomplicated leiomyomas is excellent. As most leiomyomas are benign, patients undergoing surgical excision or a hysterectomy rarely experience recurrence. Postmenopausal women with a history of leiomyoma on hormone replacement may have a recurrence. No preventive measures against developing a leiomyoma are known. Aldo C. Dumlao, M.D. 694
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For Further Information Byers, Tim, Susan J. Curry, Maria Elizabeth Hewitt, and National Cancer Policy Board. Fulfilling the Potential of Cancer Prevention and Early Detection. Washington, D.C.: National Academies Press, 2003. Dollinger, Malin, et al. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 4th ed. Kansas City, Mo.: Andrews McMeel, 2002. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Uterine Fibroids. San Diego, Calif.: Icon Health, 2002.
u
Other Resources
American Cancer Society http://www.cancer.org LeioMyoSarcoma http://www.leiomyosarcoma.info LMSarcoma Direct Research Foundation http://www.lmsdr.org The National Leomyosarcoma Foundation http://www.nlmsf.org See also Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hystero-oophorectomy; Kidney cancer; Leiomyosarcomas; Mitochondrial DNA mutations; Urinary system cancers; Uterine cancer.
u Leiomyosarcomas Category: Diseases, symptoms, and conditions Related conditions: Gastrointestinal stromal tumors (GISTs), leiomyomas Definition: Leiomyosarcomas are rare malignant tumors that arise from smooth muscle, most commonly in between the muscular and mucosal layers of the digestive tract and the myometrium (muscular layer) of the uterus. The stomach and small intestine are the most commonly involved organs. The ileum is the most common region of small bowel affected. Risk factors: Shared factors implicated in endometrial cancer and leiomyosarcoma include nulliparity (no births), obesity, and diabetes. Pelvic irradiation and chlorophenol exposure were associated specifically with extrauterine leiomyosarcoma in some studies. Concomitant Crohn disease was found in 6 percent of patients in another study.
Salem Health: Cancer Etiology and the disease process: The malignant cells are clones of a single, spindle-shaped cell transformed by an external mutagen. Biological etiologies such as Epstein-Barr virus (EBV), as seen in leiomyosarcomas with EBV deoxyribonucleic acid (DNA) from immunosuppressed patients such as transplant recipients and patients infected with the human immunodeficiency virus (HIV), are possible mutagens. One characteristic of a leiomyosarcoma’s growth differentiating it from other tumors is its propensity to grow outward into the abdominal cavity instead of inward, causing obstructive symptoms relatively late in the disease. Malignant transformation of a preexisting uterine leiomyoma is possible but has been estimated to occur in only 0.2 percent of cases. Incidence: While comparatively rare, leiomyosarcomas account for around 2 to 9 percent of all extrauterine sarcomas, with 20 percent of these found within the digestive tract. Uterine leiomyosarcomas make up 4 percent of all uterine cancers. In the United States, the overall occurrence of extrauterine leiomyosarcomas is estimated at 1.4 cases per 100,000. Symptoms: Most symptoms of a leiomyosarcoma mimic those of other, more common digestive tract cancers such as colorectal cancer. These include overt symptoms such as bleeding or obstruction (constipation) in large tumors. Bleeding may be acute and severe enough to require blood transfusions if a blood vessel has been eroded by a tumor. Patients may complain of vague symptoms such as fatigue, weight loss, malaise (from long-term blood loss), and abdominal pain. Some patients may have no symptoms, delaying diagnosis. In uterine leiomyosarcomas, a mass may be felt through the abdominal wall and mistaken for pregnancy. However, a pregnancy test would be negative. Other symptoms may include menometrorrhagia (increased, frequent, and irregular bleeding from the vagina), infertility and pressure symptoms causing difficulty in swallowing, and compression or invasion of the bladder and ureter (urine duct from the kidney to the bladder). Screening and diagnosis: A diagnosis of an extrauterine leiomyosarcoma may be confirmed by ultrasound-guided biopsy. Ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) are not as helpful. The tumor type is diagnosed by a pathologist, who can determine cancerous changes in cells and the histologic grades (number of cell divisions, defined as five or more in ten microscopic field samples). Immunohistochemical identification may be useful for differentiating leiomyosarcoma from gastrointestinal stromal tumors (GISTs) by identify-
Leiomyosarcomas
Stage at Diagnosis and Five-Year Relative Survival Rates for Adult Leiomyosarcoma, 1988-2001 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
51.0 18.6 21.9 8.5
71.8 44.4 13.6 45.4
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
ing GIST markers such as CD34 and tyrosine kinase c-kit (CD117); GIST treatment differs from that for leiomyosarcoma. Specific screening tests other than regular pelvic examinations are not available for leiomyosarcoma of the uterus. A pelvic ultrasound may reveal a vague mass darker than the surrounding normal tissue within the myometrium. An endometrial biopsy is also performed to rule out endometrial cancer in bleeding women. The American Joint Committee on Cancer (AJCC) uses the TNM (tumot/lymph node/metastasis) classification for tumor staging of intestinal tumors: • Stage I: The tumor is less than 5 centimeters (cm), low grade, with no sign of lymph node spread or spread to other parts of the body. • Stage II: The tumor is greater than 5 cm, localized, low grade, and has not spread to lymph nodes or other parts of the body. • Stage III: The tumor is either high grade of any size or has spread to regional lymph nodes or the peritoneum. • Stage IVA: The tumor has metastasized or is deemed unresectable. • Stage IVB: Tumor rupture has occurred in spite of resection. For uterine leiomyosarcomas, the staging criteria for uterine cancers developed by the International Federation of Gynecology and Obstetrics (FIGO) is used: • Stage I: Tumor is limited to the endometrium and myometrium. • Stage II: Endocervical and cervical stroma are involved. 695
Leptomeningeal carcinomas
Salem Health: Cancer
• Stage III: Invasion of serosa or adjacent reproductive organs has taken place, or malignant cells are found in peritoneal, vaginal, pelvic, or para-aortic lymph nodes. • Stage IVA: Bladder or bowel mucosa invasion or distant metastases have taken place. Note that cell grade is not as significant in staging of uterine leiomyosarcomas as in staging intestinal leiomyosarcomas.
See also Fibrosarcomas, soft-tissue; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Leiomyomas; Sarcomas, soft-tissue; Testicular cancer; Uterine cancer; Vaginal cancer.
Treatment and therapy: Irrespective of location, radical surgical resection of the leiomyosarcoma through abdominal surgery (bowel resection or hysterectomy) is warranted. Although lymph node spread is an ominous sign, it rarely occurs. In such cases, removal of lymph nodes draining the immediate area of the tumor is sufficient. In unresectable tumors, palliative therapy is carried out. This may include intestinal bypass of the tumor followed by radiotherapy. In cases of metastases, palliative resection, radiotherapy, and chemotherapy are carried out.
Category: Diseases, symptoms, and conditions Also known as: Leptomeningeal carcinomatosis (LC), leptomeningeal metastasis, leptomeningeal seeding, carcinomatous meningitis, neoplastic meningitis
Prognosis, prevention, and outcomes: Prognosis is based on the cellular grade and size of the tumor upon diagnosis and surgical staging. The five-year survival rate for operable extrauterine leiomyosarcoma is approximately 50 percent. Liver metastasis may occur in as many as 55 percent of patients with recurrence. Aldo C. Dumlao, M.D. u
For Further Information Byers, Tim, Susan J. Curry, Maria Elizabeth Hewitt, and National Cancer Policy Board. Fulfilling the Potential of Cancer Prevention and Early Detection. Washington, D.C.: National Academies Press, 2003. Dollinger, Malin, et al. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated and Managed Day to Day. 4th ed. Kansas City, Mo.: Andrews McMeel, 2002. Morra, Marion E., and Eve Potts. Choices. 4th ed. New York: HarperCollins, 2003. u
Other Resources
American Cancer Society http://www.cancer.org LeioMyoSarcoma http://www.leiomyosarcoma.info LMSarcoma Direct Research Foundation http://www.lmsdr.org The National Leomyosarcoma Foundation http://www.nlmsf.org 696
u Leptomeningeal carcinomas
Related conditions: Metastasized cancers most often of the breast, lung, and gastrointestinal tract; malignant melanoma; lymphoma Definition: Leptomeningeal carcinoma is the growth of cancer in the central nervous system (brain and spinal cord) as a result of the metastasis of a primary cancer. Risk factors: People develop leptomeningeal carcinoma because they have another type of cancer that spreads (metastasizes) to the central nervous system. Small-cell lung cancers, malignant melanoma, cancers of the gastrointestinal tract, cancers of the blood, and breast cancer are the most likely to metastasize into leptomeningeal carcinoma. Etiology and the disease process: The central nervous system (CNS) consists of the brain and spinal cord. Three membranes cover the brain. The pia mater is a thin, delicate membrane that lies tightly on top of the cells in the brain and spinal cord. The arachnoid mater is the middle membrane surrounding the central nervous system. It fits loosely, creating space between the pia mater and the arachnoid mater. This space is called the subarachnoid space. The subarachnoid space is filled with cerebrospinal fluid (CSF). This fluid brings nutrients to the nerve cells, removes wastes, and cushions the central nervous system during movement. Once cancer cells enter the cerebrospinal fluid, they can move freely to any central nervous system location. Leptomeningeal carcinoma develops in the subarachnoid space and usually is found in multiple locations. The outer membrane, or dura mater, does not play a role in this cancer. Leptomeningeal carcinoma develops secondary to another type of cancer, almost always after the original cancer has been treated and then returned. Blood cancers and cancer cells that have been shed by solid tumors travel
Salem Health: Cancer through the circulatory system and enter the cerebrospinal fluid, often by burrowing through the wall of a blood vessel. This process is called leptomeningeal seeding. Once in the cerebrospinal fluid, the cancer cells multiply. They are transported through the cerebrospinal fluid and eventually attach to nerve cells in the brain and spinal cord. Here they grow into either flat sheets of tissue (often in the brain) or masses of cells. The cancer cells also tend to spread along nerves emerging from the spinal column. Incidence: The frequency with which patients develop leptomeningeal carcinoma is not clear, and the disease is probably underdiagnosed. Between 1 and 8 percent of cancer patients are diagnosed with leptomeningeal carcinoma, but on autopsy, about 20 to 25 percent have evidence of the disease. Leptomeningeal carcinoma can occur in adults and children. Symptoms: Symptoms depend on where the leptomeningeal carcinoma is located. In the brain, masses of cells may interrupt the flow of cerebrospinal fluid and cause an increase in pressure in the brain. Symptoms associated with leptomeningeal carcinoma in the brain include headaches accompanied by nausea and vomiting, disturbances in balance and gait, memory problems, and behavior changes. Symptoms associated with leptomeningeal carcinoma along the cranial nerves (twelve pairs of nerves that originate in the brain and enervate the head, neck, and upper chest) include double vision or other vision problems, hearing loss, problems swallowing, and dizziness. These are the most common symptoms, occurring in more than 90 percent of patients. More than one cranial nerve is usually involved, so multiple symptoms are present in the same individual. Symptoms associated with leptomeningeal carcinoma in nerves that originate in the spine include neck and back pain, incontinence, and leg weakness. Most often, patients have a combination of symptoms because multiple sites are affected. Screening and diagnosis: Diagnosis is made by multiple lumbar punctures. In a lumbar puncture, a small amount of cerebrospinal fluid is withdrawn from the subarachnoid space using a fine needle. Since the physician has little idea where in the central nervous system the leptomeningeal carcinoma is located, the likelihood of correctly diagnosing leptomeningeal carcinoma with a single lumbar puncture is only about 50 percent. When lumbar puncture is repeated three times at different sites, the likelihood of making a positive diagnosis increases to almost 90 percent. Diagnosis also involves contrast-enhanced imaging scans (magnetic resonance imaging, computed tomogra-
Leptomeningeal carcinomas phy, myelography) to identify the location of the leptomeningeal carcinoma for treatment. Because leptomeningeal carcinoma is the result of metastasis of a primary cancer, it is, by definition, Stage IV cancer. Treatment and therapy: The goal of treatment is to prevent the development of additional symptoms and prolong the survival of the patient. Treatment options are often limited because leptomeningeal carcinoma is a sign of advanced cancer. Radiation directed to the sites where the cancer is located and chemotherapy drugs injected by lumbar puncture directly into the cerebrospinal fluid are the two main treatments available. Prognosis, prevention, and outcomes: Leptomeningeal carcinoma is a sign of terminal cancer. If untreated, the average survival time is four to six weeks. When treated, the average survival time is three to seven months, depending on the type of primary cancer. Usually the individual dies from either the primary cancer or complications of cancer treatment rather than directly from leptomeningeal carcinoma. Martiscia Davidson, A.M. u
For Further Information Bruno, M. K., and J. Raizer. “Leptomeningeal Metastases from Solid Tumors (Meningeal Carcinomatosis).” Cancer Treatment and Research 125 (2005): 31-52. Jaeckle, K. A. “Improving the Outcome of Patients with Leptomeningeal Cancer: New Clinical Trials and Experimental Therapies.” Cancer Treatment and Research 125 (2005): 181-193. Kaal, E. C., and C. J. Vecht. “CNS Complications of Breast Cancer: Current and Emerging Treatment Options.” CNS Drugs 21, no. 7 (2007): 559-579. Penthoroudiaks, G., and Palvidis, N. “Management of Leptomeningeal Malignancy.” Expert Opinion on Pharmacotherapy 6, no. 7 (June, 2005): 1115-1125.
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Other Resources
eMedicine.com Leptomeningeal Carcinomatosis http://www.emedicine.com/RADIO/topic390.htm National Cancer Institute http://www.cancer.gov See also Brain and central nervous system cancers; Carcinomatous meningitis; Lumbar punctures; Meningeal carcinomatosis. 697
Leukapharesis
Salem Health: Cancer
u Leukapharesis
cause the procedure involves skin penetration and open access to blood vessels, infection is a risk.
Category: Procedures Also known as: Apheresis, hemapheresis
Results: Stem cells infused into the bloodstream of a patient receiving chemotherapy will travel to the marrow of certain bones and stimulate the production of cells that eventually mature into healthy blood cells, replacing the normal cells that are lost during high-dose chemotherapy. Terry A. Anderson, B.S.
Definition: Leukapharesis is a process of filtering whole blood to remove stem cells or white blood cells. Cancers treated: Most forms of leukemia, lymphoma, and myeloma Why performed: Because high-dose chemotherapy destroys normal blood-producing stem cells in the bone marrow, these cells must be replaced in order to restore blood cell production. Stem cell transplantation is often performed to support high-dose chemotherapy as a treatment option for many forms of leukemia, lymphoma, and myeloma. Autologous transplant means that a patient donates his or her own blood cells for reinfusion after chemotherapy; allogeneic transplant means that a donor supplies blood cells for infusion into another person. Patient preparation: Donors and patients undergo a complete blood count to determine the number of platelets, red and white blood cells, and hemoglobin levels. The collection of stem cells and white blood cells is usually performed on an outpatient basis. For the treatment of some blood and lymphatic cancers, a donor may be injected for five days with a drug to stimulate the production and release of large numbers of stem cells and white blood cells from the marrow into the bloodstream. Steps of the procedure: An intravenous catheter is inserted into the donor. Blood passes out of the patient and circulates through a cell separator machine. The fraction of the blood containing stem cells or white cells is separated via centrifugation from the blood that is not required for the transplant; the latter blood fraction is then remixed and returned to the donor through the catheter. When a patient’s own stem cells are used, they may be frozen and stored until needed; stem cells from a donor can be collected when they are needed. After the procedure: Donors are generally free to leave the clinic after the procedure. Patients receiving treatment may leave after their marrow begins producing sufficient new blood cells and treatment complications have been addressed. Risks: Patients may experience temporary light-headedness and numbness or tingling of the nose, lips, or fingers. Possible complications include bleeding at the needle site, clotting in blood vessels, and similar complications. Be698
See also Autologous blood transfusion; Bone marrow transplantation (BMT); Leukemias; Lymphomas; Myeloma; Myeloproliferative disorders; Pheresis; Transfusion therapy.
u Leukemias Category: Diseases, symptoms, and conditions Also known as: Hematologic malignancy, liquid tumor Related conditions: Myelodysplastic syndrome (MDS) Definition: Leukemias are cancers of the blood that result in abnormally high numbers of white cells, called leukocytes, in the blood and bone marrow. There are some rare forms of leukemia, but the main ones are acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Leukemias are named for the type of malfunctioning blood cell and the intensity of how the cancer progresses. Acute leukemia occurs suddenly and usually involves large numbers of abnormal cells. Chronic leukemia grows more slowly and may go undetected until the disease progresses. AML is a fast-growing leukemia that involves mature white cells. CML is slow growing, has a disease marker called the Philadelphia chromosome, and affects mature white cells. ALL affects mature lymphocytes and grows rapidly. CLL also affects mature lymphocytes but grows slowly. Risk factors: Exposure to certain chemicals, such as benzene, is a risk factor for leukemia. Chemicals, solvents, and ionizing radiation can alter deoxyribonucleic acid (DNA), one of the acids found within the nucleus of cells. The damaged DNA causes chromosomal abnormalities linked to cancer. Another risk factor is prior treatment with chemotherapy, or cytotoxic drugs. Leukemia emerging after treatment of another cancer is known as a secondary leukemia. Etiology and the disease process: The cause of leukemia is unknown, but it is thought that substances that damage
Salem Health: Cancer
Leukemias Incidence: Leukemia makes up about 3 percent of cancers. New cases of leukemia, estimated by the Leukemia and Lymphoma Society of America, were expected to number 44,240 in 2007. There are 7 percent more cases of chronic versus acute leukemias. The incidence is much higher for the elderly, with half of all cases occurring after the age of sixty-seven. Leukemias account for about 33 percent of all cancers in children up to the age of fourteen. The most common form of leukemia among children under the age of nineteen is ALL. AML is the most common leukemia in adults, with 13,410 new cases projected in 2007. The estimate for CML was 4,570 new cases for 2007. The incidence of all leukemias is about 30 percent higher for men than women. The highest incidence is among whites. Hispanic children of all races under the age of twenty have the highest rates of leukemia among children. Leukemia is not a hereditary disease, because most people with leukemia report no family history of the disease.
DNA lead to the development of leukemia. The proliferation of abnormal white blood cells crowds out red blood cells, platelets, and healthy white cells. The different types of white blood cells are neutrophil, eosinophil, basophil, monocyte, and lymphocyte, and each has a specific role in fighting infection. Red blood cells carry oxygen to the body, and platelets enable blood to clot. Normal white cells, which help the body fight infection by keeping blood and tissues free of contaminants such as bacteria, viruses, and fungi, cannot function properly in the presence of leukemia. White blood cells, as well as red blood cells and platelets, originate from stem cells that mature, or differentiate, into specific types of cells inside the bone marrow. Immature white cells are called blasts, and increased numbers are found in the bone marrow, and sometimes blood, of people with AML and ALL. The presence of leukemic cells leaves less room for the normal white cells, compromising and suppressing the immune system. Myelodysplastic syndrome (MDS) is a disease that affects the normal maturation process of blood cells and may evolve into AML.
Symptoms: The early signs of leukemia may manifest as generalized symptoms such as fatigue and shortness of
Incidence of Leukemia per 100,000 People, by Gender 18 16.7
Men
Women
16 14
13.2 11.8
12 10
9.9 9.2 8.1
8
8.0 6.5 5.8
6
6.1
4 2 0 White
Black
Hispanic
Asian/Pacific Islander
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
699
Leukemias
Salem Health: Cancer
Normal blood White cells fight infection Red cells transport oxygen Platelets help blood clot Blood in leukemia
Abnormal white cells Fewer platelets Fewer red cells
Leukemias are characterized by abnormally high numbers of white cells in the blood.
breath that result from a lack of oxygen in the body because of reduced numbers of red blood cells. Pale skin, infection, and wounds that heal slowly are other symptoms. Bruising or bleeding may result when platelets are reduced by the abnormally high white cell counts. Enlarged lymph nodes and joint pain may also be noticed. A complete workup is necessary to determine the cause of the symptoms. There are multiple medical conditions that cause the same symptoms, and therefore these symptoms should not be assumed to be caused by leukemia. However, as leukemia is potentially fatal and early intervention is critical, particularly with acute leukemia, symptoms should be reported promptly to a health care provider. Screening and diagnosis: Routine blood tests such as a complete blood count (CBC) are used to screen for abnormalities in white and red blood cells and platelets. Diagnosis is made by testing blood and bone marrow in conjunction with a thorough review of medical history and a physical examination. Bone marrow is obtained though a procedure called a biopsy. A small sample of bone marrow is obtained by inserting a needle into bone, typically near the hip. The sample is examined under a microscope to look for malignant cells and through testing called immunophenotyping. White blood cells can be identified by their size and by the way they look when stains are applied. Staining allows visualization of the different cell lines and 700
makes it easier to quantify or estimate the number of each present in the sample. The number of blast cells found in bone marrow or blood is used to diagnosis leukemia versus myelodysplastic syndrome. An increase in the number of blasts may be indicative of conversion from myelodysplastic syndrome to AML. Genetic testing is the key to diagnosing leukemia because it identifies the cell defect causing the leukemia. Chromosome testing, which reveals important genetic information about type and aggressiveness of the leukemia, is used to guide treatment. Immunophenotyping is a process that enables examination of individual cells in a sample of blood or bone to determine the types of proteins and antigens on their surface. This process helps determine the percentage of abnormal markers on cells, which determines leukemia type. The specific abnormalities found through this testing give a picture of the genetic defect and prognosis for the leukemia. Karyotyping is done to gain additional information about the genetic features of the chromosomes and thereby confirm a diagnosis of leukemia and identify its subtype. The type of genetic abnormality needs to be determined before treatment begins to ensure utilization of the correct regimen. The abnormality may be a deletion, addition, or translocation of a segment of DNA that controls cell replication and function. The Philadelphia chromosome describes the abnormality of a translocation that confirms the diagnosis of CML. It is the switch of part of chromosome 9 to chromosome 22 and part of chromosome 22 to chromosome 9. Fluorescence in situ hybridization (FISH) is another genetic test that can confirm or rule out a diagnosis. This test detects abnormalities that may be missed on normal karyotyping. Some abnormalities are more favorable than others in terms of prognosis. The Philadelphia chromosome is also found in approximately a third of the cases of ALL. The information about the leukemia cells gained through cytogenetic testing aids oncologists and hematologists in helping patients weigh the chances of recovery against potential risks inherent in chemotherapy. Radiographs, such as X rays, computed tomography (CT) scans, and magnetic resonance images (MRI), may be needed to rule out other conditions or medical problems. The staging of leukemia differs for each type. For example, a common staging system for AML is the FrenchAmerican-British (FAB) system, which uses eight subtypes labeled MO to M7. The World Health Organization’s classification is another system used to identify the extent of disease. CML may cause few or no symptoms initially and may be discovered during a routine doctor visit when blood
Salem Health: Cancer samples are obtained. CML is diagnosed according to chronic, accelerated, and aggressive phases based on how far the disease has progressed. CLL is diagnosed and monitored through examination of lymphocytes, a type of white blood cell. Treatment and therapy: Treatment options depend on the type and aggressiveness of the leukemia as well as the patient’s age and other health considerations. Severe symptoms, associated with acute leukemia, require immediate hospitalization and treatment. Chemotherapy, radiation, and bone marrow or stem cell transplantation are possible modes of therapy. Chemotherapy is most frequently used and may involve multiple drugs in different combinations, called regimens. Treatments evolve with ongoing research as more is learned about the mechanisms that cause and arrest the disease. Targeted therapies show promise in the treatment of cancer, including some leukemias. The development of imatinib mesylate (Gleevec) has been important for the treatment of CML. This drug works by depressing an enzyme that causes CML to grow. In the process of killing leukemia cells, normal cells may be affected, causing side effects that must be closely monitored and treated in a health care setting. In acute leukemia, the white cell count may be dangerously high, requiring treatment with hydroxyurea to reduce the number of white cells before treatment for the leukemia begins. The initial treatment phase of leukemia is called induction and is designed to put the leukemia into remission. When testing shows improvement in the leukemia but diseased cells remain, it is regarded as a partial remission and the patient may be given a second induction. Consolidation or intensification therapy is another treatment step that increases or improves the chance of a cure. It is given after a remission is achieved with induction therapy. Patients may continue to get other drugs during a maintenance phase of treatment that is given to reinforce remission. A stem cell or bone marrow transplant is the process of replacing diseased cells with normal or disease-free cells and may be an option after remission to prolong survival. An autologous transplant uses an individual’s own cells, and an allogeneic transplant involves cells from another person, called a donor. Chemotherapy and sometimes total body irradiation (TBI) are used to clear as much of the disease as possible prior to the transplant. A person diagnosed with leukemia often needs transfusions of whole blood and platelets and other supportive care while undergoing treatment for the leukemia. Drugs that have shown promise in the laboratory and in preliminary clinical trials with humans may be an option
Leukemias for the treatment of leukemia. These drugs are considered investigational and are available only through participation in a clinical trial. Oncologists and other physicians who treat leukemia can help patients learn if there is a clinical trial option appropriate for a particular diagnosis. Prognosis, prevention, and outcomes: Preventive strategies include undergoing routine health screenings to check blood counts and avoiding prolonged exposure to chemicals. Outcomes depend on type of leukemia, availability of treatment options, age, and overall state of health. Survival rates are excellent for children with ALL under the age of fifteen, with almost all cases cured. Treatment for the elderly can be limited by the toxic effects of some chemotherapy regimens that are poorly tolerated by individuals in this age group. The prognosis after treatment for ALL is less favorable in patients who have the Philadelphia chromosome. Acute leukemia that goes into remission after treatment is considered cured after five years. Linda August Vrooman, R.N., B.S.N., O.C.N. u
For Further Information Ball, Edward D., and Gregory A. Lelek. One Hundred Questions and Answers About Leukemia. Sudbury, Mass.: Jones and Bartlett, 2003. Keene, Nancy. Childhood Leukemia: A Guide for Families, Friends, and Caregivers. 3d ed. Sebastopol, Calif.: O’Reilly, 2002. Lackritz, Barbara. Adult Leukemia: A Comprehensive Guide for Patients and Families. Sebastopol, Calif.: O’Reilly, 2001. Sinclair, Alison. “Genetics 101: Cytogenetics and FISH.” Canadian Medical Association Journal 167 (2002): 373-374.
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Other Resources
American Cancer Society http://www.cancer.org American Society of Hematology http://www.hematology.org The Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute http://www.cancer.gov National Marrow Donor Program http://www.marrow.org See also Acute lymphocytic leukemia (ALL); Acute myelocytic leukemia (AML); Aleukemia; Amyloidosis; Ane701
Leukoencephalopathy mia; Aplastic anemia; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Burkitt lymphoma; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Cutaneous T-cell lymphoma (CTCL); Disseminated intravascular coagulation (DIC); Down syndrome and leukemia; Eosinophilic leukemia; Fanconi anemia; 5Q minus syndrome; Hairy cell leukemia; Hemolytic anemia; Hodgkin disease; Human T-cell leukemia virus (HTLV); Hypercalcemia; Leukopenia; Leukoplakia; Lymphocytosis; Lymphomas; Multiple myeloma; Myelodysplastic syndromes; Myelofibrosis; Myeloma; Myeloproliferative disorders; Myelosuppression; Neutropenia; Pheresis; Polycythemia vera; Richter syndrome; Sézary syndrome; Stem cell transplantation; Superior vena cava syndrome; Thrombocytopenia; Thymomas; Thymus cancer; Transfusion therapy; Umbilical cord blood transplantation; Waldenström macroglobulinemia (WM).
u Leukoencephalopathy Category: Diseases, symptoms, and conditions Also known as: Multifocal demyelinating disease, progressive multifocal leukoencephalopathy (PML) Related conditions: Acute hemorrhagic leukoencephalopathy, leukoencephalopathy with vanishing white matter, multiple sclerosis Definition: Leukoencephalopathy is a life-threatening, rapidly progressing disease of the nerves and muscles that affects patients who have a suppressed immune system. It is thought to be caused by a reactivated viral infection that changes form to take advantage of a suppressed immune system. In this disease, the myelin sheath, composed of the fatty tissue that forms a protective covering of the nerve fibers (sometimes called white matter), is destroyed. Risk factors: This disease occurs only in patients who have had their immune systems suppressed by another disease or for medical procedures that depend on a suppressed immune system, such as organ transplant. It is considered to be an opportunistic infection, or one that takes advantage of a suppressed immune system to damage some part of the body or one of its systems. This disease is also linked to the JC virus (a polyomavirus named with the initials of the first patient to have been diagnosed with this virus), to which more than 80 percent of the general population has been exposed, most likely in childhood. Some studies show that 85 percent of children have been exposed to this virus before the age of 702
Salem Health: Cancer nine. However, in most of the population, this virus stays dormant. This disease is a rare side effect of some types of cancer treatment that suppress the immune system, which may happen with some types of chemotherapy or with certain types of procedures, such as a bone marrow transplant. Cancer patients—particularly those with Hodgkin disease, leukemia, lymphoma, or sarcoidosis—who have received chemotherapy treatment with methotrexate or radiation therapy are at risk of developing this disease. However, the disease is not limited to cancer patients and may be developed by those who have other immunocompromising diseases or factors such as acquired immunodeficiency syndrom (AIDS) or organ transplants. This disease is, in fact, most common in AIDS patients. Other factors that are thought to increase risk in combination with a suppressed immune system are exposure to toxic substances, injuries, ischemia (a decrease in blood flow to a body part), and some types of metabolic disorders. Etiology and the disease process: This disease is thought to be caused by activation of the JC virus. Most of the people exposed to this virus never develop the disease, even if they have a suppressed immune system. The virus lies dormant, mostly in the kidneys, until the immune system is suppressed somehow. In cancer patients, this suppression is usually through radiation or chemotherapy as part of a treatment strategy, but patients with AIDS or those who have had organ transplants may also get this disease because treatment involves suppressing the immune system. The virus becomes active, taking advantage of the suppressed immune system, and changes into a form that is able to attack the brain. It begins destroying, or perhaps interfering with the formation of, the myelin sheath. The myelin sheath is the fatty substance that covers and protects the nerve fibers in the brain and spinal column. Like other myelin-attacking diseases, such as multiple sclerosis (MS), the process by which the myelin is destroyed is not completely understood. This loss of the myelin protective sheath keeps nerve signals from traveling to the rest of the body. Other abnormalities or cell growths may also begin to occur in the brain, and these complications further damage healthy brain cells. This eventually leads to progressive loss of muscle coordination and mental dysfunction. These symptoms are extremely varied and depend on the location (where in the brain or spinal column) and the severity (how deep or wide) of the damage to the myelin sheath. Eventually, this disease results in seizures and coma before death. The patient usually dies within a year of diagnosis.
Salem Health: Cancer Incidence: This disease occurs only in patients with a suppressed immune system. Even in those patients, only a very small number of people will develop this disease. Only about 5 percent of people living with AIDS will develop this disease; the incidence for cancer patients is even less. However, the incidence of this disease is rising, as more people with cancers that are being treated in ways that suppress the immune system are surviving longer. It is classified as a rare disease by the National Institutes of Health Office of Rare Diseases. This means that this disease affects less than 200,000 people in the entire population of the United States. This number includes patients with AIDS as well as cancer patients. Symptoms: Symptoms include clumsiness, difficulty walking, facial weakness, fatigue, headaches, loss of muscle coordination, loss of appetite, loss of speech, memory failure, mental dysfunction or deterioration, paralysis on one side of the body, partial or total blindness (sometimes affecting half of the vision in each eye), seizures, slow movements, stammering, stuttering, and weakness. Symptoms may vary greatly because they depend on where in the brain or spinal column the myelin sheath is being destroyed and how much damage has been done. Screening and diagnosis: There is no screening test or staging developed for this disease. Diagnosis can be uncertain at first. The disease is suspected in patients with compromised immune systems who develop unexplained brain dysfunction. Magnetic resonance imaging (MRI) or computed tomography (CT) scans may suggest this disease by showing lesions or sores on the myelin or white matter in the brain or spinal column. Spinal fluid may be analyzed to determine if the JC virus is present, which can help strengthen a diagnosis. Blood tests are not helpful in diagnosing this disease; there is no effect on the blood, only on the nerves and muscles. The only sure diagnosis is done by stereotaxic biopsy (a special type of removal of tissue using a computer and a three-dimensional scanning device) of the brain tissue in the affected area. However, this type of biopsy is not generally warranted for this disease because a brain biopsy is a high-risk procedure, especially for those with an already compromised immune system. Generally, the diagnosis of the disease is made by observing by its rapid progression with symptoms becoming more pronounced and widespread. Treatment and therapy: No treatment or therapy currently exists to reliably cure this disease. Antiviral medications may help by reducing the viral load in the body, in-
Leukoencephalopathy creasing the body’s T-cell count and generally improving the immune system. However, these medications often have toxic side effects or are not tolerated well by patients, particularly those who already have suppressed immune systems. Sometimes, other attempts are made to slow the progress of this disease—for example, altering chemotherapy or removing nonvital transplanted organs so that immunesuppressing drug therapy can be stopped—but these treatments have, at best, inconclusive results. Treatment is generally supportive, which means that the treatment attempts to reduce the severity of the symptoms and make a patient as comfortable as possible without truly addressing the main cause of the disease. Prognosis, prevention, and outcomes: There is no cure for leukoencephalopathy, nor is there any way to prevent the disease other than attempts to keep the immune system healthy and functioning properly. Prognosis and outcomes are very poor, with most patients (80 percent) dying within six months to a year of diagnosis. Those who survive this disease (about 20 percent) are often left with severe disabilities, both mental and physical. Marianne M. Madsen, M.S. u
For Further Information Icon Health. The Official Patient’s Sourcebook on Progressive Multifocal Leukoencephalopathy: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2003. St. Georgiev, Vassel. Infectious Diseases in Immunocompromised Hosts. Boca Raton, Fla.: CRC Press, 1998. Uziel, G., and F. Taroni, eds. Hereditary Leukoencephalopathies and Demyelinating Neuropathies in Children. Eastleigh, England: John Libbey Eurotext Ltd, 2004.
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Other Resources
Cleveland Clinic Center for Consumer Health Information Progressive Multifocal Leukoencephalopathy http://www.clevelandclinic.org/health/health-info/ docs/1300/1322.asp?index=6101 Merck Online Medical Library Progressive Multifocal Leukoencephalopathy http://www.merck.com/mmpe/sec16/ch217/ ch217f.html#sec16-ch217-ch217f-1055 703
Leukopenia National Institute of Neurological Disorders and Stroke Progressive Multifocal Leukoencephalopathy http://www.ninds.nih.gov/disorders/pml/pml.htm See also Cognitive effects of cancer and chemotherapy; HIV/AIDS-related cancers; Oligodendrogliomas.
u Leukopenia Category: Diseases, symptoms, and conditions Also known as: Neutropenia, low white blood cell count, leucopenia Related conditions: Neutropenia, which is a subset of leukopenia Definition: Leukopenia is an abnormally low number of white blood cells, or leukocytes. The laboratory standard measurement of leukocytes ranges from approximately (4.0 to 11.0) × 109 per liter. Risk factors: Leukopenia may be related to use of certain drugs (such as barbiturates and chemotherapeutics), radiation therapy, bone marrow or stem cell transplant, severe infections, or bone marrow diseases such as leukemia, myelodysplastic syndromes, acquired immunodeficiency syndrome (AIDS), aplastic anemia, or lupus. Patients older than the age of seventy and those with comorbid diseases, such as diabetes, are at great risk for leukopenia during chemotherapy. Etiology and the disease process: Chemotherapy and radiation therapy for cancer target the rapidly dividing cancer cells as well as other rapidly dividing cells, that is, hematopoietic stem cells. It takes about ten days for a new leukocyte to differentiate and mature from a hematopoietic stem cell, which means that a patient receiving chemotherapy or radiation therapy can have a low number of leukocytes for days. The role of leukocytes is to safeguard against infection by destroying bacteria. Leukopenia and its associated impaired immunity make a patient more susceptible to infections and may lead to septicemia. Untreated, leukopenia may require hospitalization and use of intravenous anti-infective drugs. Incidence: Most patients who are receiving chemotherapy, radiation therapy, or a bone marrow transplant experience leukopenia, and very often chemotherapy must be delayed because of it. Symptoms: Symptoms include recurrent infections, highgrade fever and chills, and diarrhea. 704
Salem Health: Cancer Screening and diagnosis: Leukopenia is defined as a leukocyte count less than approximately 4.0 × 109per liter. Mild leukopenia is defined as a leukocyte count of (1.0 to 2.0) × 109per liter, and severe as a leukocyte count less than 0.5 × 109per liter. Leukopenia is determined by a blood test. Treatment and therapy: At this time, white blood cell transfusions are not a treatment option, primarily because of the abbreviated life span of a leukocyte, which is estimated to be between twenty-four and forty-eight hours. Most patients with leukopenia receive hematopoietic growth factors such as filgrastim (Neupoegen), pegfilgrastim (Neulasta), or sargramostim (Leukine) to increase the number of circulating white blood cells. Prognosis, prevention, and outcomes: Hematopoietic growth factors are the standard for treatment of severe leukopenia at many cancer centers and can rapidly, within hours in some cases, increase leukocyte counts. Left untreated, the patient is at risk for serious and possibly lifethreatening infections. MaryAnn Foote, M.S., Ph.D. See also Antineoplastics in chemotherapy; Aplastic anemia; Azathioprine; Candidiasis; Chemotherapy; Colonystimulating factors (CSFs); Fever; Immunotherapy; Infection and sepsis; Lymphocytosis; Myelosuppression; Neutropenia; Side effects; Thrombocytopenia; Topoisomerase inhibitors; Young adult cancers.
u Leukoplakia Category: Diseases, symptoms, and conditions Also known as: Smoker’s keratosis Related conditions: Erythroplakia and hairy leukoplakia Definition: Leukoplakia is a whitish precancerous lesion found on the mucous membranes of the mouth and tongue that cannot easily be scraped off. Risk factors: Tobacco use (smoking, chewing, snuff), long-term alcohol use, and chronic irritation of the gums or cheeks from poor dental work increase the risk of developing leukoplakia. Etiology and the disease process: The grayish-white patches that characterize leukoplakia grow slowly. They begin as smooth plaques, then gradually become rough, wrinkled, and hard. The cells in these plaques often show precancerous changes and may progress to oral cancer. Hairy leukoplakia is a related, noncancerous condition
Salem Health: Cancer
Leukoplakia
Leukoplakia in the mouth of a pipe smoker. (©Lester V. Bergman/Corbis)
caused by infection with the Epstein-Barr virus. It is common in people infected with human immunodeficiency virus (HIV) and does not develop into oral cancer. Erythroplakia is a rough, red, precancerous lesion. Sometimes erythroplakia and leukoplakia are found in mixed plaques.
the microscope for cancer and to rule out other possible causes, such as a fungal infection.
Symptoms: The main symptom is a whitish growth inside the mouth. Lesions are painless but may be sensitive to spicy foods or to touch. Precancerous leukoplakia lesions develop hard surfaces, while hairy leukoplakia growths are fuzzy.
Treatment and therapy: Individuals with leukoplakia should stop using tobacco products. If no cancer cells are found in the biopsy, the lesion may be observed for several months or it may be removed. Many lesions disappear without treatment once tobacco use is stopped. Medications derived from vitamin A and vitamin E have been used to shrink leukoplakia plaques, but these drugs have significant negative side effects. If abnormal cells are present in the biopsy, the lesion is removed either surgically or by using a laser or very cold probe that freezes and destroys the cells.
Screening and diagnosis: Most cases of leukoplakia are found during dental visits. When a suspect white patch appears in the mouth, a tissue sample (biopsy) is taken to determine whether the patch shows signs of cancer. A few cells may be collected using a spinning brush, or the entire lesion may be removed. The sample is examined under
Prognosis, prevention, and outcomes: In about 3 to 5 percent of people, leukoplakia progresses to oral cancer. In many cases, leukoplakia disappears spontaneously. Avoiding tobacco, especially smokeless tobacco products, is the most effective way to prevent leukoplakia. Martiscia Davidson, A.M.
Incidence: Fewer than 1 percent of adults have leukoplakia. It occurs most often in men over the age of forty.
705
Leydig cell tumors See also Alcohol, alcoholism, and cancer; Chewing tobacco; Cigarettes and cigars; Epidermoid cancers of mucous membranes; Erythroplakia; Head and neck cancers; Keratosis; Lip cancers; Oral and oropharyngeal cancers; Prevention; Smoking cessation; Tobacco-related cancers.
u Leydig cell tumors Category: Diseases, symptoms, and conditions Also known as: Testicular tumors, interstitial cell tumors Related conditions: Sertoli-Leydig cell tumors Definition: Leydig cell tumors are a rare type of testicular (or, rarely, ovarian) tumor. They arise from the Leydig cells, which produce testosterone and other male hormones in the testicles. Most often these tumors are benign, but they can sometimes be cancerous. Risk factors: There are no known risks for this condition; however, it is much more common in men than in women. Etiology and the disease process: The cause of Leydig cell tumors is unknown, but animal studies have suggested that these tumors may grow following exposure to the female hormone estrogen. Leydig cell tumors secrete testosterone and sometimes estrogen. Incidence: This condition is most common in men between the ages of thirty and sixty, although it can occur in prepubescent boys and in women (in the ovaries). Only 1 to 3 percent of all testicular tumors are Leydig cell tumors. In about 3 percent of men who develop Leydig cell tumors, the tumors are found in both testicles. Only about 10 percent of Leydig cell tumors are cancerous. Symptoms: Boys who develop Leydig cell tumors can develop feminine symptoms such as breast tenderness or nipple soreness, and they often go into early puberty. In men, the symptoms more commonly include erectile dysfunction, decreased sexual drive, and infertility. Women with Leydig cell tumors may develop masculine characteristics, such as excessive hair growth and increased muscle mass. Screening and diagnosis: The doctor will feel the testicles to check for an enlarged mass. An ultrasound can confirm the diagnosis. Blood tests can be used to identify elevated testosterone and estrogen levels. Liver function tests are sometimes performed on patients who have cancerous Leydig cell tumors. 706
Salem Health: Cancer Treatment and therapy: Most Leydig cell tumors can be treated with surgery to remove the tumor. Malignant Leydig cell tumors can be treated with surgery, but they do not tend to respond well to chemotherapy or radiation. Prognosis, prevention, and outcomes: The prognosis for people with benign Leydig cell tumors is excellent, because surgery can usually treat the problem. However, those with malignant tumors have an average survival rate of only two years. Stephanie Watson, B.S. See also Germ-cell tumors; Infertility and cancer; Orchiectomy; Sertoli cell tumors; Spermatocytomas; Teratocarcinomas; Testicular cancer; Testicular self-examination (TSE); Urologic oncology.
u Li-Fraumeni syndrome (LFS) Category: Diseases, symptoms, and conditions Related conditions: Li-Fraumeni-like syndrome (LFL), soft-tissue sarcoma, breast cancer, leukemia, adrenal gland (SBLA) syndrome Definition: Li-Fraumeni syndrome (LFS) is a genetic abnormality that predisposes individuals to developing cancer at an early age and to developing multiple primary cancers during their lifetime. Risk factors: About 70 percent of the time, Li-Fraumeni syndrome develops because of a mutation (change) in the deoxyribonucleic acid (DNA) of the TP53 gene (also called p53) on chromosome 17. This gene can be inherited from either parent, and the mutation is present in all cells in the body. Changes in another gene, CHEK2 (also called CHK2), on chromosome 17 and spontaneous (noninherited) changes in these genes account for the remaining 30 percent of individuals with LFS. People who have a mutation causing LFS have a 50 percent chance of passing this mutation to their children whether or not they develop cancer. Etiology and the disease process: TP53 is a tumorsuppressor gene. A normal TP53 controls cell growth and cell death. When it mutates, it loses the ability to regulate cell growth, allowing cells to grow wildly and become malignant. The CHEK2 gene controls another step in the regulation of cell growth, but when it mutates, the result is the same. People inherit one copy of TP53 from each parent. In Li-Fraumeni syndrome, one copy of TP53 is normal, and
Salem Health: Cancer the other has mutated. This, in itself, does not cause cancer, because both copies of the gene must be mutated for cancer to occur. However, a mutation in the second copy of the gene is common. Researchers do not understand what triggers this second mutation. The type of cancer a person gets depends on which type of cell in the body develops the second mutation. The most common types of cancer for people with LFS are breast cancer, soft-tissue sarcomas (cancer arising in cartilage, muscle, fat, or blood vessels), leukemia, osteosarcoma (bone cancer), malignant melanoma, and cancer of the brain, pancreas, esophagus, adrenal cortex, and colon. People with LFS are also at higher risk of developing more than one type of primary cancer during their life, especially if they develop and are cured of a childhood cancer. Incidence: Li-Fraumeni syndrome appears to be rare. Only about 400 families have been identified as having the mutation. However, the ability to screen for this mutation is relatively new, so the incidence is not well defined. Men and women are equally affected, as are all races and ethnicities. Although LFS is rare (it is, for example, thought to account for only 1 percent of breast cancer cases), for people who have this condition, the chances of developing cancer are staggeringly high. Various studies have found the following to be true: • Only about 10 percent of individuals who develop cancer in the general population are diagnosed before age forty-five, while more than 50 percent of people with LFS develop cancer before this age. • About 85-90 percent of people with LFS develop cancer by age sixty. • About 40 percent of people with LFS develop cancer before age sixteen. • About 15 percent of people with LFS whose cancer is cured develop a second primary cancer. Some 4 percent develop a third cancer and 2 percent a fourth cancer. • People who develop cancer before age sixteen are at highest risk of developing multiple primary cancers. Symptoms: Li-Fraumeni syndrome has no symptoms. Cancer symptoms depend on the type of cancer the individual develops. Screening and diagnosis: People are formally diagnosed with Li-Fraumeni syndrome when they meet all three of the following conditions: • They are diagnosed with sarcoma before age forty-five. • A biological parent, sibling, or child is diagnosed with any cancer before age forty-five.
Li-Fraumeni syndrome (LFS)
•
A parent, sibling, child, grandparent, aunt, uncle, niece, or nephew related by blood is diagnosed with any cancer before age forty-five or a sarcoma at any age. With genetic screening it is possible to detect about 95 percent of TP53 mutations that cause LFS. Genetic screening is controversial. It is normally offered only when a close blood relative is diagnosed with LFS. Screening should be accompanied by genetic counseling, so that individuals can make informed decisions about their future and the risks of passing this mutation on to any children they might have. Prenatal screening is possible through chorionic villi sampling or amniocentesis. Researchers have found, however, that as many as 60 percent of eligible relatives do not consent to screening for LFS.
Treatment and therapy: No treatment can prevent or reverse this mutation. Cancers are treated as they arise. Prognosis, prevention, and outcomes: Li-Fraumeni syndrome strongly predisposes individuals to develop cancer at an early age. Individuals who know they come from a family with LFS are encouraged to have complete annual physical examinations and to get prompt medical care for any symptoms that may be an early warning of cancer. Outcomes depend on the type of cancer the individual develops and how soon it is treated. Martiscia Davidson, A.M. u
For Further Information Field, S. S. Shanley, and J. Kirk. “Inherited Cancer Susceptibility Syndromes in Paediatric Practice.” Journal of Paediatrics and Child Health 43, no. 4 (April, 2007): 219-229. Hottinger, A. F., and Y. Khakoo. “Update on the Management of Familial Central Nervous System Tumor Syndromes.” Current Neurology and Neuroscience Reports 7, no. 3 (May, 2007): 200-207. Lalloo, Fiona, ed. Risk Assessment and Management in Cancer Genetics. New York: Oxford University Press, 2005. Strahm, B., and D. Malkin. “Hereditary Cancer Predisposition in Children: Genetic Basis and Clinical Implications.” International Journal of Cancer 119, no. 9 (November 1, 2006): 2001-2006. u
Other Resources
Genetics Home Reference Li-Fraumeni Syndrome http://ghr.nlm.nih.gov/condition=lifraumenisyndrome 707
Limb salvage Stanford Cancer Center Li-Fraumeni Syndrome http://cancer.stanford.edu/information/ geneticsAndCancer/types/lifrmni/ See also Adrenal gland cancers; Adrenocortical cancer; Astrocytomas; Bone cancers; Brain and central nervous system cancers; Breast cancers; Childhood cancers; Family history and risk assessment; Fibrosarcomas, soft-tissue; Genetic testing; Leukemias; Mediastinal tumors; Mutagenesis and cancer; Neuroectodermal tumors; Rhabdomyosarcomas; Sarcomas, soft-tissue; TP53 protein.
u Limb salvage Category: Procedures Also known as: Limb sparing Definition: Limb salvage surgery includes all surgical procedures designed to accomplish removal of a malignant tumor and resection of the limb with an acceptable oncologic, functional, and cosmetic result. Cancers treated: Soft-tissue neoplasias (malignant fibrous histiocytoma, fibrosarcoma, liposarcoma, rhabdomyosarcoma, synovial sarcoma); bone malignancies (osteosarcoma, chondrosarcoma, adamantinoma, Ewing sarcoma) Why performed: In the recent past, most sarcomas were treated by amputation. Tumor recurrence, metastasis, and a generally dismal prognosis had been powerful deterrents to any progress in the surgical treatment of such tumors. Since the late 1980’s, however, limb salvage has all but replaced amputation as the treatment of choice for sarcomas of the extremities. This dramatic change came about as a result of two important developments: effective chemotherapy and precision imaging technology. Today, up to 85 percent of extremity sarcomas are treated with limb salvage surgery. Limb salvage surgery (LSS) can result in survival rates and disease-free intervals that equal those previously achieved with amputation. The presumed functional and psychological advantages of LSS over amputation, however, have yet to be established. LSS appears to offer the possibility of better psychological functioning with a more intact body image, but it is more complex and demanding than amputation and is associated with increased morbidity. The duration of surgery is longer. Infection, pain, and other complications are more common with LSS. Barriers to limb salvage include major vascular involvement, incasement of a major motor nerve, and a pathologic fracture of the involved bone. 708
Salem Health: Cancer Patient preparation: Both imaging studies and biopsy results are used to stage bone and soft-tissue sarcomas. Staging of the tumor influences preoperative chemotherapy or radiation treatments and allows the surgeon to begin planning the limb salvage procedure. The preoperative treatment period provides an opportunity for the surgeon to meet with the patient and family to discuss the choice of the surgical treatment. Treatment by amputation remains a viable and sometimes preferable option and should be openly discussed with the patient in an unbiased manner. Currently, every patient with a malignant tumor of the extremity should be considered for LSS if the tumor can be excised with an adequate tissue margin resulting in a limb worth saving. A limb worth saving needs an acceptable degree of function and cosmetic appearance with a minimal amount of pain, and it needs to be durable enough to withstand the demands of normal daily activities. Steps of the procedure: Surgical treatment of musculoskeletal neoplasms of the extremities is complex and varied. Tumors occur in all anatomic locations of the extremity and, therefore, surgical procedures must be tailored to the anatomic location. Three principles are involved in any operation for extremity sarcomas: excision of the tumor, skeletal reconstruction, and soft-tissue reconstruction. Obtaining an adequate surgical margin takes precedence over all other considerations. If an adequate surgical margin can be achieved only with an amputation, then the patient must be so informed and must understand that to do less will compromise the chances for long-term survival. After the procedure: The rehabilitation process is performed by a multidisciplinary team. Steps in the process include a preoperative physical examination of limb function and disability. Pretraining of the patient is necessary to reduce the rehabilitation time and to lessen the emotional stress following surgery. Age, surgical site, use of allograft bone, the implementation of soft-tissue flap coverage, residual function of associated joints, the possibility of joint reconstruction, use of appropriate orthoses and/or splints, and palliative care will influence, modify, and direct physical and occupational therapies. Risks: LSS is an extensive series of procedures involving masses of soft tissues, bones, and joints. In contrast to ordinary orthopedic procedures, in which the goal is to solve a local problem with minimal exposure and damage, limb salvage deliberately damages many anatomic areas and may cause the following problems:
Salem Health: Cancer
• • • •
bone and joint damage muscle damage skin damage nerve damage (due to mobilization of major nerves and direct damage resulting from radiotherapy and neurotoxic agents) • vascular damage (vessel damage and spasm during surgical exploration and excision of major vessels as a result of tumor involvement) • damage to the lymphatic system (resulting in chronic swelling and limb edema) • scars (pain, dysesthesias, restricted range of movement) • infections (in 18.7 percent of cases) • effects of cancer treatments (radiotherapy, chemotherapy) Radiotherapy damages the skin, subcutaneous tissues, and muscles, causing fibrosis, decreased tissue elasticity, and contractures. Radiation can result in increased bone fragility and the additional risk of fractures. Chemotherapy may cause chronic weakness and fatigue. It requires repeated hospitalizations, which make it difficult to maintain the intensity and continuity of a rehabilitation program. Results: Limb-sparing surgery is now widely accepted as a treatment option for extremity sarcomas. Numerous reports confirm low recurrence rates after tumor resection with adequately wide margins. Studies about functional loss following such procedures are limited. John L. Zeller, M.D., Ph.D. u
For Further Information DeVita, Vincent, Jr., Samuel Hellman, Steven A. Rosenberg, et al., eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Malawer, Martin, and Paul H. Sugarbaker, eds. Musculoskeletal Cancer Surgery: Treatment of Sarcomas and Allied Diseases. Washington, D.C.: Kluwer Academic, 2001. Schwartz, Herbert S., ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors 2. 2d ed. Rosemont, Ill.: American Academy of Orthopaedic Surgeons, 2007. Schwarzbach, M., Y. Hormann, U. Hinz, et al. “Results of Limb-Sparing Surgery with Vascular Replacement for Soft Tissue Sarcoma in the Lower Extremity.” Journal of Vascular Surgery 42, no. 1 (July, 2005): 88-97. Skinner, Harry B., ed. Current Diagnosis and Treatment in Orthopedics. 4th ed. New York: Lange Medical Books/McGraw-Hill, 2006.
Linear accelerator u
Other Resources
American Academy of Orthopedic Surgeons http://www.aaos.org See also Amputation; Bone cancers; Fibrosarcomas, softtissue; Hyperthermic perfusion; Orthopedic surgery; Rhabdomyosarcomas; Sarcomas, soft-tissue; Self-image and body image; Surgical oncology; Synovial sarcomas.
u Linear accelerator Category: Procedures Also known as: Linac, radiation therapy machine Definition: A linear accelerator (linac) is a machine that can produce high-energy X rays and electrons that are used to kill cancer cells and shrink tumors. A linear accelerator’s beam is shaped and sized to treat the tumor and protect surrounding normal tissue. Cancers treated: Most solid-tumor cancers, such as breast, colorectal, prostate, and brain cancers; leukemia and lymphoma; cancer symptom management Why performed: External radiation used to kill cancer cells at the site of the tumor provides effective local cell death and discourages regrowth. Patient preparation: A computed tomography (CT) scan or other radiology test is done to determine the tumor site to be treated. The doctor, a radiation oncologist, reviews the patient’s chart and marks the tumor site. This information is loaded into a treatment-planning computer that calculates how much radiation the patient is to receive. The calculations are then programmed into the linear accelerator. The treatment planning may take several hours. Patients may also be fitted with positioning devices that help to hold the body still during treatment. Steps of the procedure: Treatments on the linear accelerator are usually given once a day for four to six weeks. Treatments are not usually given on Saturday and Sunday in order to allow normal cells to recover. Depending on the site being treated, patients change into gowns or wear street clothes. The patient is carefully positioned on the treatment table or chair by the staff. The staff leaves the room, but an intercom allows the patient to call for help if needed. The treatment is painless and takes just a few minutes, during which the patient must lie still. The equipment is noisy, the machine rotates around the patient, and the treatment table may move. Treatments are usually on an outpatient basis, and patients return home each day. 709
Lip cancers
Salem Health: Cancer
After the procedure: Once all treatments are complete, the patient will see a doctor to determine the status of the tumor and plan any necessary follow-up treatment. It is safe for the patient to be around others, including children and pregnant women, because no radiation is in the body. Risks: Side effects depend on the site treated and may include redness and skin irritation, urinary symptoms, diarrhea, fatigue, eating problems, shortness of breath, and hair loss at the treatment site. Results: External radiation from a linear accelerator provides effective local control of cancer cells. As part of a comprehensive plan of care, radiation therapy can lead to a cure. Patricia Stanfill Edens, R.N., Ph.D., FACHE See also Accelerated partial breast irradiation (APBI); Acoustic neuromas; Colorectal cancer; External beam radiation therapy (EBRT); Intensity-modulated radiation therapy (IMRT); Radiation oncology; Radiation therapies; Stereotactic radiosurgery (SRS); Veterinary oncology.
u Lip cancers Category: Diseases, symptoms, and conditions Related conditions: Other oral or skin cancers Definition: Lip cancers are malignant tumors that form in the surface layer cells of the upper or lower lip. Though lip cancers are generally similar to skin cancers, they are often grouped with oral cancers. Risk factors: Smoking, especially smoking a pipe or cigar, and exposure to sunlight are the two best-documented risk factors for lip cancers. According to some studies, 90 percent of people who have any type of oral cancer smoke. The aging process itself is also a risk factor; as lip cells age and change, they are more susceptible to cancer cell generation. These factors (smoking, exposure to sunlight, and the aging process) may all work in combination to increase risk. Alcohol consumption is a risk factor for developing other types of oral cancer (about 75 percent of patients with any type of oral cancer drink alcohol frequently) and may contribute to lip cancers as well. 710
Other risk factors include viral infection (especially with the human papillomavirus, or HPV), poor oral hygiene, a suppressed immune system (often due to organ transplant treatment), or vitamin deficiency. Etiology and the disease process: Lip cancers almost always (about 90 percent of the time) originate in the flat skin cells (squamous cells) that form the outside covering layer of the lips. These cancers behave like skin cancers. The other 10 percent of lip cancers are basal cell carcinomas or melanomas. This type of cancer begins with a sore, usually a bleeding sore that does not heal. If not treated, this cancer may move into other portions of the mouth, such as the tongue and the mucous membranes inside the lips. The next spread of the cancer may be into the lymph nodes, and the cancer may spread even farther into other areas of the body. Generally, cancers that begin in the upper lip (about 60 percent of all lip cancers) are more aggressive than those that originate in the bottom lip and may be more likely to spread. Incidence: Most people (around 90 percent) who develop lip cancers are over the age of forty-five, and as age increases, this type of cancer is even more likely. Men are more likely (up to two to three times) than women to get this cancer. Fair-skinned people are also more likely than those with darker skin to develop lip cancer. About 13 out of 100,000 people in the United States will be diagnosed with lip cancers. The incidence of lip cancers is increasing, especially among women. This is thought to be because people are exposing themselves to the sun more often
Squamous cell carcinoma of the lip. (Dr. P. Marazzi/Photo Researchers, Inc.)
Salem Health: Cancer without using sunscreen, or perhaps because people are less likely to wear a hat as sun protection. Symptoms: Symptoms include lumps, sores, or white spots on the lips, particularly a bleeding or open sore that does not heal in a reasonable time. Lumps or white spots may or may not be painful. Pain may also be felt in a lymph node near the lip area. Nearly 40 percent of lip cancers begin in the lower lip. Screening and diagnosis: Dentists often perform a screening for lip and other oral cancers at a regular dental checkup by examining the lips and mouth for suspicious symptoms. X rays may also help spot a lip cancer. Noncancerous sores, lumps, and white spots often occur on the lips, and lip cancer may resemble these conditions. Because of this, biopsy (removing a small piece of tissue and examining it under a microscope for cancerous cells) is the generally preferred method of diagnosis. Staging of lip cancer is broken into four parts based on how large the tumor or sore is and how far the cancer has spread. • Stage I: The tumor is less than 2 centimeters (cm) and has not spread. • Stage II: The tumor is more than 2 cm but less than 5 cm and has not spread. • Stage III: The tumor is larger than 4 cm, or the tumor is any size and the cancer has spread to a lymph node in the neck on the side that the cancer is located with the lymph node being no more than 3 cm. • Stage IV: The cancer has spread to the mouth or other areas around the lip (with or without lymph node involvement); the cancer is any size and has spread to more than one lymph node on the same side of the neck, has spread to lymph nodes on both sides of the neck, or has spread to any lymph node that measures more than 6 cm; or the cancer is any size and has spread to other parts of the body. Treatment and therapy: Surgery is generally the first line of treatment for lip cancer, especially in Stages I and II. Chemotherapy (using chemicals in the bloodstream to kill cancer cells) or radiation therapy (using high-energy rays to focus on and kill cancer cells) may also be necessary depending on whether the cancer has spread. Chemotherapy or radiation therapy may also be used before surgery to shrink a tumor. In Stages III and IV, the lymph nodes affected by the cancer are also surgically removed. Some other types of treatment may be possible depending on the size or extent of the cancer. These types of treatment may involve freezing or burning the cancerous cells on the lips or using chemicals in an acid, cream, solution, or ointment applied to the lips to kill the cancerous cells.
Lip cancers
Stage at Diagnosis and Five-Year Relative Survival Rates for Lip Cancers, 1988-2001 Stage Stage I Stage II Stage III Stage IV Unstaged
Cases Diagnosed (%)
Survival Rate (%)
83.2 5.5 1.5 2.2 7.6
96.3 82.7 56.7 48.1 88.3
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Surgical treatment of this type of cancer always takes into consideration the patient’s ability to eat and speak following tissue removal. If treatment of a lip cancer involves surgical removal, reconstructive surgery may be needed. Even with reconstructive surgery, however, there may be significant changes in eating and speaking abilities, especially if muscle tissue is removed. Occupational or speech therapy may improve those functions. Other treatment may involve counseling for issues dealing with scars or disfigurement from the surgery. Patients may need to work with a nutritionist to ensure proper nutrition and eating habits after surgery or during radiation therapy, when the lips and mouth may be sore, making eating difficult. A promising treatment for lip cancer therapy is hyperthermia, a process that uses heat to kill cancer cells. In this type of therapy, a special machine heats the body for a certain amount of time. Cancer cells are often more sensitive to heat than healthy cells, so this treatment may kill the cancer while leaving healthy cells intact. This type of therapy may also be combined with other types of therapy, such as freezing or burning the cancer cells. Prognosis, prevention, and outcomes: Quitting smoking is the most effective prevention for any type of oral cancer. Quitting pipe smoking is helpful for lip cancer in particular, as it is more closely associated with lip cancer. It is thought that the heat of the pipe stem on the lips increases the likelihood of cancer developing on the lips. Other preventive measures include avoiding sun exposure, using lip balm or lipstick with an sun protection factor (SPF) rating of 15 or more, limiting use of alcohol, and increasing consumption of fruits and vegetables. 711
Liposarcomas
Salem Health: Cancer
Prognosis and outcomes are very good for patients when lip cancer is discovered early, especially in Stage I or II, and the cancer is squamous-cell based, with survival rates of over 90 percent. If the cancer is at Stage III or IV when discovered, survival rates fall to about 50 percent. Survival rates for those with lip cancers that are carcinoma based are about 10 to 20 percent less than the squamousbased survival rates. Early identification and diagnosis of lip cancer have improved prognosis. Only about 112 individuals die from this cancer each year in the United States. Marianne M. Madsen, M.S.
malignant soft-tissue tumors and usually manifests as a nonspecific soft-tissue mass. Frequently the fat it contains is not radiographically detectable. Liposarcoma demonstrates a wide range of manifestations and prognoses, ranging from a well-differentiated nonmetastasizing neoplasm with good prognosis to a high-grade sarcoma with hematogenous metatastases to the lung and the visceral organs.
u For Further Information Brockstein, Bruce, and Gregory Masters, eds. Head and Neck Cancer. Boston: Kluwer Academic, 2003. “Disorders of the Oral Region: Neoplasms.” In The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers and Robert Berkow. 17th ed. Whitehouse Station, N.Y.: Merck Research Laboratories, 1999. Scully, Crispian, et al. Dermatology of the Lips. Oxford, England: Isis Medical Media, 2000.
Etiology and the disease process: Liposarcoma is a malignant tumor of mesenchymal origin with the microscopic appearance of adipose tissue, although in some cases it does not contain visible fat. It is made up of several cell types. The well-differentiated type of liposarcoma, which has the best prognosis, has mature lipocytes with varying degrees of nuclear atypia. It is seen in only 15 percent of cases. The most common type, accounting for 40 to 50 percent of all liposarcomas, is the myxoid type, which is composed of proliferating fibroblasts with less than 10 percent fat. This type of tumor often metastasizes to serosal and pleural surfaces, subcutaneous tissue, and bone. The pleomorphic type is seen in approximately 20 percent of cases and is a highly anaplastic tumor with pleomorphic (many sized and shaped) cells growing in a disorderly fashion. The round-cell type is seen in less than 10 percent of cases, is poorly differentiated, and is often associated with hemorrhage and necrosis. It is highly cellular, composed of primitive small round cells. Retroperitoneal liposarcoma is a slow-growing variant that rarely metastasizes and usually displaces rather than infiltrates or invades surrounding tissues.
u
Other Resources
National Cancer Institute Lip and Oral Cavity Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ lip-and-oral-cavity/patient Support for People with Oral and Head and Neck Cancer http://www.spohnc.org See also Chewing tobacco; Cigarettes and cigars; Epidermoid cancers of mucous membranes; Erythroplakia; Head and neck cancers; Hyperthermia therapy; Leukoplakia; Oral and maxillofacial surgery; Oral and oropharyngeal cancers; Risks for cancer; Skin cancers; Symptoms and cancer; Tobacco-related cancers.
u Liposarcomas Category: Diseases, symptoms, and conditions Also known as: Soft-tissue liposarcomas Related conditions: Soft-tissue sarcomas Definition: Liposarcomas are the second most common malignant soft-tissue sarcomas in adults after malignant fibrous histiocytoma (MFH). Liposarcoma, a mesenchymal sarcoma, accounts for between 12 and 18 percent of all 712
Risk factors: A relationship to trauma has been reported. The myxoid and round-cell type of liposarcoma are associated with a reciprocal translocation between chromosomes 12 and 16.
Incidence: Liposarcomas represent between 12 and 18 percent of all malignant soft-tissue tumors, and annually 2.5 cases occur per 1 million population. Symptoms: Liposarcoma usually manifests as a large, painless mass between 2 and 30 centimeters (cm) in size, associated with weight loss in a patient between the ages of fifty and sixty. It is slightly more common in men than in women. Liposarcoma can be painful in 15 percent of patients because of the compression of the adjacent neurovascular bundle or adjacent abdominal organs. Retroperitoneal tumors can weigh several pounds. Screening and diagnosis: Liposarcomas are best diagnosed by magnetic resonance imaging (MRI) with gadolinium intravenous contrast. The tumor appears as a large
Salem Health: Cancer
Liposarcomas
Stage at Diagnosis and Five-Year Relative Survival Rates for Liposarcoma, 1988-2001 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
65.9 21.3 5.7 7.1
90.9 74.4 30.8 70.1
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
hypervascular septated mass containing fat and soft tissue. In contradistinction to a lipoma, liposarcoma enhances with intravenous contrast. Liposarcoma can have large areas of necrosis and hemorrhage and can be located in the trunk or retroperitoneum in approximately 42 percent of cases, in the lower extremities in 41 percent of cases, in the upper extremities 11 percent of the time, and in the head and neck in 6 percent of cases, with predilection for the thigh and retroperitoneum. The more differentiated the tumor, the closer the signal characteristics of the tumor approach that of fat. Myxoid and pleomorphic tumors may demonstrate little or no fat on computed tomography (CT) scans. On nuclear medicine positron emission tomography (PET) scans, the tumor is fluorodeoxyglucose (FDG) avid. According to the World Health Organization classification, liposarcoma includes well-differentiated, myxoid, pleomorphic, and round-cell types, with the most common type being the myxoid type (50 percent of all liposarcomas). Myxoid liposarcoma can appear benign on MRIs. These gelatinous lesions can demonstrate a cystlike appearance. High-grade liposarcoma often contains no recognizable fat and as such is indistinguishable from other soft-tissue malignancies. As with most malignant musculoskeletal tumors, surgical staging depends on pathology, compartmentalization, and presence or absence of metastases: • Stage Ia: Low grade, intracompartmental • Stage Ib: Low grade, extracompartmental • Stage IIa: High grade, intracompartmental • Stage IIb: High grade, extracompartmental
•
Stage IIIa: Low or high grade, intracompartmental, presence of metastases • Stage IIIb: Low or high grade, extracompartmental, presence of metastases Treatment and therapy: The treatment depends on the stage at diagnosis. Stage I lesions are handled with surgical resection with wide margins. Stage II lesions are treated with more radical resection, possible amputation, and radiation therapy. Therapy for Stage III lesions includes surgical resection with radiation and chemotherapy. Prognosis, prevention, and outcomes: The well-differentiated type of liposarcoma has the best prognosis, with overall five-year survival rates exceeding 80 percent. However, even with the well-differentiated type, there can be local recurrence. The well-differentiated type rarely metastasizes, unlike the pleomorphic and round-cell types, which metastasize and have a five-year survival rate of only 50 percent. A size greater than 15 centimeters connotes a poor prognosis. Retroperitoneal liposarcoma is the most radiosensitive of all soft-tissue sarcomas, with an overall five-year survival of 32 percent. Debra B. Kessler, M.D., Ph.D. u
For Further Information Bergquist, Thomas H. MRI of the Musculoskeletal System. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001. Kumar, Vinay, et al., eds. Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Elsevier Saunders, 2005. Stoller, David W. Magnetic Resonance Imaging in Orthopedics and Sports Medicine. Philadelphia: J. B. Lippincott, 1993. Stoller, David W., et al. Diagnostic Imaging: Orthopedics. Salt Lake City, Utah: Amirsys, 2006. u
Other Resources
The Liddy Shriver Sarcoma Initiative Liposarcoma http://liddyshriversarcomainitiative.org/Newsletters/ V01N05/Liposarcoma/liposarcoma.htm Sarcoma Foundation of America http://www.curesarcoma.org/ See also Afterloading radiation therapy; Agent Orange; Alveolar soft-part sarcomas; Fibrosarcomas, soft-tissue; Hemangiosarcomas; Hyperthermic perfusion; Magnetic resonance imaging (MRI); Malignant fibrous histiocytoma (MFH); Malignant tumors; Mesenchymomas, malignant; Sarcomas, soft-tissue; Synovial sarcomas. 713
Liver biopsy
u Liver biopsy Category: Procedures Also known as: Liver needle biopsy, fine needle aspiration biopsy, laparoscopic liver biopsy, transvenous or transjugular liver biopsy Definition: A liver biopsy is the removal of a small sample of liver tissue through a needle or surgically. The tissue sample is examined in the laboratory for the presence of cancer cells. Cancers diagnosed: Liver cancer Why performed: A liver biopsy is performed to diagnose liver disease and assess the degree of liver damage (disease staging). It may be performed when a liver abnormality is found during an ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI) test or nuclear scan. It may also be performed to determine the cause of unexplained jaundice (yellowing of the skin) or abnormal results of liver function blood tests. Patient preparation: One week before the procedure, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician. Ablood test will be performed before the procedure to evaluate the patient’s blood and platelet count and clotting ability of the blood. Patients must not eat or drink for eight hours beforehand. Steps of the procedure: In fine needle aspiration biopsy, an intravenous (IV) line is inserted into a vein in the patient’s arm to deliver medications. In many hospitals, a sedative is given to the patient before the procedure (conscious sedation), so that the patient is awake but relaxed and able to respond to the physician’s instructions during the procedure. The patient lies on the back, with the right hand above the head, remaining as still as possible during the procedure. The biopsy site is cleansed, and a local anesthetic is injected into the area where the needle will be inserted. A small incision is made on the right side of the chest, near the rib cage. Ultrasound is often used to guide the biopsy needle that is placed through the incision into the liver. The physician may ask the patient to hold his or her breath for up to ten seconds while the needle is placed in the liver. A small sample of liver tissue is removed through the needle for analysis in a laboratory. During a laparoscopic biopsy, a laparoscope (a small camera on a thin tube) is inserted into a small abdominal incision. The laparoscope transmits magnified images of the liver onto a video monitor to guide the physician as laparoscopic instruments are inserted through additional 714
Salem Health: Cancer small abdominal incisions to remove tissue samples from one or more parts of the liver. General anesthesia is usually used with this type of biopsy. A laparoscopic biopsy may be used when a tissue sample is needed from more than one area of the liver or when a larger tissue sample is needed. During a transvenous biopsy (also called transjugular biopsy), a catheter (thin tube) is inserted into a vein in the neck and guided to the liver. A biopsy needle is inserted through the catheter to collect the sample of liver tissue. This technique is not common, but it may be used for certain high-risk patients, including those who have a bloodclotting disorder, fluid in the abdomen, or liver failure or who are morbidly obese. After the procedure: The patient stays in a recovery room and lies on the right side for four to six hours after the procedure. Pain medication may be prescribed, if needed, to relieve minor discomfort or pain in the shoulders or back. The patient should not drive or operate machinery for eight hours after the procedure. Depending on the physician’s instructions, the patient may be required to stay on bed rest at home for eight to ten hours after the procedure. The patient should avoid vigorous physical activity and heavy lifting, as directed by the physician. The patient may feel discomfort at the incision site and in the right shoulder for a few hours to a few days after the procedure. For one week after the biopsy, the patient should avoid aspirin and products containing aspirin, ibuprofen, and anticoagulants, as these medications decrease blood clotting, which is necessary for healing. The patient may take acetaminophen (Tylenol) to relieve pain as needed after the procedure. Risks: With ultrasound guidance, liver biopsy is a relatively safe procedure, with a 0.6 percent risk of complications. Although rare, the complications of a liver biopsy include puncture of the lung or gallbladder that may result in bile leakage, internal bleeding, and infection. The risk of death (mortality rate) of the liver biopsy procedure is approximately 1 in 10,000 to 12,000. Results: The tissue sample that was removed during the procedure may be benign (noncancerous) or malignant (cancerous). The type of cancerous cells and extent of disease will help guide the patient’s treatment. Angela M. Costello, B.S. u
For Further Information Grant, A., and J. Neuberger, for the British Society of Gastroenterology. “Guidelines for the Use of Liver Biopsy in Clinical Practice.” Gut 45, suppl. 4 (1999): IV1IV11.
Salem Health: Cancer Scheuer, Peter J., and Jay H. Lefkowitch. Liver Biopsy Interpretation. 7th ed. Philadelphia: Elsevier Saunders, 2006. Siegel, C. A., et al. “Liver Biopsy 2005: When and How?” Cleveland Clinic Journal of Medicine 72, no. 3 (2005): 199-224. u
Other Resources
American Liver Foundation http://www.liverfoundation.org American Society for Gastrointestinal Endoscopy (ASGE) http://www.askasge.org International Foundation for Functional Gastrointestinal Disorders http://www.iffgd.org National Digestive Diseases Information Clearinghouse (NDDIC) http://digestive.niddk.nih.gov/index.htm See also Alcohol, alcoholism, and cancer; Biopsy; Chemoembolization; Computed tomography (CT) scan; Gastrointestinal oncology; Hemochromatosis; Hepatitis B virus (HBV); Hepatitis C virus (HCV); Hepatomegaly; Laparoscopy and laparoscopic surgery; Liver cancers; Needle biopsies; Oncogenic viruses; Risks for cancer; Surgical biopsies; Virus-related cancers.
u Liver cancers Category: Diseases, symptoms, and conditions Also known as: Hepatocellular carcinoma (HCC), malignanat hepatoma, silent disease Related conditions: Hepatoblastoma, bile duct cancer, angiosarcoma Definition: Liver cancer is a condition in which the liver develops tumors both internally and externally, with severe disruptions to its normal functioning. When tumors develop as a result of mutations in liver cells (called hepatocytes), the result is primary liver cancer. Liver cancer also occurs as a result of tumors developing in other parts of the body and migrating to the liver through a process called metastasis (secondary liver cancer). Risk factors: A number of factors are considered potential risks for the development and metastasis of liver cancer.
Liver cancers
•
Chronic liver infections: Certain types of viruses such as hepatitis B (HBV) and hepatitis C (HCV) invade liver cells and induce chronic liver infections. Of these, HBV infection is more common in South Asia and in Africa, while HCV infection is more prevalent in Japan and the Western countries. HBV infection is acquired at birth and becomes persistent because of exposure to certain substances such as aflatoxins, while HCV infection occurs mainly because of contaminated blood and is spread through intravenous drug usage. People diagnosed with chronic liver infections face the highest risk for developing liver cancers. • Cirrhosis: When liver cells become heavily damaged, often because of drug or alcohol abuse, a condition called cirrhosis arises. Cirrhosis is the cause of tumor development in 5 percent of liver cancers. • Aflatoxins: Aflatoxins are produced by some molds and are formed commonly in nuts, corn, and grains. Aflatoxin B1 is a major environmental factor in inducing hepatocellular carcinoma. Evidence shows that aflatoxins can induce mutations in certain beneficial genes called tumor-suppressor genes and activate the Wnt signaling pathway (a family of cell-signaling molecules) leading to hepatocellular carcinoma. • Race, gender, and age: The highest prevalence of liver cancer is seen in Southeast Asia (particularly in Vietnam) and sub-Saharan Africa. Men are twice as likely to have the disease as women. In the United States, African Americans are more prone to develop hepatocellular carcinoma. People above the age of sixty also have a higher probability of developing liver cancer. • Chemicals: Exposure to chemicals such as arsenic and polyvinyl chloride (PVC) poses a risk for development of liver cancer. • Genetic factors: Certain genetic disorders such as hemochromatosis and Wilson disease predispose individuals to hepatocellular carcinoma. • Diabetes mellitus: There is increasing evidence to show a correlation between hepatocellular carcinoma and diabetes mellitus. Etiology and the disease process: Primary liver cancer, like most cancers, commences with a cell that undergoes disruptive mutations affecting normal growth and death processes. These mutations occur primarily through specific interactions between viral infections and chemicals such as aflatoxins. Chronic liver infections with the hepatitis B virus cause inflammation of the liver, resulting in the release of free radicals, chemokines, and cytokines. In high concentrations, these are capable of damaging deoxyribonucleic acid (DNA), resulting in mutations of genes. 715
Liver cancers
Salem Health: Cancer
Viral infections also result in upregulation (an increase in the number of receptors on target cells) of certain proinflammatory cytokines (proteins secreted by the immune system) such as tumor necrosis factor-alpha (TNFα), interferons (IFNs), and interleukins (ILs). Such changes induce DNA damage, rapidly resulting in mutations of specific genes involved in cancer, called tumor-suppressor genes. A tumor-suppressor gene that has been extensively implicated in many types of cancers, including liver cancers is TP53. Mutations in the TP53 gene result in either prevention of damaged proteins from undergoing apoptosis or blockade of cell-cycle checkpoint controls. These effects result in uncontrolled growth of mutated cells, ultimately leading to tumor formation. Tumors then establish themselves by developing new blood vessels and deriving oxygen and nutrients from their environment. In patients with cirrhosis, liver cancer starts with the development of small nodules called dysplastic nodules. These are distinct structures and can be easily distinguished from surrounding normal cells by their size, color, or texture. Transforming growth factor-alpha (TGFα) and
insulin growth factor 2 (IGF-2) are some of the cytokines that are released during this phase, triggering extensive proliferation of hepatocytes. Incidence: Liver cancer is the most rapidly growing cancer in the United States and the fifth most common malignancy around the world. It is the third most common cause of cancer-related deaths. According to studies by the National Cancer Institute based on data from 2000 to 2004, the incidence rate for liver cancer in the United States is higher for men than for women. The age-adjusted mortality rate was 7.1 per 100,000 people per year for men and 3.1 per 100,000 for women. The overall five-year survival rate from 1996 to 2003 was 10.8 percent. In 2007, new cases of liver cancer were estimated to reach about 13,650 in men and 5,510 in women, and deaths from liver cancer were estimated at 11,280 men and 5,500 women. Symptoms: Major symptoms of liver cancer include abdominal pain on the right side that might spread to the back and shoulder, weight loss, loss of appetite, feeling easily satiated, nausea and vomiting, jaundicelike symptoms, and fever.
A liver covered in widespread secondary cancers. (CNRI/Photo Researchers, Inc.)
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Salem Health: Cancer Screening and diagnosis: Screening of liver cancer involves the following procedures: • Computed tomography (CT) scans: CT scans are screening techniques by which information about internal organs is computed using X rays. • Tests for tumor markers: Certain substances are secreted by tumors and thus can be used as tumor markers. Alfa-fetoprotein (AFP) is a typical example of such a marker. Normally the highest amounts of AFP are secreted in fetuses, and the level of the protein gradually decreases in adulthood. Almost a hundredfold increase in levels of AFP can be detected in liver tumor cells. However, some concerns have arisen about false positives and the most appropriate fraction of AFP to use as a tumor marker. Other liver tumor markers include hepatoma-specific gammaglutamyl transpeptidase (HS-GGT), TGF-β1 and IGF-2. • Magnetic resonance imaging (MRI): MRI is a technique used to decipher structural details of internal organs using their responses to magnetic fields. MRI has excellent soft-tissue contrast and is ideal for tissues with air spaces and bones. Also, MRI is very flexible with imageplane control, enabling better resolution of details. A tumor can be easily picked up because of its differential responses compared with normal tissue. • Biopsy: A small amount of tissue removal is called biopsy. Tissue obtained is scrutinized under a microscope to study the cellular architecture. A cancer cell is distinct in its morphology compared with a normal cell and can easily be distinguished. A variety of methods like fine-needle aspirations, cone biopsy, or laparoscopy can be used to excise the sample tissue. Staging is an important process in cancer testing. Staging determines the extent of cancer formation, and treatment options are decided based on the stage of the cancer at the time of diagnosis. Stages are determined based on the following criteria: size of the tumor, development of tumor in one or both lobes of the liver, growth of tumors in and around major blood vessels, and spread of cancer to lymphatic nodes and other organs of the body. Based on these criteria, liver cancer is divided into four stages, Stages I through IV, some stages having a few subclasses within. Treatment and therapy: Surgery is still the standard treatment for liver cancers. The choice between the two surgical options, resection and liver transplantation, depends on the stage and extent of spread. When the tumor is small, has not spread to other regions, and is not complicated by cirrhosis, resection is possible. The process, called partial hepatectomy, removes the portions of the liver beset with the tumor. Liver cells
Liver cancers
Stage at Diagnosis and Five-Year Relative Survival Rates for Cancer of the Liver and Intrahepatic Bile Duct, 1996-2004 Stage Localizeda Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
33 25 20 21
22.3 7.3 2.8 4.4
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
have the remarkable capacity to regenerate following surgery, and surgical methods take advantage of this property. When resection is not possible because of poor liver function or metastasis, whole-liver transplantation is considered the treatment of choice. Tumors are assessed on the basis of the Milan criteria, which help determine the suitability for liver transplantation. Typically, patients whose cancers measure up to the following limits—one nodule greater than or equal to 5 centimeters (cm), two to three nodules greater than or equal to 3 cm—are considered to be within limits defined by the Milan criteria and are eligible for liver transplantations. Sometimes these criteria can be expanded, depending on the circumstances. Liver transplantation requires the availability of either a complete or partial liver, depending on the state of the donor. If the donor is deceased, a whole liver is required, but if the donor is alive, a small portion of the liver is sufficient. Patients slated for whole-liver transplantation have to undergo long periods of waiting (usually close to a year), and this often leads to large numbers of dropouts as well as patients in whom the cancer has spread and who no longer meet the Milan criteria. With liver transplants from living donors, only small portions of the liver are needed, and more patients can benefit from a single donor. However, the acceptable rate of recurrence has not been defined well in cases involving living donors, and there are still lingering concerns about donor safety. In some cases, nonsurgical options are preferred, and many of these methods have proven to be effective at vari717
Liver cancers ous stages of liver cancer. Transarterial chemo embolization (TACE) can be used when the tumor is larger than 4 cm and there are multiple lesions. This treatment takes advantage of the fact that the liver receives its blood supply from two main sources—the hepatic artery and the hepatic portal vein—and that the major supplier of blood to the liver is the hepatic artery. In this way, the liver is a unique organ. During TACE, an angiographic catheter is introduced in the branches of the hepatic artery. An anticancer drug (for example, doxorubicin) is injected through the catheter, and the hepatic artery is blocked with occluding agents such as polyvinyl alcohol beads, which get transported to terminal hepatic arteries and occlude the vessels. The liver can still be healthy and functional using a blood supply derived from the alternative route of portal veins. Percutaneous ethanol injection (PEI) is more effective with a small hepatocellular carcinoma. Cancer cells are susceptible to treatment with ethanol, which is injected directly into the tumor under the guidance of percutaneous ultrasound. Because of the soft nature of the hepatocellular carcinoma within the hardened cirrhotic liver, diffusion of the alcohol is easily attained. Chemotherapy uses drugs to cure tumors or to alleviate pain. A single class or a combination of a few classes of drugs may be administered in specific cases. Most commonly used drugs are doxorubicin, uracil-tegafur (UFT), or sorafenib. Tumors that are between 2 and 4 cm are treated with radio frequency ablation. Tumors are exposed to small electrodes emitting radio frequency waves. The energy generated by these waves destroys a specific zone comprising the tumor and a small region surrounding it. Magnetic resonance-guided microwave coagulation therapy (MR-MCT) makes use of a vertical type, openconfiguration magnetic resonance system as opposed to the horizontal type that is typically used. Immunotherapy involves modifying genes that are part of the body’s immune system to combat cancer. The most common immunotherapy strategies are making the tumor more capable of immunogenic responses, modifying the microenvironment surrounding the tumor and making it less immune suppressive, and activation of both specific and nonspecific immune responses. All these methods have selective advantages and have improved chances of cure and survival in liver cancer patients. Prognosis, prevention, and outcomes: Generally the prognosis for liver cancer is poor, because this particular cancer is difficult to diagnose while in the early stages.
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Salem Health: Cancer Once the symptoms manifest themselves, the cancer generally has already spread to some extent. Therefore, survival rates among people diagnosed with liver cancer are low. Preventive measures include vaccination against known viruses (such as hepatitis B) as well as a healthy diet, avoidance of chemical exposures, and abstinence from alcohol. The efficacy of various interferons in the treatment of liver cancer is under investigation. Clinical trials involving the targeted drug sorafenib have produced tremendous improvements in patients with advanced liver cancer. Advances in imaging techniques and a better understanding of the molecular mechanisms involving the development of liver cancers have improved the outcomes of this disease. Geetha Yadav, Ph.D. u
For Further Information Butterfield, L. H. “Recent Advances in Immunotherapy for Hepatocellular Cancer.” Swiss Medical Weekly 137 (2007): 83-90. Hanahan, D., and R. A. Weinberg. “Hallmarks of Cancer.” Cell 100 (2000): 57-70. Kulik, L. M. “Advancements in Hepatocellular Carcinoma.” Current Opinion in Gastroenterology 23 (2007): 268274. Schwartz, M., et al. “Strategies for the Management of Hepatocellular Carcinoma.” Nature Clinical Practice (Oncology) 4 (2007): 424-432.
u
Other Resources
American Cancer Society http://www.cancer.org Cancer Backup Primary Liver Cancer http://www.cancerbackup.org.uk/Cancertype/Liver/ Primarylivercancer Cancer.Net http://www.cancer.net/portal/site/patient/ National Cancer Institute http://www.cancer.gov See also Bile duct cancer; Hepatic arterial infusion (HAI); Hepatitis B virus (HBV); Hepatitis C virus (HCV); Hepatomegaly; Liver biopsy; Percutaneous transhepatic cholangiography (PTHC); Virus-related cancers.
Salem Health: Cancer
u Living will Category: Social and personal issues Also known as: Advanced directives for terminal health care Definition: A living will is a legal document that indicates the care a person wishes to receive if afflicted by a terminal illness that is irreversible and certain to prove fatal. Patients with certain types of cancers or late-stage cancers may find this document useful for dealing with end-of-life issues. Who executes a living will? Those establishing living wills are often people in good health who wish to make provision for their end-of-life care should they become gravely ill. However, some gravely ill people (such as a person with late-stage cancer) execute such a document after their health has deteriorated to the point that there is no hope of recovery. The person executing a living will must be of legal age and of sound mind. Related documents: Besides a living will, it is advisable for those implementing such a document to sign a medical power of attorney (MPOA). This document, signed and notarized, should be held by a trusted friend or relative or by the person’s attorney. The MPOA authorizes a designated person or persons to make decisions relating to the an individual’s care should that person be unable to make such decisions. Whoever holds the MPOA should be trustworthy and sufficiently objective to make informed decisions regarding treatment. The person or people holding the MPOA should have a realistic view of what the patient would want if he or she were making the needed medical decisions. It is desirable to have both living wills and MPOAs drawn up by an attorney, although standard forms for executing these documents are available at most hospitals or through the National Hospice and Palliative Care Organization. Procedures to be specified in a living will: No one can foresee every eventuality in end-of-life situations, but commonly used procedures for extending life should be carefully considered when executing a living will. Sometimes terminally ill patients, especially those suffering from some forms of cancer, experience excruciating pain, so the living will should specify that if medical opinion considers a patient terminal, palliatives available to reduce or control that pain should not be withheld. Some terminal patients are not conscious, are unaware of their surroundings, or may be brain-dead. When this is the case, ventilators or respirators keep them alive. Even if
Living will they are conscious, these instruments may limit their ability to communicate. A living will should specify whether mechanical ventilation should be employed if a patient is unable to make such a decision. The living will might indicate the conditions under which ventilators or respirators should be used and for how long their use should continue. The hearts of terminally ill patients may stop beating, but often such patients can be revived through cardiopulmonary resuscitation (CPR) or electrical stimulation. The living will can specify that treatments of this sort are not to be employed if the heart stops and that the patient’s chart should be clearly marked do not resuscitate (DNR). Terminally ill patients in comas may be kept alive through the use of some of the measures noted above, but they require nutrients and liquids to sustain their lives. The living will should stipulate whether nutritional and hydration measures should be used if it is clear that they can prolong life. Such treatment can be administered intravenously or through a stomach tube. The living will should indicate the extent to which such measures are to be implemented and, if they are used, for how long their use should continue. Many patients who suffer renal failure are kept alive through dialysis, a procedure that removes harmful and potentially fatal waste from the blood and controls the body fluids that healthy kidneys control automatically. In addressing the question in a living will, it is important to realize that dialysis may be necessary only temporarily but that some types of kidney failure will require it on a sustained basis. Those with kidney cancer should consider the ramifications for their situation. The living will should specify how the person signing it wishes to be treated if infections develop that would normally indicate the use of antibiotics. Those making living wills must ask whether they would wish to have an infection controlled through medication, mechanical ventilation, or other means to recover only from the infection but not from the condition that has rendered them terminally ill. A living will can also indicate the postmortem disposition of organs and body parts for transplantation. Not every eventuality can be foreseen by the person drawing up a living will. It is both desirable and necessary, therefore, to execute a MPOA that leaves medical decisions in the hands of a responsible person. Legal considerations: If a living will is not on file, medical facilities and their employees risk legal action for malpractice or even manslaughter if a patient dies who might have been kept alive through available treatments. The living will absolves medical facilities and personnel from legal action in cases in which terminally ill patients die 719
Living with cancer because life-prolonging treatments specified in the document have been withheld. Some physicians have moral reservations about permitting patients to die if they can be kept alive by artificial means. When a living will is on file, patients’ desires are clearly stated. Any physician who disagrees with their desires can withdraw from the case. R. Baird Shuman, Ph.D. u
For Further Information Colen, B. D. The Essential Guide to a Living Will: How to Protect Your Right to Refuse Medical Treatment. New York: Prentice Hall, 2001. Hamas, Edward A. How to Write Your Own Living Will. Naperville, Ill.: Sphinx, 2002. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003. Raymond, Joan. “A Guide for Caregivers.” Newsweek, June 18, 2007, 62-64. u
Other Resources
National Cancer Institute Advance Directives http://www.cancer.gov/cancertopics/factsheet/ support/advance-directives National Hospice and Palliative Care Organization http://www.nhpco.org See also Advance directives; Cardiopulmonary resuscitation (CPR); Caregivers and caregiving; Case management; Counseling for cancer patients and survivors; Donot-resuscitate (DNR) order; End-of-life care; Hospice care; Long-distance caregiving; Palliative treatment; Transitional care.
u Living with cancer Category: Social and personal issues Definition: Living with cancer means being alive and as active as possible to enjoy life after having been diagnosed with and treated for cancer. Diagnosis: Cancer affects about 10.5 million Americans who are at various stages of living with their cancer. Although cancer mortality statistics are generally improving, people fear the diagnosis of cancer. When people first learn that they have this disease, the response may be disbelief. They may think the worst and feel overwhelmed. Many questions will surface and may not have definite an720
Salem Health: Cancer swers. To provide the best care, the health care team will need to make certain tests and stage the cancer to see how far the disease has spread. With this information, patients and their health care providers can make decisions on treatments to cure, to control the disease, or to minimize symptoms. Each person experiences cancer differently; becoming a partner in the treatment plan means making choices in many aspects of life. Education: C. Everett Koop, former surgeon general of the United States, advised that “the best prescription is knowledge.” One effective way for patients to face life with cancer is for them to learn as much as possible about the specific diagnosis. Numerous sources are available to provide further education on cancer in general and in detail. Cancer patients may want to know about statistics, risk factors for their type of cancer, staging terms and what they mean, treatment options, and the likelihood of the patient to survive and recover from the cancer and treatments (prognosis). The first contact for patient education is the health care provider. These professionals can offer information specific to the patient such as the type of cancer, stage of cancer involvement, and options for therapy. Cancer patients should take the initiative to talk with their health care providers to fully understand their unique situation. With that information, patients can pursue other avenues of education. There are many sources for learning more about cancer. Information can range from simple explanations to complex scientific documentation. Patients can read articles in popular magazines, buy books on most aspects of cancer care, study health care journals, or look up their cancer on the Internet. Generally, reliable information comes from well-respected and well-established cancer care centers, cancer care organizations, government agencies, or health care organizations. Another source of education is other cancer patients. Attending local support groups and conversing with others who are at different stages of cancer can support and encourage patients. Online Web sites offer message boards where cancer patients can share their personal experiences. Though these can be useful, it is important to remember that this type of information comes from a particular person’s point of view. Cancer patients need to seek further information and clarification from their health care providers or other reliable sources before acting on what another cancer patient says. Coping with cancer: A cancer diagnosis can be stressful for both patients and their families. Patients respond in different ways to their cancer. Many emotions may surface,
Salem Health: Cancer
Living with cancer
Cancer can be a long-term disease, and patients gradually turn from focusing on the disease to living their lives. (Digital Stock)
such as shock, disbelief, fear, sadness, anxiety, depression, anger, and guilt. Patients may question why they have cancer and what lies ahead. Disbelief may come to those who feel physically well. Fear is a common emotion, but the reasons may range from fear of the treatments and side effects to fear of death and the impact on remaining family members. Fear feeds anxiety, which can interfere with normal daily functioning. Guilt is another common emotion of cancer patients. Patients may replay their lifestyle choices and wonder if something they did caused the cancer. They may feel guilt over the decisions they made that stole precious time from their life or guilt about their priorities. As some cancers tend to be hereditary, cancer patients may worry about the impact on their children. Feelings of sadness and hopelessness can block recovery and resumption of meaningful life activities. Depression can come with sleep problems, loss of appetite, feelings of worthlessness, decreased energy, irritability, or lack of interest in activities once enjoyed. Physical symptoms such as headache or digestive problems may occur. Feeling sad is a normal reaction when people learn that
they have cancer, but if depression continues and thoughts of suicide surface, patients may require help through counseling and prescribed medications. Cancer patients experience the feeling of loss—loss of control, autonomy, dreams, choices, or the future. Loss is a normal feeling and allows cancer patients to grieve over actual or perceived interruptions in their lives. Counseling may be useful for both cancer patients and their families. Taking action: Cancer can be a long-term disease and last for many years. Cancer patients experience an initial adjustment to their diagnosis and treatment. The focus of their first thoughts may be on dying, but as time goes on, these thoughts shift to their normal lives. Taking certain steps can help cancer patients reengage in their usual activities of daily living. One helpful step is paying attention to personal needs for rest, nutrition, recreation, and relationships. Relaxation activities such as meditation and guided imagery can assist in healing and encourage good mental health. Adequate nutrition is important to keep the immune system at an optimal level. 721
Living with cancer Participating in activities that patients enjoy, such as going to the movies, listening to music, going to lunch with friends, or pursuing their hobbies, can relieve depression. Creative expression though journaling, writing poetry or stories, reading, or drawing can keep patients’ minds off cancer and minimize projecting into the future. Simply going shopping can be a boost to the morale. Starting or resuming an exercise program can help cancer patients increase strength, improve flexibility, and build endurance. Studies show that exercise can also improve long-term survival. Radiation treatments can result in fatigue, but light or moderate walking can boost energy and stimulate the appetite. Another benefit of exercise is that the release of natural body chemicals, called endorphins, can improve patients’ moods and help relieve pain. Various levels of exercise, such as walking, swimming, cleaning the house, gardening, or dancing, can provide pleasure as well as health benefits. Almost daily the media reports on the value of alternative or complementary therapies. Cancer patients may become interested in these therapies as ways to relax, to reduce side effects of cancer treatment, or to cure their disease. Some of these practices, such as massage, guided imagery, acupuncture, or hypnosis, may be useful when used along with traditional cancer treatments. Vitamins and herbal supplements have gained monumental popularity in the United States. Although some sources claim that herbs and vitamins can cure cancer, these statements are often unfounded. Cancer patients should speak with their health care providers before using alternative therapies. Sometimes cancer patients are unable to perform activities of daily living without assistance. However, by seeking help they can continue to go to the grocery or to church. Friends and family often welcome the opportunity to provide meals or transportation so that they can show love to the cancer patient. Asking for help is not always comfortable for cancer patients who covet their autonomy. However, taking action to seek help is a healthy behavior. Sexuality: Having cancer does not alter the human need for sex and intimacy. However, having this disease can temporarily alter people’s attitudes and desires. Changes in emotions are normal for cancer patients but can affect their relationship with their partners. Physical side effects from cancer treatments such as nausea, vomiting, and fatigue can decrease interest in sex. Cancer therapies can affect the patients’ body image and lessen the confidence in their attractiveness. Women may experience dryness of the vagina, and men may have trouble having or maintaining an erection. Some people believe that cancer can be passed to an722
Salem Health: Cancer other person by intimacy. Partners may be hesitant to engage in sexual intercourse with cancer patients. Also, cancer patients may need to refrain from sex for a period of time because of surgery or a lowered immune system. This can be difficult for both the cancer patient and the partner. Communication is key to resolving misunderstandings. Cancer patients should be open and honest about their concerns with their health care professionals. These professionals can help make referrals for counseling and support when needed. Family dynamics: Cancer changes all aspects of family life. Priorities change and unresolved emotions may surface. There may be more struggles in the family dynamics. Roles may change as cancer patients must use energy and time to take treatments or care for themselves. A reassignment of roles can be overwhelming, especially for older children or youths who now become caregivers. Patients must be allowed to continue to fill as many parts of their family role as possible and not be treated as an invalid. If the dynamics of family life become dysfunctional, a family counselor can help. Spiritual support: Cancer is a serious illness that can challenge people’s spiritual beliefs. Spiritual distress (unresolved spiritual conflict or doubt) can compromise patients’ coping skills. Unlike religion (a set of beliefs, practices, or doctrine), spirituality includes the person’s sense of purpose, relationship to others, and beliefs about life’s meaning. Some cancer patients may feel they are being punished by a higher power or may lose their faith, while others experience a deepening of their faith during their illness. Pastors, rabbis, or other faith leaders may be valuable resources during this difficult time. Some home health and hospice care agencies have chaplains on their interdisciplinary teams and offer home support for cancer patients. The best person for cancer patients to talk with is the one who provides compassionate and supportive communication. Spiritual support can create an improved quality of life for cancer patients. Patients may experience decreased stress, anxiety, or pain. Connecting to others results in less isolation. Spirituality can help cancer patients tolerate treatments better and bring peace in a time of chaos. Life after cancer: Cancer survivors face different challenges. Intensive cancer therapy can leave people with lifelong health concerns. After the treatments or surgery are complete, patients have new questions. Will the cancer come back? Will my life be the same as before I was diagnosed with cancer? Will I need continued observation? Where do I go from here?
Salem Health: Cancer There will be follow-up care that includes regular medical checkups, usually with the primary physician. Tests will most likely occur at specific intervals to check for continued remission (when the cancer is reduced or disappears). If any tests indicate concerns, cancer patients are referred to the cancer health care provider for further assessment. Many survivors say that life has new meaning for them, and they see life in a new light. Priorities have changed. Their bodies have changed. Cancer patients may have made new friends and developed new relationships. Even their diets may have changed. Life and all it has to offer have changed forever. Marylane Wade Koch, M.S.N., R.N. u For Further Information Felder, Tamika. “What Cancer Taught Me About Living.” Essence, July, 2006. Harpman, Wendy Schlessel. After Cancer: A Guide to Your New Life. New York: W. W. Norton, 1994. Kaelin, Carolyn M., and Francesca Coltrera. “Cancer and Staying Fit.” Newsweek, March, 2007. _______. Living Through Breast Cancer. New York: McGraw-Hill, 2005. Krychman, Michael L. One Hundred Questions and Answers for Women Living with Cancer: A Practical Guide for Survivorship. Sudbury, Mass.: Jones and Bartlett, 2007. Ovitz, Joanne K. Facing the Mirror with Cancer: A Guide to Using Makeup to Make a Difference. Chicago: Belle Press, 2004. Stafford, Jacqui. “A Whole New Outlook.” Shape, October, 2004. u
Other Resources
American Psychosocial Oncology Society http://www.apos-society.org Cancer Survivor Network http://www.acscsn.org Cancer.Net http://www.cancer.net/portal/site/patient National Center for Complementary and Alternative Medicine http://nccam.nih.gov Still You Fashions http://www.stillyoufashions.com The Wellness Community http://www.thewellnesscommunity.org
Lobectomy See also Advance directives; Anxiety; Caregivers and caregiving; Case management; Cognitive effects of cancer and chemotherapy; Counseling for cancer patients and survivors; Depression; Elderly and cancer; Electrolarynx; Esophageal speech; Family history and risk assessment; Fertility issues; Financial issues; Grief and bereavement; Home health services; Hospice care; Informed consent; Insurance; Integrative oncology; Karnofsky performance status (KPS); Living will; Medical marijuana; Medicare and cancer; Pain management medications; Palliative treatment; Personality and cancer; Poverty and cancer; Prayer and cancer support; Psycho-oncology; Psychosocial aspects of cancer; Relationships; Second opinions; Selfimage and body image; Sexuality and cancer; Side effects; Singlehood and cancer; Stress management; Support groups; Survivorship issues; Transitional care; Watchful waiting.
u Lobectomy Category: Procedures Also known as: Pulmonary lobectomy, lung lobe removal Definition: Lobectomy is the surgical removal of a lobe of a lung. Cancers treated: Lung cancer Why performed: Lobectomy is a surgical procedure used to treat lung cancer when the tumor is limited to one area of the lung. It may also be used to treat bronchiectasis, tuberculosis, lung abscess, localized fungal infections, or blebs associated with emphysema. Patient preparation: Before surgery, studies are performed to check for abnormalities and establish a baseline for postoperative comparison. These studies include a chest X ray, electrocardiogram (ECG), bleeding time, and blood tests to check kidney function, electrolytes, hemoglobin, oxygen levels, and white blood cell count. Pulmonary function tests are performed to evaluate lung function. A blood sample is also drawn to check the patient’s blood type in case a transfusion is needed during surgery. The patient must not eat or drink for at least eight hours before surgery, and an intravenous (IV) catheter is inserted for fluids and medications. An indwelling urinary catheter may also be inserted so that urine output can be monitored closely during and after the procedure. Steps of the procedure: When the patient arrives in the operating suite, an arterial catheter may be inserted to monitor the patient’s blood pressure and oxygenation. Af723
Lobectomy
Salem Health: Cancer
lobe bronchus and vessels tied off
Lobectomy segment bronchus and vessels tied off
Segmentectomy
main bronchus and vessels tied off
Pneumonectomy suture line
Wedge Resection
Four types of lung surgeries, including a lobectomy. (Custom Medical Stock Photo)
ter the patient is anesthetized, the surgeon makes an incision into the chest cavity. When the chest cavity is entered, the lung collapses. The surgeon locates and ties off sources of bleeding, spreads the ribs, and exposes the area of the lung for removal. The surgeon removes the affected lung lobe and repairs the vessels and lung passages from where it was removed. The surgeon inserts one or two chest tubes to drain fluid and reexpand the lung. Then, the surgeon closes the chest cavity and applies a sterile dressing. After the procedure: The patient is typically transferred to the intensive care unit (ICU) and attached to a monitor that displays heart rhythm, blood pressure, and oxygen saturation. These devices help the ICU nurses closely monitor the patient’s condition. The patient receives supplemental oxygen and IV fluids. The nurses check the chest tube drainage frequently to monitor for excess bleed-
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ing. The patient is encouraged to turn, cough, breathe deeply, and use an incentive spirometer to prevent pneumonia. Sequential compression devices are attached to the patient’s legs to help prevent blood clots. Risks: The risks of lobectomy include surgical site infection, pneumonia, hemorrhage, and respiratory failure. Results: Pathologic examination of the lung specimen reveals the type of cancer. Collette Bishop Hendler, R.N., M.S. See also Bilobectomy; Bronchoalveolar lung cancer; Esophagectomy; Lung cancers; Mesothelioma; Pleural effusion; Pleurodesis; Pneumonectomy; Surgical biopsies; Thoracoscopy; Thoracotomy.
Salem Health: Cancer
u Lobular carcinoma in situ
(LCIS) Category: Diseases, symptoms, and conditions Also known as: Lobular neoplasia Related conditions: Lobular carcinoma, atypical lobular hyperplasia, ductal carcinoma in situ (DCIS), ductal carcinoma Definition: Lobular carcinoma in situ (LCIS) is a type of noninfiltrating breast cancer that originates in the breast lobules. It differs from other breast cancers in its propensity to develop in multiple sites in one or both breasts. Unlike other in situ cancers, LCIS is considered a marker rather than a premalignant lesion for subsequent development of invasive breast cancer. Only 25 to 35 percent of patients with lobular carcinoma in situ develop invasive cancer, compared with patients with other in situ lesions, such as ductal carcinoma in situ (DCIS). Between 25 and 70 percent of those with DCIS will develop invasive breast cancer. Risk factors: Being a woman is a significant risk factor because men do not possess developed lobular breast tissue. Increasing age (forty and above) also contributes to the risk of LCIS. A family history of breast cancer, especially in first-degree relatives, is another significant risk factor, although not specific to any type of breast cancer. White patients have a twelvefold increased risk of LCIS compared with the general population; however, patients of African American origin have a higher rate of recurrence. Other risk factors include obesity, late (or not) first childbirth (older than thirty years), and a prior history of breast cancer. Etiology and the disease process: The etiology of LCIS has been linked in some studies to loss of heterozygosity in chromosome 16q, 17p, and17q (BRCA1 tumor-suppressor gene), which predisposes people to unregulated monoclonal proliferation. An alteration in the E-cadherin adhesion complex has also been noted in LCIS. Lobular carcinoma in situ originates from the terminal duct-lobular apparatus, where it is thought that monoclonal cells from the cellular lining (epithelium) of this apparatus undergo uninhibited proliferation within the lobule. Cells do not possess the atypical findings of other cancer cells, such as increased nucleus-to-cytoplasm ratios, increased cellular division, and loss of cellular cohesion or necrosis. However, the cells are enlarged and possess characteristic mucoid globules that help distinguish LCIS from DCIS. An interesting characteristic of LCIS is that invasion of tis-
Lobular carcinoma in situ (LCIS) sue outside the lobule does not ensue, leaving lobular tissue architecture intact. As a result, LCIS can develop in multiple lobules undetected by clinical breast examinations and mammography. In spite of this, development of invasive cancer from LCIS is slow and may take as long as fifteen to twenty years. Incidence: The overall incidence of LCIS, as documented by breast biopsies with a suspicious mammogram, is estimated at 2 to 5 percent. LCIS accounts for 9.8 percent of all breast malignancies. The diagnosis of LCIS peaks around the mid-forties. It is also interesting to note that more than 90 percent of women diagnosed with lobular carcinoma in situ are premenopausal, which suggests a plausible role of estrogen in LCIS proliferation. Symptoms: LCIS is often missed due to the lack of overt signs and symptoms like those associated with other breast lesions, such as incidental discovery of a breast mass on self-examination, changes in the skin or nipples, and the presence of pain or nipple discharge. More often than not, LCIS is an incidental finding in otherwise normal breast biopsies. The presence of “neighborhood calcifications” in normal tissue surrounding the lesion on mammography is unique to LCIS and may aid in diagnosis. Screening and diagnosis: Screening for all breast cancer follows the American Cancer Society (ACS) recommendations. ACS guidelines recommend that breast examinations be conducted every three years as part of a routine checkup beginning at age twenty (annually beginning at age forty) and that screening mammographies be conducted annually starting at age forty. Diagnosis of LCIS depends on the pathologic findings obtained by needle core biopsy. LCIS may accompany invasive cancer in 5 percent of cases. On microscopic examination, cancer cells may be densely packed and occupy the lobular spaces (acini), terminal ducts, or ductules completely without spread to adjacent structures. The cell nucleus, nucleolus, and cytoplasm are dark-staining and large. Immunohistochemical studies may also reveal E-cadherin-negative cells. Treatment and therapy: Definitive surgical treatment of LCIS is geared toward removal of the multiple sites presumed to be contained in one breast. This is accomplished by surgical removal of the entire breast (total mastectomy) with optional dissection of axillary lymph nodes. The latter is optional because of the rare (less than 1 percent) occurrence of lymph node spread. Prophylactic removal of the opposite breast in the absence of pathological findings is not recommended in spite of the possibility of development of LCIS. Other treatment options include clinical 725
Long-distance caregiving observation and yearly mammography. Tamoxifen, an estrogen-receptor antagonist may be used in reducing the further development of LCIS in the remaining breast. A bilateral total mastectomy is also an option for patients with a familial inheritance of the BRCA1 gene as demonstrated by genetic studies. Prognosis, prevention, and outcomes: Prognosis is generally excellent with complete excision. However, progression to multiple or bilateral LCIS is high, approaching 90 percent and 70 percent, respectively. Simultaneous invasive cancer incidence is 5 percent. Aldo C. Dumlao, M.D. u For Further Information Harding, Fred. Breast Cancer: Cause—Prevention—Cure. Rev. ed. London: Tekline Publishing, 2007. Knox, Sally M., and Janet K. Grant. The Breast Cancer Care Book: A Survival Guide for Patients and Loved Ones. Grand Rapids, Mich.: Zondervan, 2004. Simone, John. The LCIS and DCIS Breast Cancer Fact Book. Raleigh, N.C.: Three Pyramids Publishing, 2002. u
Other Resources
American Cancer Society http://www.cancer.org Cancer Backup Lobular Carcinoma in Situ http://www.cancerbackup.org.uk/Cancertype/Breast/ DCISLCIS/LCIS National Cancer Institute Lobular Cancer in Situ http://www.cancer.gov/cancertopics/pdq/treatment/ breast/HealthProfessional/page6 See also Breast cancer in children and adolescents; Breast cancers; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Ductal lavage; Invasive ductal carcinomas; Invasive lobular carcinomas; Mastectomy; Medullary carcinoma of the breast; Microcalcifications; Mucinous carcinomas; Tubular carcinomas.
u Long-distance caregiving Category: Social and personal issues Definition: Long-distance caregiving is providing for the well-being of another person without being physically present. Caregiving is considered long distance when the 726
Salem Health: Cancer caregiver lives an hour’s travel or farther from the care receiver. The people who receive care usually live in homes, apartments, and other independent living situations. Support services: People who provide long-distance caregiving arrange, manage, or hire one or more of several support services: • Home health care: Physical and respiratory therapy, nursing, home health aides, psychological or psychiatric care, medication assistance, and home medical treatments • Personal care: Help with activities of daily living, such as dressing, bathing, eating, using the toilet, and grooming • Homemaker services: Meal preparation, house cleaning, laundry, shopping for food and other items • Companionship: People who regularly make supportive visits or telephone calls • Live-in assistance: Help provided by people who cook, clean, and perform other nonmedical services in exchange for housing, meals, and a salary • Transportation: Rides to and from medical appointments, religious services, and other places Prevalence: Millions of families and friends live far apart, and millions of people have cancer and other health challenges. Career, education, family situations, and other life demands often separate caregivers from care receivers. Physical distance does not free caregivers from the responsibility of managing the care of others who deal with cancer and other illnesses. Health care organizations estimate that more than 5 million people in the United States provide long-distance caregiving services for others. Strategies: Successful long-distance caregivers organize networks of volunteers and professionals, including their care receivers, who are central to the networks. Teamwork and communication are the guiding principles of these networks. Long-distance caregivers often assign responsibility for components of care. For example, they ask neighbors to do yardwork, or friends to run errands. They stay in contact with these local caregivers to monitor the welfare of the care receiver. When possible, long-distance caregivers join their care receivers at medical appointments to learn about diagnoses, treatments, and ways to manage needs. They also seek advice about care options from doctors, oncology nurses, and social workers. Some long-distance caregivers benefit from creating care notebooks on paper or in computers. They use them to write notes, create lists, and organize information, re-
Salem Health: Cancer
Loop electrosurgical excisional procedure (LEEP) u
sources, medications, and schedules. They log contact information for doctors, therapists, medical facilities, emergency contacts, friends, neighbors, and clergy. Resourceful caregivers might use telephone books from care receivers’ locations or the Internet to find assistance. They gather information about medical facilities, assisted living facilities, nursing homes, hospice care providers, and other resources. They also frequently call or send letters and e-mail messages to care receivers to communicate love and support and to monitor needs. They make regular visits to reassure care receivers that they care and to determine whether home care situations work. Successful long-distance caregivers plan for sudden and unexpected needs. They expect change in care receivers’ situations and plan ahead to deal with it. They prepare to make unexpected visits by researching quick and easy ways to travel to their care receivers. Effective long-distance caregivers make decisions with their care receivers about legal and financial matters. They help organize care receivers’ key legal, financial, and insurance documents. They also ensure that living wills, health directives, and medical and legal powers of attorney are in order and communicated to appropriate professionals.
For Further Information American Medical Association. American Medical Association Guide to Home Caregiving. New York: John Wiley & Sons, 2001. Heath, Angela. Long Distance Caregiving: A Survival Guide for Far Away Caregivers. Atascadero, Calif.: American Source Books, 1993. Karp, Freddie, ed. So Far Away: Twenty Questions for Long-Distance Caregivers. Bethesda, Md.: National Institute on Aging, National Institutes of Health, U.S. Department of Health and Human Services, 2006. Rosenblatt, Bob, and Carol Van Steenberg. Handbook for Long-Distance Caregivers. San Francisco: Family Caregiver Alliance of the National Center on Caregiving, 2003. Sparks, Martha E. Cherish the Days: Inspiration and Insight for Long-Distance Caregivers. Indianapolis, Ind.: Wesleyan, 2004.
Strengths and limitations: Long-distance caregivers have strengths and limitations. They know that distance creates limitations, and they occasionally feel guilty, stressed, anxious, or overwhelmed by the challenges of their responsibilities. They do not keep their caregiving a secret. They ask for help as a sign of strength and a means to improve care. They stay as flexible as possible and allow themselves to accept others’ help. Sometimes they hire a professionally certified care manager to resolve issues before crises arise. Wise long-distance caregivers are kind, caring, and patient with themselves. They make their own physical, emotional, and spiritual health a priority. They meet their own needs and take respite breaks from caregiving. They accept support from family, friends, and their faith communities. Many of them reach out to caregiver support groups, online bulletin boards, and buddy systems. They are receptive to care receivers’ existing informal support systems—the friends, neighbors, and others on whom care receivers depend. They bring these resources into their care networks and ask the people to contact them when they have new information or learn about problems requiring assistance. Susan E. Ullmann, M.T. (ASCP), M.A.
National Hospice and Palliative Care Organization http://www.nhpco.org
u
Other Resources
American Cancer Society http://www.cancer.org Cancer.Net http://www.cancer.net/portal/site/patient
See also Advance directives; Aging and cancer; Anxiety; Brief Pain Inventory (BPI); Cancer education; Caregivers and caregiving; Case management; Counseling for cancer patients and survivors; Elderly and cancer; Financial issues; Home health services; Insurance; Living will; Living with cancer; Oncology social worker; Pain management medications; Relationships; Support groups; Transitional care.
u Loop electrosurgical
excisional procedure (LEEP) Category: Procedures Also known as: Large loop excision of the transformation zone (LLETZ), large loop excision of the cervix (LLEC), loop cone biopsy of the cervix Definition: Loop electrosurgical excisional procedure (LEEP) is a procedure that may be used to excise or cut away abnormal, possibly precancerous cells (cervical intraepithelial neoplasia) on the surface of the cervix as indicated by the results of a Pap test. 727
Lumbar puncture
Salem Health: Cancer
Cancers diagnosed or treated: Cervical intraepithelial neoplasia or dysplasia (CIN), abnormal cell changes on the surface of the cervix
ment to perform a colposcopy to check that all abnormal cells have been removed and perform a Pap test to confirm this.
Why performed: A LEEP removes abnormal, possibly precancerous cells indicated by results of a Pap test and seen on colposcopy (a noninvasive device used to see inside the cervix) on the surface of the cervix. A LEEP may also be used as a diagnostic procedure when abnormal cells are suspected high in the cervical canal and are not visible using a colposcope.
Risks: The LEEP is very safe. The benefits of treating potentially precancerous cells with the procedure outweigh its minimal risks. Those risks may include heavy bleeding, bleeding with clots, severe abdominal cramping, fever, foul-smelling discharge, incomplete removal of abnormal tissue, cervical stenosis (narrowing of the cervix), infection, and possibly cutting or accidental burning of normal tissue if the patient moves during the procedure.
Patient preparation: While there is no standard preparation needed for a LEEP, the patient should consult with her doctor or provider. A LEEP is not performed while a patient is menstruating. Steps of the procedure: The patient, unclothed from the waist down, draped with a cloth or paper, lies on an exam table as for a typical pelvic exam with feet raised in stirrups. A speculum is inserted in the vagina to allow the physician to see inside the vagina and cervix to guide the colposcope to the area where the abnormal cells are located. A tube is attached to the speculum to remove any smoke caused by the procedure. Then an electrosurgical dispersive pad is placed on the thigh, which allows the electric current to return safely. The physician will attach a single-use disposable loop electrode to the generator hand piece. A vinegar (acetic acid) or iodine solution will be used to prepare the cervix, allowing the physician to assess the extent of the abnormal cells. If a cervical block or anesthetic will be used to numb the cervix, then a pain medication will be administered beforehand. Once the local anesthetic or block is injected into the cervix, the electroloop is generated and the wire loop will pass through the surface of the cervix. Finally, an electrosurgical generator sends a painless electrical current that cuts away the affected cervical tissue as the loop wire moves through the cervix, causing the abnormal cells to burst. The procedure takes about ten to twenty minutes to complete. After the procedure: The patient may go home following the procedure. While rare, complications may include mild cramping, mild discomfort or pain, bleeding, heavy vaginal discharge, or strong vaginal odor. The patient should report any significant side effect to her doctor. The patient is typically advised not to engage in sexual intercourse for four weeks following the procedure. Ibuprofen (Motrin, Advil) may be taken for cramping. The patient is advised not to lift heavy objects, douche, or use tampons for four weeks following the procedure and is advised to take showers instead of baths to reduce the risk of infection. The patient’s doctor will make a follow-up appoint728
Results: Typically, the patient returns to normal activity within one to three days after the LEEP. The doctor will disclose the results of the histologic specimen obtained from the LEEP regarding whether invasive cancer may have developed deep in cervical tissue. A follow-up appointment is made to perform a colposcopy to confirm that all abnormal cells have been removed, a Pap test is repeated to confirm their removal, and the patient is advised to return on a regular basis for Pap tests to track the possible recurrence of abnormal cervical cells. Susan H. Peterman, M.P.H. See also Afterloading radiation therapy; Antiviral therapies; Benign tumors; Biological therapy; Birth control pills and cancer; Carcinomas; Carcinomatosis; Cervical cancer; Colposcopy; Conization; Diethylstilbestrol (DES); Endometrial cancer; Exenteration; Fertility drugs and cancer; Gynecologic cancers; Human papillomavirus (HPV); Hysterectomy; Hystero-oophorectomy; Infectious cancers; Pap test; Pelvic examination; Pregnancy and cancer; Vaccines, preventive; Vaginal cancer; Virus-related cancers.
u Lumbar puncture Category: Procedures Also known as: Spinal tap Definition: Lumbar puncture is the insertion of a needle between two vertebrae in the lower back (lumbar region) into the spinal canal in order to obtain a sample of cerebrospinal fluid (CSF) for analysis. Cancers diagnosed or treated: Cancers of the central nervous system (brain and spinal cord), such as meningeal carcinomatosis Why performed: Although usually used for diagnosing disease, sometimes the procedure is used to provide a mechanism for the introduction of medications to treat dis-
Salem Health: Cancer
Lumbar puncture
A lumbar puncture. (©Kevin A. Somerville/Phototake—All rights reserved)
ease, to introduce agents for further study of possible disease, or as actual treatment for some disease. Lumbar puncture results are used to help diagnose diseases such as meningitis, subarachnoid hemorrhage, Guillain-Barré syndrome, and multiple sclerosis. In addition, dyes for myelograms or anesthetics for pain relief may be introduced using lumbar puncture. Patient preparation: A computed tomography (CT) scan or magnetic resonance imaging (MRI) scan is sometimes completed prior to lumbar puncture, but these scans are not always indicated. Certain blood tests are taken to compare the results from the blood to the results from the cerebrospinal fluid collected during the lumbar puncture, including serum chemistry panels (glucose) and complete blood counts (white blood cell count). Ideally, medications such as aspirin, ibuprofen, or other antiplatelet agents should be discontinued forty-eight to seventy-two hours before an elective lumbar puncture. Steps of the procedure: The patient is placed on his or her side with knees drawn up toward the chest and back flexed toward the legs. Sterile procedure is completed, including sterile gloves, alcohol swabbing, iodine preparation, and isolation of the puncture area with sterile towels or paper
drapes. The health care professional performing the procedure palpates (feels) the spine to locate the best position to insert the needle in the patient’s lower back. In adults, the spinal cord extends down to the first lumbar vertebra (five lumbar vertebrae are present, with the highest on the back labeled as number 1), so the health care professional locates an area below vertebra11, usually between the third and fourth lumbar vertebrae or the fourth and fifth lumbar vertebrae. Infants require a 14-15 insertion area since the spinal cord terminates at a lower level in infants than in adults. A local anesthetic with a tiny needle is used to numb the insertion site for the larger lumbar puncture needle. After the procedure: The patient should lie flat on the back for about two hours following the procedure. Rising too fast after a lumbar puncture can increase the risk of the most frequent complication of an lumbar puncture, a positional headache. Risks: A headache that changes with position is the most frequent complication, occurring in about 25 percent of cases. These headaches usually resolve with rest and hydration. Uncommon complications include damage to nerves in the head and facial region that typically resolve 729
Lumpectomy within four months. Rare complications include tumors and cysts that form in the area of the needle insertion site. People with leukemia may have an increased risk of hematoma (clot) formation at or near the insertion site of the lumbar puncture needle. Lenworth N. Johnson and Michael A. Meyer have reported in Neuro-ophthalmology (2005) that leukemia patients who have a traumatic lumbar puncture can suffer contamination of the CSF with cancer cells, and the median survival time of these patients can be reduced in this situation. The gravest complication of a lumbar puncture is herniation of the brain stem, where the lower portion of the brain is suddenly pulled down by the pressure release of opening the spinal canal to remove fluid. This can happen if a brain tumor or growth has increased pressure in the spinal canal, since the fluid in the spinal canal is physically in contact with fluid surrounding the brain (hence the term “cerebrospinal fluid,” with “cerebro” referring to the brain). This rare occurrence is minimized by screening with neurological and ophthalmologic examinations and CT/MRI scanning as indicated. Results: Normal cerebrospinal fluid is clear and colorless. Sometimes, blood discolors the CSF, giving it a reddish color. If blood is present, then it can indicate a very serious condition known as subarachnoid hemorrhage. Usually, if blood is present in the CSF, then the blood comes from what is known as a “traumatic tap,” resulting from the inadvertent puncture of small blood vessels with the lumbar puncture needle. A traumatic tap is not usually a serious problem, but the blood source requires identification. Four or five small tubes of CSF are collected from a typical lumbar puncture. Blood from a traumatic tap diminishes from the first tube collected to the last tube collected. Other tests can be completed to help determine the source of blood found in a lumbar puncture. Laboratory tests routinely completed on CSF include protein, glucose, and white and red blood cell counts. Cultures and studies for bacteria, fungi, and viruses may be completed. Cells found in the CSF may be microscopically examined to determine if cancers of the brain or spinal cord are present. The pressure of the fluid as it initially drains out of the spinal canal, called the opening pressure, is measured, as is the closing pressure at the end of the procedure. Elevated pressures can indicate tumors or masses in the cranial cavity. Richard P. Capriccioso, M.D. u For Further Information Fischbach, Frances Talaska, and Marshall Barnett Dunning III. A Manual of Laboratory and Diagnostic Tests.
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Salem Health: Cancer 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2004. Johnson, Lenworth N., and Michael A. Meyer. “Lumbar Puncture.” In Neuro-ophthalmology: The Practical Guide, edited by Leonard A. Levin and Anthony C. Arnold. New York: Thieme Medical, 2005. Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006. u
Other Resources
WebMD Lumbar Puncture http://www.webmd.com/brain/LumbarPuncture?page=1 See also Acute lymphocytic leukemia (ALL); Blood cancers; Carcinomatous meningitis; Leptomeningeal carcinomas; Medulloblastomas; Meningeal carcinomatosis; Nuclear medicine scan; Pineoblastomas; Retinoblastomas.
u Lumpectomy Category: Procedures Also known as: Breast-conserving surgery, partial mastectomy Definition: A lumpectomy is breast-conserving surgery and is the most common form of breast surgery performed for cancer. It is usually done as an inpatient procedure, or as “day surgery,” under general or local anesthesia, when a lump or mass is found in only one section of the breast by physical examination, mammogram, ultrasound, or magnetic resonance imaging (MRI) of the breast. During a lumpectomy, the lump and some of the surrounding normal-appearing breast tissue are removed and the margins between the lumpectomy and the rest of the breast are examined for any residual tumor. Cancers diagnosed or treated: Breast cancer Why performed: A lumpectomy is performed to remove cancer as a breast-conserving method; it is also sometimes called partial mastectomy, as opposed to complete removal of the breast, known as mastectomy. Patients may not be candidates for lumpectomy and radiation if they have more than one cancer in the same breast, have a connective tissue disease such as lupus or vasculitis, are pregnant, or have already had radiation to the same breast. Sentinel node biopsy may also be performed on the same day of the operation in order to examine the lymph
Salem Health: Cancer nodes in the armpit or axilla of the breast affected for the presence of cancer that may have spread from the primary lump or site in the breast to the lymph nodes. Patient preparation: Lumpectomy is usually preceded by a breast biopsy performed by a radiologist or breast surgeon that confirms the presence of breast cancer and in most cases tells the surgeon the type of breast cancer present. This latter information allows the surgeon to decide on the need for the surgery and the type of operation necessary. Patient instructions are NPO (from the Latin nulla per os, or “nothing by mouth”) after midnight on the day before the surgery. If sentinel node biopsy is performed in conjunction with lumpectomy, then the patient will need to be injected with radionuclide the day before the breast surgery. The injection is usually done around the nipple or areola by a nuclear medicine physician or radiologist. In the operating room the next day, the surgeon then uses a probe that is sensitive to small doses of gamma radiation emitted by the radiotracer to identify and remove the main
Lumpectomy draining node or nodes in the axilla, thereby eliminating the need to sample all the nodes in the axilla and thus reducing the risk of lymphedema, a swelling of the affected arm that can occur after full axillary node dissection. Steps of the procedure: If the lump cannot be felt, then a procedure to mark the location of the mass will be performed, usually in the radiology suite the morning of the surgery. A thin wire or needle is inserted using mammography or ultrasound to guide the radiologist, depending on if the lesion was visible on prior mammogram or ultrasound. This is called a breast needle (or wire) localization. The surgery itself lasts about an hour. After general anesthesia is given, the surgeon will make a curved incision in the breast, usually in the form of a smile or frown which follows the contour of the breast in order to minimize scarring. After the lump and the surrounding breast tissue are removed with a scalpel, a drain may be left in place to collect excess fluid or blood, and the surgeon will then close the wound with stitches and apply a sterile dressing over the wound.
A breast tumor is removed during a lumpectomy. (St. Bartholomew’s Hospital/Photo Researchers, Inc.)
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Lumps After the procedure: The patient will awake in the recovery room and may be required to stay overnight, depending on many factors, including the procedure itself, the general health of the patient, and how easily the patient recovers from anesthesia. Risks: The risks of general anesthesia are the same regardless of the procedure; patients who have any questions about anesthesia or any part of the operation should discuss these issues with their referring physician or health care provider. There may be some loss of sensation in the affected breast, and the breasts may not match in size and shape after the surgery, which may or may not be acceptable to the patient. Results: Once the pathology results are back, the doctor will review the pathology report and discuss the next steps, including the need for additional therapy. Lumpectomy is usually, but not always, followed by radiation therapy to eliminate any possibility of microcancers (cancer that are too small to identify by physical examination or radiologic means). If the margins are not clean of cancer, then a second operation, called a reexcision, may be necessary. Debra B. Kessler, M.D., Ph.D. u For Further Information Benedet, Rosalind. Understanding Lumpectomy: A Treatment Guide for Breast Cancer. Omaha, Nebr.: Addicus Books, 2003. Dewar, J. A., R. Arriagada, S. Benhamous, et al. “Local Relapse and Contralateral Tumor Rates in Patients with Breast Cancer Treated with Conservative Surgery and Radiotherapy.” Cancer 76 (1995): 2260-2265. Giulano, A., D. M. Kirgan, J. M. Guenther, et al. “Lymphatic Mapping and Sentinel Lymphadenectomy for Breast Cancer.” Annals of Surgery 220 (1994): 439442. Reiber, A., K. Schramm, G. Helms, et al. “BreastConserving Surgery and Autogeneous Tissue Reconstruction in Patients with Breast Cancer: Efficacy of MRI of the Breast in the Detection of Recurrent Disease.” European Journal of Radiology 13 (2003): 780787.
See also Accelerated partial breast irradiation (APBI); Biopsy; Breast cancers; Breast self-examination (BSE); Breast ultrasound; Clinical breast exam (CBE); Lumps; Mammography; Mastectomy; Needle biopsies; Needle localization; Sentinel lymph node (SLN) biopsy and mapping; Stereotactic needle biopsy; Surgical biopsies; Surgical oncology; Wire localization. 732
Salem Health: Cancer
u Lumps Category: Diseases, symptoms, and conditions Also known as: Masses Related conditions: Cysts, fibromas Definition: Lumps are abnormal masses or swellings on the skin or in the body. Risk factors: There are many conditions that may cause lumps, such as a cyst, fibroma, injury, or cancer. Etiology and the disease process: The likely causes of lumps include benign breast diseases, a lipoma (collection of fatty tissue), exostoses (new bone formation), cancer, an injury, an enlarged organ, or a swollen lymph node. Lymph nodes often swell in response to various infections or diseases, including the common cold, infections, viruses, mononucleosis, tonsillitis, lymphoma, Hodgkin disease, and leukemia. A variety of tissues in the body respond to hormonal changes, and as a result, certain lumps are transient. As an example, breast lumps may appear at all ages. Male or female infants may develop breast lumps temporarily in response to receiving estrogen from the mother’s milk. Breast-feeding women are prone to benign breast lumps from mastitis (inflammation of the mammary gland). Other underlying conditions for breast lumps include fibrocystic breasts, fibroadenoma, cyst, abscess, fat necrosis, gynecomastia (male breasts), duct papilloma (epithelial tumor growth), sclerosing adenosis (excess growth of breast tissues), and ductal ectasia (dilatation of the subareolar ducts). Fibrocystic breasts and fibroadenomas often occur in women during the reproductive years and are considered a normal variation of breast tissue. Cysts are fluid-filled sacs that can become tender. Incidence: Lumps commonly occur and often spontaneously resolve. Symptoms: The signs and symptoma of lumps are swelling or pain, often in the breast, under the skin, and in the groin. Screening and diagnosis: Lumps are detected by touch, visually, or by the perception of pain. Medical examination can reveal their cause and whether they are benign or malignant. Most common potentially cancer-related lumps develop in the breasts. Although typically lumps in the breast are benign breast cysts, they may be indicators of breast cancer. As a result, lumps found in the breast should be immediately examined to detect potential cases of breast cancer.
Salem Health: Cancer Treatment and therapy: The nature and causes of lumps determine how they are treated. Cysts can easily be drained by a physician, but if they do not disappear, surgery may be needed. Generally, if the fluid removed from the cyst is relatively clear and the lump disappears, no further treatment is necessary. However, if the fluid is bloody, the cyst must be inspected for the possible presence of cancer cells. Prognosis, prevention, and outcomes: Lumps tend to be benign. However, if a malignancy is detected, the survival rate with early diagnosis tends to be higher than after delayed detection. Anita Nagypál, Ph.D. See also Accelerated partial breast irradiation (APBI); Biopsy; Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Breast self-examination (BSE); Breast ultrasound; Clinical breast exam (CBE); Fibrocystic breast changes; Fibrosarcomas, soft-tissue; Head and neck cancers; Lumpectomy; Mammography; Surgical biopsies; Symptoms and cancer.
u Lung cancers Category: Diseases, symptoms, and conditions Also known as: Carcinomas of the lung, small-cell lung cancer (SCLC), oat cell carcinoma, non-small-cell lung cancer (NSCLC) Related conditions: Mesothelioma Definition: Lung cancer is an uncontrolled cell growth in lung tissues, which may lead to metastasis and infiltration of other tissues beyond the lungs. Risk factors: Long-term exposure to tobacco smoke is the main risk factor (90 percent of the cases) for the development of lung cancer. The lifetime risk of developing lung cancer among male smokers is 17.2 percent, and among female smokers the risk is 11.6 percent. This lifetime risk is significantly lower among nonsmokers, accounting for 1.3 percent of cases of lung cancers in men and for 1.4 percent of cases in women. The occurrence of lung cancer in nonsmokers (less than 10 percent of the cases) may be due to genetic factors, secondhand smoke, air pollution, and exposure to occupational respiratory carcinogens such radon gas, chromium, asbestos, and inorganic arsenic. There are more than four thousand chemicals in tobacco smoke, making the identification of the contributing factors to lung carcinogenesis challenging. Genetic predisposition might also contribute to the risk of lung cancer development. First-degree relatives of pa-
Lung cancers tients with lung cancer have an increased risk of lung cancer compared with those of controls. However, familial aggregation of lung cancer might in part be caused by shared exposure to tobacco smoke. A major autosomal susceptibility locus for inherited lung cancer was found at chromosome 6q23-25, which contains numerous potential genes of interest, including SASH1, LATS1, IGF2R, PARK2, and TCF21. Genetic aberrations associated with lung cancer often encompass multiple genetic aberrations, including deoxyribonucleic acid (DNA) sequence alterations, copy number changes, allele loss, and abnormal promoter methylations. Etiology and the disease process: The lung is a common place for metastasis of tumors that originate from tissues other than the lung. The site of origin identifies these nonprimary lung cancers. For example, a breast cancer metastasis to the lung is still called breast cancer. These metastatic lung cancers usually have a distinctive round appearance on chest X ray. Primary lung cancers typically metastasize to the adrenal glands, liver, brain, and bone. The majority of lung cancers arise from epithelial cells. The two main types of lung carcinomas are histologically defined as SCLC and NSCLC. At diagnosis, it is essential to distinguish which type of lung cancer is present because their treatment varies. SCLC is usually treated with chemotherapy, while NSCLC is often treated with surgery. There are three main subtypes of NSCLC: squamous cell lung carcinoma, adenocarcinoma, and large-cell lung carcinoma. Squamous cell lung carcinoma, which accounts for 31 percent of lung cancers, usually originates near a central bronchus and often grows more slowly than other cancer types. Adenocarcinoma is associated with smoking, accounts for about 29 percent of lung tumors, and usually arises in peripheral lung tissue. Despite its link to smoking, adenocarcinoma is the most common form of cancer among patients who have never smoked. Variants of adenocarcinoma are adenocarcinoma (not otherwise specified), bronchoalveolar carcinoma, pdenosquamous carcinoma, papillary adenocarcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and other specified adenocarcinomas. Bronchoalveolar carcinoma is more common in women who have never smoked. Large-cell lung carcinoma often develops around the surface of the lung, and it is an aggressive, fast-growing type of NSCLC that tends to metastasize early. This type of malignancy accounts for about 11 percent of lung cancers. SCLCs are strongly associated with smoking, but they are less common than NSCLCs. SCLCs usually originate in the larger breathing tubes and develop rapidly. Although SCLCs respond well to chemotherapy initially, 733
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Salem Health: Cancer chronic coughing or change in regular coughing pattern, wheezing, pain in the chest or abdomen, cachexia (weight loss), fatigue, loss of appetite, dysphonia (hoarse voice), clubbing of the fingernails (uncommon), and dysphagia (difficulty swallowing). At the time of diagnosis, the most common symptom of lung cancer (occurring in more than half of patients) is coughing. Other common symptoms at the time of diagnosis are weight loss and intermittent aching chest pain, which occurs in up to 50 percent of patients. Approximately 60 percent of lung cancer patients develop dyspnea, and up to 35 percent of patients have hemoptysis. Symptoms and signs of development depend on the organ involved in the spread of disease. With a tumor in the mainstem bronchi, the initial symptom is most often wheezing that may be accompanied by a cough. If the cancer spreads to the left pharyngeal nerve, resulting in left vocal cord paralysis, and hoarseness of the voice occurs, this indicates an unresectable tumor. In addition to laryngeal nerve involvement, the left phrenic nerve is also commonly affected, which could result in paralysis of the left hemidiaphragm. Right paratracheal adenopathy or central
they often are metastatic at diagnosis and have a worse prognosis than NSCLCs. Incidence: Lung cancer is the most common cause of cancer-related death in men and the second most common in women worldwide. Lung cancer is responsible for 1.3 million deaths worldwide annually. The incidence of the disease increases with age up to about age seventy. Worldwide, approximately twice as many men as women develop lung cancer. This ratio decreases in areas in which the prevalence of cigarette smoking among women is high. The highest numbers of new lung cancers are found in the United States and Europe. In 2005, the estimated number of new cases in the seven major commercial markets was 393,000, and by 2015 new cases of lung cancer are estimated to reach approximately 561,000. About 80 percent of lung cancers are NSCLC, and 17 percent are SCLC. Over 50 percent of NSCLC patients are diagnosed with an advanced stage of the disease. Symptoms: Lung cancer symptoms may include dyspnea (shortness of breath), hemoptysis (coughing up blood),
Incidence of Lung Cancer per 100,000 People, by Gender 120 Women
Men
107.6 100
79.3
80
60
54.6
54.9
54.3
53.9 44.2 39.7
40
28.0
25.4
20
0 Black
White
American Indian/ Alaska Native
Asian/Pacific Islander
Hispanic
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
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Lung cancers
Centrilobular emphysema in a lung, characteristic of smoking, a major risk factor for lung cancer. (Centers for Disease Control and Prevention)
enlargement of a tumor in the right upper lobe of the lung often obstructs the superior vena cava. Such a tumor position often causes the patient to have facial or upper extremity swelling, venous swelling in the neck or chest, a cough, and dyspnea. A tumor localized in the apex of the lung usually causes shoulder and upper chest pain. Tumors located in the top of the lung may also cause damage to the brachial plexus and result in Horner syndrome (injury to the sympathetic nerves). Approximately 8 to 15 percent of lung cancer patients have pleural involvement and experience pleuritic chest pain or dyspnea. Screening and diagnosis: Lung tumors are typically detected by chest radiography done during a general checkup or in response to reported symptoms. When a neoplasm is confirmed, staging of disease is required to develop the appropriate treatment plan and prognosis. Computed tomography (CT) scans and whole-body positron emission tomography (PET) scans are noninvasive staging methods. If clinical symptoms indicate the disease may have spread, other parts of the body may also be scanned.
Invasive staging modalities are used for confirmation of the diagnosis. Pathological diagnosis of neoplastic growth is obtained by sputum (mucus) cytology of tissues extracted from the tumor. Specimen sampling is crucial for diagnostic accuracy of cytology. Typically, transthoracic needle aspiration or endoscopic ultrasound with fine needle aspiration is used for sensitive diagnosis confirmation. For centrally located tumors, flexible bronchoscopy is one of the most common techniques, and it is often accompanied by bronchial washings. Transbronchial needle aspiration with fluoroscopic or CT scan guidance is used for submucosal or peribronchial tumors. In case of peripheral lung lesions, transthoracic lung biopsy offers high sensitivity sampling, and mediastinoscopy is the preferred method to evaluate a tumor in the mediastinal lymph node. Pulmonary function tests are also used. Lung cancer staging is an assessment of the disease’s progression from its original source. Precise staging of lung cancers is essential to develop prognosis and treatment. The most widely used staging system for NSCLC is the International Staging System (ISS), which uses TNM 735
Lung cancers (tumor/lymph node/metastasis) categories that describe four stages of disease. SCLC is classified as limited-stage if it is confined to one half of the chest; otherwise it is extensive-stage. Treatment and therapy: Treatment depends on the histological type of cancer, the stage, and the patient’s performance status (how well the patient is able to perform daily living activities). Treatments include surgery, chemotherapy, and radiotherapy. Commonly used systemic agents are bevacizumab (Avastin), carboplatin, cisplatin, docetaxel (Taxotere), erlotinib (Tarceva), etoposide, gemcitabine (Gemzar), ifosfamide (Mitoxana), irinotecan (Camptosar), mitomycin (Mutamycin), paclitaxel (Taxol), pemetrexed (Alimta), vinblastine (Velban), and vinorelbine (Navelbine). The gold-standard therapy for advanced or metastatic disease is platinum-based chemotherapy, a cytotyic theropy that prolongs survival, controls symptoms, and improves quality of life compared with best supportive care (treatment to prevent, control, or relieve side effects or complications and to improve the patient’s quality of life). However, patients with poor performance status do not benefit from cytotoxic chemotherapy. Bevacizumab (a monoclonol antibody) plus chemotherapy or chemotherapy alone is beneficial in patients with low performance status, as indicated by the Eastern Cooperative Oncology Group (ECOG) score of 0 to 1. In cases of advanced NSCLC, concurrent chemotherapy with radiation (chemoradiation) is better than sequential chemoradiation, and it is superior to radiation alone. Carboplatin or cisplatin is effective in combination with docetaxel, etoposide, gemcitabine, irinotecan, paclitaxel, vinblastine, and vinorelbine. Erlotinib is often used for nonsmoker patients with active epidermal growth factor receptor mutations or gene amplification. Single agents, such as docetaxel, pemetrexed, tyrosine kinase inhibitor, or erlotinib, are offered for second-line patients. Docetaxel is superior to best supportive care as second-line therapy in terms of quality of life. In addition, erlotinib is also superior to best supportive care in terms of survival as second- and third-line therapy. Prognosis, prevention, and outcomes: The primary way to prevent lung cancer is to eliminate tobacco smoking. Approximately 42 percent of lung cancer patients survive for at least one year. Worldwide, the five-year survival rate is 14 percent with treatment. In particular, the five-year survival is 16 percent in the United States and 10 percent in Europe. Five-year survival decreases when advanced disease or NSCLC is present at diagnosis. For both men and 736
Salem Health: Cancer women, age-standardized lung cancer mortality rates are highest in the United States compared with Japan and many European countries, including France, Germany, Italy, Spain, and the United Kingdom. Anita Nagypál, Ph.D. u
For Further Information American Cancer Society. Quick Facts Lung Cancer: What You Need to Know—Now. Atlanta: Author, 2007. Desai, Sujal R., ed. Lung Cancer. New York: Cambridge University Press, 2007. Eckardt, John R., and Julia E. Kimmis. Understanding Lung Cancer: A Guide for Patients and Their Families. Manhasset, N.Y.: CMP Healthcare Media, 2005. Gilligan, David, and Robert Rintoul. Your Guide to Lung Cancer. London: Hodder Arnold, 2007. Hunt, Ian, Martin Muers, and Tom Treasure, eds. ABC of Lung Cancer. Malden, Mass.: Blackwell, 2008. Mountain, C. F. “Revisions in the International System for Staging Lung Cancer.” Chest 111 (1997): 1710-1717. Roth, Jack A., James D. Cox, and Waun Ki Hong, eds. Lung Cancer. 3d ed. Malden, Mass.: Blackwell, 2008.
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Other Resources
American Cancer Society http://www.cancer.org American Lung Association Facts About Lung Cancer Http://www.lungusa.org/site/pp.asp?c= dvLUK9O0E&b=35427 Lung Cancer Online Foundation http://www.lungcanceronline.org/ LungCancer.org http://www.lungcancer.org National Cancer Institute Lung Cancer http://www.cancer.gov/cancertopics/types/lung See also Air pollution; Bilobectomy; Bronchoalveolar lung cancer; Bronchography; Bronchoscopy; Coughing; Hemoptysis; Klinefelter syndrome and cancer; LambertEaton myasthenic syndrome (LEMS); Lobectomy; Mesothelioma; Pleural biopsy; Pleural effusion; Pleurodesis; Pneumonectomy; Pneumonia; Smoking cessation; Soots; Thoracentesis; Thoracoscopy; Thoracotomy; Tobaccorelated cancers.
Salem Health: Cancer
u Lutein Category: Lifestyle and prevention Also known as: Xanthophyll, non-provitamin A carotenoid Definition: Lutein is a yellow pigment and micronutrient found in some vegetables, fruits, and eggs, and also in the human retina. It is best known as a carotenoid, a plant phytochemical thought to have antioxidant properties that protect against cell-damaging molecules known as free radicals. Cancers treated or prevented: Prostate, breast, colon, lung, and ovarian cancers Delivery routes: Oral via food or dietary supplements. The most significant food sources for lutein are broccoli, brussels sprouts, collards, kale, peas, pumpkin, spinach, turnip, mustard and dandelion greens, summer and winter squash, and sweet yellow corn. Egg yolks contain a more quickly absorbed form of lutein. Lutein absorption is increased from the intestine when combined with a dietary fat source, such as oil or margarine.
Lycopene pecially in pregnant or lactating women, should be used with lutein supplements because the risks are still unknown. Alice C. Richer, R.D., M.B.A., L.D. See also Amenorrhea; Antiandrogens; Antioxidants; Carotenoids; Complementary and alternative therapies; Craniopharyngiomas; Dietary supplements; Free radicals; Fruits; Lycopene; Nutrition and cancer prevention; Pituitary tumors.
u Lycopene Category: Lifestyle and prevention Also known as: Non-provitamin A carotonoid Definition: Lycopene is the red pigment in some fruits and vegetables that gives them their colorful appearance. It is best known as a carotenoid, a plant-produced phytochemical well known for its antioxidant properties.
How this substance works: Lutein is chemically similar to the micronutrient zeaxanthin, and they often work together to provide protective benefits. Lutein, also known as a non-provitamin A carotenoid, cannot convert into vitamin A when needed by the body. Most studies find that lutein protects the eyes from disease, such as age-related macular degeneration and cataracts. Some studies find lutein effective against cancer because it decreases the growth of blood vessels to cancerous tumors, increases cancer cell destruction, and improves cell deoxyribonucleic acid (DNA) repair. Overall study results are mixed, however, with one study showing lutein reduced prostate cancer by 25 percent (and as much as 32 percent when combined with the carotenoid lycopene) and another showing an increase in stomach cancer. In general, most studies find that lutein provides some protection against breast, colon, lung, ovarian, and prostate cancers. The dosage and safety of lutein dietary supplements are still unknown. Doses of lutein up to 20 milligrams per day have been determined to be safe. Consuming lutein from food sources is advised, however, because of its interaction with other compounds found within these foods. Side effects: Caution is advised for individuals with allergies or sensitivities to eggs or lutein-containing vegetables. In general, no toxicities or drug interactions have been reported with lutein from food sources. Caution, es-
Tomatoes are a major source of lycopene. (U.S. Department of Agriculture)
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Lymphadenectomy Cancers treated or prevented: Prostate, lung, and stomach cancers Delivery routes: Oral via food or dietary supplements. The most common food sources for lycopene are tomatoes and tomato products. Other significant food sources are apricots, guava, watermelon, papaya, and pink grapefruit. Processed tomatoes and tomato products provide more available lycopene than raw forms. The absorption of lycopene is increased when combined with a dietary fat source, such as the oil used in preparing pizza or tomato sauce. How this substance works: Lycopene is believed to act as an antioxidant, blocking the destructive action of celldamaging molecules known as free radicals. Also known as a non-provitamin A carotenoid, it cannot convert into vitamin A in the body, like some other carotenoids, when needed. Lycopene is fat-soluble; thus it is stored in the body and broken down in the intestine for use. Because of this, including dietary fat with a lycopene source increases its absorption. Lycopene is believed to play a role in preventing many diseases, such as cancer, heart disease, and macular degeneration, and it may slow the progression of some cancers. Some studies show the strongest protective evidence against lung, stomach, and prostate cancers. Other nutrients and compounds in fruits and vegetables are thought to combine with lycopene, however, and this synergy may actually be responsible for the protective benefits seen in these studies. The dosage and safety of dietary lycopene supplements are still unknown. Many studies have found positive benefits from consuming lycopene from fruit and vegetable sources, rather than dietary supplements, with no known safety issues. Side effects: Caution is advised for individuals with allergies or sensitivities to tomatoes and tomato products or to fruits, vegetables, and dietary supplements that include lycopene. The high level of acid in tomatoes may irritate stomach disorders. While there is some belief that lycopene could decrease the side effects of radiation and chemotherapy, it may also decrease their effectiveness. As a rule, lycopene dietary supplements should be avoided during cancer treatment. Lycopene from food sources, however, has not been found to interfere with treatment. Some drugs may also decrease lycopene absorption. Alice C. Richer, R.D., M.B.A., L.D. See also Antioxidants; Carotenoids; Chemoprevention; Complementary and alternative therapies; Dietary supplements; Free radicals; Fruits; Lutein; Nutrition and cancer prevention. 738
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u Lymphadenectomy Category: Procedures Also known as: Lymph node dissection Definition: Lymphadenectomy is the surgical removal of lymph nodes. It is used to diagnose and treat almost all types of cancers because lymph nodes are found throughout the body and are one of the first places to which cancer spreads. Lymphadenectomy is an especially common procedure in diagnosing and treating breast cancer because of the number of lymph nodes located near the breast. Cancers diagnosed and treated: Most, especially breast cancer Why performed: The lymphatic system is part of the immune system, which helps keep the body free of disease. Lymph is a clear, yellowish fluid that oozes out of blood vessels and is carried in channels throughout the body. Eventually it is funneled back into a vein and reenters the blood circulatory system. Interspersed along the lymph channels are about six hundred enlarged areas called lymph nodes. Lymph nodes filter bacteria, viruses, and cancer cells out of the lymph. These undesirable cells are then destroyed by white blood cells (lymphocytes) stored in the lymph nodes. There are many lymph nodes in the head and neck, another large cluster near the breast and under the armpit, and another group in the groin. When bacteria, viruses, or cancer cells overwhelm lymph nodes, the nodes swell and can be felt on the surface of the body. For example, when the lymph nodes behind the ears and along the throat are enlarged, people often say they have “swollen glands,” although lymph nodes are not true glands. Lymph nodes can be surgically removed either as a diagnostic tool or as a therapeutic procedure to treat cancer. In a lymph node biopsy, several samples of lymph node tissue are removed and examined under the microscope to see if they contain cancer cells. Based on the results of the biopsy, full removal of some nodes (a lymphadenectomy) may be performed. One newer approach to lymphadenectomy aimed at preventing unnecessary surgery involves identifying sentinel nodes and removing them first. Sentinel nodes are the first nodes to which lymph travels after it leaves the area where cancer is present. They provide an early warning that the cancer has begun to spread. The location of sentinel nodes is determined before surgery by lymphangiography and other imaging tests. Lymphangiography involves slowly injecting a fluorescent dye into the lymphatic system and tracing its progress using X rays.
Salem Health: Cancer
Lymphadenectomy
If no cancer is found in the sentinel nodes, then the cancer probably has not spread to the lymphatic system and no additional nodes need to be removed. If cancer has spread to the sentinel nodes and beyond, then lymphadenectomy becomes a treatment for cancer and lymph nodes suspected of containing malignant cells are surgically removed. Patient preparation: Before a lymphadenectomy, various tests such as a lymphangiogram (dye injected into the lymphatic system) and other imaging scans are done to locate the cancer, determine where it is likely to have spread, and indicate to the surgeon which lymph nodes should be removed. The patient is prepared for major surgery. In addition to tests to locate the cancer, the patient is given standard preoperative blood and liver function tests, meets with an anesthesiologist, and is required to fast for about eight hours before surgery.
Steps of the procedure: Lymphadenectomy is usually performed under general anesthesia in a hospital. An incision is made in the appropriate area, and lymph nodes and surrounding tissue are removed. Often the sentinel lymph nodes or a sampling of other lymph nodes are removed and examined under a microscope while the patient is still on the operating table. The condition of these nodes then dictates how much other tissue the surgeon will remove. Temporary drains are inserted under the skin to remove excess lymph that accumulates, and the incision is closed. After the procedure: This procedure normally requires a hospital stay. The length of stay and the recovery period depend on the number of nodes removed and the general health of the patient. The patient may feel temporary numbness or a tingling or burning sensation in the region where the lymph nodes were removed. Radiation therapy or chemotherapy may be given after lymphadenectomy to help kill any cancer cells that remain in the body.
Breast cancer
Lymph nodes to be removed
Removal of axillary lymph nodes during lymphectomy. (©Visuals Unlimited/Corbis)
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Lymphangiography
Salem Health: Cancer
Risks: All surgery carries the risk of bleeding, infection, and allergic reaction to anesthesia. Nevertheless, the greatest risk related to lymphadenectomy is the development of lymphedema after the operation. Lymphedema occurs when the lymphatic system is overwhelmed by large amounts of lymph. The lymph seeps into the surrounding tissue and causes swelling. About 15 percent of individuals have mild lymphedema, with 1 to 2 percent reporting severe swelling. Postoperative radiation therapy increases the risk of developing lymphedema. Results: For diagnostic lymphadenectomy, if no malignant cells are found in the removed lymph nodes, then it is unlikely that cancer has spread beyond the primary tumor. If lymph nodes are enlarged and malignant cells are found, then there is a high chance that the cancer may metastasize. Therapeutic lymphadenectomy may slow cancer but does not, by itself, cure it. The success of this treatment depends on the stage of the cancer and how many lymph nodes are involved. Martiscia Davidson, A.M. u For Further Information Khatri, Vijay P., ed. Lymphadenectomy in Surgical Oncology. Philadelphia: Saunders, 2007. Leong, Stanley P. L. Selective Sentinel Lymphadenectomy for Human Solid Cancer. New York: Springer, 2007. Sato, K., R. Shigenaga, S. Udea, et al. “Sentinel Lymph Node Biopsy for Breast Cancer.” Journal of Surgical Oncology 96, no. 4 (September 15, 2007): 322-329.
u
Other Resources
BreastCancer.org Lymph Node Removal http://www.breastcancer.org/treatment/surgery/ lymph_node_removal/index.jsp
u Lymphangiography Category: Procedures Definition: Lymphangiography is the injection of a dye or radioactive material into the lymphatic system so that the location and condition of lymph nodes and lymph vessels can be determined using X rays. Cancers diagnosed: Most often used to determine the location of sentinel lymph nodes in breast cancer or to determine the condition of lymph nodes prior to biopsy or removal; sometimes used to diagnose lymphomas
Enlarged cervical nodes affected by lymphoma
Spleen Bone marrow
WebMD Cancer Health Center Lymph Node Biopsy http://www.webmd.com/cancer/lymph-nodebiopsy See also Axillary dissection; Biopsy; Breast cancers; Lumpectomy; Lymphangiography; Lymphangiosarcomas; Lymphedema; Lymphocytosis; Lymphomas; Metastasis; Sentinel lymph node (SLN) biopsy and mapping; Surgical oncology. 740
Major nodes of the lymphatic system; enlarged nodes can be caused by lymphomas and other cancers.
Salem Health: Cancer
Lymphangiosarcomas
Why performed: The lymphatic system is part of the immune system. It consists of a network of channels that carries lymph, a clear, yellowish fluid, and about six hundred nodes, or enlarged spaces. The lymph nodes trap bacteria, viruses, and cancer cells so that they can be destroyed by white blood cells stored in the nodes. Lymph nodes are one of the first places to which cancer spreads, so knowing if there are cancer cells in the nodes is important in staging and treating all cancers. Lymphangiography helps the surgeon determine where to biopsy or which lymph nodes to remove. The sentinel nodes are the first nodes through which lymph flows after it passes the primary tumor. In some women with breast cancer, the sentinel node is located using lymphangiography and then removed. If no cancer is found, then no additional nodes need to be removed, thus reducing the amount of surgery that the patient needs.
u Lymphangiosarcomas
Patient preparation: Minimal preparations are needed for lymphangiography. The patient may be asked not to drink for several hours before the test, since the lymphangiography takes up to seven hours and requires that the patient remain still.
After the procedure: The site where the dye was infused is cleaned and closed. The patient’s urine may be bluish for several days. Dye can remain in the body for up to two years.
Etiology and the disease process: Lymphangiosarcoma begins in the cells of the lymphatic vessels. This tumor is seen in the upper arms approximately five to fifteen years after a classical radical mastectomy, specifically in individuals who have long-standing lymphedema. Although the breast cancer may have been cured with the radical mastectomy, a secondary cancer diagnosis of lymphangiosarcoma has a poor prognosis. The radical mastectomy procedure is now outmoded and has been replaced with a more conservative surgical procedure. Lymphangiosarcomas can also arise in individuals with long-standing idiopathic lymphedema of several years. The signs of lymphangiosarcoma are a purple or bruised area on an extremity (usually the upper arm) that becomes a sore that does not heal with necrosis (breakdown) of the skin and underlying tissue. There are often satellite spots from the original site. The tumor metastasizes quickly.
Risks: Allergic reaction to the dye and infection at the infusion site are the main risks.
Incidence: Lymphangiosarcoma is rare; the occurrence in patients who had a radical mastectomy for breast cancer is less than 1 percent.
Steps of the procedure: A dye is infused into the hand or foot. The dye enters the lymph system and highlights the lymph channels and nodes. The dye may cause a mild burning feeling. It enters the body very slowly, and the patient must remain still during this time.
Results: From this test, the physician can tell if the lymph nodes are swollen or clogged, a condition that may indicate cancer. The surgeon can also determine which nodes are sentinel nodes. Martiscia Davidson, A.M. See also Biopsy; Breast cancers; Cystography; Embolization; Imaging tests; Lymphadenectomy; Lymphangiosarcomas; Lymphedema; Lymphocytosis; Lymphomas; Metastasis; Sentinel lymph node (SLN) biopsy and mapping; Testicular cancer; X-ray tests.
Category: Diseases, symptoms, and conditions Also known as: Lymphatic vessel tumors, angiosarcomas, lymphangioendotheliomas, StewartTreve syndrome, hemangiosarcomas Related conditions: Primary or secondary lymphedemas, classical radical mastectomy Definition: A lymphangiosarcoma is a rare malignant tumor that begins in the cells of the lymph vessels, usually in the upper extremities of individuals who have lymphedema. Risk factors: Risks factors for lymphangiosarcomas are a history of primary or secondary lymphedema, having had a classical radical mastectomy, or having radiation or chronic infections in a lymphodemous limb.
Symptoms: Symptoms of lymphangiosarcoma are purple or bruised areas on the skin of the arms or legs. Screening and diagnosis: The appearance of purplish, bruised-looking areas on the extremities of an individual with long-standing lymphedema is an indication for further evaluation. A biopsy is taken from the site; diagnosis is made by histologic examination and rules out metastatic disease from a primary tumor or another sarcoma (such as Kaposi sarcoma). Treatment and therapy: There is not an effective treatment or therapy for lymphangiosarcoma. The lymphan741
Lymphedema giosarcoma site is removed surgically, and amputation of the affected limb may be necessary. Chemotherapy may also be given after surgical treatment. Prognosis, prevention, and outcomes: The rate of recurrence is high, and the long-term survival rate is poor, in large part because of the rapid spread of the tumor to the chest wall, the liver, and to bone. Vicki Miskovsky, B.S., R.D. See also Angiosarcomas; Breast cancers; Fibrosarcomas, soft-tissue; Lymphadenectomy; Lymphedema; Mastectomy.
u Lymphedema Category: Diseases, symptoms, and conditions Also known as: Lymphatic obstruction Related conditions: Cancer, malformations of the lymph system Definition: Lymphedema is a blockage in the lymphatic system that results in swelling, or edema. The lymph system is a network of channels that move lymph, a clear fluid, around cells and through nodes that filter harmful substances such as bacteria. Risk factors: Surgery and radiation are most often associated with lymphedema. If the patient receives radiation to the underarm or has lymph nodes removed during surgery or as part of a sentinel lymph node biopsy, the lymph channel may be damaged. Lymph node removal for biopsy related to cancer spread is common and may also be done in the chest, groin, pelvic, and neck areas. Tumor growth may also cause lymphedema by compression. Etiology and the disease process: There are two kinds of lymphedema, primary and secondary. Primary lymphedema is a rare condition inherited at birth, and secondary lymphedema is caused by blockages from infection, surgery, radiation therapy scar tissue, pressure on lymph nodes from a growing tumor, or removal of lymph nodes during surgery. Primary lymphedema is due to a malformation in the lymph system present at birth. Secondary lymphedema is a mechanical interruption in the normal flow of lymph. When an interruption in the lymph system occurs, the ability to transport fluid is impaired, leading to swelling as the fluid collects in the tissues below the area of blockage. For example, if lymph nodes under the arm or in the groin are removed, the arm or leg may swell. The fluid that col742
Salem Health: Cancer lects is interstitial fluid, which causes inflammation. As the fluid collects, the swelling progresses, and the patients note an increase in the size of their arms, legs, or abdomen depending on the site of the blockage. Because the disease is progressive, the swelling continues and may lead to fatigue, the inability to fit clothing over the affected area, and the inability to carry on the activities of daily living. As the disease progresses, the skin in the affected area may become thickened and begin to resemble an orange peel, known as peau d’orange. The skin may break down easily, leading to oozing of fluid through the skin and ultimately infection. Incidence: Incidence rates for secondary lymphedema vary significantly by site. Some 10 to 40 percent of breast cancer patients with lymph node removal under the arm develop lymphedema. In women with major gynecologic surgery for ovarian and other cancers, the incidence rate ranges from 15 to 44 percent. A limited number of studies of head and neck cancer patients report that up to 5 percent experience lymphedema. Symptoms: Swelling is the most common and obvious symptom of lymphedema. The patient may also report a feeling of heaviness in the affected body part. Pain and weakness in the limb may be obvious to the patient. Sensations may decrease, including an inability to feel heat or cold. As the disease progresses, the skin becomes hard and loses its elasticity, and the limb may become two to three times its normal size. Lymphedema in the abdominal area may result in bowel and bladder problems. If untreated, fluid oozing from the skin may be noticed, and the skin may seem to disintegrate, leading to open sores. Screening and diagnosis: Patients at risk for lymphedema should be screened at each doctor’s visit and educated to the signs and symptoms of lympedema. Diagnosis of lymphedema is generally made after patients complain of symptoms, such as swelling and fullness. Physical examination, a medical history including medicines taken, and changes since the previous examination are important in diagnosis. There are no specific tests for diagnosing lymphedema. There is no staging of lymphedema, but measurement and recording of the circumference of the affected area are important to monitor progression of the disease. Treatment and therapy: Treatment of lymphedema is primarily mechanical: elevation of the affected area, manual lymphatic drainage using gentle massage to move fluid toward the center of the body (decongestive therapy), wearing of custom-fitted compression garments on the affected limb, and practicing good skin care and injury pro-
Salem Health: Cancer tection. Antibiotics may be necessary to prevent or treat infections, but other drugs are not generally effective. Patients are often encouraged to watch their weight, exercise appropriately, and eat protein-rich foods. Bowel and bladder complications such as constipation and urine retention may require treatment. Surgery for lymphedema is not recommended. Because the disease is progressive and treatment is based on symptoms, management and control are the therapies of choice. Patient education is critical to treatment and must be an important part of the therapy for lymphedema. Prognosis, prevention, and outcomes: There are no clinical studies that support actions to prevent lymphedema. There is no cure for lymphedema so the prognosis depends on the patient’s compliance with treatment measures. The use of sentinel lymph node biopsy rather than aggressive lymph node removal may be contributing to a decreasing incidence of the disease. The key to an optimal outcome is early recognition and treatment of the symptoms and compliance with ongoing treatment. Patricia Stanfill Edens, R.N., Ph.D., FACHE u For Further Information Fu, M. R. “Breast Cancer Survivors’ Intentions of Managing Lymphedema.” Cancer Nursing 28, no. 6 (2005): 446-457. Golshan, M., and B. Smith. “Prevention and Management of Arm Lymphedema in the Patient with Breast Cancer.” Journal of Supportive Oncology 4, no. 8 (2006): 381-386. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Lymphedema http://www.nci.nih.gov/cancertopics/pdq/ supportivecare/lymphedema/patient National Lymphedema Network http://www.lymphnet.org See also Axillary dissection; Edema; Endotheliomas; Lumpectomy; Lymphadenectomy; Lymphangiosarcomas; Mastectomy; Radiation therapies; Side effects.
Lymphocytosis
u Lymphocytosis Category: Diseases, symptoms, and conditions Also known as: Raised lymphocyte count Related conditions: Lymph symptoms, absolute lymphocytosis, hematological malignancy, lymphoma, leukemia, lymphoproliferative disorders Definition: Lymphocytosis is an abnormal excess of lymphocytes in the blood. Lymphocytes are a type of white blood cell that help fight infections. A healthy adult has an absolute lymphocyte count (ALC) of 1,300 to 4,000 per microliter of blood. ALC over 4,000 indicates lymphocytosis; however, this number may be higher in children up to six years of age, as their ALC is significantly higher than in adults. Risk factors: There are more than thirty medical condition that may underlie lymphocytosis. The most common causes include viral and bacterial infections, such as mononucleosis (glandular fever), influenza, pertussis (whooping cough), or tuberculosis. Malignant blood diseases, such as chronic lymphocytic leukemia, follicular lymphoma, hairy cell leukemia, and leukopenia, may also cause lymphocytosis. Etiology and the disease process: Lymphocytosis indicates an underlying problem, but it is not a disease in itself. The lymph nodes are the most commonly affected organs. Transient stress lymphocytosis may also occur after trauma or extensive psychological or physical stress, and it typically resolves within two days of diagnosis. Transient stress lymphocytosis may be in part mediated by modulation of catecholamine and steroid hormones and cell adhesion molecules. Incidence: Lymphocytosis is common and occurs in most people throughout life, usually in association with viral infections. Symptoms: Symptoms of lymphocytosis may include sore throat, fever, and fatigue. However, lymphocytosis typically causes no symptoms and is often discovered incidentally via a routine blood test. Screening and diagnosis: A complete blood count will identify lymphocytosis. Further investigation is done by assessing the major lymphocyte subsets, such as T cells, B cells, and natural killer cells. The subgroups of T cells are CD4 T cells (helper cells) and CD8 T cells (cytotoxic cells). In a healthy person, approximately 75 percent of lymphocytes are T cells, with a 2:1 ratio of CD4 to CD8, 743
Lymphomas and about equal proportions of the remainder cells are B cells and natural killer cells. A marked increase in lymphocytes may indicate a serious condition, such as the presence of chronic lymphocytic leukemia. Many types of blood cancer are often identified after diagnosing lymphocytosis. Treatment and therapy: For the best therapy, it is necessary to address the underlying issue that caused lymphocytosis. If a malignant blood disease is detected, cancer treatment may be needed. Prognosis, prevention, and outcomes: Depending on the cause of lymphocytosis, it may spontaneously resolve or may need medical interaction to relieve its symtoms. Anita Nagypál, Ph.D. See also Acute lymphocytic leukemia (ALL); Ataxia tel angiectasia (AT); Biological therapy; Blood cancers; Childhood cancers; Chronic lymphocytic leukemia (CLL); Complete blood count (CBC); Cutaneous T-cell lymphoma (CTCL); Edema; Hairy cell leukemia; Hodgkin disease; Immune response to cancer; Leukemias; Leukopenia; NonHodgkin lymphoma; Richter syndrome; Sézary syndrome; Thymomas; Thymus cancer.
u Lymphomas Category: Diseases, symptoms, and conditions Also known as: Hodgkin disease, non-Hodgkin lymphoma, Burkitt lymphoma Related conditions: Cancer of the lymph nodes, cancer of the spleen, leukemia, acquired immunodeficiency syndrome (AIDS) Definition: Lymphatic cancer is a blood cancer that involves the lymphocytes (white blood cells). Cancerous cells grow and multiply, mostly in the lymph nodes and spleen, where they cause swelling and a suppression of the body’s natural immune system. Lymphoma occurs in two forms, Hodgkin disease and non-Hodgkin lymphoma. The presence of abnormal cells known as Reed-Sternberg cells after the scientists who discovered them indicates Hodgkin disease and differentiates this lymphoma from all other types, including Burkitt lymphoma, which are designated non-Hodgkin lymphoma. Risk factors: As the causes of both Hodgkin disease and non-Hodgkin lymphoma are unknown, the risk factors cannot be definitively determined. However, in non744
Salem Health: Cancer Hodgkin lymphoma, it is thought that the suppression of the immune system, particularly in high-risk patients such as those who have undergone organic transplantation and are on antirejection medications, is a significant risk factor. A spike in the incidence of non-Hodgkin lymphoma has been detected among people who have had the human immunodeficiency virus (HIV) for four or more years, largely because their immune systems have been compromised. A link has been detected between the development of lymphoma and exposure to flour in some agricultural jobs. Also, in more advanced cases of the disease, a link has been found to exposure to X rays and to certain forms of chemotherapy. Heredity appears to have little effect in the development of lymphomas, although physicians who diagnose the disease do record genetic details in their diagnoses. Etiology and the disease process: The causes of lymphoma are not fully understood. The fact that lymphoma is not a single disease with clear-cut boundaries has made it difficult to understand and assess. Some lymphomas are relatively easy to treat and have good survival rates, whereas other forms of the disease grow very rapidly and aggressively so that successful treatment is more problematic. In the United States, lymphoma has been found most often among the well educated and those in more affluent socioeconomic situations. The lymphatic system contains two types of cells, the B cells and the T cells. The former manufacture antibodies designed to fight infections. The T cells, on the other hand, regulate the immune system. More than 90 percent of lymphomas in the United States originate in the B cells. Lymphatic cancer cells can be present in the stomach and the intestines, the bones, the skin, the sinuses, and in the lymph nodes. More than thirty types of non-Hodgkin lymphomas have been identified microscopically, each unique in its morphology. As a result, treatment is most effective if it is directed toward a specific variety of the disease. Incidence: In 2007, 71,380 were estimated to be diagnosed with lymphoma, and 19,730 were estimated to die of it. The age-adjusted incidence rate was 22 per 100,000 people per year. Both Hodgkin disease and non-Hodgkin lymphoma are found more often in men than in women. Non-Hodgkin lymphoma affects more people in their twenties and in the fifty-five to seventy age group. One variety of non-Hodgkin lymphoma, Burkitt lymphoma, is found largely in the Tropics and in Africa. It is thought to be related in some way to the Epstein-Barr virus. Non-
Salem Health: Cancer
Lymphomas
Hodgkin lymphoma is the fifth most frequently occurring cancer in the United States. It is also the third fastest-growing cancer worldwide, with the highest incidence of the disease found in North America, western Europe, and Australia. Symptoms: The most frequent symptom is a swelling in the lymph nodes in the neck, under the arms, or in the groin, usually referred to as swollen glands. In some cases, particularly in young children, the thymus gland in the upper chest may also be swollen. The swelling is clearly visible in most cases and usually is not painful. It is sometimes accompanied by other symptoms— loss of appetite, fever, weight loss, and night sweats—that are frequently mistaken for influenza. These symptoms may disappear after a short time, only to reappear. People suffering from lymphoma often have an overall feeling of illness characterized by lethargy, headaches, and ulceration of the skin accompanied by itching. If the disease has spread to the abdominal area, it may be accompanied by pain and bleeding as well as by swelling. In such cases, the patient may vomit blood or have blackened A lymphangiogram reveals lymphoma in a child’s pelvic lymph glands. (Zephyr/ stools indicating internal bleeding. Photo Researchers, Inc.) Because non-Hodgkin lymphoma usually grows slowly, it may be asymptomatic or may produce only minor symptoms that can easily be ig• Stage I: Cancer cells have been found in only one section of the lymph nodes or in just one confined area outside nored in the early stages of the disease. Therefore, this the lymph nodes. type of lymphoma is frequently diagnosed at Stage III or IV rather than in the earliest stages when the cure rate is • Stage II: Cancer has been detected in two or more lymph nodes on the same side of the diaphragm. greatest. Hodgkin disease, on the other hand, grows and spreads rapidly. Its early symptoms may cause its victims • Stage III: Cancer cells have been found on both sides of the diaphragm and may have spread to surrounding areas, to seek medical intervention in the earlier stages of the notably the spleen, the lungs, the liver, or the bone marrow. disease. • Stage IV: Cancer cells are found in more than one spot within the lymphatic system or in organs located at a sigScreening and diagnosis: The usual method for diagnosnificant distance from the lymphatic area. ing lymphoma involves the removal and microscopic examination of tissue from the lymph nodes for biopsy. If Treatment and therapy: A biopsy not only determines cancer cells are found, further diagnosis may be indicated whether cancer cells are present but also can more specifiand usually will involve X rays of the chest or lymph cally identify the kinds of cancer cells that are present. It glands, removal of bone marrow to be biopsied, ultrais important to customize treatment for each individual sound, and scanning by computed tomography (CT), magpatient to the greatest degree possible; therefore, identifinetic resonance imaging (MRI), or positron emission tocation of the precise kinds of cancerous cells is vital. mography (PET). For patients with Stage I and Stage II lymphomas, the The Ann Arbor staging system is used for Hodgkin disease and non-Hodgkin lymphoma: first avenue of treatment is radiation therapy. If there are 745
Lymphomas
Salem Health: Cancer
Age at Death for Lymphoma, 2001-2005 Age Group
Deaths (%)
Under 20 20-34 35-44 45-54 55-64 65-75 76-84 85 and older
0.6 2.4 3.4 7.6 13.9 22.9 32.8 16.5
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age at death from 2001 to 2005 was seventyfour, with an age-adjusted death rate of 7.8 per 100,000 men and women per year.
signs that the malignancy has spread, radiation may be supplemented by chemotherapy. If the disease has advanced considerably or is likely to, the treatment of choice may be a bone marrow transplant. When a bone marrow transplant—considered a treatment of last resort—is used, it is also combined with continued radiation therapy and chemotherapy. The patient undergoing such treatment usually has a badly compromised immune system so that the postoperative treatment involves isolation under sterile conditions for an extended period to prevent infection from some of the opportunistic diseases that are found in hospitals. An alternative treatment is the mini bone marrow transplant. This method involves the use of low-level, minimally toxic chemotherapy or radiation therapy to kill some of the patient’s bone marrow, leaving some cancer cells. Cancer-free bone marrow from a donor is then introduced into the patient’s bone marrow. In time, this cancer-free bone marrow produces cancer-free cells that attack and destroy the remaining cancerous cells. Stem cell research also appears to have considerable promise in the treatment of lymphoma. Prognosis, prevention, and outcomes: There is no clearcut way to prevent lymphoma, although avoiding some occupational and environmental hazards may decrease the likelihood that it will develop. Links have been made between increases in the spread of the disease and such environmental hazards as hydrocarbons and noxious fumes. Avoiding polluted air and water is certainly essential. 746
Also, diet has profound effects in combating many forms of cancer, including lymphoma. A diet low in fats, limited in animal protein, and containing few refined carbohydrates will strength the immune system and lead to a sense of overall well-being. People should routinely eat at least five servings of fruits and vegetables every day. The outlook for those suffering from lymphoma depends largely on the stage at which the cancer was detected. Many Stage I patients are cured of the disease. The five-year survival rate among Stage I and Stage II patients approaches 80 percent. Among Stage IV patients, the twoyear survival rate is about 50 percent. Each year the statistics are more encouraging as new medications and techniques are developed and employed in treating the disease. Certainly the key to survival is early diagnosis. Any symptoms should receive the attention of a qualified physician. Particularly dangerous are phantom symptoms, those that disappear after a short time but then return. The interval between their first appearance and their return is crucial because this is the period in which the disease is most susceptible to treatment designed to eliminate it. R. Baird Shuman, Ph.D. u
For Further Information Adler, Elizabeth M. Living with Lymphoma: A Patient’s Guide. Baltimore: Johns Hopkins University Press, 2005. Freedman, Jeri. Lymphoma: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Holman, Peter, Jodi Garrett, and William Jansen. One Hundred Questions and Answers About Lymphoma. Sudbury, Mass.: Jones and Bartlett, 2004. Litin, Scott C., Jr., ed. Mayo Clinic Family Health Book. 3d ed. New York: HarperCollins, 2003. National Institutes of Health. What You Need to Know About Hodgkin’s Disease. Bethesda, Md.: National Institutes of Health, 1999. _______. What You Need to Know About Non-Hodgkin’s Lymphoma. Bethesda, Md.: National Institutes of Health, 1999. Park, Alice. “The Cancer Test: Exposing a Growing Tumor’s Secrets May Be as Simple as Drawing Blood.” Time, June 25, 2007, 53. Teetley, Peter, and Philip Bashe. Cancer Survival Guide. Rev. ed. New York: Broadway Books, 2005.
u
Other Resources
American Cancer Society http://www.cancer.org
Salem Health: Cancer The Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Lymphoma Information Network http://www.lymphomainfo.net/lymphoma/ whatis.html Lymphoma Research Organization http://www.lymphoma.org MedlinePlus Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html See also Burkitt lymphoma; Castleman disease; Cutaneous T-cell lymphoma (CTCL); Epstein-Barr virus; Hemo-
Lymphomas lytic anemia; Hepatitis C virus (HCV); HIV/AIDS-related cancers; Hodgkin disease; Human T-cell leukemia virus (HTLV); Immune response to cancer; Immunocytochemistry and immunohistochemistry; Immunotherapy; Klinefelter syndrome and cancer; Lambert-Eaton myasthenic syndrome (LEMS); Leukapharesis; Lymphangiography; Lymphocytosis; Malignant fibrous histiocytoma (MFH); Mantle cell lymphoma (MCL); Mucosa-associated lymphoid tissue (MALT) lymphomas; Mycosis fungoides; Myeloma; Nijmegen breakage syndrome; Non-Hodgkin lymphoma; Organ transplantation and cancer; Primary central nervous system lymphomas; Richter syndrome; Sézary syndrome; Simian virus 40; Sjögren syndrome; Thymomas; Thymus cancer; Virus-related cancers; Waldenström macroglobulinemia (WM); Young adult cancers.
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M. D. Anderson Cancer Center
u M. D. Anderson Cancer
Center Category: Organizations Definition: M. D. Anderson Cancer Center is an academic and patient care facility that is in the Texas Medical Center in Houston and part of the University of Texas system of academic institutions. The center’s mission statement is “to eliminate cancer in Texas, the nation, and the world through outstanding programs that integrate patient care, research and prevention, and through education for undergraduate and graduate students, trainees, professionals, employees and the public.” M. D. Anderson Cancer Center is one of thirty-nine comprehensive cancer centers in the United States as designated by the National Cancer Institute, National Institutes of Health. It is also one of twenty-one member institutions that make up the National Comprehensive Cancer Network, a nonprofit consortium
Salem Health: Cancer of patient care facilities dedicated to improving the quality of cancer care. History: Munroe Dunaway Anderson, a wealthy banker and cotton merchant, created a sizable charitable foundation several years before his death that would eventually fund the cancer hospital bearing his name along with other institutions within the Texas Medical Center. In 1941, the Texas state legislature appropriated $500,000 for the creation of a center for cancer research and treatment within the University of Texas system. Originally funded as the Texas State Cancer Hospital and the Division of Cancer Research, the institution was renamed the following year after the trustees of the M. D. Anderson Foundation proposed matching the state’s grant to launch the center on the condition that the institute would be located in Houston. Biomedical research at the new institution commenced in 1943, and patient care services began the following year. By the mid-2000’s, M. D. Anderson employed more than
At the M. D. Anderson Proton Therapy Center, a radiation therapist and oncologist use X rays to determine the position of a patient’s tumor in the left lung before using a proton beam to attack the tumor. (AP/Wide World Photos)
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Salem Health: Cancer 15,000 faculty and staff, and its annual operating budget exceeded $2 billion. Patient care: M. D. Anderson Cancer Center’s patient care resources include 512 inpatient beds, an emergency center, and numerous outpatient clinics organized primarily by specialty. M. D. Anderson provides patient care to more than 74,000 people each year, with about one-third of patients coming from outside the state of Texas. In addition to its services for patients with known cancers, the facility also operates a cancer prevention clinic that offers diagnostic evaluation, risk assessment, genetic testing, and counseling in risk reduction and preventive medicine. Most patient care activities are conducted on the main campus within the Texas Medical Center, although M. D. Anderson also coordinates care in several satellite clinics in the Houston metropolitan area. M. D. Anderson patients have access to several types of support services to accompany their treatment, including patient education classes, a resource library, psychosocial and pastoral care services, and complementary therapies such as nutritional counseling and massage. For patients who have completed treatment, M. D. Anderson operates a rehabilitation program and a medical clinic for long-term follow-up. A number of nonhealth-related patient services are provided for patient comfort and convenience, such as an onsite hotel, a travel agency, and activities for patients and family members. Research: In 2005, M. D. Anderson Cancer Center spent approximately $342 million on medical research. The center has been consistently among the top recipients of research grants from the National Cancer Institute. Of note, the institution houses ten National Cancer Institute Specialized Programs of Research Excellence focusing on leukemia, melanoma, and cancers of the bladder, breast, endometrium, head and neck, lung, ovary, pancreas, and prostate. Research at the center is organized within several divisions that in turn are subdivided into more focal research areas. For example, the Division of Basic Research houses scientific programs in areas such as cancer genetics, biomedical engineering, and immunology. Other divisions are organized according to clinical specialty, such as medicine, surgery, imaging, and prevention science. Research efforts are closely integrated with patient care services. Accordingly, M. D. Anderson houses the largest clinical trial program of any cancer center in the United States. In 2005, more than 12,000 of the center’s patients participated in basic, clinical, and population-based research studies.
M. D. Anderson Cancer Center Education: Through supervised rotations, residencies, and fellowships, M. D. Anderson offers clinical training to medical students, physicians, nurses, pharmacists, and other health professionals. More recently, the center began offering undergraduate degrees and certificates in several allied health professions through its own School of Health Sciences. Baccalaureate degrees and certificates are granted in clinical laboratory science, cytogenetic technology, cytotechnology, diagnostic imaging, histotechnology, medical dosimetry, molecular genetic technology, and radiation therapy. M. D. Anderson offers formal research training aimed primarily at graduate and postdoctoral students. The center contributes to graduate-level research training programs in health sciences as a partner within the multiinstitutional University of Texas Graduate School of Biomedical Sciences. The graduate school awards master’s and doctoral degrees in a variety of disciplines, including basic sciences such as cell biology and genetics as well as applied sciences such as medical physics and pathology. Andrea Bradford, M.A. u
For Further Information Elliott, Frederick C. The Birth of the Texas Medical Center: A Personal Account. College Station: Texas A&M University Press, 2004. M. D. Anderson Hospital and Tumor Institute. The First Twenty Years of the University of Texas, M. D. Anderson Hospital and Tumor Institute. Houston: Author, 1964. Slaga, Thomas J. “Fifty Years of the University of Texas M. D. Anderson Cancer Center and the Study of Carcinogenesis.” Molecular Carcinogenesis 4, no. 6 (1991): 417-418.
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Other Resources
M. D. Anderson Cancer Center http://www.mdanderson.org National Cancer Institute Cancer Centers Program http://cancercenters.cancer.gov/index.html National Comprehensive Cancer Network M. D. Anderson Cancer Center http://www.nccn.org/members/profiles/mda.asp Texas Medical Center http://www.texmedctr.tmc.edu/root/en See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American In749
Macrobiotic diet stitute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Macrobiotic diet Category: Lifestyle and prevention Definition: Macrobiotics is a lifestyle and philosophy that includes an approach to nutrition based on whole grains, beans, vegetables, and the Chinese principle of yin and yang. A macrobiotic diet usually consists of organic and locally grown foods, seasonal vegetables, complex carbohydrates, and fewer fats, sugars, and chemically processed foods than in a typical Western diet. The philosophy also promotes physical activity, avoidance of pesticides and other chemicals, and stress reduction. History: The word “macrobiotic” comes from the Greek words for “great life” and was first used by Hippocrates, the father of medicine. In the eighteeth century, German physician Christoph Hufeland to used this term describe a program for good health. The modern macrobiotic diet was developed in the twentieth century by George Ohsawa and has evolved under Michio Kushi. It was further popularized in the 1980’s when a number of books were published—including books by several medical professionals—who credited the diet for their recovery from cancer and other illnesses. The diet: On a typical day, the standard macrobiotic diet includes complex carbohydrates from brown rice, millet, barley, whole wheat, oats, and other whole grains (40 to 60 percent of calories), vegetables (20 to 30 percent of calories), beans and bean products (such as tofu), sea vegetables, pickles, vegetable oil, and seasonings. Fruit, fish or seafood, and sweets are eaten occasionally (once a week), and red meat, eggs, poultry, and dairy are consumed on a limited basis (once a month or less). The diet is modifiable based on a person’s age, sex, activity level, personal needs, and environment. Benefits: Few studies have been done on the macrobiotic diet for cancer prevention, and most of the research to date has been inconclusive. The diet may affect hormone metabolism; for example, women consuming a macrobiotic diet have much higher levels of phytoestrogens (plant hor750
Salem Health: Cancer mones) in their urine than women consuming an omnivorous diet. This may result in a lower risk for hormonally influenced cancers (such as breast cancer). In addition, the macrobiotic diet is consistent with general cancer prevention guidelines of reducing fat intake, animal products, and processed foods while increasing intake of whole grains, vegetables, and fruits. Risks: In the late 1980’s, there were reports that children and adolescents eating a macrobiotic diet showed belowaverage growth and some nutrient deficiencies (vitamins B12 and D). Most nutritionists recommend that people on macrobiotic and vegan diets make sure to get enough vitamins B12 and D from fortified foods or supplements. Lisa M. Lines, M.P.H. See also Antioxidants; Carotenoids; Complementary and alternative therapies; Dietary supplements; Green tea; Herbs as antioxidants; Integrative oncology; Sun’s soup.
u Magnetic resonance imaging
(MRI) Category: Procedures Definition: Magnetic resonance imaging (MRI) is a noninvasive and pain-free diagnostic imaging test performed using powerful magnets and radio waves rather than ionizing radiation. The magnets cause the protons in the hydrogen ions found in the body’s water to arrange themselves in a certain way in relation to the magnetic field. Once the protons are aligned, the radio waves are bounced off the tissues. This is the “resonance” part of the test. The signals that return to the scanner are analyzed by computer. An MRI takes slicelike images of the body, but it is able to acquire these images in several planes, so that it provides three-dimensional images. MRI can provide high image resolution and significant detail. Consequently, it provides more information than computed tomography (CT). Most MRI machines consist of a large cylinder, called a bore, with a thick casing around it. The magnets surround the patient when he or she is being scanned. Open MRI units have been developed, but they are not available everywhere. In open MRI machines, the magnets do not surround the patient, as there are gaps in the magnets. This change does affect the quality of the images created to some degree, but it also permits the scanning of very obese patients and those with claustrophobia (fear of closed spaces).
Salem Health: Cancer
Magnetic resonance imaging (MRI)
In order to receive a clear image, several types of magnets are used in an MRI machine: resistive magnets, permanent magnets, superconducting magnets, and gradient magnets. Resistive and superconducting magnets consist of coils of wire around a cylinder. They become magnetic only when electrical current is passed through them. Superconducting magnets are bathed in liquid helium, which is extremely cold at a temperature of −452.4 degrees Fahrenheit. This greatly decreases the resistance of the wire coil. As a result, superconducting magnets require a great deal less electrical current to magnetize. A permanent magnet is always a magnet and requires no electrical current to flow through it. The gradient magnets are very low-strength magnets and are used to localize the magnetic field to the portion of the body being examined. There are several drawbacks to MRI. A large percentage of patients are excluded from MRI testing because the test cannot be performed if the patient has any metal in or on the body or if he or she is on any machinery for monitoring or life support. Patients with pacemakers, cochlear implants, clips in the brain, An MRI allows doctors to see soft tissues in the brain. (Digital Stock) artificial heart valves, older vascular stents, intrauterine devices, metal plates or screws, particularly effective at evaluating tumors in the central surgical staples, implanted drug infusion ports, and renervous system, spine, joints, extremities, breasts, and cently replaced artificial joints should not have MRIs. Paliver. tients who are on a ventilator, a cardiac monitor, or an infusion pump or in traction should not have an MRI. Why performed: An MRI is performed to evaluate abnorAnother drawback is that the patient must lie perfectly malities in body tissue. These abnormalities include tustill during the exam in order for the imaging to be clear. mors, congenital abnormalities, vascular abnormalities, An MRI can be difficult for a patient with claustrophobia tissue inflammation, infection, bleeding, and edema. because the scan is performed with the part to be examined Patient preparation: Before an MRI, a patient must rein the center of the tube. Another drawback is that exmove all metal from the body, such as jewelry, watches, tremely obese patients cannot be scanned by the closed belt buckles, hearing aids, removable dental work, and scanner if they are too large for the bore. In addition, MRIs hairpins. The clothing must have no metal on it, such as usually are not performed on pregnant patients because zippers or metal decorations. The patient is also asked to there has not been enough research done to ensure the empty the pockets prior to the MRI. Since the MRI uses a safety of the fetus. strong magnet, any metal objects could become projectiles once the MRI is turned on, potentially causing injury to the Cancers diagnosed: An MRI can diagnose most kinds of patient. The patient may be asked to wear hospital pajamas cancer. It can be used to assess the blood vessels, lungs, if there is metal on the clothing. The patient is asked to liver, heart, stomach, large and small intestines, biliary remove any makeup before the MRI because the iron in tract, kidneys, brain and nerves, spleen, pancreas, male some makeup can be affected by the MRI. Also, medicatestes and prostate, female uterus and ovaries, and the peltion patches should be removed prior to an MRI because vic, knee, and hip bones. To identify structures in the abthe procedure can cause a burn on the site of the patch. domen, it is helpful to use oral contrast, such as liquid barium, and/or intravenous dyes, such as gadolinium. MRI is The patient is often given earplugs because the MRI 751
Malignant fibrous histiocytoma (MFH) scanner makes loud noises. It is essential that the patient lie still while in the scanner, so he or she may be given a sedative prior to the test. This is more likely if the patient has claustrophobia or is confused. Positioning devices are used to keep the body part to be scanned in a stationery position. If the patient is to receive contrast dye, then an intravenous line will be inserted into the arm. The patient may be given a liquid contrast to drink before the test. For some parts of the body, small coils are positioned by the area to be scanned. These devices enhance the radio waves and thus improve the MRI images. Steps of the procedure: For an MRI, the patient lies on a table in the center of the MRI machine. Foam blocks and straps may be used to position the patient. If intravenous contrast is to be used, then it will be injected at this time. Once the patient is positioned, the table slides into the bore of the MRI. The MRI scanner is turned on and the scan is performed. The scan usually includes several runs and can take from fifteen to forty-five minutes depending on what part of the body is being scanned and the reason for the scan. There is a microphone in the room with the MRI machine so that the patient can communicate with the technician. The patient may be given prism glasses to wear so that he or she can see the MRI technician. After the procedure: After the procedure, there is no special follow-up care required unless the patient has received a sedative prior to the MRI. In this case, the patient will need to be driven home. Risks: There are few risks associated with an MRI, unless the person has metal on or in the body or there are metal objects in the room where the test is performed. There is a small risk that a patient might be allergic to the radioactive dye, if it is used. Results: The MRI yields multidimensional computer images of the tissue being examined. A radiologist who reviews these images is able to differentiate between cancer, edema, infection, bleeding, and inflammation. The patency of blood vessels can also be exhibited. MRI is particularly effective for examining the central nervous system. Christine M. Carroll, R.N., B.S.N., M.B.A. u For Further Information Westbrook, Catherine. MRI in Practice. 3d ed. Malden, Mass.: Blackwell, 2005. Huettel, Scott, et al. Functional Magnetic Resonance Imaging. Sunderland, Mass.: Sinauer Associates, 2004. Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Manual of Diagnostic and Laboratory Tests. 3d ed. St. Louis: Mosby Elsevier, 2006.
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Other Resources
How Stuff Works How MRI Works http://health.howstuffworks.com/mri.htm Neurosciences on the Internet Use of Functional Magnetic Resonance Imaging to Investigate Brain Function http://www.neuroguide.com/gregg.html Radiology Info MRI of the Body Http://www.radiologyinfo.org/en/info.cfm?pg= bodymr&bhcp=1 WebMD Magnetic Resonance Imaging (MRI) http://www.webmd.com/a-to-z-guides/magneticresonance-imaging-mri See also Angiography; Bone scan; Brain scan; Bronchography; Computed tomography (CT)-guided biopsy; Computed tomography (CT) scan; Cystography; Ductogram; Endoscopic retrograde cholangiopancreatography (ERCP); Gallium scan; Hysterography; Imaging tests; Lymphangiography; Mammography; Nuclear medicine scan; Percutaneous transhepatic cholangiography (PTHC); Positron emission tomography (PET); Radionuclide scan; Thermal imaging; Thyroid nuclear medicine scan; Urography; X-ray tests.
u Malignant fibrous
histiocytoma (MFH) Category: Diseases, symptoms, and conditions Also known as: MFH, sarcoma, histiocytoma Related conditions: Lymphoma, multiple myeloma, hematologic diseases Definition: Malignant fibrous histiocytoma (MFH) is the most common primary malignant soft-tissue tumor of adulthood. It can also be present in bone. It is usually seen in late adulthood with a peak at age fifty. These are aggressive tumors with a tendency to recur and metastasize. Risk factors: Malignant fibrous histiocytoma is the most common radiation-induced sarcoma; MFH of bone is more frequent in whites, with a male-to-female ratio of 1.5:1. Etiology and the disease process: Malignant fibrous histiocytomal cells is thought to derive from primitive
Salem Health: Cancer
Malignant rhabdoid tumor of the kidney
mesenchymal cells, with four cell types predominating: storiform/pleomorphic, myxoid, giant cell, and inflammatory.
u Malignant rhabdoid tumor of
Incidence: Malignant fibrous histiocytoma accounts for 20 to 30 percent of all soft-tissue sarcomas. It is the most common malignant sarcoma of older adults.
Category: Diseases, symptoms, and conditions Also known as: Rhabdoid tumor of the kidney, MRT
Symptoms: Soft-tissue malignant fibrous histiocytoma usually presents as a painless soft-tissue mass with progressive enlargement over months. Any deep-seated, painless, invasive intramuscular mass in a patient over the age of fifty is most likely MFH. Patients with retroperitoneal MFH have symptoms of fatigue, weight loss, abdominal pressure, fever, and malaise. Osseous MFH usually presents with pain over several months with or without swelling and can be associated with pathologic fracture.
Definition: Malignant rhabdoid tumor of the kidney is an extremely aggressive and lethal cancer that occurs only in infants and young children.
Screening and diagnosis: Soft-tissue malignant fibrous histiocytoma is best diagnosed with magnetic resonance imaging (MRI) with gadolinium contrast. This tumor usually appears as a well-defined hypervascular heterogeneous soft-tissue mass with areas of hemorrhage and necrosis. Osseous MFH usually presents as an aggressive Stage IIb lesion associated with pathologic fracture in approximately 20 percent of cases. Staging depends on pathology, compartmentalization, and presence or absence of metastases: • Stage Ia: Low grade, intracompartmental • Stage Ib: Low grade, extracompartmental • Stage IIa: High grade, intracompartmental • Stage IIb: High grade, extracompartmental • Stage III: Presence of metastases Treatment and therapy: Treatment for Stage I tumors involves surgical resection with wide margins, whereas treatment for Stage II involves surgical resection with adjuvant radiation or chemotherapy. Prognosis, prevention, and outcomes: Prognosis depends on tumor size, depth, location, histologic subtype, and presence of metastases. Local recurrence is seen in approximately 20 to 31 percent of cases. The five-year survival rate is 80 percent if the tumor is under 5 centimeters (cm) but drops to approximately 40 percent if the tumor is greater than 10 cm at diagnosis (however, for retroperitoneal tumors, the five-year survival is 15 to 20 percent). Metastases can occur to the lung, lymph nodes, bone, and the liver. Debra B. Kessler, M.D., Ph.D. See also Amputation; Fibrosarcomas, soft-tissue; Limb salvage; Liposarcomas; Mesenchymomas, malignant.
the kidney Related conditions: Wilms’ tumor
Risk factors: Malignant rhabdoid tumor of the kidney is caused by a mutation or deletion of the INI1 gene. However, there are no known risk factors associated with its development. Etiology and the disease process: Malignant rhabdoid tumor of the kidney is made up of an overgrowth of rhabdoid (rod-shaped) cells. These cells may appear like epithelial (skin), neural (nerve), muscle, or mesenchymal (rare soft-tissue tumor) cells. A single rhabdoid tumor may include all these types of cells or only one or two. The cells tend to infiltrate the kidney tissue and to metastasize early. A common site of metastasis is the brain. Incidence: Malignant rhabdoid tumor of the kidney is a rare tumor. According to the National Wilms’ Tumor Study (NWTS) group data, only 1.6 percent of cases of childhood renal tumors are malignant rhabdoid tumors. Malignant rhabdoid tumors are equally common in both sexes, and the median age at which it occurs is eleven months. Symptoms: The most common symptoms observed are fever, hematuria (blood in the urine), fussiness, and hypertension. Other symptoms are those of brain metastasis, such as seizures and loss of previously achieved motor skills. Screening and diagnosis: There is no routine screening for malignant rhabdoid tumor of the kidney. The most definitive testing includes abdominal ultrasound and abdominal computed tomography (CT) scan. Then the tumor is biopsied. The staging for malignant rhabdoid tumor of the kidney was devised by the NWTS group and then modified by the Children’s Oncology Group (COG). The stages are as follows: • Stage I: The tumor has not spread beyond the one kidney. • Stage II: The tumor is localized to the area around the kidney, and there is no evidence of tumor spread. • Stage III: The tumor has spread into the abdomen. 753
Malignant tumors
• Stage IV: There are metastases outside the abdominal or pelvic cavities. • Stage V: There are bilateral tumors. Treatment and therapy: The primary treatment is surgical removal of the kidney. It is usually removed through direct incision, to avoid any spillage of cancer cells. At this time, lymph nodes are sampled and the adrenal gland may be removed. Bilateral tumors are not removed. Chemotherapy is performed on all patients with malignant rhabdoid tumor of the kidney. Prognosis, prevention, and outcomes: The prognosis for malignant rhabdoid tumor of the kidney is poor, with an average survival time of less than one year. There is no way to prevent it. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Childhood cancers; Wilms’ tumor.
u Malignant tumors Category: Diseases, symptoms, and conditions Also known as: Cancerous tumors Related conditions: Most cancers Definition: Malignant tumors are those that invade surrounding tissue. Commonly known as cancer, cells of malignant tumors are abnormal in morphology, tend to be larger than normal, and have odd shapes and large and irregular nuclei. By entering into the bloodstream or the lymphatic system, these cells spread to surrounding tissue, where they damage the tissues and organs. A sarcoma is a cancer of the connective tissue, and carcinomas are of epithelial origin. Malignant tumors are named using the Latin or Greek root of the organ of origin as a prefix and “sarcoma” or “carcinoma” as the suffix. For example, a malignant tumor of the liver is called hepatocarcinoma; a malignant tumor of the fat cells is called liposarcoma. Risk factors: The most common risk factors for development of malignant tumors include tobacco use; exposure to ultraviolet (UV) radiation, ionizing radiation, certain chemicals, and viruses; and family history. Etiology and the disease process: A mutated cell that continues to divide is a hallmark of cancer. The deoxyribonucleic acid (DNA) repair mechanisms are damaged, and the immune system is compromised such that the tumor cells rapidly multiply undeterred. Additionally, the tumor has an extensive vasculature that provides nutrients and oxygen for its growth. 754
Salem Health: Cancer Symptoms: Unusual bleeding or discharge, a change in the shape or coloration of a wart or mole, a sore throat that does not heal, unexplained weight loss, persistent cough, and anemia are some warning signs. Many symptoms are caused by the fatigue, pain, and stress imposed on the body by malignant tumors. Screening and diagnosis: X rays, ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scans are used to detect changes in tissues or organs, and blood tests are used to monitor abnormal cell counts. Presence of tumor markers such as prostate specific antigen (PSA), carcinoembryonic antigen (CEA), and human chorionic gonadotropin hormone in the blood are used to screen high-risk individuals. Treatment and therapy: Malignant tumors can be removed before they metastasize (spread), but frequently they grow back. Besides a person’s age, general health, and response to treatment, the outcome depends on the type and location of the cancer, the stage of the disease (the extent to which the cancer has spread), or its grade (how abnormal the cancer cells look and how quickly the cancer is likely to grow and spread). Treatment includes surgery, radiation therapy, chemotherapy, hormone therapy, or biological therapy. However, most often a combination of therapies is required for complete eradication of the malignancy. Choice of a healthy, active, tobacco-free lifestyle with a minimum exposure to harmful UV rays can go a long way in preventing cancer. Banalata Sen, Ph.D. See also Cancer biology; Carcinomatosis; Invasive cancer; Metastasis; Tumor markers.
u Mammography Category: Procedures Also known as: Breast X ray Definition: Mammography is a radiographic procedure used to examine internal breast tissue for possible abnormalities. Three types of mammograms are performed: screening mammogram, diagnostic mammogram, and digital mammogram. In a screening mammogram, X-ray images of the breast are recorded on X-ray film (conventional method) or electronically (digital method). The recommendation for screening mammograms is once every two years for those women who are forty to forty-nine years old and once every year for women fifty years old and above. Patients with
Salem Health: Cancer
Mammography
Women are advised to have mammograms once every two years between ages forty and forty-nine and once every year after reaching the age of fifty. (PhotoDisc)
a family history of breast cancer, however, should have the first mammogram before forty years of age and should continue to have them yearly. Also, regardless of age, patients who have been diagnosed as having breast cancer should have a mammogram yearly. In a diagnostic mammogram, a series of X-ray images of the breast from various angles are recorded on X-ray film (conventional method) or electronically (digital method). Diagnostic mammograms are used to diagnose lumps that a woman feels during self-examination or a health care provider detects during a clinical breast examination if other unexpected symptoms—such as change in breast shape or size, or occurrence of nipple discharge, breast pain, or thickening of breast skin—are present. During a diagnostic mammogram, more X rays are taken than during a screening mammogram in order to get views from many angles. A diagnostic mammogram may be required if the patient has breast implants in order to be able to view breast tissue that can be hidden by the implant. In a digital mammogram, X-ray images of the breast are recorded electronically and are stored on a computer. The
images can then be manipulated via computer software for further evaluation. The average dose of radiation used is lower than that for film mammography. In terms of cancer detection, no differences between digital imaging and traditional film imaging have been found for the general population. Digital mammography is considered preferable, however, for those women who are under the age of fifty, have dense breasts, or are premenopausal or perimenopausal. In addition, the National Cancer Institute (NCI) is supporting research to develop new procedures for detecting breast tumors. Technologies currently being investigated are magnetic resonance imaging (MRI) and positron emission tomography (PET). Other methods being investigated are those to detect genetic markers for breast cancer, which involve analysis of blood, urine, or fluid aspirated from the nipple. Cancers diagnosed: Breast cancer Why performed: In the United States, the most frequently occurring cancer for women is breast cancer. By 755
Mammography
Salem Health: Cancer
Categories of the Breast Imaging Reporting and Database System (BI-RADS) Category Assessment
Follow-up
0 1 2 3 4 5 6
Additional imaging needed before a category can be assigned Continue annual screening mammography (for women over age 40) Continue annual screening mammography (for women over age 40) Receive a 6-month follow-up mammogram May require biopsy Requires biopsy Biopsy confirms presence of cancer before treatment begins
Need additional imaging evaluation Negative Benign (noncancerous) Probably benign Suspicious abnormality Highly suggestive of malignancy (cancer) Known biopsy—proven malignancy (cancer)
age eighty, approximately one of every nine women will develop this cancer. Mammography allows for the screening and early detection of breast-tissue abnormalities. Statistics indicate that use of mammography can result in detection of breast cancer one to two years before it can be detected by breast self-examination. Early detection of breast cancer improves the chances for successful treatment of this form of cancer. Patient preparation: The patient should shower or bathe prior to the mammogram and should not use deodorant, body lotions, sunscreens, creams, powders, or perfume on the chest or underarms, as they may cause “artifacts” (false images) to appear on the X-ray image. Steps of the procedure: Patients who have breast implants should mention that fact when making the mammogram appointment. Both the technologist who performs the mammogram and the radiologist who interprets the mammogram must have experience in working with implants. Prior to undergoing mammography, the patient will be asked if she has undergone any type of breast surgery, as this may affect the way in which the X-ray films are interpreted. She will then be asked to remove all clothing and jewelry from the waist up. The patient will be given a short gown and asked to put it on so that it opens in the front. The procedure begins with the radiologic technologist placing one of the breasts on a platform and lowering a plastic plate onto the breast until it is flattened as much as possible. This allows for the successful X-ray visualization of as much breast tissue as possible. The technologist then positions the X-ray machine, stands behind a protective barrier, and takes the image. A front-view X ray (from the upper surface down) and a side-view X ray of the breast will be taken. Next, the technologist repeats this procedure with the other breast. While the patient may feel uncomfortable when the breast is being flattened, this discomfort is short in duration. 756
After the procedure: The patient will be asked to wait while the X-ray films are developed and then viewed by a radiologist to make sure that none of the images need to be retaken. Once this has been confirmed, the patient will be allowed to redress and use deodorant. The patient should ask how long it will take to get the results of the mammography and whether those results will be sent to the patient as well as to the doctor. She may also want to ask where the “films” will be stored, so that they can be retrieved if the patient moves out of the area and needs to have future mammograms performed at another location. This is important because the new radiologist may use those earlier images as a reference to determine if there have been any changes in breast tissue over time. Risks: Mammography uses low-dose radiation and is considered to be very safe. Patients who are pregnant or think they may be pregnant, however, should not have a mammogram. A pregnant woman should not be exposed to X rays because of the possible risk to the fetus. The safety and reliability of mammograms are mandated by a federal law called the Mammography Quality Standards Act (MQSA). This law requires that all mammography facilities in the United States meet stringent quality standards, including those for the medical physicist, who tests the mammography equipment; the technologist, who takes the mammogram; and the radiologist, who interprets the mammogram. The facilities must also maintain certification by the Food and Drug Administration (FDA) and undergo an annual inspection. Results: A normal result means that the X-ray films revealed no obvious signs of breast cancer. In certain instances, however, breast cancer may still be present. This false negative result is more common for those women with breast tissue that is more dense, as is typical for younger women. The more dense the breast tissue, the more difficult it is to visualize abnormal spots on the X-ray image.
Salem Health: Cancer
Managed care
An abnormal result means that something has been identified that needs to be looked at more closely. The abnormality may be an unusual-looking area of breast tissue or a type of cyst or lump. Even the presence of a lump, however, does not necessarily indicate cancer. A lump can be either benign (noncancerous) or malignant (cancerous). Therefore, additional testing—such as a diagnostic mammogram, ultrasound, or biopsy—may be required to determine if the abnormality is the result of breast cancer. The most common type of biopsy is known as a needle biopsy. This procedure consists of inserting a small-gauge needle into the area in question and removing a small tissue sample. That sample is then sent to a laboratory for determination if any cancerous cells are present. An abnormality that is interpreted as breast cancer when none is present is called a false positive result. Like the false negative result, it is more common for younger women. It is also more common for those women who have a family history of breast cancer, have had a previous breast biopsy, or are taking estrogen. The American College of Radiology (ACR) has established a system for uniform reporting of mammogram results called the Breast Imaging Reporting and Database System (BI-RADS) that consists of seven categories. Radiologists and physicians use it to help determine appropriate patient care. Cynthia L. De Vine, B.A.
National Cancer Institute Cancer Information Service http://cis.nci.nih.gov
u For Further Information Lanyi, M. Mammography: Diagnosis and Pathological Analysis. New York: Springer, 2003. Pisano, E. D., C. Gatsonis, E. Hendrick, et al. “Diagnostic Performance of Digital Versus Film Mammography for Breast-Cancer Screening.” New England Journal of Medicine 353 (October 27, 2005): 1773-1783. Qasee, A., et al. “Screening Mammography for Women Forty to Forty-nine Years of Age: A Clinical Practice Guideline from the American College of Physicians.” Annals of Internal Medicine 146, no. 7 (April 3, 2007): 511-515.
Category: Social and personal issues Also known as: Health maintenance organizations (HMOs), preferred provider organizations (PPOs)
u
Other Resources
American Cancer Society http://www.cancer.org American College of Radiology http://www.acr.org/index.asp National Breast and Cervical Cancer Early Detection Program http://www.cdc.gov/cancer/nbccedp/index.htm
National Women’s Health Information Center http://www.womenshealth.gov Susan G. Komen Breast Cancer Foundation http://www.komen.org See also Accelerated partial breast irradiation (APBI); Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Breast implants; Breast ultrasound; Calcifications of the breast; Childbirth and cancer; Clinical breast exam (CBE); Comedo carcinomas; Duct ectasia; Ductal carcinoma in situ (DCIS); Ductal lavage; Ductogram; Estrogen-receptorsensitive breast cancer; Fibroadenomas; Fibrocystic breast changes; Hormone replacement therapy (HRT); Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Lumpectomy; Medullary carcinoma of the breast; Microcalcifications; Needle biopsies; Needle localization; Nipple discharge; Peutz-Jeghers syndrome (PJS); Phyllodes tumors; Tubular carcinomas; Wire localization.
u Managed care
Definition: Managed care is a process used by health insurance plans to pay for and coordinate the delivery of health care services to people covered under the managed care plan. Prevalence of managed care: Managed care is the most predominant form of health insurance in the United States. The majority of private health insurance plans are managed care plans. The Kaiser Family Foundation and the Health Research and Educational Trust survey estimated that 97 percent of employees enrolled in an employer’s group health insurance were covered under a managed care plan in 2006. The prevalence of managed care in public health insurance plans has grown rapidly since 1990. Approximately 60 percent of people enrolled in Medicaid receive services through managed care, representing a 900 percent increase from 1991. The Medicare program, which has traditionally provided public health insurance through an indemnity plan, has seen increasing enrollments in its managed care Medicare Advantage plans. 757
Managed care Principles of managed care: Health insurance was once primarily organized as an indemnity or fee-for-service system. Persons covered under an indemnity health insurance plan can visit any physician or medical facility they choose and submit a claim to the insurer for reimbursement of a certain percentage of the medical expenses. In response to escalating health care costs, managed care systems were developed and promoted as a way to pay for medical services and control the quality, accessibility, utilization, and cost of those services. As a result, persons covered under a managed care plan have limitations on which health care providers they can use and must follow the plan’s procedures in accessing the health care providers to receive coverage. Managed care has many different forms, but there are a few fundamental principles and processes shared by all managed care plans. Managed care plans control the access of persons covered under the plan (covered persons) to medical services. Medical services are covered only if they are provided by certain health care providers that are either on the staff of the managed care plan or under contract with the plan. Covered persons are assigned to or can choose from a list of primary care physicians, who are usually family doctors, internists, pediatricians, or obstetricians/gynecologists. The primary care physician’s role in coordinating care is to eliminate inappropriate and unnecessary services; he or she provides preventive and routine care to covered persons and acts as a gatekeeper to arrange for and authorize care from other health care providers. The patient must therefore obtain a referral from the primary care physician before seeking nonemergency medical care from a specialist, hospital, or outpatient facility. Managed care plans also use “utilization reviews” to determine the medical necessity or appropriateness of services. Reviews can take place before, during, or after services have been rendered. Because these reviews determine whether or not the plan will cover the medical expenses, patients are encouraged to seek “preauthorization” for services requiring review. For example, a cancer patient who has been advised to undergo an operation to biopsy or remove a tumor may need to arrange for preauthorization of the surgery in order to determine the amount of coverage the plan will provide, if any. Clearly, therefore, managed care plans can influence the quality of care delivered to covered persons. The plans impose standards for selection of health care providers that are associated with the plan. The plans also have formal programs of quality assurance and provide incentives for plan doctors to use best practice protocols or treatment guidelines, which are based on standards of care set by medical experts. Through case or disease management 758
Salem Health: Cancer programs, plans identify covered persons with chronic health care needs and coordinate with the primary care physician to establish a cost-effective treatment plan and monitor patient outcome. At the same time, to manage costs, plans may restrict certain treatments or limit inpatient admissions and lengths of stay, favoring outpatient care when possible. Health care providers associated with managed care plans are reimbursed at negotiated rates. Some plans pay a fixed amount, called a “capitation payment,” for each health care provider providing services to covered persons, regardless of the number or type of services rendered. Other plans negotiate with providers and reimburse them for actual expenses based on a discounted rate. Clearly, then, the incentives built into such plans can be financial as well as oriented toward a good health outcome for the patient. Types of plans: Three primary types of managed care plans exist: health maintenance organization (HMO) plans, point-of-service (POS) plans, and preferred provider organization (PPO) plans. HMOs are the oldest and strictest form of managed care. Enrollment in HMO plans peaked in 1996 and began to decline thereafter, but HMOs are still a prevalent form of managed care. HMOs pay for services delivered by health care providers who are employees of the HMO or health care providers who are under contract with an HMO as so-called network providers. The covered person is usually responsible only for a fixed copayment. Care is delivered through a primary care physician, and care from other providers must be authorized by the primary care physician in order for it to be covered. Typically, the other providers must also be associated with the HMO. A POS plan is usually offered by an HMO and may be referred to as an “open-ended” HMO plan. Under a POS plan, the covered person can receive services from a health care provider who is not an employee or network member of the HMO. These services are available at higher cost to the covered person through a deductible and coinsurance and frequently do not require a referral from a primary care physician. A PPO plan is a form of managed care offered by insurers other than HMOs and is currently the most popular form of managed care plan. The insurer contracts with a network of area health care providers who agree to accept set fees for services given to covered persons. The plan offers financial incentives for covered persons to receive care from in-network providers, such as low copayments. Covered persons can receive care from health care providers, including primary care physicians, who are not members of the PPO network, but only at a higher cost through
Salem Health: Cancer deductibles and coinsurance. Covered persons may also be responsible for paying the difference between what the insurer paid the out-of-network health care provider and what the provider charged. Covered persons can often make self-referrals and do not need to get a referral from a primary care physician. Consumer protections: Because managed care plans make coverage decisions that can ultimately restrict access to care, many states have passed consumer protection laws governing managed care practices. These laws apply only to managed care plans that are state-regulated. Many states allow a covered person with a chronic illness to pick a specialist as a primary care physician, since going through a primary care physician for referrals is time-consuming. Other states allow primary care physicians to give standing referrals to persons with chronic illnesses, such as cancer, who need special medical care over a long period of time. Managed care plans can deny coverage of a service based on their assessment that coverage is not provided for under the contract, the proper procedures in obtaining the services were not followed, or the services were not appropriate or medically necessary. Managed care plans must follow state and federal rules for internally reviewing covered persons’ complaints and appeals concerning denial of coverage. Most states have enacted procedures for external or independent reviews, especially when denial of coverage was based on a determination by the insurer that services rendered were not appropriate or medically necessary. Several states require persons employed by insurance companies who make decisions on medical necessity of care to have medical credentials or have a current in-state medical license. Many states have established an ombudsman office to act on behalf of covered persons during disputes with insurers over denial of coverage. States have prohibited managed care plans from compromising physicians’ medical opinions. Most states prohibit gag clauses in health care provider contracts that would keep doctors from informing patients of their treatment options. Federal law bans the use of gag clauses in Medicaid and Medicare plans. States have also banned the practice of rewarding doctors for performing less costly procedures or prescribing less costly drugs. Finally, many states produce a report card on the performance of managed care plans. The report cards detail how well a managed care plan handles complaints, covers and delivers care, and gives access to specialized care. Some reports also include measurers of health care providers associated with managed care plans. Amanda McQuade, Ph.D.
Mantle cell lymphoma (MCL) u
For Further Information Buckley, John F., and Nicole D. Prysby. 2005 State by State Guide to Managed Care Law. New York: Aspen, 2005. Kongstvedt, Peter R. Managed Care: What It Is and How It Works. 2d ed. New York: Aspen, 2004. Marcinko, David E., and Hope R. Hetico, eds. Dictionary of Health Insurance and Managed Care. New York: Springer, 2006.
u
Other Resources
Agency for Healthcare Research and Quality http://www.ahrq.gov Centers for Medicare and Medicaid Services U.S. Department of Health and Human Services http://www.cms.hhs.gov Kaiser Family Foundation http://www.kff.org Kaiser State Health Facts http://www.statehealthfacts.org MedlinePlus http://www.nlm.nih.gov/medlineplus/ managedcare.html Patient Advocate Foundation http://www.patientadvocate.org See also Financial issues; Health maintenance organizations (HMOs); Insurance; Medicare and cancer; Preferred provider organizations (PPOs); Second opinions; Social Security Disability Insurance (SSDI).
u Mantle cell lymphoma (MCL) Category: Diseases, symptoms, and conditions Also known as: Non-Hodgkin lymphoma, B-cell lymphoma Related conditions: Hodgkin lymphoma Definition: Mantle cell lymphoma (MCL), or B-cell lymphoma, is a rare form of non-Hodgkin lymphoma (NHL), with 6 to 8 percent of cases of NHL accounting for MCL. MCL primarily affects the B lymphocytes of the lymphatic system. The lymphatic system is made up of lymph nodes that are linked by lymph vessels responsible for delivering fluid throughout the body, as well as collecting waste from tissues, purifying it, and then returning it to the blood. 759
Mantle cell lymphoma (MCL) MCL has two distinct groups: indolent or low-grade lymphoma and aggressive or high-grade lymphoma. Risk factors: There are no risk factors for MCL. Etiology and the disease process: Causes for MCL have not been identified; however, it is known that Caucasian males are more susceptible to MCL and that it is most prevalent in adult populations. It has been determined that patients with MCL have an overexpression of cyclin D1, which is a protein that encourages cellular growth. This cyclin D1 overexpression has been traced to a translocation between chromosomes 11 and 14. Incidence: MCL is found typically in adults in their sixties, affecting males more often than females at a ratio of 3:1. Cases of MCL have been steadily increasing since the 1970’s. As the initial symptoms of MCL often go undetected, upon diagnosis the majority of patients already have Stage IV disease. Symptoms: MCL is often detected because of swelling in the lymph nodes of the neck, groin, or armpit that is painless yet noticeable either visibly or to the touch. Accompanying symptoms often include fatigue, decreased appetite, fever, night sweating, weight loss, itchiness, and breathlessness. Screening and diagnosis: MCL is diagnosed following surgical removal of a portion of the swollen lymph node. The tissue collected is then sampled to review its cells under a microscope to make the diagnosis. Additional supportive tests may include blood tests, bone scans, marrow biopsies, and X rays to provide information on the extent of the spread of the lymphoma and its type. The information gained from these tests will assist the doctor in determining the appropriate treatment plan for the cancer. The Ann Arbor staging for non-Hodgkin lymphoma, which is the definitive disease process guide for lymphomas, defines four stages of the disease. Stage I is lymphoma limited to a primary lymph node, organ, or tissue site in one body area. Stage II includes two or more lymph nodes or regions of lymph nodes either on the upper or lower half of the body. Stage III includes two or more lymph nodes or regions of lymph nodes on both the upper and lower parts of the body, and Stage IV includes lymphoma that has spread from the lymph nodes to one or more organs in the body. Each stage also includes a subclassification of either A or B, to identify either the absence of symptoms (A) or the presence of symptoms (B). Additionally, lymphoma that has spread beyond the lymph nodes to the organs can be classified with an E for extranodal. 760
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Relative Survival Rates for Mantle Cell Lymphoma, 1988-2001 Years
Survival Rate (%)
1 2 3 5 8 10
83.9 72.6 65.2 51.1 37.4 34.3
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Treatment and therapy: Treatment for MCL is dependent upon the patient’s stage of disease. Patients with indolent MCL who are asymptomatic often manage their disease with a “watch and wait” approach without medication until symptoms appear. As most patients with MCL are diagnosed, however, already at Stage IV, aggressive therapy is often prescribed. Aggressive therapy can consist of chemotherapy alone; however, this is often not enough to treat the cancer. Aggressive therapy typically includes a combination of chemotherapy and radiation. Allogenic stem cell transplantation has also been used to introduce stem cells that are not cancerous into the body to assist the body in its fight against the cancer. Allogenic stem cell transplantation, however, causes side effects which are often deemed intolerable by the patient, is difficult to perform, and is rarely used as a treatment option. Additional therapy, such as treatment with a monoclonal antibody, can also be used in combination with chemotherapy, to target and kill select cancer cells. The patient may also be given medications to counteract the side effects caused by the first-line therapies, such as steroids to combat nausea, or interferons to allow the body to increase its immune response. Prognosis, prevention, and outcomes: Prognosis for MCL can be determined by its classification as either indolent or aggressive, and indolent MCL typically has a better prognosis than aggressive MCL. As the majority of cases of MCL are diagnosed as Stage IV, MCL has only a moderate prognosis. Patients diagnosed with MCL most often have an average survival of three to four years. Even in patients with a good or fair prognosis, curing MCL is uncommon. Anna Perez, M.Sc.
Salem Health: Cancer u For Further Information Clarke, C. A., and S. L. Glaser. “Changing Incidence of Non-Hodgkin Lymphomas in the United States.” Cancer 94 (2002): 2015-2023. Norton, A. J., J. Matthews, V. Pappa, et al. “Mantle Cell Lymphoma: Natural History Defined in a Serially Biopsied Population over a 20-Year Period.” Annals of Oncology 6 (1995): 249-256. u
Other Resources
American Cancer Society http://www.cancer.org Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org National Cancer Institute www.cancer.gov/search/geneticsservices See also Angiogenesis inhibitors; Burkitt lymphoma; Non-Hodgkin lymphoma; Proteasome inhibitors; Richter syndrome; Virus-related cancers.
u Mastectomy Category: Procedures Definition: A mastectomy is the surgical removal of a breast. Cancers diagnosed or treated: Breast cancer Why performed: A mastectomy is performed to remove a breast that has been affected by cancer. It is very important to remove all the cancerous tissue so that the cancer cannot spread to other parts of the body. Many women who have been diagnosed with breast cancer are given the option to choose between mastectomy and breast-conserving surgery (lumpectomy) plus radiotherapy. For these women, many factors may need to be weighed before making a decision. Mastectomy is usually recommended for certain types of patients, including women who have previously had radiotherapy to the affected breast, women with two or more areas of cancer in the same breast, women with connective tissue diseases (such as scleroderma) that make them inappropriate candidates for radiotherapy, and male breast cancer patients. Although breast cancer in men (accounting for less than 1 percent of cancer cases in men), is relatively rare its treatment, including mastectomy, is the same as it is in women. Women believed to be at moderate or high risk of developing breast cancer may choose to have one or both breasts removed prophylactically to prevent, rather than to
Mastectomy treat, breast cancer. It is believed that preventive mastectomy reduces the chance of developing breast cancer by about 90 percent in such women. Patient preparation: The patient will probably meet with the surgeon a few days before the surgery. The surgeon will want to know about any medications the patient is taking that could interfere with surgery. A routine blood workup, urinalysis, and an electrocardiogram (ECG) may be performed a few days before the surgery. Patients will normally be instructed not to eat or drink for at least eight hours before surgery. If the patient is to have a sentinel lymph node biopsy during the procedure, then a small amount of a radioactive substance and a blue dye will be injected into the area several hours before surgery. Steps of the procedure: There are four types of mastectomy. A simple mastectomy involves removal of all of the breast tissue. Asimple mastectomy with node sampling involves removal of the breast tissue and some of the lymph nodes from under the arm. A modified radical mastectomy involves removal of all breast tissue plus all lymph nodes from under the arm. A radical mastectomy involves removal of all breast tissue and all lymph nodes from under the arm, plus the muscles from the chest wall. This procedure was the most commonly performed type of mastectomy in the past, but it is rarely performed today. Studies have shown that the modified radical mastectomy is equally effective, and therefore it has become the most common type of procedure for removing the entire breast. The procedure is performed under general anesthesia. A diagonal or horizontal cut is made across the breast, and the breast tissue is removed. Small nerves are cut between the breast tissue and the skin area. Some of the lymph nodes from under the arm on the side of the cancer are usually removed during the procedure, so that the surgeon can check them for cancer cells. The exact number of lymph nodes under the arm will vary from person to person, but there are approximately twenty. A few lymph nodes may be removed to check for cancer cells, a procedure known as axillary gland sampling. Sometimes all of the lymph nodes under the arm are removed, a procedure known as axillary clearance. Sometimes a procedure known as sentinel lymph node biopsy is used. In this procedure, a small amount of radioactive liquid and a blue dye are injected into the area before the operation. This allows the surgeon to identify the draining lymph nodes for the area, the ones most likely to contain cancer cells if the cancer has started to spread. These sentinel lymph nodes are usually one to three in number. They will contain radioactivity that can be de761
Mastectomy
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tected with a handheld Geiger counter and will appear blue in color. These lymph nodes are removed and tested to see whether they contain cancer cells. If a sentinel lymph node contains cancerous cells, then more lymph nodes will need to be removed. If it is obvious that a sentinel lymph node contains cancer, then the surgeon can proceed to the remove additional lymph nodes at the time of the mastectomy. If cancer is detected in a sentinel lymph node after the mastectomy through microscopic study by a pathologist, then additional lymph nodes will need to be removed in another procedure. If the sentinel nodes are cancer-free, then it is very unlikely that the cancer has spread to other lymph nodes. In this case, the patient can avoid the potential side effects of full lymph node surgery. A plastic or rubber drainage tube will most likely be inserted to drain fluid from the wound area before the incision is closed up with stitches. A pressure dressing is
placed over the wound area to minimize oozing after the surgery. After the procedure: The patient will experience shortterm pain and swelling and will have a scar. Possible complications include wound infection. The patient will most likely have one or more drainage tubes coming from the wound area to drain blood and tissue fluid to prevent them from collecting and causing swelling or infection. These tubes will be removed several days after the surgery. Occasionally, fluid collects around the wound after the tubes have been removed and needs to be drained. The extent of the surgery will determine the length of hospital stay, but it will probably be from one to several days. After going home, the patient will need considerable rest. Lifting or carrying of heavy objects should be avoided, and the patient should not drive for a few weeks. Gentle
A. Incision
B. Excision
Breast tissue Lymph nodes
A total mastectomy. (©Visuals Unlimited/Corbis)
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Salem Health: Cancer exercises may be recommended to relieve pain and stiffness and to encourage circulation to the area. Many patients experience a pulling sensation near or under the arm after a mastectomy. Patients may experience phantom breast sensations such as unpleasant itching, “pins and needles,” pressure, or throbbing after a mastectomy. One study showed that more than one-third of the patients experienced such sensations and that the incidence was similar whether or not the patient had had breast reconstruction. These sensations are believed to be caused by the cutting of small nerves during the procedure and are analogous to phantom pains that can occur after limb amputations. Undergoing a mastectomy can be an emotional time for a patient. Patients may find it helpful to talk to others who have been through the operation, both before and after the surgery. If a breast reconstruction procedure is not done at the time of the mastectomy, then the patient can use a prosthesis inside her bra to provide the shape of a breast. Risks: A mastectomy is normally a safe and effective operation. There are extremely rare risks associated with the use of general anesthesia. In rare cases, hematoma, an accumulation of blood in the wound area, or seroma, an accumulation of clear fluid in the wound area, may occur. Both of these conditions can be treated. Removing lymph nodes can sometimes lead to fluid buildup and swelling in the affected arm, which can cause pain and tenderness in the arm and hand. This condition, called lymphedema, usually starts months or years after the surgery and develops slowly over time. It is more likely to occur if all of the lymph nodes and vessels are removed. Lymphedema cannot be cured, but the symptoms can be reduced by early recognition of the condition and careful management. Other possible side effects of the removal of lymph nodes are limitation of arm and shoulder movement and numbness of the upper arm. Results: If breast cancer is detected early, then mastectomy results in a ten-year survival rate of more than 90 percent. Jill Ferguson, Ph.D. u
For Further Information Dickson, R. B., and M. E. Lippman. “Cancer of the Breast.” In Cancer: Principles and Practice of Oncology, edited by Vincent DeVita, Jr., et al. 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2001. Singletary, S. E. “Techniques in Surgery: Therapeutic and Prophylactic Mastectomy.” In Diseases of the Breast, edited by J. R. Harris et al. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2004.
Mastocytomas Vazquez, B., D. Rousseau, and T. C. Hurd. “Surgical Management of Breast Cancer.” Seminars in Oncology 34 (2007): 234-240. u
Other Resources
American Cancer Society Surgery for Breast Cancer http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Surgery_5.asp?sitearea= Cancer Backup Breast Cancer Information Centre http://www.cancerbackup.org.uk/Cancertype/Breast Imaginis: The Breast Cancer Resource Mastectomy http://www.imaginis.com/breasthealth/ mastectomy.asp National Cancer Institute Preventive Mastectomy: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Therapy/preventive-mastectomy See also Breast cancers; Breast implants; Breast reconstruction; Lumpectomy; Lymphedema; Mammography; Sentinel lymph node (SLN) biopsy and mapping.
u Mastocytomas Category: Diseases, symptoms, and conditions Also known as: Mast cell tumors Related conditions: Mastocytosis Definition: Mastocytomas are lesions found in mastocytosis, a disease characterized by an abnormal increase in tissue mast cells. Mastocytomas do not lead to the hematogenous spread of mast cells; there is no known association with mastocytomas and a predilection to develop mast cell leukemia. Risk factors: Mastocytomas typically develop only in people with mastocytosis. Etiology and the disease process: Mast cells are ubiquitous throughout the body and are found in almost all body tissues. They release proinflammatory mediators such as histamine on activation. Mastocytosis may be limited to the skin, in which case it is referred to as cutaneous mastocytosis, or may involve systemic organ systems, in which case it is referred to as systemic mastocytosis. Mastocytomas—along with urticaria pigmentosa, diffuse 763
Matrix metalloproteinase inhibitors cutaneous mastocytosis, and telangiectasia macularis eruptive perstans—make up the spectrum of cutaneous disease. Accumulations of mast cells in the skin result in these conditions. Mastocytomas can appear as solitary or multiple lesions and typically affect only children before the age of six months. Mastocytomas more commonly appear as solitary lesions, and if a second lesion or multiple lesions develop, they typically do not occur more than two months after the first lesion. They are rare in adults because they usually resolve early in life. Although mastocytomas most commonly are localized to the skin, other organs, such as the gastrointestinal system, may be affected. They are nodular, usually range in size from three to four centimeters, and frequently occur on an extremity. Incidence: The incidence of mastocytomas is unknown. Symptoms: Lesions may be asymptomatic or may intermittently become itchy, red, and swollen if the lesions are stroked. More commonly, lesions are symptomatic. Screening and diagnosis: The lesions typically demonstrate Darier’s sign. Darier’s sign occurs when a lesion is stroked and the lesion and the surrounding area become itchy, red, and swollen. On histological examination, mastocytomas show marked tumorlike aggregates of mast cells throughout the dermis. Treatment and therapy: Mastocytomas that cause mechanical problems or systemic problems can be treated locally with PUVA therapy (psoralen combined with longwave ultraviolet light). Potent topical steroids under occlusive dressings are also utilized. Surgical excision is also an option but should be considered only as a last option, as the natural course of the lesions is to resolve. Prognosis, prevention, and outcomes: Mastocytomas usually appear in infancy, and the occurrence of the lesions resolves by adolescence. Sarah Kasprowicz, M.D. See also Benign tumors; Veterinary oncology.
u Matrix metalloproteinase
inhibitors Category: Chemotherapy and other drugs Definition: Matrix metalloproteinase inhibitors suppress the enzymatic activity of extracellular matrix metalloproteinases secreted by cancer cells. 764
Salem Health: Cancer Cancers treated: Several matrix metalloproteinase inhibitors are currently in clinical trials. Their efficacies in treating cancers are unknown at this time. Delivery routes: Oral, intraperitoneal, intrapleural How these drugs work: Matrix metalloproteinases are a family of enzymes normally secreted by connective tissue cells and inflammatory cells (phagocytes). They are called metalloproteinases because they contain a zinc atom at their catalytic (active) site. These enzymes play a role in several normal physiologic processes, including embryo implantation and normal angiogenesis associated with tissue growth and wound healing. Malignant tumors undergo invasive growth and metastasis. The viscous connective tissue matrix, composed of collagens, laminins, fibronectins, elastins, and proteoglycans, forms the scaffolding for cellular organization in tissues and provides a barrier to cancer cell migration. Cancer cells, however, can also secrete matrix metalloproteinases, which allows metastasis to proceed by breaking down the connective tissue extracellular matrix. Matrix metalloproteinases are also important contributors to abnormal angiogenesis, the process by which cancer cells stimulate the production of new blood capillaries that deliver nutrients to the tumor cells and are essential for their continued growth. Researchers identified compounds in tissues that inhibited the activity of the matrix metalloproteinases and have developed new inhibitors by chemical synthesis. The inverse relation between matrix metalloproteinase activity and clinical outcome in cancer has led to the development and testing of these inhibitors in pancreatic, colon, and liver tumor model systems. Since 1993, matrix metalloproteinase inhibitors have undergone rapid clinical development for efficacy in treating colon, ovarian, pancreatic, prostate, gastric, skin, and both non-small-cell and smallcell lung cancers. The most promising inhibitors are those that can be administered orally, making them suitable for chronic administration, which appears to be necessary for optimal effect. Targeting matrix metalloproteinases in cancer is complicated by the fact that they are absolutely necessary for normal physiological processes; thus researchers must find a delicate balance between disease treatment and the progression of these processes. Unfortunately, clinical trials conducted on synthetic broad-spectrum inhibitors (those targeting several matrix metalloproteinases) have yielded disappointing results in cancer pathology. Nevertheless, researchers are making intensive efforts to find new classes of matrix metalloproteinase inhibitors that have high (rather than broad) selectivity against specific metalloproteinases.
Salem Health: Cancer Side effects: Reported side effects from matrix metalloproteinase inhibitors include abdominal pain, fever, elevated liver enzymes, musculoskeletal pain and stiffness, mild thrombocytopenia, skin rash, and cutaneous phototoxicity. Bernard Jacobson, Ph.D. See also Angiogenesis; Cancer biology; Carcinomatosis; Malignant tumors; Metastasis.
u Mayo Clinic Cancer Center Category: Organizations Definition: The Mayo Clinic is the first and largest integrated group practice in the world. Based in Rochester, Minnesota, it contains hospital facilities, research laboratories, and a medical school. Together with its satellite hospitals and practices in Jacksonville, Florida, and Scottsdale, Arizona, the clinic treats more than half a million patients annually and operates by the philosophy that the needs of the patient come first. Mayo Clinic is consistently ranked as one of the best hospitals in the United States by authorities throughout the world. It began as a small outpatient operation but now is a comprehensive health care institution for southern Minnesota and its neighboring states, providing a full range of inpatient and outpatient services. Its research department is also world-renowned, publishing more than 2,800 publications a year in biomedical journals. The Mayo Clinic College of Medicine offers programs in graduate education and clinical medicine. Statistics: Mayo Clinic is Minnesota’s second-largest not-for-profit organization. In 2004 it acquired $5.6 billion. In 2007, it employed more than 3,300 physicians, scientists, and researchers, and 46,000 allied health staff. Between its founding in 1915 and 2007, the oldest of Mayo Clinic’s five graduate medical schools trained more than 17,000 students. Mayo medical school trained more than 1,000 physicians between 1972 and 2007. History: Mayo Clinic began as a small practice founded by William Worrall Mayo and his two sons, William James Mayo and Charles Horace Mayo. W. W. Mayo, originally from the United Kingdom, immigrated to the United States in 1846. He began practicing medicine as the examining surgeon for the Union Army in southern Minnesota. His sons, William and Horace, returned to Rochester to join their father’s practice after graduating from medical school. In 1883, a devastating tornado struck, leaving many casualties and Rochester in ruins. The trio
Mayo Clinic Cancer Center and a nun, Mother Alfred Moes from the Sisters of St. Francis, recognized the need for a large facility to treat the ill and injured and built the twenty-seven-bed Saint Mary Hospital in 1889. This hospital remains in operation in the twenty-first century with 1,157 beds. Two years later, Henry Stanley Plummer joined the practice. Ideologies and systems of group practice that Plummer developed and incorporated then are still widely used. The most notable examples include the centralized, individual, dossierstyle medical record and the interconnecting telephone communication system. In 1905, Louis B. Wilson joined the clinic to implement and run the experimental laboratories. He is considered the father of research in Rochester and is known for his contribution of the fresh-frozen tissue method for pathological diagnosis. In 1914 Wilson was appointed as the first director of the Mayo Foundation for Medical Education and Research. W. W. Mayo’s philosophy, “No one is big enough to be independent of others,” greatly influenced his sons. From the outset of their professional careers, the Mayo brothers encouraged collaboration and learning among the medical practitioners. In 1906 six visiting surgeons established the Surgeons Club and formalized the open-door policy. The brothers’ practice has not always been called the Mayo Clinic. The brothers originally included their names in the title and the name Mayo Clinic was coined by their medical colleagues who visited the Mayo brothers and preferred to refer to the duo practice as the Mayo Brothers’ Clinic or the Mayos’ Clinic. In 1939 the brothers passed away two months apart. Charlie Mayo passed away from lobar pneumonia, and William Mayo died in his sleep because of complications of his stomach cancer. Even after the passing of the founders, Mayo Clinic continued to contribute greatly to society. During World War II, the clinic offered its aero-medical research services to the military for one dollar per year. During this time, the antiblackout suit was developed for military pilots. The suit technology is still in use. In 1950, Edward Kendall and Philip Hensch became corecipients of the Nobel Prize in Physiology or Medicine for their work in isolating hormones of the adrenal cortex. Oncological services: Every year, thousands of patients flock to Mayo Clinic oncology departments, which treat more than two hundred different kinds of cancer. The medical oncology department administers chemotherapy and immunotherapy, and the radiation oncology department administers radiation therapy. These departments work in sync with the Mayo Clinic Comprehensive Cancer Center, which conducts cancer research, clinical trials, clinical treatments, and education. Innovative and advanced cancer 765
Mediastinal tumors care is available at Mayo Clinic. Patients also have access to novel drug, immunologic, and gene therapies through ongoing clinical trials. The oncology department services include bone marrow transplantation, electronic portal imaging device (EPID) target localization, familial cancer genetics screening and counseling, stereotactic radiosurgery, high-dose-rate (HDR) brachytherapy, hyperthermia, intensity-modulated radiation therapy (IMRT), intraoperative radiation therapy, intravascular brachytherapy, lowdose-rate brachytherapy, permanent prostate brachytherapy, radiofrequency ablation of tumors, and small field conformal radiation therapy. Institutional features: The Mayo Clinic employs a comprehensive patient financial counseling system. First, patients are provided an estimate of costs and informed of financial support that could be provided by their insurance companies. Although fees tend to be higher than those in standard practice, the costs are well managed by the clinic’s financial counseling system. Mayo Clinic also operates by group practice principles, which tend to reduce future health costs. Rena C. Tabata, M.Sc. u For Further Information Braasch, W. F. Early Days in the Mayo Clinic. Springfield, Ill.: Thomas, 1969. Sheperd, J. T. Inside the Mayo Clinic: A Memoir. Afton, Minn.: Afton Historical Society Press, 2003. Wilder, L. The Mayo Clinic. New York: Harcourt, Brace, 1942. u
Salem Health: Cancer
u Mediastinal tumors Category: Diseases, symptoms, and conditions Also known as: Mediastinal neoplasias Related conditions: Pericardial cysts, ectopic thyroid, bronchiogenic cysts Definition: Mediastinal tumors are benign or malignant growths in the mediastinum, which is the central chest cavity that separates the lungs and contains the heart, aorta, esophagus, thymus, and trachea. Risk factors: Risk factors include neurofibromatosis (von Recklinghausen disease), Li-Fraumeni syndrome, and a family history of Hodgkin disease. Etiology and the disease process: The mediastinum is divided into the front, middle, and posterior mediastinum. The anterior mediastinum lies between the heart and the sternum. The middle mediastinum extends from the surface of the heart to the trachea (windpipe), and the posterior mediastinum begins behind the trachea and ends at the front of the vertebral column (backbone). Each mediastinal compartment is subject to specific types of tumors. Anterior mediastinal tumors include tumors of the thymus (thymomas), lymphomas, teratomas, and thyroid tumors. Thymomas usually occur in adults, but 15 percent of them occur in children. Lymphomas account for 10 to 20 percent of anterior mediastinal tumors. Hodgkin disease causes most adult cases of mediastinal lymphomas.
Other Resources
Mayo Clinic Cancer Center http://cancercenter.mayo.edu/ National Cancer Institute Cancer Centers Program: Mayo Clinic Cancer Center http://cancercenters.cancer.gov/cancer_centers/ mccc.html See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center. 766
Mediastinal tumors. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Salem Health: Cancer Teratomas (germ-cell tumors) account for 10 to 15 percent of mediastinal tumors. Thyroid tumors grow from goiters and primarily occur in women. Tumors of the middle mediastinum include lymphomas (most common), mesenchymal tumors, and carcinomas. Mesenchymal tumors account for 6 percent of primary mediastinal tumors and are also called soft-tissue tumors that originate in connective tissue within the chest (about half are malignant). Neurogenic tumors (derived from nerve cells) are the most common tumors of the posterior mediastinum and include malignant schwannomas and neuroblastomas. Some 19 to 39 percent of mediastinal tumors are neurogenic and are usually benign in adults but malignant in children. Endocrine and mesenchymal tumors are also found in the posterior mediastinum. Though typically diagnosed in people between the ages of thirty and fifty, mediastinal tumors can occur at any age and in any tissue that passes through the chest. Incidence: Thymomas occur at a rate of 3 cases per million people per year. Lymphoblastic lymphomas in children occur at a rate of 6 cases per million. There are about 6 cases of mediastinal germ-cell tumors per million in children per year. Some 125 children per year in the United States are diagnosed with mediastinal neuroblastomas. Symptoms: Half of mediastinal tumors produce no symptoms, but masses in the chest can compress other tissues and prevent proper functioning. The most common symptoms are cough, shortness of breath, and chest pain. Accompanying symptoms include trouble swallowing (dysphagia), chest pain, fever, chills, night sweats, coughing up blood (hemoptysis), hoarseness, unintentional weight loss, wheezing, tender or swollen lymph nodes (lymphadenopathy), and stridor (high-pitched, noisy respiration). Between 35 and 50 percent of people with thymomas experience myasthenia gravis-like symptoms that include weakness of eye muscles, drooping of one or both eyelids (ptosis), and fatigue. Certain mediastinal tumors can produce neurotransmitters (catecholamines) that significantly raise blood pressure (hypertension). Other types of neurosarcomas can make insulinlike substances that can cause low blood sugar concentrations (hypoglycemia). Blood work may show abnormally high levels of serum calcium (hypercalcemia) and abnormally low levels of antibodies (hypogammaglobulinemia), circulating blood cells (cytopenia), and normal red blood cells (pernicious anemia). Screening and staging: Many different types of imaging tests can detect mediastinal tumors. Chest X rays are es-
Mediastinal tumors sential to determine the location of mediastinal tumors. Computed tomography (CT) and magnetic resonance imaging (MRI) scans are common imaging methods for detecting mediastinal masses. CT scans are also used to direct needle biopsies of potentially tumorous masses. Positron emission tomography (PET) scans are used to determine the spread of the tumor to other parts of the body. If the tumor is located in a difficult-to-reach spot, then laparoscopic surgery called mediastinoscopy is used to biopsy the mass. Most mediastinal tumors are solid tumors, which are graded by TNM (tumor/lymph node/metastasis) staging. T refers to the primary tumor and grades it from 0 to 4. N specifies the spread of the cancer to nearby lymph nodes (ranked 0 to 3). M represents metastasis or spread of the tumor beyond the lymph nodes to other parts of the body (0 or 1). Treatment and therapy: Thymomas are primarily treated with surgery, followed by radiation or chemotherapy. For lymphomas, chemotherapy followed by radiation is the treatment of choice. For neurogenic tumors, surgery is the treatment of choice. It is possible to surgically resection some mesenchymal tumors and radiation can help in some cases, but some fibrosarcomas are not treatable with surgery or chemotherapy. Malignant schwannomas are very aggressive tumors that require multiagent chemotherapy. Prognosis, prevention, and outcomes: The outcome is highly dependent on the type of tumor. If untreated, the prognosis is very poor. If properly treated, the prognosis for thymomas, lymphomas, thyroid tumors, teratomas, and some neurogenic tumors is generally quite good. Mesenchymal tumors tend to have a poor prognosis. Michael A. Buratovich, Ph.D. u
For Further Information Duwe, Beau V., Daniel H. Sterman, and Ali I. Musani. “Tumors of the Mediastinum.” Chest 128 (2005): 28932909. Huang, Tsai-Wang, et al. “Middle Mediastinal Thymoma.” Respirology 12, no. 6 (2007): 934-936. Quint, Leslie E. “Imaging of Anterior Mediastinal Masses.” Cancer Imaging 7 (2007): S56-S62. Strollo, Diane C., Melissa L. Rosado de Christenson, and James R. Jett. “Primary Mediastinal Tumors: Part 1, Tumors of the Anterior Mediastinum.” Chest 112 (1997): 511-522. _______. “Primary Mediastinal Tumors: Part 2, Tumors of the Middle and Posterior Mediastinum.” Chest 112 (1997): 1344-1357. 767
Mediastinoscopy u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov See also Klinefelter syndrome and cancer; Lung cancers; Mediastinoscopy; Stent therapy; Superior vena cava syndrome; Surgical biopsies; Thoracoscopy.
u Mediastinoscopy Category: Procedures Also known as: Thoracoscopic mediastinal biopsy Definition: Mediastinoscopy is an endoscopic procedure used to examine the mediastinum (space between and in front of the lungs). Compared to open-chest surgery, which requires one 6-inch to 8-inch incision, mediastinoscopy uses several small, 1-inch incisions to access the mediastinum, thereby minimizing trauma, decreasing postoperative pain, and promoting a shorter hospital stay and a quicker recovery. Cancers diagnosed or treated: Sarcoidosis, lung cancer, lymphoma, Hodgkin disease, myasthenia gravis, mesothelioma, mediastinal or neurogenic tumors, thymomas Why performed: Mediastinoscopy is performed with a biopsy to evaluate abnormal mediastinal tissue, lymph nodes, inflammation, or infection. It can be used as a staging procedure to evaluate non-small-cell lung cancer. Mediastinoscopy is also used to remove malignant lymph nodes and mediastinal tumors. Benign and malignant mediastinal tumors that are not removed can interfere with the normal function of the organs in the mediastinum, including the aorta, vena cava, heart, and pericardium. Patient preparation: Tests may include a chest X ray, computed tomography (CT) scan, and magnetic resonance imaging (MRI). One week before the procedure, patients must stop taking anticoagulants, as directed by the physician. In general, patients must not eat or drink for eight to ten hours before the procedure. Steps of the procedure: A sedative may be given before the patient receives general anesthesia. A mediastinoscope (small videoscope) is inserted under the sternum through a small incision at the base of the neck. The mediastinoscope is manipulated, and images of the abnormal area are displayed on a computer screen to guide the surgeon 768
Salem Health: Cancer during the procedure. CT may also be used during the procedure. Other surgical instruments are inserted through two or three small chest incisions, and a tissue sample is removed. After the procedure: The hospital recovery is about one to two days, and some patients may be able to go home the day of the procedure. Before going home, the patient receives a follow-up schedule and aftercare instructions. The patient can generally return to normal activities within three to four weeks after discharge. Risks: The risks of mediastinoscopy include bleeding, infection, allergic reaction to the anesthetic, blood vessel damage, a tear in the esophagus, laryngeal nerve injury that can cause permanent vocal hoarseness, or collapse of a lung (pneumothorax). The overall complication rate is reportedly low, at under 2.5 percent, with major complications under 0.5 percent and mortality under 0.5 percent. Results: The biopsy tissue is examined for malignancy, inflammation, or infection. The type and extent of disease will help determine the patient’s treatment. Angela M. Costello, B.S. See also Bronchoalveolar lung cancer; Endoscopy; Lung cancers; Mediastinal tumors; Mesothelioma; Pneumonectomy; Surgical biopsies; Thoracoscopy.
u Medical marijuana Category: Social and personal issues Definition: Medical marijuana involves use of the plant Cannabis sativa, and its chemical derivatives, for treating medical complaints and conditions. In the United States, at the federal level, marijuana for medicinal purposes currently comes in the form of dronabinol (Marinol) and nabilone (Cesamet). Marinol comes in capsule form and is a synthetic version of delta-9-tetrahydrocannabinol (THC), the active ingredient in Cannabis sativa. Cesamet is a derivative of THC that also comes in pill form. Individuals also use marijuana in dried form, such as by eating it, smoking it, or using it in a vaporizing device, to attempt to achieve certain medicinal effects. Access to medical marijuana: Federal law in the United States supports the use of Marinol and Cesamet but does not support the use of other forms of marijuana for medicinal purposes. There are some conflicts, however, between state and federal law in the United States. By 2008, twelve
Salem Health: Cancer
Medical marijuana
states had passed legislation legalizing medical marijuana in one way or another. In some cases, there were statelevel rules governing possession of dried forms of the drug and/or plants in varying quantities for patients and care providers; in others, circumstances varied county by county. Many required users of medical marijuana to obtain the drug in certain ways and/or maintain registration for medical purposes. Rules varied from country to country as well. Holland, for instance, permitted use of marijuana by the public for any purpose in establishments called coffee shops. Even in Holland, however, there were strict guidelines on where it could be used, the amount permitted to be given to each user or to be present in each shop, and other matters, such as the impact of the coffee shop on the surrounding community. Medicinal effects and uses: Marinol and Cesamet address appetite problems, as well as nausea and its associated vomiting. In terms of nausea, they are used typically in individuals undergoing chemotherapy for cancer, and particularly in individuals who have not responded to other forms of treatment for those conditions. In terms of appetite, they are used typically in clients with acquired immunodeficiency syndrome (AIDS) to combat a loss of appetite and its associated weight loss. Other, diverse conditions have been reported as potentially benefiting from medical marijuana, including Alzheimer’s disease, anorexia, cancer, chronic or debilitating pain, cramping, Crohn disease, glaucoma, human immunodeficiency virus (HIV), multiple sclerosis, seizures, muscle spasms, and wasting syndrome (cachexia). This list does not include all conditions that varying state laws recognize as eligible for marijuana use. Many of the states that have legalized medical marijuana have, as part of the law, clauses that either allow the list of treatment-eligible conditions to be amended or are open-ended and subject to physician approval. Scientific reports continue to generate speculation about conditions that may receive benefit from treatment, such as depression. Use of marijuana for all of these conditions, however, remains the subject of great debate and is illegal in most states. Controversies of medical marijuana: Despite the fact that synthetic THC and THC derivatives serve medical purposes, and despite the fact that twelve states allowed the use of marijuana for medicinal purposes as of 2008, medical marijuana is a controversial topic. Opponents of medical marijuana are quick to point out that Marinol and Cesamet exist as pharmaceuticals regulated by the Food and Drug Administration (FDA) and are adequate to cover the conditions most often treated with marijuana. Proponents of medical marijuana counter that those drugs do not
Cannabis sativa in flower. (©Gary Boisvert/Dreamstime.com)
work well for everyone and that they are only to be used for certain conditions. In the light of pain and suffering caused by other conditions, they argue, why not allow medical marijuana use? Again, opponents answer that other viable treatments exist that are better to try as treatment options, that the evidence for marijuana’s efficacy in treating these other conditions is weak, and that there are strong social, physical, mental, and behavioral cons to the use of marijuana and its alternative forms. Typical cons cited are posed in terms of short-term and long-term risks. In the short term, these may include memory and learning difficulties, panic, anxiety, coordination problems, and impaired problem solving. In the long term, these may include problems related to addiction, such as abuse or dependence, motivational problems, daily cough, phlegm problems, respiratory problems, impact on the immune system, and possibly cancer. Proponents argue that the pros outweigh the cons and that, despite evidence that some may consider weak, this method of treatment for such debilitating conditions deserves further study. 769
Medical oncology
Salem Health: Cancer
The debate continues, however, from state to state and country to country. Future studies focusing on the risk impacts of marijuana use are to be expected. Expanding the use of Marinol to other conditions may be on the horizon. The fight to allow studies examining the utility of marijuana for treating health conditions faces continued struggles in the United States and elsewhere. Nancy A. Piotrowski, Ph.D.
Subspecialties: Gynecological oncology, medical oncology/hematology, pediatric oncology/hematology, radiation oncology
u
Training and certification: Medical oncologists first obtain a four-year medical degree from an accredited program and board certification from the American Board of Internal Medicine, then complete a one-year internship in a clinical setting, followed by three years of postgraduate residency training in the use of medical and chemotherapeutic treatments of adult cancerous conditions. Oncology fellows who specialize in combined hematology and oncology receive an additional year of training. Medical oncology fellows are eligible to take a Certification Exam in Medical Oncology, offered by the American Board of Internal Medicine, after completing a minimum of three years of successful training. They become certified as diplomates of the American Board of Internal Medicine after passing this exam. Once certified, medical oncologists may further their training by participating in one or more years of clinical or laboratory research. Medical oncologists are trained in the basic science and clinical expression of cancer in adults. They are involved in patient care, teaching, and research. They study the etiology of cancer as well as its evaluation, diagnosis, and management in ambulatory and hospitalized patients. Medical oncologists acquire experience in treating a wide variety of neoplastic diseases and in managing the entire spectrum of medical complications of cancer and its treatments. Specific areas of study include chemotherapy, surgery, radiation therapy, and biological therapy. Medical oncologists may specialize in certain types of cancer or certain therapies such as immunotherapy, but they have the expertise to treat all forms of cancer with a variety of drug therapies. Oncology clinical practice guidelines, quality care standards, and quality assurance measures in the United States have been established primarily by the American Society of Clinical Oncology (ASCO), a nonprofit organization representing more than 25,000 cancer professionals worldwide. It offers scientific and educational programs and a wide range of initiatives to promote the exchange of cancer information. ASCO publishes clinical practice guidelines and the National Initiative on Cancer Care Quality, which includes quality-of-care indicators. It also supports the Quality Oncology Practice Initiative, an
For Further Information Earleywine, Mitch. Understanding Marijuana: A New Look at the Scientific Evidence. New York: Oxford University Press, 2002. Gerber, Rudolph Joseph. Legalizing Marijuana: Drug Policy Reform and Prohibition Politics. Westport, Conn.: Praeger, 2004. Rosenthal, Ed, and Steve Kubby. Why Marijuana Should Be Legal. New York: Thunder’s Mouth Press, 2003. Russo, Ethan B., and Franjo Frotenhermen, eds. Handbook of Cannabis Therapeutics: From Bench to Bedside. Binghamton, N.Y.: Haworth Press, 2006. Russo, Ethan B., Melanie Dreher, and Mary Lynn Mathre, eds. Women and Cannabis: Medicine, Science, and Sociology. Binghamton, N.Y.: Haworth Press, 2002. Selvanathan, Saroja, and Eliyathamby A. Selvanathan. The Demand for Alcohol, Tobacco, and Marijuana: International Evidence. Burlington, Vt.: Ashgate, 2005. See also Antinausea medications; Appetite loss; Delta-9tetrahydrocannabinol.
u Medical oncology Category: Medical specialties Also known as: Chemotherapy, immunotherapy, biological therapy Definition: Medical oncology is the medical specialty for the treatment of cancerous diseases with chemotherapy, hormonal therapy, biological therapy, and other drugs. Medical oncology complements other cancer treatment modalities, including surgery, radiation therapy, rehabilitation, and palliative care. Medical oncologists are physicians who specialize in the assessment and management of patients with cancer and are trained to administer chemotherapy and other cancer medications. Medical oncology practices can be found in university medical centers, community hospitals, specialized cancer hospitals, and comprehensive cancer centers. 770
Cancers treated: Various, especially blood-related cancers such as acute leukemia as well as gastric, breast, bladder, testicular, colorectal, lung, prostate, and ovarian cancers
Salem Health: Cancer oncologist-led, practice-based quality improvement program to promote excellence in cancer care. Services and procedures performed: A medical oncologist is often the main health care provider for adults diagnosed with cancer. The medical oncologist plans and coordinates the diagnosis and treatment of new or recurrent malignancies. Oncologists coordinate the patient’s diagnostic tests, develop a treatment plan, determine the appropriate systemic or adjunctive drug regimen to treat the patient’s condition, and supervise the dosage, schedule, and administration of cancer drugs to treat localized or metastatic malignancies. Medical oncologists also develop cancer treatment protocols, participate in clinical trials and research, and ensure that quality standards for chemotherapy delivery are followed. Medical oncologists are part of a multidisciplinary team of cancer health care providers whose goals are to provide early detection; accurately diagnose the condition; offer prompt, appropriate treatment to improve quality of life and survival; provide psychological guidance through complex treatment phases; reduce long-term effects of chemotherapy and radiation therapy; and provide long-term follow-up. Medical oncologists are trained in chemotherapy drug indications and toxicities so that they can safely administer these therapies while minimizing side effects and appropriately managing complications. Related specialties and subspecialties: Medical oncologists work with a multidisciplinary team that includes the primary care physician and other specialists, such as clinical oncologists; oncologist surgeons including urologic surgeons, orthopedic surgeons and neurosurgeons; diagnostic radiologists; radiation oncologists; infectious disease specialists; pathologists; oncology nurses; physical therapists; and oncology social workers and other allied health care professionals, such as educational specialists, registered dietitians, and pharmacologists. Communication between the medical oncologist and the patient’s primary care physician is essential to ensure the continuum of care. Medical oncologists consult with radiation oncologists and oncologist surgeons so that chemotherapy can be combined with radiation and surgery to ensure the best outcome for the patient. Oncologist surgeons use surgical techniques such as laparoscopy and thoracoscopy to diagnose and treat cancers. They first obtain a four-year medical degree from an accredited program and board certification from the American Board of Surgery, then complete five years of residency training in an accredited general surgery pro-
Medical oncology gram and at least two years of fellowship training in oncological surgery. Diagnostic radiologists obtain and interpret medical images to determine what disease the patieint has. They obtain a four-year medical degree from an accredited program and board certification from the American Board of Radiology or the American Osteopathic Board of Radiology, then must pass a licensing examination and complete at least four years of residency training in an accredited radiology program. Radiation oncologists, also known as clinical oncologists, treat cancers using radiation. In the United States, most radiation oncologists complete residency training in radiation oncology in a program approved by the American Council of Graduate Medical Education or the American Board of Radiology. Infectious disease specialists are physicians who concentrate on the diagnosis and treatment of infectious diseases. Their training consits of a four-year medical degree from an accredited program, board certification from the American Board of Pediatrics, three or more years of residency training, and two to three years of additional training in infectious diseases. Pathologists are physicians who specialize in the pathology of hematologic malignancies and solid tumors. They use immunochemistry and molecular techniques to assess malignancies. Their training consists of a four-year medical degree from an accredited program, board certification from the American Board of Internal Medicine, three or more years of residency training, and one to two years of additional training in pathology. The Oncology Nurses Society facilitates the professional development of oncology nurses. Oncology nurses educate patients and family, provide medical care, and administer medications. Oncology clinical nurse specialists are registered nurses with a master’s degree in oncology nursing. They understand treatment protocols and how to manage treatment complications and prepare and administer medications, including chemotherapy. Oncology nurse practitioners are registered nurses with a master’s or doctoral degree. Angela M. Costello, B.S.
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For Further Information Abeloff, M. D., et al. Clinical Oncology. 3d ed. Edinburgh, Scotland: Churchill Livingstone, 2004. Cavalli, F., et al., eds. Textbook of Medical Oncology. 3d ed. New York: Informa Healthcare, 2004. Kantarjian, H. M., et al. The M. D. Anderson Manual of Medical Oncology. New York: McGraw-Hill, 2006. 771
Medicare and cancer u
Organizations and Professional Societies
American Board of Internal Medicine http://www.abim.org American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 National Comprehensive Cancer Network http://www.nccn.org 275 Commerce Drive, Suite 200 Fort Washington, PA 19034 Oncology Nurses Society http://www.ons.org 125 Enterprise Drive Pittsburgh, PA 15275 u
Other Resources
CancerCare http://www.cancercare.org Cancer.Net http://www.cancer.net/portal/site/patient Chemocare.com http://www.chemocare.com National Cancer Institute Chemotherapy and You: Support for People with Cancer http://www.cancer.gov/cancertopics/ chemotherapy-and-you See also Dermatology oncology; Endocrinology oncology; Gastrointestinal oncology; Gynecologic oncology; Hematologic oncology; Molecular oncology; Neurologic oncology; Occupational therapy; Oncology; Oncology clinical nurse specialist; Oncology social worker; Pediatric oncology and hematology; Pharmacy oncology; Psychooncology; Radiation oncology; Surgical oncology; Urologic oncology; Veterinary oncology; Viral oncology.
u Medicare and cancer Category: Social and personal issues Definition: Medicare is the health insurance program of the United States government for people aged sixty-five or older and for younger citizens who have specific disabilities or end-stage renal disease (ESRD), a condition in which the person has permanent kidney failure and requires dialysis or transplant. 772
Salem Health: Cancer History: The Medicare program has affected the lives of millions of Americans since President Lyndon B. Johnson signed into law the Medicare bill of 1965. The roots of this universal health care coverage for seniors and the disabled reach back to 1935, when the federal government introduced the first government health insurance bill. In 1945 President Harry S. Truman became the first president to endorse government health insurance for the elderly and would become the first person to enroll twenty-one years later, receiving the first issued Medicare card. In 1972 benefits for disabled and end-stage renal disease (ESDR) patients were added. The Supplemental Security Income (SSI) program came next, and then benefits for hospice were added temporarily in 1982 and confirmed permanent in 1986. With the threat of budgetary problems, the diagnosis-related group (DRG) prospective payment system began in 1983. Until that time, Medicare reimbursed for most covered medical charges that were of a “reasonable cost.” Several other changes evolved over time, including provisions for Medicare health maintenance organizations (HMOs) and the voluntary Part D outpatient prescription drug program, available to beneficiaries in 2006. Medicare is funded by the Social Security Administration. To receive benefits, participants must have paid into the plan through their employers. The Medicare budget is about 10 percent of the entire budget of the Unites States government. In the mid-2000’s, about 40 million Americans were receiving health insurance under the Medicare program. Medicare basics: The Medicare program is divided into several parts. Part A is hospital insurance and covers inpatient stays with some follow-up costs after hospitalization. Also covered is care in a skilled nursing facility. Part B is medical insurance and pays for physicians, nurse practitioners, and outpatient services. Part C offers several plans as options, and Part D covers outpatient prescription drugs. Anyone who has worked and paid into the social security plan has the Part A benefit, but Parts B and D are optional, provided for a monthly fee. For some benefits, the Medicare patient must meet annual deductibles before full plan coverage takes place. Medicare is less comprehensive than many private insurance plans available to younger Americans. Many seniors opt to pay for secondary insurance coverage to pay the difference or gap in Medicare coverage for provision of needed services. Unfortunately, the high costs of many therapies and drugs have left many seniors and disabled persons without adequate insurance coverage and without access to new modalities of treatment.
Salem Health: Cancer Coverage for cancer prevention and screening: In 2005, the Centers for Medicare and Medicaid Services (CMS) launched two national decisions for improving the care of cancer patients. Insurance coverage was expanded to include diagnostic tests and chemotherapy treatments for Medicare beneficiaries. One part of the preventive program is coverage for a “Welcome to Medicare” physical examination. This one-time benefit is designed to reduce the risk of serious health problems in the future. Other services are now covered as preventive health. For example, research shows that breast cancer risk increases with age. To screen for breast cancer, annual mammograms with digital technology are covered for all women the age of forty or older on Medicare. Any Medicare recipient between the ages of thirty-five and thirty-nine receives one baseline mammogram. The participant pays 20 percent of the Medicare-approved amount with no Part B deductible. Cervical cancer screening is provided through a Pap smear and pelvic examination (with breast examination) every twenty-four months. If the participant has an established high risk for cervical or vaginal cancer, arrangements can be made for these tests each year. The Pap test itself is covered, but the participant pays 20 percent of the Medicare-approved cost with no Part B deductible. Discovery of precancerous polyps (growths in the colon) and removal can decrease the incidence of colon cancer. Medicare participants the age of fifty or older and at average risk for colorectal cancer are allowed fecal occult blood tests every year, flexible sigmoidoscopy once every four years, colonoscopy once every ten years (but not within four years of a sigmoidoscopy), and barium enema once every four years (instead of a colonoscopy or sigmoidoscopy). If the age fifty or older Medicare recipient is at high risk for cancer, the colonoscopy is provided every two years and barium enema once every two years (instead of the colonoscopy or sigmoidoscopy). The fecal test is free but for other tests, the Medicare recipient pays 20 percent of the Medicare-approved amount after meeting the annual Part B deductible. The flexible sigmoidoscopy or colonoscopy costs 25 percent of Medicare-covered charges if done on an outpatient basis. The last cancer-screening procedure included in Medicare is the prostate cancer test for men over the age of fifty. Coverage includes a digital exam and prostate-specific antigen (PSA) test every year or more often if needed for diagnostic purposes. The digital exam requires a 20 percent copay with no coinsurance or Part B deductible for the PSA.
Medicare and cancer sis and treatment of cancer. In a clinical trial, research is conducted with participants to improve new ways of providing quality and effective cancer care. Participants have access to promising new therapies as researchers find better and more effective ways to treat cancer. Many positives can come from participation, including being the first to benefit from a new treatment, gaining access to new treatments not available to the general public, having access to high-quality physician specialists, and helping future patients. The less attractive part of clinical trials is that new drugs may have unknown side effects, the new treatment may be less effective than the traditional one, and being in a clinical trial may require more doctor visits. Although clinical trials are not for everyone, Medicare recipients now have choices with assurance of insurance coverage. To be covered, clinical trials must be funded by the National Cancer Institute (NCI) or NCI-sponsored groups. Medicare Modernization Act: The Medicare Modernization Act of 2006 provided prescription drug coverage for Medicare recipients as Medicare Part D coverage. Drugs listed on the approved formulary are covered in this voluntary plan. Key drugs needed by cancer patients such as oral chemotherapy, immunotherapy, and hormonal therapy are covered. Other useful medications on this plan are drugs for the side effects of cancer treatments such as nausea and low blood counts. The plan is administered by diverse companies with variation in coverage, deductibles, and out-of-pocket expenses. Medicare patients have options but need to research which plan is best for them. It is recommended that Medicare participants keep a complete updated list of their prescription drugs and ask if a less expensive brand is available that is as effective. Local Social Security Offices have information to help participants compare plans to meet specific needs. Even with Medicare drug insurance, medications used by the cancer patient can be expensive. Sometimes state pharmaceutical assistance programs provide additional assistance to complement Medicare coverage. Sometimes the cancer patient can qualify for a low-income subsidy through Social Security. The oncology social worker can assist the participant to identify ways to get help for drug coverage and other services. Robert W. Koch, D.N.S., R.N. u
Coverage in clinical trials: Medicare offers members more choices to participate in clinical trials for the diagno-
For Further Information Field, Marilyn J., Robert L. Lawrence, and Lee Zwanziger, eds. Extending Medicare Coverage for Preventive and 773
Medullary carcinoma of the breast Other Services. Washington, D.C.: National Academy Press, 2000. Muller, Charlotte, et al. Costs and Effectiveness of Cervical Screening in Elderly Women. Washington, D.C.: Office of Technology Assessment, 1990. U.S. Congress. Office of Technology Assessment. Breast Cancer Screening for Medicare Beneficiaries. Washington, D.C.: Author, 1987. _______. Cost and Effectiveness of Prostate Screening in Elderly Men. Washington, D.C.: Author, 1995. u
Other Resources
AARP Centers for Medicare and Medicaid Services http://www.cms.hhs.gov Medicare http://www.medicare.gov AARP.org Medicare Prescription Drug Coverage http://www.aarp.org/research/medicare/drugs/ Medicare Rights Center http://www.medicarerights.org Social Security Online http://www.ssa.gov State Health Insurance Assistance Programs http://www.shiptalk.org See also Advance directives; Aging and cancer; Elderly and cancer; Financial issues; Health maintenance organizations (HMOs); Insurance; Managed care; Preferred provider organizations (PPOs); Second opinions; Social Security Disability Insurance (SSDI).
u Medullary carcinoma of the
breast Category: Diseases, symptoms, and conditions Also known as: Infiltrating breast cancer Definition: Medullary carcinoma is a rare but invasive breast cancer distinguished microscopically by a welldefined boundary, presence of cells from the immune system at its edges, and large, misshapen cancer cells. Related conditions: Familial breast cancer 774
Salem Health: Cancer Risk factors: Medullary breast carcinoma is more frequent in women with a genetic predisposition. Mutations in tumor-suppressor genes, whether genetic or unknown in origin, can prevent their normal function of suppressing abnormal growth. This mutation occurs at the BRCA1 and BRCA2 genes. In some studies, medullary carcinomas account for up to 19 percent of all cancers in women with a BRCA1 mutation. In women with a family history of reproductive-system cancers, smoking increases breast cancer risk significantly. Estrogen can stimulate breast cancers. Changes in deoxyribonucleic acid (DNA), which carries the instructions for all cells, can cause normal cells to become cancerous, and such changes are more likely to occur with age. Etiology and the disease process: Estrogen exposure tends to encourage breast cancer, and hormones can boost breast cancer growth. Gene mutations can inhibit the body’s defenses. Incidence: These infrequent cancers make up 2 to 7 percent of breast cancer cases. Symptoms: Most cancers start without symptoms, detectable if at all by only mammography or ultrasound. As the cancer develops, a lump or thickening may begin. An unusual lump in the breast or armpit area, one that feels firm or unlike other breast tissue, or a lump that seems “fixed” and immobile, needs to be investigated. Screening and diagnosis: Medullary carcinomas are distinguishable by histology (microscopic examination). Monthly self-examination and regular mammography increase early detection. Staging for medullary carcinomas is as follows: • Stage I: Cancerous cells have invaded nearby tissue. • Stage II: Cancerous cells are in lymph nodes in the armpit. • Stage III: Cancerous cells have invaded lymph nodes, breastbone, and other tissues above the waist. Treatment and therapy: Treatment is the same as for invasive ductal carcinoma: usually a combination of local therapy (affecting only the cancer site, such as surgery and radiation) and systemic therapy using drugs (chemotherapy, hormone therapy, and immunotherapy), either by mouth or intravenously, to kill cancer cells that might have spread elsewhere but are not yet detectable. Prognosis, prevention, and outcomes: When caught early, medullary breast cancers are curable and prognosis is good, with 70 percent of patients surviving for ten years. Good, balanced nutrition with avoidance of dietary fat and a healthy lifestyle that avoids smoking and includes
Salem Health: Cancer exercise are among the best strategies for decreasing the chance of developing cancer. Jackie Dial, Ph.D. See also BRCA1 and BRCA2 genes; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Carcinomatosis; Invasive ductal carcinomas; Invasive lobular carcinomas.
u Medulloblastomas Category: Diseases, symptoms, and conditions Related conditions: Supratentorial primitive neuroectodermal tumors, neurofibromatosis (von Recklinghausen disease), Gorlin syndrome Definition: Medulloblastomas are malignant (cancerous) or benign (noncancerous) tumors that form in the cerebellum of the brain. The cerebellum controls balance and movement, posture, and speech. These tumors occur more often in children but may rarely appear in adults. Risk factors: There is no known cause of medulloblastomas, but, scientists are uncovering changes in genes and chromosomes that may influence the development of these tumors. A small percentage of tumors may tend to occur in families, particularly in families with neurofibromatosis (von Recklinghausen disease), an inherited disease that causes benign tumors to occur on peripheral nerves in the body. A few individuals with Gorlin syndrome, an inherited disease related to basal cell carcinoma and other conditions, also develop medulloblastoma. Etiology and the disease process: Medulloblastoma is a relatively rare disease, with no known cause other than a familial tendency. The tumor is considered fast growing. Because of the location of the tumor, walking and talking disruptions are common as the disease progresses. Incidence: The tumor occurs more often in boys than girls, and generally before the age of eight, with a peak incidence between five and ten years of age. In the United States, the incidence of medulloblastoma is 1.5 to 2 cases per 100,000 population (children). Approximately 1,000 cases are diagnosed annually, with 1 in 5 brain tumors in children diagnosed as medulloblastoma. Symptoms: The classic, initial symptoms of medulloblastoma are morning headaches, nausea, vomiting, and other flulike symptoms. Because the symptoms mimic flu, the tumor may go undiagnosed until symptoms progress to balance problems. Older children may be more easily di-
Medulloblastomas agnosed than infants, as infants may initially exhibit an increase in head size and irritability, both common in infants as they grow and develop. Vomiting may make the person feel better, as the intracranial pressure is temporarily relieved. Symptoms increase as the tumor grows. Screening and diagnosis: There is no screening test for medulloblastoma. Diagnosis begins with a history of symptoms and neurological examination. Radiology studies include magnetic resonance imaging (MRI), including the use of a contrast dye, to identify the presence of a brain tumor, and a positron emission tomography (PET) scan, used to determine if the tumor is active and growing. Other procedures, such as a lumbar puncture to take cerebrospinal fluid (CSF), a bone marrow aspiration and biopsy, and a bone scan, may be done to look for signs of cancer. A confirmed diagnosis is made during surgery, and pathologic examination of the tumor specimen removed determines if the tumor is benign or malignant. Two risk groups are used in childhood medulloblastoma to determine treatment management, rather than the adult staging process. The average risk group and the poor risk group are differentiated based on the tumor remaining after surgery, spread of cancer cells within the brain and spinal cord, or distant spread of tumor cells to other parts of the body. Adults are staged based on the remaining tumor and whether the tumor has spread using the TNM (tumor/lymph node/metastasis) staging system. Treatment and therapy: Treatment of medulloblastoma is with surgery, radiation therapy, chemotherapy, and, if necessary, mechanical diversion of cerebrospinal fluid with a shunt to carry blocked fluid out of the brain. Surgery is used to remove as much of the tumor as possible. Imaging studies may show that the tumor is inoperable. A bi-
Relative Survival Rates for Medulloblastoma, 1988-2001 Years
Survival Rate (%)
1 2 3 5 8 10
89.2 84.6 78.4 66.4 56.8 52.5
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
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Melanomas
Salem Health: Cancer
opsy will still be done to determine the type of tumor and whether it is malignant. If the tumor has grown into the brain stem, removal may not be an option, as the side effects of removal are life-threatening. Steroids are used to decrease swelling in the brain. A shunt, or tube to drain CSF away from the brain, usually to the abdomen, may be placed during surgery. Radiation therapy to the brain and the spinal cord is then used to kill any cells remaining. Radiation may be done with stereotactic radiosurgery, intensity-modulated radiation therapy, or external beam radiation. Chemotherapy may be used in infants to postpone the use of radiation, as cranial radiation side effects may be severe. Chemotherapy may be given either intravenously (into a vein) or intrathecally (into the cerebrospinal fluid) by use of an Ommaya reservoir. In adults, chemotherapy effectiveness is less clear.
American Cancer Society http://www.cancer.org
Prognosis, prevention, and outcomes: The prognosis for medulloblastoma varies with the patient’s age at diagnosis, the size of the tumor, the amount remaining after surgery, and the level of tumor cell spread to other sites in the brain, spinal cord, or elsewhere in the body (metastasis). Approximately 70 percent of adults are alive at five years after diagnosis, and up to 80 percent of children with average-risk classification can be expected to reach five years. With poor risk classification, up to 65 percent of children may survive to five years. The outcome for infants is poor, with a 30 to 50 percent survival. There is no prevention for medulloblastoma. Quality of life may be negatively affected by the side effects of therapy, including learning disabilities, hearing loss from drug therapy, obesity, thyroid deficiency, and other problems depending on treatment and site. Recurrence is always a risk as tumors may be difficult to remove completely. Patricia Stanfill Edens, R.N., Ph.D., FACHE
Related conditions: Basal cell cancer, squamous cell cancer
u For Further Information Hargrave, D. R., and S. Zacharoulis. “Pediatric CNS Tumors: Current Treatment and Future Directions.” Expert Review of Neurotherapeutics 7, no. 8 (August, 2007): 1029-1042. Parker, W., E. Filion, D. Roberge, and C. R. Freeman. “Intensity-Modulated Radiotherapy for Craniospinal Irradiation: Target Volume Considerations, Dose Constraints, and Competing Risks.” International Journal of Radiation Oncology, Biology, Physics 69, no. 1 (September 1, 2007): 251-257. u
Other Resources
American Brain Tumor Association http://www.abta.org 776
National Cancer Institute Childhood Medulloblastoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ childmedulloblastoma/patient/ See also Brain and central nervous system cancers; Craniotomy; Neuroectodermal tumors; Turcot syndrome.
u Melanomas Category: Diseases, symptoms, and conditions Also known as: Skin cancer
Definition: Melanomas are malignant tumors of the skin that occur in the melanocytes, the cells that produce melanin (skin pigment). Risk factors: Melanomas occur most commonly in fairskinned people, particularly natural blonds and redheads, especially those with a history of sun exposure or multiple serious sunburns. A history of serious sunburns in childhood is a particular risk. Risk for the disease is strongly related to having a family history; which is characteristic of about 1 in 10 of patients with melanoma. Additional risk factors include large or multiple moles and past personal history of melanoma or of less serious skin cancers, known as basal cell or squamous cell cancers. People with diseases that suppress the immune system are at added risk for melanoma. Occupational exposure to coal tar, pitch, creosote, arsenic compounds, or radium increase a person’s risk for the disease. Celtic descent, male gender, and older age are also risk factors. Etiology and the disease process: Repeat exposure to harmful ultraviolet rays from the sun or artificial sources such as sunlamps or tanning booths appears to be the most significant factor contributing to the development of melanoma. This is borne out by the fact that the incidence of melanoma increases in the lower latitudes of the world where the sun is strongest. Additionally, in parts of the world where the ozone layer is thin, the incidence is higher. In Queensland, Australia, for example, where there is a hole in the ozone, between 1979 to 1987, the rate of melanoma doubled to 55.8 per 100,000 men and rose to 42.9 per 100,000 women. Melanomas can occur on parts of the body not usually
Salem Health: Cancer
Melanomas
exposed to the sun, including the soles of the feet and the genitals. Melanoma starts with an abnormal skin growth, which is generally quite small. When discovered at this early stage, melanomas can be easily removed and the cancer cured. If the growth is not removed, it thickens and invades surrounding tissue and nearby lymph nodes. The cancer can then spread through the lymph nodes to sites distant from the original growth, including vital organs, soft tissues, and other lymph nodes.
are ten times higher than for African Americans. However, one type of melanoma, which develops on the palms of the hands, soles of the feet, and nail beds, occurs more frequently in African Americans and Asians. Symptoms: Melanoma generally first appears as a new mole or a change in the shape, size, or color of an existing mole. The American Cancer Society describes the warning signals in terms of a mnemonic: ABCD. “A” for asymmetry, meaning that the mole is not uniformly round; “B” for border, in that the edges of the mole are irregular; “C” for color, referring to the varied colors (generally in tones of tan, brown, and black) throughout the mole; and “D” for diameter, meaning that the mole is larger than 6 millimeters (mm).
Incidence: In the 1970’s, the incidence rate of melanoma rose dramatically to about 6 percent a year. Incidence continues to rise but at a slower rate; from 1981 to 2001 the rate of growth was about 3 percent a year. The American Cancer Society estimated that 59,940 men and women in the United States would be newly diagnosed with melanoma in 2007. Melanoma affects adults of all ages as well as teenagers. Based on statistics for the years 2001 to 2003, the probability of a man in the United States developing melanoma is 1 in 49. For a woman in the United States, the probability is 1 in 73. Rates for whites
Screening and diagnosis: People with serious risk factors or symptoms should have regular full body exams by a dermatologist to identify any skin abnormalities, and baseline photographs should be taken so that any changes can be tracked. Suspect moles or skin abnormalities should be removed and analyzed for cancer cells.
Incidence of Melanoma per 100,000 People, by Gender 30 27.2
Women
Men
25
20 17.6 15
10
4.5
5
4.6
4.1 2.0
1.7
1.3
1.1
0.9
0 White
Hispanic
American Indian/ Alaska Native
Asian/Pacific Islander
Black
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
777
Melanomas
Salem Health: Cancer
Melanoma. (National Cancer Institute)
The stages of melanoma are defined as follows: • Localized, Stage 0: These melanomas involve only the top layer of skin, the epidermis. • Localized, Stages I and II: These melanomas involve the underlying layer of skin, the dermis, and are rated according to the depth they penetrate the skin (known as the Breslow depth) and their degree of ulceration (how much the epidermis is eroded and exposes the dermis below). Ulceration is determined by a pathologist, using a microscope. • Regional, Stage III: These melanomas include those in which the cancer has spread to nearby lymph nodes. • Advanced, Stage IV: These melanomas include those where cancer has spread beyond the region of the skin growth to distant sites in the body, including internal organs and distant lymph nodes. Treatment and therapy: Significant advances have been made in the early detection of melanoma. All suspect moles or skin growths should be removed and tested for cancerous cells. Removal of localized growths (Stages 0-II) can be done one of three ways: surgically, cutting out the suspect tissue; by electrodessication and curettage, using an electric current to destroy the tissue and then scraping the area with a special tool to remove any possible remaining cancer cells; or by cryosurgery, which freezes the tissue. About 83 percent of melanomas are diagnosed in these early stages while the cancer is still confined to the 778
primary skin growth. Surgery successfully removes the cancer for the majority of patients with early-stage melanoma. In some cases, radiation therapy may be directed at the area following surgery to kill any cancer cells that may remain. Patients with Stages 0 to II melanoma have an excellent prognosis. If the growth is extensive, the surgeon will remove lymph nodes to determine if the cancer has spread. After their removal, Stage III and IV melanomas may be treated with radiation or immunotherapy (agents that attempt to harness the human body’s own diseasefighting properties to kill cancer cells) or chemotherapy (toxic agents targeted to kill cancer cells). Two therapeutic agents approved by the U.S. Food and Drug Administration (FDA) for the treatment of Stage III and IV melanoma are dacarbazine (DTIC, chemotherapy) and interleukin-2 (IL-2, immunotherapy). Some patients with Stage III and IV disease experience a full recovery with chemotherapy; however, positive responses to the drug therapy, when they occur, are most often partial and brief. Much research is being done to explore other possible treatments for melanoma, including combinations of different chemotherapies and new immunotherapies. Some of these agents are not specifically approved by the FDA to treat melanoma. Patients with melanoma may be eligible to become subjects in clinical trials in which these experimental agents or combinations of agents are tested. Prognosis, prevention, and outcomes: The thickness of a patient’s tumor is the best single indicator of the prognosis. After having melanomas of less than 0.76 mm removed, about 96 to 99 percent of patients are cured. About 1 in 10 patients with melanoma is diagnosed after the cancer has already spread to nearby lymph nodes. For these patients in the regional stage (Stage III), the prognosis is not as good, but survival rates for patients with Stage III disease range widely, depending on how many lymph nodes are affected by the cancer. About 3 of 10 patients with melanoma are diagnosed in an advanced stage (Stage IV), after the cancer has already spread (metastasized) to distant sites. Those with metastases to the skin or soft tissue or to distant lymph nodes appear to fare better than those with lung or other vital organ metastases. Recommended measures to prevent melanoma include
Salem Health: Cancer avoiding excessive direct sunshine, especially during the hours when the sun is high in the sky (from about 10 a.m. to 2 p.m.); using sunscreen and protective clothing to prevent sunburn; and not using sunlamps; tanning booths, or other artificial sources of ultraviolet light. People should become familiar with the moles and spots on their bodies and report any changes that could indicate melanoma to their doctors. Charlotte Crowder, M.P.H., ELS u
For Further Information Kaufman, Howard. The Melanoma Book: A Complete Guide to Prevention and Treatment. New York: Gotham Books, 2005. Poole, Catherine M., and I. V. DuPont Guerry. Melanoma: Prevention, Detection, and Treatment. 2d ed. New Haven, Conn.: Yale University Press, 2005. Schofield, Jill R., and William A. Robinson. What You Really Need to Know About Moles and Melanoma. Baltimore: Johns Hopkins University Press, 2000. u
Other Resources
Melanoma Center http://www.melanomacenter.org Melanoma Research Foundation http://www.melanoma.org/ National Cancer Institute Melanoma http://www.cancer.gov/cancertopics/types/melanoma Skin Cancer Foundation Melanoma http://www.skincancer.org/melanoma/index.php See also Breslow’s staging; Dermatology oncology; Dysplastic nevus syndrome; Merkel cell carcinomas (MCC); Moles; Premalignancies; Risks for cancer; Skin cancers; Squamous cell carcinomas; Sunlamps.
u Melphalan Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Alkeran Related cancers: Acute leukemia Definition: Melphalan is a highly toxic anticancer drug that belongs to a family of drugs known as alkylating agents. It is a derivative of nitrogen mustard.
Melphalan Exposure routes: Orally or by intravenous injection as part of medical treatment. Skin contact or dust inhalation is possible during the manufacturing process and in handling of the drug during preparation and administration. Where found: Used in the treatment of various cancers including multiple myeloma and ovarian and breast cancer At risk: People who have been previously treated with melphalan alone or in association with other chemotherapy drugs; health professionals (nurses, pharmacists, physicians) who handle the drug during preparation, administration, and cleanup; workers involved in the manufacturing process. The general population is not considered to be at risk. Etiology and symptoms of associated cancers: Melphalan is used to treat cancer but can itself cause a secondary cancer as a long-term side effect. It is a cytotoxic drug that affects the growth of cancer cells by interfering with the deoxyribonucleic acid (DNA) within the cells. It is the damage to cellular DNA that can lead to a secondary cancer months or years after treatment with melphalan. Studies of melphalan (and other alkalating agents) indicate that the risk of secondary leukemia increases with the cumulative dose and chronicity of treatment. In one study, the ten-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after melphalan therapy was 19.5 percent for cumulative doses ranging from 730 to 9,652 milligrams (mg). In this same study, as well as in an additional study, the ten-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after melphalan therapy was less than 2 percent for cumulative doses under 600 mg. However, there is no known cumulative dose below which there is no risk of developing a secondary malignancy. The symptoms of secondary acute leukemia include recurrent infections, bone and joint pain, swollen lymph nodes, and shortness of breath. History: The nitrogen mustards were developed as a derivative of sulfur mustard gas, which was first used as a weapon of war in 1917. Observation of military personnel exposed to sulfur mustard showed that it lowered the white blood cell count. Drugs derived from nitrogen mustard, such as melphalan, were introduced into the clinical setting in 1946. Melanie Hawkins, B.S.N., R.N., O.C.N. See also Hyperthermic perfusion; Multiple myeloma. 779
Memorial Sloan-Kettering Cancer Center
u Memorial Sloan-Kettering
Cancer Center Category: Organizations Also known as: New York Cancer Hospital, Memorial Hospital for the Treatment of Cancer and Allied Diseases, MSKCC Definition: The Memorial Sloan-Kettering Cancer Center, developed from the initial U.S. cancer hospital, provides comprehensive oncology treatment and research. Its four campuses are located in Manhattan; Basking Ridge, New Jersey; Long Island; and Westchester. History: The Memorial Sloan-Kettering Cancer Center originated as the New York Cancer Hospital in Manhattan. In 1880, physician J. Marion Sims demanded the establishment of a local cancer hospital after Women’s Hospital administrators prevented him from admitting cancer patients. Philanthropists funded a medical facility specifically for cancer, which started treating patients in 1887. Twelve years later, that facility was renamed General Memorial Hospital for the Treatment of Cancer and Allied Diseases. In 1936 John D. Rockefeller gave land for construction of a new Memorial Hospital. Alfred P. Sloan, Jr., and Charles Franklin Kettering financed the Sloan-Kettering Institute (SKI) to conduct medical research next to that hospital. In 1980, SKI and Memorial Hospital joined to form the Memorial Sloan-Kettering Cancer Center, which offered pioneering U.S. oncology facilities and services and diagnostic centers specifically for breast and prostate cancers. Donors financed additional construction, such as the Rockefeller Research Laboratories. Services and procedures performed: Diverse cancer specialties practiced at the Memorial Sloan-Kettering Cancer Center and innovative procedures and technology developed by its experts benefit patients. Its radiologists evaluate malignant tumors with computed tomography (CT) scanning or magnetic resonance imaging (MRI) to determine their three-dimensional shape so that intensitymodulated radiation therapy (IMRT) can hit tumors directly without damaging other organs. Memorial SloanKettering Cancer Center personnel devised ways to deliver chemotherapy and radiation simultaneously. The center’s High-Throughput Screening (HTS) Core Facility enables physicians to identify chemicals most effective to fight specific cancers. Its surgical centers incorporate robotic processes. The Memorial Sloan-Kettering Cancer Center operates affiliated outpatient clinics in New York and New Jersey. 780
Salem Health: Cancer The center’s staff developed the Symptom Tracking and Reporting (STAR) Web site for patients outside the office to alert physicians regarding symptoms and side effects. The Memorial Sloan-Kettering Cancer Center offers the Clinical Genetics Service, which evaluates people’s hereditary risks for specific cancers. The center’s counselors provide individual discussion and support groups. Survivor services for adult and children encourage patients’ continued contact during remission to monitor their cancer-free status. Education: In addition to providing cancer education services for patients and the community, the Memorial SloanKettering Cancer Center promotes advanced oncology educational opportunities for scientists, physicians, and other medical professionals. Postdoctoral fellows conduct research in its laboratories. Clinical fellowships enable physicians to interact with patients in various departments within the center. The center created the Louis V. Gerstner, Jr., Sloan-Kettering Graduate School of Biomedical Services in 2004 for students to earn doctorates specializing in biological aspects of cancer. This program educates scientists to envision how their research might aid patients. Other Memorial Sloan-Kettering Cancer Center educational resources include such publications as the SloanKettering Institute cancer series, conference proceedings, annual reports, and books written by center’s medical professionals. The center’s site posts Web casts of CancerSmart lectures from the center. Outreach: Memorial Sloan-Kettering Cancer Center medical professionals have provided free screening for breast and cervical cancers at the Breast Examination Center of Harlem since 1979. The center and North General Hospital in Harlem offer cancer screening and treatment at the Ralph Lauren Center for Cancer Care and Prevention. A Memorial Sloan-Kettering Cancer Center mobile van has also made mammograms available. Research: Memorial Sloan-Kettering Cancer Center research and clinical trials contribute to more effective cancer therapies and drugs that oncology professionals have adopted worldwide. Center scientists tested implanting radioactive seeds in cancers. Researchers have investigated using magnetic resonance spectroscopy with MRI for more effective tumor evaluation chemically and physically. The center’s personnel devised nomograms in which breast cancer patients’ responses to health questionnaires revealed how malignancies might spread. The center’s Human Oncology and Pathogenesis Program (HOPP) applies molecular investigation results to
Salem Health: Cancer strengthen cancer prevention, diagnosis, and treatment. Its scientists analyze how pharmaceuticals affect detrimental proteins in genes they detect in breast cancer and other malignant cells. The center’s experts contribute to improving the Information Hyperlinked over Proteins database, which maintains information regarding how genes and proteins interact. Specialized units such as the Brain Tumor Center enhance Memorial Sloan-Kettering Cancer Center’s research efforts. In 2001 the Memorial SloanKettering Cancer Center began presenting the biennial Paul A. Marks Prize for Cancer Research. Elizabeth D. Schafer, Ph.D. u For Further Information Bevilacqua, José Luiz B., et al. “Doctor, What Are My Chances of Having a Positive Sentinel Node? A Validated Nomogram for Risk Estimation.” Journal of Clinical Oncology 25, no. 24 (August 20, 2007): 36703679. Horner, Peter. “O.R. in the O.R.: Saving Lives as Well as Money, Memorial Sloan-Kettering Center Earns the Edelman with Breakthrough Modeling and Computational Techniques for Treating Prostate Cancer.” OR/ MS Today 34, no. 3 (June, 2007): 18-22. Kovner, Abba. Sloan-Kettering: Poems. Translated from the Hebrew by Eddie Levenston. New York: Schocken Books, 2002. Lang, Joan. “Making Comfort Healthy: Cancer Center’s New Chef Finds Ways to Satisfy Patients’ Need for Comfort.” Food Service Director 20, no. 8 (August, 2007): 40. Pérez-Peña, Richard. “A $100 Million Gift to SloanKettering.” New York Times, May 10, 2006, p. B3. Straus, Joan Sutton. A Legacy of Caring: The Society of Memorial Sloan-Kettering Cancer Center. New York: The Society of Memorial Sloan-Kettering Cancer Center, 1996. Winawer, Sidney J., Moshe Shike, Philip Bashe, and Genell Subak-Sharpe. Cancer Free: The Comprehensive Cancer Prevention Program. New York: Fireside/ Simon & Schuster, 1996.
u
Other Resources
Meningeal carcinomatosis National Comprehensive Cancer Network Memorial Sloan-Kettering Cancer Center http://www.nccn.org/members/profiles/memorial.asp See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
u Meningeal carcinomatosis Category: Diseases, symptoms, and conditions Also known as: Carcinomatous meningitis, leptomeningeal carcinomatosis Related conditions: Almost any type of cancer can be associated with this condition, but it is generally seen with breast, melanoma, and lung cancers. Definition: Carcinomatous meningitis is the spread of tumor cells from a primary central nervous system (CNS) source, such as a brain tumor, or from a distant source, such as a lung or breast tumor, via the blood to the subarachnoid space, where it spreads via the fluid covering the brain, called the cerebral spinal fluid (CSF) fluid, to involve the coverings of the brain, known as the leptomeninges. Risk factors: In adults, primary brain tumors such as oligodendroglioma or secondary tumors, also called metastases, from lung, breast, melanoma, lymphoma, ovarian, or gastric cancer can spread to the brain surfaces. Etiology and the disease process: Unlike other forms of meningitis, where the invading organism is a bacterium, fungus, or virus, the invaders in carcinomatous meningitis are cancer cells. In adults, meningeal carcinomatosis is usually the result of the metastasis of a primary brain tumor or a secondary cancer in a person who has lymphoma, melanoma, or lung, breast, or gastric tumors.
Information Hyperlinked over Proteins http://www.ihop-net.org
Incidence: The incidence of meningeal carcinomatosis is increasing because cancer patients are surviving longer. It is seen in about 3 to 5 percent of patients who have cancer.
Memorial Sloan-Kettering Cancer Center http://www.mskcc.org
Symptoms: Patients usually complain of nonspecific symptoms of headache, back pain, or weakness in an extremity. 781
Meningiomas Screening and diagnosis: Meningeal carcinomatosis can be diagnosed by magnetic resonance imaging (MRI) or myelography together with computed tomography (CT). A spinal tap (also called a lumbar puncture), whereby a needle is inserted into the cerebral spinal fluid within the subarachnoid space and the fluid is sampled, is the usual form of diagnosis, although cerebral spinal fluid cytology is negative in 10 percent of cases. Treatment and therapy: Meningeal carcinomatosis is difficult to cure and the aim of treatment is usually to ameliorate symptoms, usually by chemotherapy injected into the spinal fluid via lumbar puncture (intrathecal methotrexate) or by radiotherapy to the brain. Prognosis, prevention, and outcomes: Some patients respond to treatment; however, the prognosis is generally poor with death occurring within one month if the disease is untreated. Debra B. Kessler, M.D., Ph.D. See also Carcinomatous meningitis; Leptomeningeal carcinomas; Lumbar puncture.
u Meningiomas Category: Diseases, symptoms, and conditions Also known as: Meningeal tumors Related conditions: Intracranial and spinal tumors, extraaxial brain tumors, neurofibromatosis Definition: Meningiomas are tumors of the meninges, the thin layers of tissue that surround the brain and spinal cord. This type of neoplasm most likely originates from cells of the arachnoid matter, the middle element of the three meningeal coverings, and occur mainly at the base of the brain and around the cerebral convexities. Meningiomas are visibly demarcated from the brain tissue and thus are classified as extra-axial tumors. They can extend from the surface of the dura matter, the outer meningeal layer, and erode the cranial bones, causing exostosis, or growth of the bone. In general, these are solitary lesions, and more than 80 percent of them are benign. However, multiple lesions are common in patients with neurofibromatosis type 2 (NF2), a genetic disorder that affects the nervous system. Several different histological types have been described, with the meningothelial, fibrous, and transitional forms as the most frequently found. Risk factors: Although the risk factors for meningiomas are largely unknown, evidence suggests an association of 782
Salem Health: Cancer risk with a family or personal history of neurofibromatosis type 2, exposure to ionizing radiation (during full-mouth dental radiographs), and use of sex hormones (oral contraceptives or hormone replacement therapy). Other risks factors that have been explored without conclusive results are head trauma, cell phone use, breast cancer, and allergic diseases. Etiology and the disease process: The precise origin of the majority of the meningiomas is uncertain. However, several forms of this disease are clearly associated with the loss of a tumor-suppressor gene on chromosome 22, known as merlin and encoded by the NF2 gene. Merlin belongs to the 4.1 family of proteins, a group of molecules with roles in maintaining cell structure. Genetic defects in merlin account for many sporadic meningioma cases. In addition to merlin, other members of the 4.1 protein family with tumor-suppression activity have been involved in meningioma initiation (for example, 4.1B and 4.1R). However, meningioma progression seems to involve genetic changes in chromosomes other than chromosome 22. The presence of a high density of progesterone receptors in the vast majority of meningiomas suggests a functional role of progesterone-signaling pathways in the pathogenesis and might explain the twofold and tenfold higher incidence respectively of cranial and spinal meningiomas in women. Other proteins that might participate in the disease process of meningioma include telomerase, transforming growth factor-beta, and somatostatin. Incidence: Meningiomas are the most common nonglial and most common extra-axial tumors of the brain, with an annual age-adjusted incidence rate of 5 per 100,000 individuals. The relatively frequent autopsy finding of small asymptomatic undiagnosed meningiomas suggests that the actual incidence rate is significantly higher. They are more common in women, and the highest incidence is observed in the sixth and seventh decades of life. Childhood cases of meningioma are rare. Symptoms: Symptoms of meningiomas depend on the location and size of the lesion and result from increased intracranial pressure and edema of the brain structures adjacent to the tumor. The most common symptoms are headache, unilateral sensory disturbances (for example, hearing or visual loss), vertigo, imbalance, focal seizures, spastic weakness, numbness of the limbs, and painless proptosis or “bulging” eyes, among others. Screening and diagnosis: No screening tests are available. The tendency of meningiomas to calcify and their abundant blood supply allow their diagnosis by contrastenhanced computed tomography (CT), magnetic reso-
Salem Health: Cancer nance imaging (MRI), and arteriography. On both CT and MRI scans, meningiomas appear as homogeneous, smoothly outlined masses, with attachments to the dura matter. Their extra-axial location differentiates them from common intra-axial tumors of the central nervous system, and their unique image density characteristics differentiate them from Schwannoma, another extra-axial tumor. The World Health Organization (WHO) classifies meningiomas into three grades based on their histological features and the likelihood of recurrence. • Grade I: Benign meningiomas, with low risk of recurrence and aggressive growth • Grade II: Atypical meningiomas, with greater risk of recurrence and aggressive growth • Grade III: Anaplastic or malignant meningiomas, with the greatest risk of recurrence and aggressive growth Some 80 percent of all meningiomas are of WHO Grade I on diagnosis.
Merkel cell carcinomas (MCC)
An MRI image of a meningioma in the brain’s pineal region. (Living Art Enterprises, LLC/Photo Researchers, Inc.)
Treatment and therapy: The primary treatment is complete surgical excision of the tumor. Focused radiation by Gamma Knife or proton beam is used when the lesion is located around vital structures or when it is a high-grade or recurrent tumor. Although effective chemotherapy has not yet been developed, studies on the use of hormonal antagonists and other molecules are ongoing. Prognosis, prevention, and outcomes: Complete removal of the tumor is achieved in more than 70 percent of the cases, and in most patients, hearing and other functions of the nervous system are preserved. Recurrence depends on the grade of the tumor, ranging from 5 percent for WHO Grade I tumors up to 80 percent for WHO Grade III after five years of treatment. Prevention of meningiomas is difficult since the etiology is poorly understood. Reyniel Cruz-Aguado, Ph.D. u
For Further Information Claus, E. B., et al. “Epidemiology of Intracranial Meningioma.” Neurosurgery 57 (2005): 1088-1095. Lusis, E., and D. H. Gutmann. “Meningioma: An Update.” Current Opinion in Neurology 17 (2004): 687-692. Riemenschneider, M. J., A. Perry, and G. Reifenberger. “Histological Classification and Molecular Genetics of Meningiomas.” Lancet Neurology 5 (2006): 10451054.
u
Other Resources
Brain Tumor Foundation http://www.braintumorfoundation.org/about.asp MayoClinic.com Meningioma http://www.mayoclinic.com/health/meningioma/ DS00901 See also Acoustic neuromas; Brain and central nervous system cancers; Carcinomatous meningitis; Cell phones; Endotheliomas; Leptomeningeal carcinomas; Meningeal carcinomatosis; Neurofibromatosis type 1 (NF1); Pheochromocytomas; Spinal axis tumors.
u Merkel cell carcinomas
(MCC) Category: Diseases, symptoms, and conditions Also known as: Neuroendocrine carcinoma of the skin Related conditions: Ectodermal dysplasia Definition: Merkel cell carcinomas (MCC) are fast-growing cancers in Merkel cells, which are found in the deepest part of the outermost skin layer and are believed to be associ783
Merkel cell carcinomas (MCC)
Salem Health: Cancer
Relative Survival Rates for Merkel Cell Carcinoma, 1988-2001 Years
Survival Rate (%)
1 3 5 10
87.4 68.6 62.8 57.5
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
ated with the sense of touch. The structure of Merkel cells is characteristic of cells that assist in impulse transmission between an initial stimulus and the nerve impulse that carries messages to the brain. This cancer appears on the face, head, or neck as a firm, painless, shiny bump that can be red, pink, or blue, and it has been found to spread quickly to other parts of the body. Considered rare, MCC has become the second most common cause of non-melanoma skin cancer deaths, with most deaths from the disease occurring within the first three years after diagnosis. Risk factors: Risk factors include being over the age of sixty-five and having a history of repeated or prolonged sun exposure. People with weakened immune systems, such as those with human immunodeficiency virus (HIV) infection, patients with organ transplants, and those on medications that suppress the immune system, are also at increased risk of developing MCC. Etiology and the disease process: Although the exact cause of MCC is not known, it is believed that ultraviolet radiation from the sun and other sources plays a significant role in its development. One theory proposes that stem cells in the skin become cancerous and take on the characteristics of Merkel cells. Genetic abnormalities have been found in the cancer cells, leading to speculation that MCC is genetically linked. MCC grows rapidly, typically beginning on the face (especially around the eye), neck, and head. Metastasis to nearby lymph nodes, other areas of skin, liver, bone, and lungs is common and occurs early in the disease. When MCC spreads to other areas of the skin, the lesions grow rapidly and are flesh-colored to red-purple, firm, and deeper in the skin than the primary lesion. Incidence: Statistics from the National Cancer Institute indicate that about 1,200 new cases of MCC are diagnosed 784
each year in the United States. Although the number of cases is increasing, it still accounts for less than 1 percent of all skin cancers. The average age at diagnosis is sixtynine. MCC is substantially more common among white people and affects women more often than men. Symptoms: The primary skin lesions in MCC usually produce no symptoms. They usually occur as solitary, domeshaped nodules that are smaller than 2 centimeters (cm) in diameter, but can be larger than 15 cm. The skin surface is typically shiny and the color of the lesions is red, pink, or blue. Although they can develop on any skin surface, they are found on the head or neck in about 50 percent of cases. In 40 percent of the cases, they are found on the arms and legs. Because metastasis is common with MCC, other symptoms that may be reported include swollen lymph glands and fatigue. New growths, with a different appearance than the primary site, may also be reported. Screening and diagnosis: Screening for MCC should be performed as part of an annual physical. In addition, people at high risk for MCC should perform routine selfexamination. When a nodule is found, a biopsy should be performed to determine its cell type and whether it is benign tissue, MCC or, possibly, another form of cancer. If it is found to be MCC, further testing should follow as soon as possible because of how rapidly it spreads. Additional testing should include sentinel lymph node biopsy, a complete blood count, liver function tests, and a chest X ray. Computed tomography (CT) and positron emission scanning (PET) should also be performed to determine the extent of the cancer’s spread. MCC is divided into three stages depending on the severity of disease. • Stage I: The disease is localized to the skin at the primary site. • Stage IA: The primary lesion is less than or equal to 2 cm. • Stage IB: The primary lesion is greater than 2 cm. • Stage II: The cancer involves nearby lymph nodes. • Stage III: The cancer is found beyond the nearby lymph nodes. The stage at diagnosis is important in determining the possibility of tumor metastasis, the patient’s treatment options, and prognosis. Treatment and therapy: Treatment of MCC is based on the stage of the disease at diagnosis. Most commonly, surgery is performed to remove the primary lesion, along with some normal skin around the lesion’s edges. Lymph nodes
Salem Health: Cancer are also removed to test for cancer cells and spread of the disease. Radiation therapy is usually given to the site of the primary lesion and the lymph nodes. When the cancer has spread beyond the lymph nodes, treatment is mainly palliative to relieve pain. The use of chemotherapy, typically with etoposide and carboplatin, is controversial. Some studies have demonstrated positive results but recommend that it be reserved for metastatic MCC, whereas others have found that, especially with this disease, there was a trend toward decreased survival rates. Prognosis, prevention, and outcomes: Overall, the twoyear survival rate for MCC is 50 to 70 percent. Most recurrences and most deaths from this disease occur within the first three years. The only prevention for MCC is to reduce exposure to ultraviolet light, including the sun. Dorothy P. Terry, R.N. u For Further Information Allen, P. J., et al. “Merkel Cell Carcinoma: Prognosis and Treatment of Patients from a Single Institution.” Journal of Clinical Oncology 23, no. 10 (April 1, 2005): 2300-2309. Brady, Mary S. “Current Management of Patients with Merkel Cell Carcinoma.” Dermatologic Surgery 30, no. 2 (February, 2004): 321-325. Hodgson, N. C. “Merkel Cell Carcinoma: Changing Incidence Trends.” Journal of Surgical Oncology 89, no. 1 (January, 2005): 1-4. u
Other Resources
American Cancer Society Treating Merkel Cell Carcinoma http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Treatment_of_Merkel_Cell_ Carcinoma_51.asp MayoClinic.com Merkel Cell Carcinoma http://www.mayoclinic.com/health/ merkel-cell-carcinoma/DS00802 National Cancer Institute Merkel Cell Carcinoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ merkelcell/patient See also Skin cancers.
Mesenchymomas, malignant
u Mesenchymomas, malignant Category: Diseases, symptoms, and conditions Also known as: Mixed-cell sarcomas Related conditions: Soft-tissue sarcomas Definition: Malignant mesenchymomas are a type of softtissue sarcoma composed of two or more unrelated malignant forms. These rare tumors contain at least two nonepithelial mesenchymal tissues that are neoplastic, with differing histologies, that are not normally associated together in the same tumor. Risk factors: There are no readily identifiable risk factors particular to malignant memenchymoma, although several risk factors associated with soft-tissue sarcomas in general have been identified. These include exposure to chlorophenols in wood preservatives and phenoxyacetic acid in herbicides, exposure to ionizing radiation, and very rare genetic predispositions in some families. Sporadic cases of malignant mesenchymoma in patients previously treated with radiation for breast cancer have been reported. Etiology and the disease process: Etiology is not at all well understood, and connections with diet, smoking, alcohol, or preexisting conditions have not been established. Incidence: Only about 1 percent of newly diagnosed cancers are soft-tissue sarcomas, and malignant mesenchymomas represent only a small fraction of these. These tumors can develop at any age. Reports from the literature indicate ages of onset from one and a half years to eightyfour, with a median age of forty-six years and a slight preponderance of men. Symptoms: These tumors can arise in any of the connective tissues of the body, although they are most frequently encountered in the arms, legs, hands, feet, and retroperitoneum. Unusual locations such as the neck, fibula, and uterus have also been reported. They are usually first detected as a painless swelling of the soft tissue. Retroperitoneal tumors may become quite massive before detection and may be diagnosed only after the functions of adjacent organs such as the liver or kidneys have been compromised. Screening and diagnosis: No screening tests exist, although a few mesenchymomas are known to produce excessive amounts of insulin-like growth factor 2 precursor. Diagnosis is always based on direct histological examination of tumor tissue because other sarcomas of single somatic origin can develop in the same locations. 785
Mesothelioma Treatment and therapy: Surgical removal of the tumor, whenever possible, is the treatment of choice. This can be followed by radiation therapy or chemotherapy (with doxorubicin), although the benefits of these postsurgical treatments are questionable. Prognosis, prevention, and outcomes: Malignant mesenchymomas are usually described as high-grade sarcomas with a poor prognosis, although small tumors 5 centimeters or less in diameter have a much better prognosis. None of these tumors are encapsulated, so recurrence following excision is relatively common. Jeffrey A. Knight, Ph.D. See also Fibrosarcomas, soft-tissue.
u Mesothelioma Category: Diseases, symptoms, and conditions Also known as: Malignant mesothelioma (MM), pleural mesothelioma, peritoneal mesothelioma, pericardial mesothelioma Related conditions: Lung cancer, pericardial effusion Definition: Mesothelioma is a rare cancer of the mesothelium, the collective name for the membranes that surround the body’s internal organs. Particular mesothelia— the pleura (which covers the lungs), the peritoneum (which lines the abdominal cavity), and the pericardium (the sac that surrounds the heart)—lend their names to forms of mesothelioma. Pleural mesothelioma and peritoneal mesothelioma are the most common forms. At the cellular level, mesothelioma takes three main forms: epithelioid (50 to 70 percent of cases), in which the cancer cell is typically uniform and cube shaped, with a visible nucleus; sarcomatoid (7 to 20 percent), in which the cells are more irregular and oval shaped, with less visible nuclei; and biphasic (20 to 35 percent), a mixture of the two. Risk factors: About 80 percent of cases strike those exposed to asbestos, a name that refers to six silicate minerals: the serpentine mineral chrysotile and the amphibole minerals actinolite, amosite, anthophyllite, crocidolite, and tremolite. These minerals were heavily used in many industries and products from the late nineteenth century to the 1980’s. Today, although more strictly regulated, they remain components of materials for roofing, thermal and electrical insulation, cement pipe and sheets, flooring, gaskets, friction materials, coatings, plastics, textiles, paper, and other products. Those who work with these materials—in asbestos mining and milling, shipyards, building 786
Salem Health: Cancer demolition, heating and insulation, brake repair, and asbestos abatement—as well as family members exposed to their clothing, are at risk. Etiology and the disease process: Asbestos fibers generally do their damage when inhaled, although ingestion also poses risks. The microscopic fibers pierce the pleural lining and harm its mesothelial cells, resulting in the formation of malignant plaques. These fibers may be transported by the lymphatic system to the abdomen, or the infected person may cough, produce fiber-infested sputum, and reingest it into the abdomen, leading to the peritoneal form of mesothelioma. The worst asbestos fibers seem to be the long, thin fibers of the amphibole minerals. The serpentine mineral chrysotile possesses a feathery fiber that may do less damage, although it is more easily suspended in the air and possibly more subject to inhalation. Researchers do not completely understand the mechanisms whereby the fibers transform normal cells into cancerous ones, but it is believed that the fibers’ mechanical action on mesothelial cells, followed by inflammation as macrophages gather during the immune response, sets the stage. Asbestos has also been shown to mediate the entry of foreign deoxyribonucleic (DNA) into cells, resulting in mutations that lead to the activation of oncogenes, the deletion of tumor-suppressor genes, increased production of free radicals, inactivation of natural cell death (hence uncontrolled cell growth), and other errors. This process may be followed by interactions between the fibers and chromosomes that result in abnormalities, particularly of chromosome 22. Incidence: Although mesothelioma is a rare form of cancer, its incidence increased in the last two decades of the twentieth century, ranging from 7 to 40 per 1 million in Western, industrialized nations, with several thousand cases diagnosed each year in the United States. (Lung cancer from smoking, by way of comparison, typically strikes 1,000 in 1 million.) Perhaps because of the occupational risk factors, mesothelioma strikes men more often than women, and because it takes years to develop, it is diagnosed most often in those aged sixty and older. Cases in younger persons or with shorter onsets have, however, been reported, and the difficulties of diagnosis (mesothelioma is often misdiagnosed as adenocarcinoma) may mask a higher incidence. Pleural mesothelioma accounts for about 75 percent of all cases, peritoneal mesothelioma about 20 percent, and pericardial mesothelioma about 5 percent. Symptoms: Pleural mesothelioma is marked by fatigue, anemia, shortness of breath, wheezing, hoarseness, cough,
Salem Health: Cancer sputum containing blood, and chest pain resulting from the accumulation of fluid in the pleural space. Peritoneal mesothelioma is accompanied by weight loss, cachexia (wasting), abdominal swelling, and pain due to ascites (fluid buildup in the abdominal cavity); bowel obstruction, abnormal blood clotting, anemia, and fever may also appear. In advanced cases of mesothelioma, symptoms may include blood clots in the veins and consequent thrombophlebitis, severe bleeding in many body organs resulting from disseminated intravascular coagulation, jaundice, low blood sugar level, pleural effusion, blood clots in the arteries of the lungs (pulmonary emboli), and severe ascites. Other types of pain, problems in swallowing, and swelling of the neck or face may accompany metastatic tumors.
Mesothelioma If pathology confirms the suspicion of mesothelioma, the disease will require staging. The precise TNM (tumor/ lymph node/metastasis) system is usually employed: • Stage I: Mesothelioma is confined to the right or left pleura, perhaps in addition involving the lung, pericardium, and diaphragm. • Stage II: Mesothelioma extends to the chest wall and esophagus, both sides of the pleura, and perhaps the heart. • Stage III: Mesothelioma extends through the diaphragm into the abdominal cavity. • Stage IV: Mesothelioma has spread through the bloodstream to distant organs. For pleural mesothelioma, the Butchart system is most commonly used: • Stage I: Malignant melanoma is confined to the right or left pleura, perhaps in addition involving the lung, pericardium, and diaphragm. • Stage II: Malignant melanoma extends to the chest wall and esophagus, both sides of the pleura, and perhaps the heart. • Stage III: Malignant melanoma extends through the diaphragm into the abdominal cavity. • Stage IV: Malignant melanoma has spread through the bloodstream to distant organs.
Screening and diagnosis: Because the symptoms of mesothelioma are common to many conditions and because the disease takes so long to cause severe symptoms, it often remains undetected until well advanced. Unfortunately, no screening tests exist, although researchers are investigating blood levels of osteopontin, a protein associated with mesothelioma, as one means of early detection. For those whose symptoms have prompted a visit to the doctor, a history of exposure to asbestos, along with a physical examination, lung-function tests, and an X ray, are the first diagnostic steps. If the X ray reveals pleural Treatment and therapy: Treatment options for advanced thickening, computed tomography (CT) or magnetic resomesothelioma include surgery, most often pleurectomy nance imaging (MRI) scans usually follow. If these scans and decortication (removal of the chest lining) and less show an abnormal amount of fluid or a tumor, aspiration often extrapleural pneumonectomy (removal of the lung, will follow, via pleural tap or chest drain, paracentesis or interior chest lining, hemidiaphragm, and pericardium). ascitic drain, or pericardiocentesis, depending on the area These are followed by radiation and chemotherapy. Cheaffected. Cytology performed on the fluid will reveal or motherapy for pleural mesothelioma includes a combinarule out cancer; the absence of abnormal cells would sugtion of pemetrexed, cisplatin, and folic acid to mitigate gest another disease, such as tuberculosis or congestive pemetrexed’s side effects. A technique known as “heated heart failure. intraoperative intraperitoneal chemotherapy,” using a heated Even these tests, however, are not sufficient to confirm chemotherapy agent to perfuse affected abdominal and anything more than the presence of cancerous cells. To diagnose mesothelioma, a biopsy must be performed: thoroscopy Relative Survival Rates for Mesothelioma if the area is located in the chest, lapaby Area Affected, 1988-2001 roscopy if in the abdomen. These proceSurvival Rate (%) dures involve small incisions that allow both examination of the cavity and reYears Pleura and Lung Peritoneum and Retroperitoneum trieval of tissue samples. Bronchoscopy, 1 38.2 41.8 in which the physician examines the 3 10.5 25.9 lung’s airways by means of a broncho5 6.4 18.4 scope, and mediastinoscopy, a method 10 4.3 9.5 of examining the lymph nodes, are also Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. used. Open surgery may be required if SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. the samples retrieved are insufficient to 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) confirm the diagnosis. 787
Metastasis
Salem Health: Cancer
pelvic areas immediately after surgery, has been developed for peritoneal mesothelioma. Investigations into immunotherapies have seen little success, although interferon alpha has shown some promise.
diocentesis; Pleural biopsy; Pleurodesis; Pneumonectomy; Sarcomas, soft-tissue; Simian virus 40; Surgical biopsies; Thoracoscopy.
Prognosis, prevention, and outcomes: Because diagnosis generally occurs late and the disease is aggressive, survival rates are low, tending to average between six and nine months following diagnosis, depending on the type of mesothelioma. In the United States, the death rate from mesothelioma increased from 2,000 to 3,000 per year between 1980 and the late 1990’s. Radiation and chemotherapy are offered as palliative treatments in advanced cases. A thin tube or needle may be installed in the affected region (via paracentesis for the abdomen and thoracentesis for the chest cavity) to relieve fluid buildup and consequent pain. A diagnosis of mesothelioma is not necessarily a death sentence, however: Paleontologist Stephen Jay Gould, who was diagnosed with peritoneal mesothelioma, lived two decades after his diagnosis and succumbed to a different disease. Fortunately, mesothelioma remains a rare and highly preventable disease if asbestos exposure is identified and eliminated. Christina J. Moose, M.A.
u Metastasis
u For Further Information Galateau-Sallé, Françoise, ed. Pathology of Malignant Mesothelioma. London: Springer, 2006. Pass, Harvey I. One Hundred Questions and Answers About Mesothelioma. Sudbury, Mass.: Jones and Bartlett, 2004. Pass, Harvey I., Nicholas J. Vogelzang, and Michele Carbone, eds. Malignant Mesothelioma: Advances in Pathogenesis, Diagnosis, and Translational Therapies. New York: Springer, 2005. Treasure, T., et al. “Radical Surgery for Mesothelioma: The Epidemic Still to Peak and We Need More Research to Manage It.” British Medical Journal 328 (2004): 237-238. u
Other Resources
Mesothelioma Applied Research Foundation http://www.marf.org Mesothelioma Center http://www.mesotheliomacenter.org See also Acrylamides; Air pollution; Asbestos; Continuous hyperthermic peritoneal perfusion (CHPP); Erionite; Lung cancers; Mediastinoscopy; Paracentesis; Pericar788
Category: Diseases, symptoms, and conditions Also known as: Metastatic disease, metastatic cancer Related conditions: Bone cancer, lung cancer, nodal involvement Definition: Metastasis is the movement or spreading of cancer cells from their original site to other areas of the body. The capacity to metastasize is a characteristic of all malignant tumors. Cancer cells have the ability to enter the bloodstream and flow to any part of the body, making a new home for themselves. Different cancers have different patterns of spreading. When cancer comes back in a patient at a site distant from the original location although the patient appeared to be free of cancer, this is called metastatic recurrence. Risk factors: Whether cancer cells will metastasize to other parts of the body depends on many factors, including the type of cancer, the stage of the cancer, and the original location of the cancer. Tumors are usually classified as either benign or malignant. Malignant tumors can spread by invasion and metastasis, while benign tumors just grow locally. Often the term “cancer” is used only in reference to malignant tumors, not benign ones. Etiology and the disease process: Metastasis can occur through the circulatory system, the lymphatic system, or both routes. Common sites for metastasis are the adrenals, the liver, the brain, and the bones. Different cancer types have different metastatic tendencies; that is, the origin of the cancer can often predict the location of metastatic tumor formation. For example, colon cancer will often metastasize to the liver, while prostate cancer tends to metastasize to the bones. Similarly, in women, stomach cancer will often metastasize to the ovaries. It is believed that the migrating cancer cells attempt to find new organs that resemble the local environment of the primary (original) tumor, where they can engraft and thrive. Breast cancer cells, in a high-calcium environment due to the proximity of calcium-containing breast milk, will often metastasize to the bone marrow (also a site of high calcium content). Cancer will often spread to neighboring lymph nodes; however, this may be referred to as “nodal involvement” or “regional disease” rather than as metastasis. Cancers that are highly metastatic (and therefore particularly dan-
Salem Health: Cancer gerous) have been found to secrete proteins that degrade the extracellular matrix that connects cells and separates the organs. Such cells may have greater ability to leave the primary tumor location, migrate into the blood vessels, and then leave the circulation at a remote site. Once cancer cells engraft at a new location, they must induce the growth and infiltration of new microscopic blood vessels to grow in size. Some treatment approaches have attempted to target and interfere with the ability of metastatic tumors to induce new blood vessel growth. Incidence: Metastatic disease is common in many latestage cancers. Cancers that frequently are the source of metastasis are melanomas and cancers of the lung, breast, colon, kidney, prostate, and pancreas. Therefore, the incidence of metastatic cancer is similar to the incidence of these common cancers after they progress to a metastatic stage. Symptoms: The exact symptoms experienced by patients with metastatic cancer depend on the type of disease. For instance, lung metastasis can cause coughing or shortness of breath. Brain metastasis can cause symptoms of confusion, seizures, or even coma. Liver metastasis can reveal
Metastasis itself as abdominal pain or jaundice. Bone metastasis is associated with pain in the bones. Screening and diagnosis: Early metastatic disease may have no signs at all. The more advanced a cancer, the easier it usually is to detect. Each diagnosis of metastasis must be evaluated individually and with care. The extent of each cancer must be determined and all the potential sites of metastasis studied. Metastatic tumors are quite common in the late stages of cancer. Cells collected from a secondary metastatic tumor, when examined under a microscope, can often be identified as cells of the type found in the primary cancer. Therefore, an appropriate treatment regimen may be one that is known to be effective in treating the primary tumor type. The terminology used to describe a metastatic tumor refers to the primary tumor type. For example, breast cancer cells that metastasize to the bone are referred to as “metastatic breast cancer” instead of “bone cancer.” Treatment and therapy: Treatment of metastatic cancer varies widely, depending on the type of cancer and where it has metastasized. Common treatment options include surgery, radiation, and chemotherapy. Biological therapy, radiosurgery, hormone therapy, and laser-immunotherapy can also be treatment options for specific types of metastatic cancer. Treatment must address the symptoms of the metastatic disease along with the primary cancer. Other factors that must be considered in selecting the most appropriate treatment include the size of the metastatic tumor and the patient’s age and well-being. Prognosis, prevention, and outcomes: When a patient is diagnosed with cancer, it is important to determine whether the disease is local or has spread to other locations. The tendency of cancer to spread to secondary organs is what makes the disease potentially life-threatening. Michael R. King, Ph.D. u
For Further Information Icon Health. Metastasis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Liotta, L. A., and I. R. Hart, eds. Tumor Invasion and Metastasis. Boston: Kluwer, 1982. Weiss, Leonard. Principles of Metastasis. San Diego, Calif.: Academic Press, 1985.
u
A protein called autocrine motility factor (AMF) causes cancer cells to grow pseudopodia, which enable them to move to other parts of the body. (Science Source/Photo Researchers, Inc.)
Other Resources
American Cancer Society What Is Bone Metastasis? http://www.cancer.org/docroot/CRI/content/CRI_2_4 _1X_What_Is_bone_metastasis_66.asp?sitearea= 789
Metastatic squamous neck cancer with occult primary Children’s Hospital Boston How Cancer Grows and Spreads http://www.childrenshospital.org/research/Site2029/ Documents/CHB_cancer_map.pdf MetaCancer Foundation http://www.metacancer.org See also Cancer biology; Carcinomatosis; Invasive cancer; Malignant tumors; Tumor markers.
u Metastatic squamous neck
cancer with occult primary Category: Diseases, symptoms, and conditions Also known as: Metastatic squamous cell carcinoma of the neck from an unknown primary Related conditions: Head and neck cancers Definition: Metastastic squamous neck cancer with occult primary is a cancer in which squamous cells (cells from tissues that line the outside of many body organs) metastisize to lymph nodes in the neck or around the collarbone, and the location of the primary tumor is unknown. Risk factors: The risk factors for metastatic cancer are the same as those for cancer in general. They include tobacco use, unhealthful diet, alcohol abuse, and genetic factors. In addition, the human papillomavirus as a risk factor has been extensively studied in head and neck cancers. Etiology and the disease process: In the course of the disease, the cancer cells—cells that divide too quickly and without any order—travel from the organ in which they develop (the primary site), through the blood or lymphatic vessels to the lymph nodes in the neck or around the collarbone. Incidence: Metastastic squamous neck cancer with occult primary is a rare disease that afflicts less than 200,000 individuals in the United States. Symptoms: Symptoms may include a lump in the neck or throat, pain in the neck or throat, and metastasis. Screening and diagnosis: Screening tests to diagnose metastatic squamous neck cancer and the primary tumor include physical exams, biopsies, and different imaging procedures. A diagnosis of the disease is made if the primary tumor is not found during testing. Staging is the process used to determine how far the tumor has spread to other body organs, such as the liver or lungs. There is no 790
Salem Health: Cancer standard staging process for metastatic squamous neck cancer with occult primary. The tumors are described as untreated or recurrent. Treatment and therapy: The treatment of the disease depends on how many lymph nodes are affected, on whether the primary tumor has been detected, and on the patient’s age and overall health. Surgery is a common treatment, during which the physician cuts out the cancerous lymph nodes and some of the healthy ones around them. Radiation therapy, to kill the cancer cells and to shrink the tumors, may be given alone or before surgery. Chemotherapy is currently administered only in clinical trials, before or at the same time as radiation therapy. Another treatment option is participation in clinical trials of new treatments. Prognosis, prevention, and outcomes: Prognosis and outcome depend on many factors, for example, the extent of metastasis in the lymph nodes or the response of the cancer to treatment. Avoiding preventable risk factors, such as smoking, may help reduce the disease risk. Silke Haidekker, Ph.D. See also Carcinoma of unknown primary origin (CUP); Epidermoid cancers of mucous membranes; Head and neck cancers.
u Microcalcifications Category: Diseases, symptoms, and conditions Also known as: Calcifications Related conditions: Ductal cancer in situ (DCIS) Definition: Microcalcifications are tiny deposits of calcium phosphate or calcium oxylate found in soft tissues of the body such as the breast. On a mammogram, microcalcifications are seen as fine white flecks with a diameter of less than 1 millimeter. Based on their physical characteristics and location, microcalcifications may be classified as skin, vascular, eggshell, popcornlike, rodlike, punctate (round or oval), milk of calcium, or suture. Although they are very common and most often benign, microcalcifications may be a sign of precancerous changes in the breast. Risk factors: The incidence of microcalcifications increases with age. However, they are found in women and men of all ages and races. Etiology and the disease process: Microcalcifications are not associated with dietary calcium. It is thought that they are secreted by the breast cells or are mineralized resi-
Salem Health: Cancer
Microwave hyperthermia therapy
due from either normal breast metabolism or abnormal, rapid cell division. They may be related to previous trauma, surgery, infection, or radiation, or they may be an indication of ductal cancer in situ, a noninvasive Stage 0 cancer found in milk ducts of the breast.
u Microwave hyperthermia
Incidence: Microcalcifications and larger macrocalcifications are seen in approximately two-thirds of all mammograms.
Definition: Microwave hyperthermia therapy is a procedure in which microwaves are used to heat an area in which cancer is present. It is considered an experimental therapy and is not widely available, and it is usually used in combination with radiation therapy or chemotherapy.
Symptoms: The deposits are generally too small to be felt during clinical examinations and do not cause pain. Screening and diagnosis: Screening mammograms are the standard tool for detecting microcalcifications. Diagnostic mammography, computer-assisted detection software, ultrasound, and comparisons with previous mammograms are used by radiologists to analyze the structure, size, number, shape, and distribution of microcalcifications. The findings are then assigned an assessment category (from 0 to 5), which determines what, if any, followup is recommended. Treatment and therapy: Mammograms classified as categories 1 and 2 are considered negative and require no extraordinary follow-up. Category 3 microcalcifications have a high probability of being benign, but repeat mammograms are typically scheduled to watch for changes in size, number, or shape of deposits. A stereotactic or surgical biopsy of suspicious microcalcifications may be recommended with a category 4 assessment, whereas a category 5 designation indicates a likely malignancy that requires biopsy and surgery or other treatment. Category 0 is used when additional testing is needed before a diagnosis can be made. Prognosis, prevention, and outcomes: Most microcalcifications are benign. Of those biopsied, more than 80 percent are noncancerous. However, any microcalcifications (especially if they occur in both breasts) are thought to put women at greater risk for breast cancer. Judy Majewski, M.S. See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancers; Breast ultrasound; Calcifications of the breast; Cold nodule; Comedo carcinomas; Ductal carcinoma in situ (DCIS); Ductogram; Fibroadenomas; Hormone replacement therapy (HRT); Invasive ductal carcinomas; Mammography; Mastectomy; Medullary carcinoma of the breast; Tubular carcinomas; Wire localization.
therapy Category: Procedures Also known as: Heat therapy
Cancers treated: A wide variety of cancers, including prostate, breast, bladder, lung, and liver cancers Why performed: Microwave hyperthermia therapy aims either to kill tumor cells or to make them more susceptible to other cancer treatments. Patient preparation: Patient preparation for microwave hyperthermia therapy depends on the area in which the therapy will be done and whether the therapy will be localized or regional. Patients should discuss carefully with their cancer care team the possible outcomes of the therapy and what the realistic outcome expectations are. Steps of the procedure: In localized hyperthermia, a rod containing coils that produce microwaves is introduced to the tumor. The rod is then turned on and the microwaves heat up the tumor cells. The tumor cells may be heated to such an extent that they die, or they may be heated only to an extent that makes them more susceptible to chemotherapy drugs. It is very difficult to heat only the tumor cells, and normal cells surrounding the tumor may also be affected. In regional microwave hyperthermia therapy, a device that produces microwaves is aimed at a region, such as an arm or leg. The machine is then started and produces microwaves that heat the entire region. In this case the cells are heated enough to make chemotherapy drugs more effective but not enough to kill the cells. After the procedure: If the microwave hyperthermia is administered in conjunction with chemotherapy or radiation, then the patient will experience the effects that he or she usually experiences after such therapy. The patient may experience temporary feelings of pain or discomfort from the procedure. Risks: Microwave hyperthermia therapy is considered an experimental procedure. The risks will depend on the specific procedure being performed but may include pain, infection, swelling, blood clots, and nerve or muscle damage. 791
Mineral oils Results: The goal of microwave hyperthermia therapy is usually to improve the effectiveness of chemotherapy drugs or radiation therapy. In these cases, the results of the treatment may be hard to define because many other things can also affect the effectiveness of such treatments. The results will also vary depending on the area in which the tumor is located, the extent of the cancer, and whether the procedure was done on a localized or regional area. Helen Davidson, B.A. See also Bladder cancer; Breast cancers; Chemotherapy; Hyperthermia therapy; Liver cancers; Lung cancers; Prostate cancer; Radiation therapies; Radiofrequency ablation.
u Mineral oils Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Petroleum distillate, untreated and mildly refined oils Related cancers: Skin cancers, particularly squamous skin cell cancers of the scrotum, as well as stomach, bladder, pancreatic, large intestine, rectal, mouth, throat, and lung cancers Definition: Mineral oils include lubricant-based oils and other products derived from them. They are insoluble in water and are composed of complex mixtures of aliphatic hydrocarbons, naphthenics, and aromatics. Among those that are considered to be most carcinogenic are the polycyclic aromatic hydrocarbons (PAH), particularly benzopyrene, as well as nitrosamines, chlorinated paraffins, long-chain aliphatics, sulfur, N-phenyl-2-naphthylamine, and formaldehyde. Exposure routes: Mineral oils can be absorbed directly through dermal contact, via inhalation, and by ingestion of substances containing or contaminated with untreated or mildly treated mineral oils. Where found: Minerals are found at industry work sites and in the environment because about two billion liters of used (and potentially contaminated) lubricating oils are released every year. At least 750 million of these are used as road oil or in asphalt. At risk: These commonly in contact with mildly treated or untreated mineral oils include workers in the metal, glass, newspaper printing, and automobile and airplane manufacture, and cotton and jute spinning industries. Etiology and symptoms of associated cancers: Mineral oils generally cause skin cancers by dermal contact, result792
Salem Health: Cancer ing in red, swollen, and possibly painful marks or tumors on or beneath the skin. Stomach and pancreatic cancers often cause abdominal pain. Bladder, large intestine, and rectal cancers, often caused by ingestion of harmful levels of mineral oils, effect excretion of waste, making urination or excretion painful. Cancers of the mouth, throat, and lung are generally caused by inhalation or ingestion of toxic substances in mineral oils. First symptoms are flulike or coldlike irritation of breathing passages, which progressively increases to the point at which breathing and speaking are affected, eventually severely. History: Mineral oils are used as a base in the manufacture of many types of refined lubricant oils. These refined oil products are then used in construction work, metalwork, manufacturing diesel oils, and mining. Nearly half of the lubricating oils are used in automobile manufacturing and operation. These include engine oils, transmission oils, lubricating oils for gears, bearing oils, and transmission fluids. Highly refined and purified white mineral oils are used for certain medicinal, food, and pharmacological purposes. Most of the studies on mineral oils as carcinogens have involved relationships between cancers and metalworkers in the West Midlands district of the United Kingdom. Case studies revealed an excess incidence of skin cancers in these metalworkers as well as higher levels of gastrointestinal and bladder cancers. Similarly, studies of cancer incidence in printing occupations have shown increased incidence of and mortality related to a variety of respiratory cancers, including buccal cavity, pharyngeal, and lung cancers. Results from a number of animal studies show similar relationships. For example, mice treated with repeated application of mineral oils directly to the skin had dramatically increased incidence of skin cancer. Similar applications of mineral oils to rabbits and rhesus monkeys produced tumors typically associated with the skin. Despite these concerns, mineral oils are still widely used in the United States and elsewhere across the globe and are for sale everywhere. Roughly 85 percent of the manufactured mineral oil products are used for lubricants, another 12 to 14 percent are used as aromatic oils, and the remaining are produced for greases. Finally, refined mineral oils are still an important component of many industries in which lubricants are necessary. Dwight G. Smith, Ph.D. See also Carcinogens, known; Lung cancers; Occupational exposures and cancer; Pancreatic cancers; Rectal cancer; Skin cancers; Squamous cell carcinomas; Stomach cancers; Throat cancer.
Salem Health: Cancer
u Mistletoe Category: Complementary and alternative therapies Also known as: Viscum album Lorantaceae, all heal Definition: European and American varieties of mistletoe are semiparasitic, woody evergreen plants with white berries that grow on deciduous trees. Mistletoe has a long history of use in Europe and Asia as a medicinal cure-all, and the species Viscum album Lorantaceae in particular has been studied for the treatment of multiple types of cancer. Cancers treated or prevented: Breast, pancreatic, and other cancers Delivery routes: Intrauscular, subcutaneous, or intravenous (IV) injection of water-based or water-and-alcoholbased extracts How this substance works: American and European mistletoe plants both contain toxins that provide pharmacologic effects on multiple organ systems. The Viscum album species is the primary one used medicinally and provides activity via four viscotoxins, three distinct lectins
Mistletoe (M11-3), and the specific lectin viscumin. These toxins are found in the main standardized product Iscador, available in Europe and Asia but not in the United States. The cytotoxic viscotoxins and lectins provide the plant’s potential direct anticancer activity by inhibiting protein synthesis in cancer cells and by inducing programmed cancer cell death, respectively. Immunomodulation is another possible mechanism of cancer treatment and of chemotherapy side effect control. Mistletoe extract may increase white blood cell counts, protect deoxyribonucleic acid (DNA) in white blood cells exposed to damaging chemotherapy, and stimulate cellular secretions of cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6, from white blood cells. Increased natural killer cell activity has also been noted in breast cancer patients administered a single intravenous dose of standardized mistletoe preparation. Varying effects have been observed with different extracts, doses, and types of cancer. Clinical trials have been conducted in Europe, but evidence supporting mistletoe’s immune-boosting effect does not yet support the concept that enhanced immunity will help the body fight cancer cells. Side effects: Mistletoe leaves and berries are poisonous to ingest and may cause nausea, vomiting, and diarrhea leading to dehydration; decreased heart rate and increased blood pressure, with possible vasoconstriction and cardiac arrest; delirium and hallucinations; and seizures. Gastric emptying is suggested after ingestion of more than three berries or more than two leaves. Few side effects have been reported, however, with medicinal use of the mistletoe extract. Common side effects observed with extract administration include injection site reactions, headache, fever and chills, and some cases of anaphylactic shock or allergic reaction. Mistletoe is a uterine stimulant and should be avoided during pregnancy and lactation. Nicole M. Van Hoey, Pharm.D.
Mistletoe. (©Witold Krasowski/Dreamstime.com)
See also Breast cancers; Complementary and alternative therapies; Pancreatic cancers. 793
Mitochondrial DNA mutations
u Mitochondrial DNA mutations Category: Cancer biology Also known as: Mitochondrial heteroplasmy (different mitochondrial mutations are present), homoplasmy (only a single type of mitochondrial DNA, or deoxyribonucleic acid, sequence is present) Related conditions: Warburg effect Definition: Mitochondria are organelles in eukaryotic cells that produce energy (adenosine triphosphate, or ATP) by oxidative phosphorylation. Mitochondria are made from the proteins encoded by both nuclear genes and genes from the mitochondrion’s own genome. The mitochondrial genome is sixteen kilobase pairs and encodes thirtyseven genes, which function in the mitochondrion. The majority of proteins in the mitochondrion are products of nuclear-encoded genes. There are multiple copies of the mitochondrial genome in each mitochondrion and multiple mitochondria in each cell. Mitochondrial DNA mutates at a high rate, and mitochondrial dysfunction is a factor in the development of cancers. Many defects in mitochondrial function are found in tumors. The mutation process: Mitochondrial DNA (mtDNA) mutates at a rate about ten times greater than that of nuclear DNA. Likely reasons for this high mutation rate are an error-prone DNA polymerase, inefficient DNA repair enzymes, and exposure to mutagens such as oxygen radicals that are present in the mitochondrion. Cancer cells have metabolic imbalances and a decrease in mitochondrial apoptosis (programmed, or planned, cell death). In cancer, the rapid growth of tumors is possible because of the shift in the mitochondria to glycolysis rather than the normal respiration (oxidative phosphorylation) to make ATP. Changes are observed in cancer cells, including the production of more of the rate-limiting enzymes of glycolysis and the accumulation of mutations in mitochondrial DNA. Often these mutations are in genes involved in mitochondrial respiration and ATP generation. In addition, sometimes people have mitochondrial mutations (germ-line mutations) that predispose that person to develop cancer. It is thought that most mtDNA mutations are acquired during or after the start of the cancer. Mitochondrial DNA mutations are divided into two classes. The first class is severe mutations that inhibit oxidative phosphorylation and cause an increase in reactive oxygen species. Such mutations will promote tumor growth. The second class is milder mutations, which will allow tumors to adapt to new microenvironments as a tumor progresses and metastasizes. 794
Salem Health: Cancer Cancer cells are resistant to apoptosis because the induction of mitochondrial outer membrane permeabilization (MOMP) is inhibited. MOMP is a process that mediates apoptosis. In hematological cancers, when this process is inhibited, a neoplasm will occur. Some genes that code for proteins that function in the mitochondrion are located on nuclear chromosomes. Associated cancers: Changes in mtDNA sequences have been found in many different types of cancers, including lung, breast, pancreatic, gastric, colorectal, thyroid, cervical, and prostate cancers. Mutations in the nuclear DNAencoded mitochondrial genes for fumarate hydratase and succinate dehydrogenase are associated with uterine leiomyomas and paragangliomas. Studies have shown that the presence of certain mitochondrial DNA sequences (single nucleotide polymorphisms) is associated with an increase (or for other sequences, a decrease) in the risk of developing breast cancer. Germ-line mutations in mitochondrial DNA at nucleotides 10398 and 16189 are linked to breast and endometrial cancer. If the mitochondrial electron transport chain reactions are not functioning well, reactive oxygen species are made that cause oxidative stress and increase the risk of developing breast cancer. Other germline mtDNA mutations are associated with an increased risk of prostate cancer. Note that mutations in mtDNA show maternal inheritance because sperm mitochondria are generally eliminated from the embryo, so that mtDNA comes from the mother via the egg. Mutations and monitoring: Somatic mutations in the displacement loop (D-loop, where the mtDNA starts replication) occur frequently in colorectal cancers. There are hot spots in the D-loop where mtDNA mutations frequently occur. A colorectal tumor with a mutation in the D-loop is associated with a poor prognosis and resistance to fluorouracil-based adjuvant chemotherapy in Stage III colon cancers. Thus changes in mtDNA sequences are involved in the initiation and progression of cancers. Examining the mtDNA mutations in populations of cancer cells may be useful to monitor tumor progression. Analysis of these mutations may be useful for the diagnosis and treatment of the cancer. Targets for drug treatment might include glycolysis and inducing apoptosis in mitochondria. Susan J. Karcher, Ph.D. u
For Further Information Alirol, E., and J. C. Martinou. “Mitochondria and Cancer: Is There a Morphological Connection?” Oncogene 25 (2006): 4706-4716. Bai, R. K., et al. “Mitochondrial Genetic Background
Salem Health: Cancer Modifies Breast Cancer Risk.” Cancer Research 67, no. 10 (2007): 4687-4694. Brandon, M., P. Baldi, and D. C. Wallace. “Mitochondrial Mutations in Cancer.” Oncogene 25, no. 34 (2005): 4647-4662. Chatterjee, A., E. Mambo, and D. Sidransky. “Mitochondrial DNA Mutations in Human Cancer.” Oncogene 25, no. 34 (2006): 4663-4674. Garber, K. “Energy Boost: The Warburg Effect Returns in a New Theory of Cancer.” Journal of the National Cancer Institute 96, no. 24 (2004): 1805-1806. _______. “Energy Deregulation: Licensing Tumors to Grow.” Science 312 (2006): 1158-1159. Kroemer, G. “Mitochondria in Cancer.” Oncogene 25 (2006): 4630-4632. Maitral, Anirban, et al. “The Human MitoChip: A HighThroughput Sequencing Microarray for Mitochondrial Mutation Detection.” Genome Research 14 (2004): 812-819. Ohta, S. “Contribution of Somatic Mutations in the Mitochondrial Genome to the Development of Cancer and Tolerance Against Anticancer Drugs.” Oncogene 25 (2006): 4768-4776. Ruiz-Pesini, Eduardo, et al. “An Enhanced MITOMAP with a Global mtDNA Mutational Phylogeny.” Nucleic Acids Research 35 (January 1, 2007): D823-D828. u
Other Resources
MITOMAP A Human Mitchondrial Genome Database http://www.mitomap.org/ National Cancer Institute Cancer Genetics http://www.cancer.gov/cancertopics/ prevention-genetics-causes/genetics See also Breast cancers; Cancer biology; Cytogenetics; Genetics of cancer; Germ-cell tumors; Molecular oncology.
u MLH1 gene Category: Cancer biology Also known as: MutL homolog 1, colon cancer nonpolyposis type 2 (E. coli); HNPCC; FCC2; HNPCC2; mutL (E. coli) homolog 1 (colon cancer, nonpolyposis type 2) Definition: The MLH1 gene encodes a protein that is involved in deoxyribonucleic acid (DNA) mismatch repair.
MLH1 gene Normal cellular function: When a cell divides, it must replicate its genetic material, which is contained within the DNA. During DNA replication, errors can be made that need to be corrected. The DNA mismatch repair machinery recognizes the errors that are made and recruits other proteins to repair the errors. If errors are not corrected, mutations are made that could affect the production or function of important proteins. Relevance to cancer: MLH1 and MSH2, another gene that is part of the DNA mismatch repair machinery, are the two genes most frequently mutated in hereditary nonpolyposis colorectal cancer (HNPCC). Inheriting mutations in either MLH1 or MSH2 predisposes patients to developing colorectal, stomach, ovarian, and biliary duct cancers. Mutations in DNA mismatch repair genes are also present in 10 to 20 percent of sporadic (noninherited) cancers. Defects in mismatch repair proteins are correlated with tumors that show microsatellite instability (MSI). Microsatellites are regions of the genome that contain highly repetitive DNA sequences that are more likely to generate errors during DNA replication. If the DNA mismatch repair machinery does not correct these errors, this can lead to further mutations within the genome that may promote tumor formation and progression. Diagnostic and genetic testing: There are a number of tests that can identify people with inherited mutations in mismatch repair genes as well as characterize the levels of these proteins in tumor cells, both of which have important clinical implications. DNA sequencing tests are currently available for both MLH1 and MSH2, the two mismatch repair genes that are most commonly mutated in cancer. In addition to mutations in the genes themselves, other types of chromosome modifications can alter levels at which these proteins produced by these genes are expressed within the cells. Therefore, immunohistochemical analysis of tissue samples can be used to detect how much of the mismatch repair proteins are being produced. Clinical implications: Because mutations in MLH1 or MSH2 significantly increase the risk of developing cancer, patients carrying these mutations should undergo frequent screening for colon and endometrial cancer. In addition, levels of MLH1 and MSH2 protein within tumor cells can be prognostic indicators, since differential protein levels are associated with differences in cancer progression, recurrence, and treatment response. For example, one study found that cells lacking MLH1 protein were more resistant to DNA damage-inducing chemotherapy than cells that contain MLH1. Lindsay Lewellyn, B.S. 795
Mohs surgery See also Ashkenazi Jews and cancer; Bethesda criteria; Cancer biology; Family history and risk assessment; Genetics of cancer; Hereditary cancer syndromes; MSH genes; Turcot syndrome.
u Mohs surgery Category: Procedures Also known as: Mohs micrographic surgery Definition: Mohs surgery is a surgical technique for precisely excising malignant cutaneous tumors. It was developed in the 1930’s by Dr. Fredric Mohs. In 1969, Dr. Mohs reported the use of the technique for excising basal cell carcinomas and squamous cell carcinomas and claimed a five-year cure rate of 100 percent. Subsequent data and studies led to the validation of the technique within the surgical community. Mohs surgery is now commonly used for the resection of malignant and nonmalignant tumors in cosmetically sensitive areas such as the face and neck, hands, and genitalia.
Salem Health: Cancer the microscopic margins are positive, then their precise locations are noted on the Mohs map and tissue is resected only from that area. This process is repeated in stages until the entire tumor is removed and clear margins are seen. Following the complete resection of the tumor, the defect is either closed immediately using various surgical repair techniques or allowed to close by secondary intention. The type of closure depends on the type of defect and the preference of the surgeon. After the procedure: The patient should be provided with thorough wound care instructions before discharge. Risks: The risks of Mohs surgery include allergy to the numbing medication, scarring, pain, and infection. Results: The procedure ideally results in the complete clearing of the tumor in question. The patient should be counseled that recurrence is always a possibility. Sarah Kasprowicz, M.D. See also Basal cell carcinomas; Bowen disease; Dermatofibrosarcoma protuberans (DFSP); Dermatology oncology; Penile cancer; Squamous cell carcinomas.
Cancers treated: Basal cell carcinomas, squamous cell carcinomas Why performed: With Mohs surgery, the tumor can be surgically excised with precision, maintaining the best surgical and cosmetic outcome. Accurate tumor margin assessment and high cure rates are achievable with this technique. In addition, Mohs surgery allows the patient to be spared the unnecessary removal of normal tissues, ultimately providing a more functional and cosmetically optimal outcome. Patient preparation: The patient is screened for allergies to numbing medicines such as lidocaine. The surgical site is prepped in a sterile fashion. Local anesthesia is typically used, and the patient’s wound is covered between surgical stages. Steps of the procedure: Mohs surgery is typically performed under local anesthesia by a dermatologist trained in the procedure in an outpatient setting. The procedure typically takes between two and four hours and is generally very well tolerated, with a low incidence of postsurgical complications. During the procedure, the tumor, along with a small area of clinically normal-appearing skin around the tumor, is excised. The tissue is then immediately processed by a histology technician, and the margins are evaluated by the surgeon. Mohs micrographic diagrams are used to map out the tissue for the histology technician and the surgeon. If 796
u Molecular oncology Category: Medical specialties Also known as: Molecular biology of cancer Definition: Molecular oncology is a field in which physicians and researchers study and address the molecular basis for development and metastasis of cancer. Subspecialties: Medical oncology, molecular genetics, molecular virology Cancers treated: Most forms of neoplastic disease, including neoplasms of tissues and organs, such as brain, breast, gastrointestinal, and lung cancers, as well as leukemias and lymphomas Training and certification: Molecular oncology is primarily an area of research rather than a medical specialty. Development of expertise in the field may involve either predoctoral or postdoctoral training. Predoctoral training involves development of a research project addressing a question in molecular oncology and the ensuing research that will ultimately result in the doctoral degree. Postdoctoral training involves advanced research carried out following the receipt of a doctorate. Postdoctorates train, or in a sense apprentice, under the auspices of an expert in the molecular field at a university or medical school.
Salem Health: Cancer Some medical programs provide concurrent training in both research and as clinical training. The end result, usually in a three- to four-year doctor of medicine (M.D.) and doctor of philsophy (Ph.D.) program, is that the individual earns both a medical degree and a doctorate. Applicants for such programs have completed an undergraduate program at an accredited university. Certification in a clinical specialty may be established following completion of a terminal degree. The specialty reflects the clinical interest of the individual and may be in fields such as hematology, immunology, pediatrics, or medical microbiology. Interests in the molecular mechanisms underlying cancer can result in research within the field of specialty. Services and procedures performed: The main aim of molecular oncology is to conduct research into the underlying cause of cancer. Most cancers have a basis in the disruption of regulation of cell division. However, as specific genetic defects may result in cancer development, molecular oncologists may work with the physician in charge or with the cancer team in diagnosis of the disease and to provide recommendations on the best course of treatment. For example, pathology samples obtained from a patient with leukemia may be analyzed to determine whether any obvious chromosomal abnormality is present. Microscopic analysis of chromosomes may provide evidence for a particular form of leukemia or lymphoma but does not directly address the molecular mechanism underlying the disease. To do this, the molecular oncologist would carry out research to understand the disruption of regulation of the cell cycle and the progression by which the cell ultimately undergoes cell division. Defects may involve any of the steps in regulation, including overproduction of growth factors or other oncogene factors, or mutations involving receptors or signal mechanisms within the cell. Analysis of the type of surface proteins found on cancer cells may provide clues as to the course of treatment. For example, certain forms of breast cancer develop or are characterized by estrogen receptors on the surface of cells. The molecular oncologist, as part of the medical team, may recommend the use of estrogen analogs or inhibitors as one course of treatment for the disease. Although the cause of most forms of breast cancer is unknown, approximately 5 to 10 percent of such malignancies have a genetic basis and are associated with mutations in one of two specific genes: BRCA1 and BRCA2. Areas of molecular oncology address the molecular basis by which mutations in these genes produce a high risk for cancer. Screening of women for the presence of these
Molecular oncology genes may allow for early intervention or monitoring in hopes of either preventing the disease or catching it at an early stage in women at risk. Related specialties and subspecialties: Hematology is the clinical field addressing disorders of the blood, including leukemias and lymphomas. Although some forms of such cancers may be associated with infectious agents— for example, viruses are known to be the etiological agents for certain T cell lymphomas and Burkitt lymphoma—in general blood cancers are the result of molecular disorders that disrupt normal regulation of cell division. Hematologists who research such disorders are trained in molecular biology or biochemistry. Pediatric oncology is a specialty dealing with cancers in children. Physicians in this area with an interest in research into the molecular basis for such diseases have undergone advanced training in the molecular field. Much the same may be said of researchers in cancer relevant to any field of specialty: The medical degree establishes the specialty of interest, while further training is carried out for research into the molecular or biochemical basis of cancer. Richard Adler, Ph.D. u
For Further Information Pecorino, Lauren. Molecular Biology of Cancer. 2d ed. New York: Oxford University Press, 2008. Pelengaris, Stella, and Michael Khan. The Molecular Biology of Cancer. Malden, Mass.: Blackwell, 2006. Tannock, Ian, et al. The Basic Science of Oncology. Columbus, Ohio: McGraw-Hill, 2005. Weinberg, Robert. Molecular Biology of Cancer. New York: Garland Science, 2006.
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Organizations and Professional Societies
American Association for Cancer Research http://www.aacr.org 615 Chestnut Street, 17th Floor Philadelphia, PA 19106 American Society for Biochemistry and Molecular Biology http://www.asbmb.org 9650 Rockville Pike Bethesda, MD 20814-3996 American Society of Gene Therapy http://www.asgt.org 555 East Wells Street, Suite 1100 Milwaukee, WI 53202 797
Moles u
Other Resources
National Center of Competence in Research in Molecular Oncology http://www.nccr-oncology.ch National Foundation for Cancer Research http://www.nfcr.org See also Blood cancers; Cancer biology; Cytogenetics; Cytology; Hematologic oncology; Pathology; Pediatric oncology and hematology; Sputum cytology; Viral oncology.
u Moles Category: Diseases, symptoms, and conditions Also known as: Nevi (singular, nevus or naevus) Related conditions: Common acquired nevi (acquired in early decades of life), congenital nevi (acquired at birth), freckles, seborrheic keratoses, lentigos (age spots), dysplastic nevi, melanoma, basal cell carcinoma, squamous cell carcinoma Definition: Moles, or nevi, are clustered melanocytes or nevus cells that appear on the skin, usually brown in color. Melanocytes are cells in the skin that produce the pigment called melanin that protects human skin from the damage of ultraviolet (UV) rays in sunlight. Risk factors: Although almost everyone has moles, some factors may increase the risk of moles. People with lighter skin and with freckles have a slightly greater risk of developing melanoma. Exposure to ultraviolet rays from the sun can increase the number of moles, and the more moles a person has, the greater the risk of developing melanoma. Damage to the melanocyte deoxyribonucleic acid (DNA) can cause a mole to become cancerous. Lowered immune systems such as those in persons with the human immunodeficiency virus (HIV) or who have had an organ transplant can increase development of moles. Etiology and the disease process: Nevus cells (melanocytes) are normally localized in the basal layer of the skin (epidermis). A mole of itself is not dangerous and remains a stable part of the skin unless it becomes damaged and then can change into cancer. Within sunlight are two types of invisible rays: infrared radiation (the sun’s heat) and ultraviolet radiation (ultraviolet light). Ultraviolet (UV) light is necessary for plants to live and generate energy. However, UV light can also cause sunburn, aging, and, under the right conditions, skin 798
Salem Health: Cancer cancer. UV rays are further differentiated into UVA, UVB, and UVC. Studies are investigating UVA, once thought to be harmless, as a possible cause of skin cancer. Researchers believe that damaged melanocytes may reproduce in an uncontrolled and abnormal way, possibly causing melanoma, one dangerous form of skin cancer. The exact mechanisms by which skin cancer or malignant moles occur is still unclear. Incidence: Most people have some form of moles, depending on their age, sun exposure, and genetic makeup. Usually people have few moles as an infant or child but may develop moles from puberty to the age of thirty. Often after that time, moles begin to disappear so that older adults may have fewer moles. White adults have an average of twenty-five or fewer moles, but an average person can have ten to forty moles over a lifetime, with a risk of 1:100 turning into a malignant melanoma. With lifestyle changes and more exposure to sunlight, this number can increase. The number of moles a person has is determined by genetics and exposure to sunlight. Moles are more common on parts of the body that are exposed to sunlight. Some evidence points to a role by the immune system in developing moles because they tend to develop in people with depressed immune systems such those infected with HIV and those who have had organ transplants. Studies suggest that malignant nevi such as melanoma arise from preexisting moles. If this proves true, the more moles a person has, the higher the incidence of malignant nevi. The percentage of persons with melanoma has increased 100 percent (doubled) in the past thirty years. Symptoms: Moles come in various colors and shapes. Some are brown and others are pink. Some are yellow, dark blue, or black. Moles can be flat or raised. Most moles are harmless but people should monitor their moles for changes in color, size, and texture, and for the development of asymmetrical or irregular borders. A benign or noncancerous mole will remain stable in size, color, and shape for years. During pregnancy or puberty, moles may naturally change in color and size, becoming darker and larger. When a mole bleeds, itches, enlarges, turns multipigmented, or evolves with irregular edges, the patient should see a dermatologist, as this mole may need testing for cancer. Screening and diagnosis: Health care providers can check their patients’ moles during routine physicals or checkups. Also, people can check their own moles periodically. One way to check moles for signs of melanoma is called the
Salem Health: Cancer
Moles provide a series of tests called staging. These tests may indicate whether the cancer has spread beyond the original site. Treatment and therapy: Generally nevi require no treatment unless they change into a cancerous mole. However, sometimes they occur in an uncomfortable place and may be surgically removed. Failure to remove such a mole may result in bleeding from irritation. When a mole is found to be cancerous, the mole, along with some surrounding tissue, is surgically removed.
While most moles, like the one on this young woman’s face, are harmless, they should be watched for changes in size, color, or shape that could possibly indicate the beginning of cancer. (©James Blinn/Dreamstime.com)
ABCDs of melanomas. “A” stands for asymmetry and indicates that the halves of a single mole should be checked to see if they are different or asymmetrical; a normal mole has identical halves. “B” means to look at the borders or edges of the mole to see if they are irregular; usually a noncancerous mole has regular distinct edges. “C” means that moles should be examined for color that varies within a single mole; ordinary moles are one color, not multipigmented. “D” is a reminder that the diameter of the mole should not exceed the size of a pencil eraser. If changes appear in the mole, the patient should see a dermatologist who can provide more in-depth testing or removal of the mole. Some symptoms that may need evaluation are bleeding, itching, or an unusual change. The eyes alone cannot diagnosis a malignant mole. The dermatologist will biopsy or excise the mole for the pathologist to inspect. If the mole is malignant, the pathologist can
Prognosis, prevention, and outcomes: Most moles are harmless and are just part of everyday life. However, there are known risk factors that increase the incidence of moles, and some can cause adverse changes in the structure of the moles, leading to malignancies. People at high risk for melanoma should be vigilant for changes in their moles. Although some exposure to sunlight is healthful because it supplies the body with vitamin D, intense exposure to UV rays—such as tanning—puts people at risk. Sunburn experienced years earlier can still bring about changes in the skin that can precipitate a malignant mole. Young people often will not see the effects of overexposure to the sun’s rays until years later, so they may not feel motivated to change their behavior. To decrease the risk of moles as well as the conversion of moles to cancer, people should use sun protection such as sunglasses, sunscreen, long-sleeved garments, and hats. Robert W. Koch, D.N.S., R.N. u
For Further Information Barnhill, Raymond, Michael Piepkorn, and Klaus Busam. Pathology of Melanocytic Nevi and Malignant Melanoma. 2d ed. New York: Springer, 2006. Hearing, Vincent J., and Stanley P. L. Leong, eds. From Melanocytes to Melanoma: The Progression to Malignancy. Totowa, N.J.: Humana Press, 2006. Poole, Catherine M., and Dupont Guerry IV. Melanoma: Prevention, Detection, and Treatment. 2d ed. New Haven, Conn.: Yale University Press, 2005. Schofield, Jill R., and William A. Robinson. What You Really Need to Know About Moles and Melanoma. Baltimore: Johns Hopkins University Press, 2000.
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Other Resources
American Academy of Dermatology Moles http://www.aad.org/public/publications/pamphlets/ common_moles.html 799
Monoclonal antibodies American Cancer Society http://www.cancer.org Medline Plus Moles http://www.nlm.nih.gov/medlineplus/moles.html See also ABCD; Basal cell carcinomas; Carney complex; Chordomas; Choriocarcinomas; Craniosynostosis; Dermatology oncology; Dysplastic nevus syndrome; Gestational trophoblastic tumors (GTTs); Hereditary cancer syndromes; Human chorionic gonadotropin (HCG); Hydatidiform mole; Melanomas; Premalignancies; Sjögren syndrome; Skin cancers; Squamous cell carcinomas; Ultraviolet radiation and related exposures.
u Monoclonal antibodies Category: Chemotherapy and other drugs Definition: Monoclonal antibodies are antibodies that recognize only one antigen and that are mass-produced in the laboratory from a single clone of a B cell, the type of immune system cell that makes antibodies. Cancers treated: Lymphoma, leukemia, breast cancer, head and neck cancers, colorectal cancer, lung cancer Subclasses of this group: Murine (composed entirely of mouse sequences), chimeric (composed of approximately one-third mouse and two-thirds human sequences), humanized (composed of at least 90 percent human sequences), and human (antibodies that are fully human in composition) Delivery routes: As a result of their molecular size and susceptibility to enzymatic digestion in the gut if administered orally, monoclonal antibodies must usually be administered by intravenous (IV) infusion. How these drugs work: Antibodies are proteins that bind to a specific site, or epitope, on a specific target molecule. In response to infection or immunization with a foreign agent, the immune system generates many different antibodies that bind to the foreign molecules. This pool of polyclonal antibodies contains a mixture of different antibody molecules, each of which binds to a specific epitope. Isolation of a single antibody from a polyclonal antibody pool would yield a highly specific molecular tool with the ability to bind to a single epitope. Georges Köhler, César Milstein, and Niels Kaj Jerne invented the process of producing monoclonal antibodies in 1975 and shared the 1984 Nobel Prize in Physiology or Medicine for their dis800
Salem Health: Cancer covery. Since then, monoclonal antibodies have become an important tool in biological research and in medicine. The process of producing monoclonal antibodies involves fusing an individual B cell, which produces a single antibody with a single specificity but which has a finite life span, with a long-lived myeloma tumor cell. The B cell is taken from the spleen or lymph nodes of an animal that has been challenged with the antigen of interest. The combination of the B cell and the myeloma cell produces a hybridoma cell, a kind of perpetual antibody-producing factory. The hybridoma cell produces the single specific antibody and can be grown in culture indefinitely, allowing the production of large amounts of the monoclonal antibodies. Monoclonal antibodies are potentially more effective than conventional drugs in treating cancer, since conventional drugs attack not only cancer cells but also normal cells. Monoclonal antibodies attach only to the specific target molecule. Since monoclonal antibodies are specific for a particular antigen, one designed to bind to ovarian cancer cells, for instance, will not bind to colorectal cancer cells. The first monoclonal antibodies were made from mouse B cells. When administered into humans, mouse antibodies are recognized by the human immune system as foreign (because they are from a different species) and can elicit an immune response against them, causing allergic-type reactions. Researchers have since learned how to replace some portions of the mouse antibody sequences with human antibody sequences. The application of genetic engineering techniques has allowed the production of chimeric, humanized, and, more recently, fully human monoclonal antibodies. An antibody molecule is composed of two heavy polypeptide chains and two light polypeptide chains. Both heavy and light chains are composed of a region that varies from antibody to antibody, the variable region, and a constant region that is conserved. By combining human sequences for the constant region with murine sequences for portions of the variable region, the amount of murine sequence can be decreased. Depending on how much murine sequence is left, the result is either a chimeric (with approximately one-third murine and two-thirds human sequence) or a humanized (with at least 90 percent human sequence) monoclonal antibody. Genetically engineered mice strains are now available that contain a large portion of human deoxyribonucleic acid (DNA) that codes for the antibody heavy and light chains, with the mouse’s own heavy and light chain genes inactivated. Using these mice to produce B cells for the construction of hybridomas allows the generation of fully human antibodies, which are likely to be safer and may be more effective than the previous generation of monoclonal antibodies.
Salem Health: Cancer
Monoclonal antibodies
Common Monoclonal Antibodies Drug
Brands
Subclass
Alemtuzumab Bevacizumab Cetuximab Epratuzumab Gemtuzumab ozogamicin Ibritumomab tiuxetan Lym-1 Panitumumab Rituximab Tositumomab Trastuzumab
Campath Avastin Erbitux LymphoCide Mylotarg Zevalin Oncolym Vectibix Rituxan Bexxar Herceptin
Humanized Humanized Chimeric Humanized Humanized Murine Murine Human Chimeric Murine Humanized
One potential treatment for cancer involves using monoclonal antibodies that bind only to a cancer cell-specific component of interest and induce an immunological response against the target cancer cell (referred to as “naked” monoclonal antibodies). Monoclonal antibodies can also be designed for the delivery of another (nonspecific) agent, such as a toxin, radioisotope, or cytokine, to the cancer cell for the purpose of killing it (referred to as “conjugated” monoclonal antibodies). Some naked monoclonal antibodies bind to cancer cells and exert their action by marking the cells to help the body’s immune system destroy them. Rituxan (rituximab) and Campath (alemtuzumab) are examples of this type of monoclonal antibody. Rituximab binds to the CD20 antigen, a protein found on B cells, and is used to treat B-cell non-Hodgkin lymphoma. Alemtuzumab binds to the CD52 antigen, another protein present on B and T cells, and is used to treat some patients with B-cell chronic lymphocytic leukemia. Some naked monoclonal antibodies bind to functional parts of cancer cells or other cells that help cancer cells grow and act by interfering with the cancer cells’ ability to grow. Herceptin (trastuzumab), Erbitux (cetuximab), and Avastin (bevacizumab) are examples of this type of monoclonal antibody. Trastuzumab binds to the HER2/neu protein, a protein present in large numbers on tumor cells in some cancers that, when activated, helps these cells grow. Trastuzumab acts by inactivating these proteins. It is used to treat some breast cancers. Cetuximab binds to the epidermal growth factor receptor (EGFR) protein, which when present in high levels on cancer cells helps them grow. Cetuximab blocks the activation of EGFR and is used to treat some advanced colorectal cancers and some head and neck cancers. Bevacizumab binds to the vascular
Delivery Mode IV IV IV IV IV IV IV IV IV IV IV
Cancers Treated Chronic lymphocytic leukemia Lung cancer, colorectal cancer Head and neck cancers, colorectal cancer B-cell leukemia Acute myelogenous leukemia B-cell lymphoma Lymphoma Colorectal cancer B-cell lymphoma B-cell lymphoma Breast cancer
endothelial growth factor (VEGF), a protein that cancer cells produce to attract the new blood vessels they need for growth. Bevacizumab prevents VEGF from functioning and is used to treat some colorectal, lung, and breast cancers. Some of these monoclonal antibodies have been used in cancer treatment for many years. At first they were used mainly after other treatments had failed, but as more studies have been done the trend is to use them earlier in the course of cancer treatment. Conjugated monoclonal antibodies (also called “tagged” or “loaded” monoclonal antibodies) are attached to anticancer (chemotherapy) drugs, toxins, or radioactive substances and used as vehicles to deliver these toxic agents directly to cancer cells. Radiolabeled monoclonal antibodies are attached to radioactive substances; treatment with such agents is called radioimmunotherapy. Chemolabeled monoclonal antibodies are attached to anticancer drugs, and immunotoxins are monoclonal antibodies attached to toxins. Zevalin (ibritumomab tiuxetan) and Bexxar (tositumomab) are examples of radiolabeled monoclonal antibodies. Both bind to an antigen on cancerous B lymphocytes and are used to treat some B cell non-Hodgkin lymphomas. Mylotarg (gentuzumab ozogamicin) is an example of an immunotoxin. It contains the toxin calicheamicin attached to a monoclonal antibody that binds to the CD33, a protein antigen present on most leukemia cells, and is used to treat some acute myelogenous leukemias. Clinical trials of monoclonal antibody therapy are in progress for patients with almost every type of cancer. As more cancer-associated antigens have been identified and studied, it has been possible for researchers to make monoclonal antibodies against more types of cancer. 801
Motion sickness devices
Salem Health: Cancer
Side effects: Antibodies that contain murine sequences can be recognized by the human immune system as foreign, causing systemic inflammatory effects such as fever, chills, weakness, headaches, nausea, vomiting, and diarrhea. Some monoclonal antibodies also have side effects associated with the antigen that they target. For example, some monoclonal antibodies can affect the bone marrow’s ability to produce blood cells, which can result in an increased risk of bleeding or infection in some patients. Jill Ferguson, Ph.D.
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u For Further Information George, Andrew J. T., and Catherine E. Urch, eds. Diagnostic and Therapeutic Antibodies. Totowa, N.J.: Humana Press, 2000. Melero, I., et al. “Immunostimulatory Monoclonal Antibodies for Cancer Therapy.” Nature Reviews Cancer 7 (2007): 95-106. Reichert, J. M., and V. E. Valge-Archer. “Development Trends for Monoclonal Antibody Cancer Therapeutics.” Nature Reviews Drug Discovery 6 (2007): 349356. Zafir-Lavie, I., Y. Michaeli, and Y. Reiter. “Novel Antibodies as Anticancer Agents.” Oncogene 28 (2007): 3714-3733.
Delivery routes: Motion sickness relief bands are worn on the wrist and are available over the counter at pharmacies and drugstores.
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Other Resources
Access Excellence Monoclonal Antibody Technology: The Basics http://www.accessexcellence.org/RC/AB/IE/ Monoclonal_Antibody.html American Cancer Society Monoclonal Antibodies http://www.cancer.org/docroot/ETO/content/ ETO_1_4X_Monoclonal_Antibody_Therapy_ Passive_Immunotherapy.asp Lymphoma Information Network Monoclonal Antibody Therapy http://www.lymphomainfo.net/therapy/ immunotherapy/mab.html See also Biological therapy; CA 15-3 test; CA 19-9 test; CA27-29 test; Carcinoembryonic antigen antibody (CEA) test; Carcinomas; Chemotherapy; Chronic lymphocytic leukemia (CLL); Colorectal cancer; Flow cytometry; Immunotherapy; Non-Hodgkin lymphoma; Oral and oropharyngeal cancers; Polyps; Radiation oncology; Radiopharmaceuticals; Receptor analysis; Richter syndrome. 802
Category: Complementary and alternative therapies Also known as: ReliefBand, Sea-Band stimulators, BioBands Definition: Nausea relief wristbands are economical devices that may decrease the nausea associated with cancer treatments such as chemotherapy and radiation therapy. Though these devices are not scientifically proven effective, many patients report relief of nausea when wearing a relief band on the wrist.
Cancers treated: One common and disturbing side effect of cancer treatments, such as chemotherapy or radiation, is nausea and vomiting. These therapies are used as treatment for nearly all cancers. Why used: Cancer patients who are receiving chemotherapy may feel a queasy feeling in the stomach (nausea), which can trigger vomiting, the forceful elimination of food or contents from the stomach. An estimated 70 to 89 percent of chemotherapy patients have this side effect. As many as 50 percent of cancer patients delay therapy because of fear of nausea and vomiting. Cancer patients who are receiving radiation therapy may experience a similar feeling of nausea that can lead to vomiting. Successful cancer treatment with chemotherapy or radiation depends on the patient’s ability to tolerate this side effect. How these bands work: These bands are usually made of a soft, elastic material that clings to the wrist. When a cancer patient puts on a motion sickness relief band, a small bead embedded in the band applies acupressure by pressing down on the neiguan, or P6, acupressure point. When this point on the median nerves of the inner wrist is stimulated, the trigger for nausea is suppressed. Risks and results: Acupressure wristbands offer a costefficient and drug-free way to manage nausea and vomiting during cancer treatment. The therapy is safe for all ages, from children to older adults, as well as for pregnant and nursing women. The only risk is that they will not work for all people. However, the cost to try this therapy is minimal and does not require a doctor’s prescription. Marylane Wade Koch, M.S.N., R.N. See also Acupuncture and acupressure for cancer patients; Adjuvant therapy; Chemotherapy; Cobalt 60 radiation; Complementary and alternative therapies; Nausea and vomiting.
Salem Health: Cancer
u MSH genes Category: Cancer biology Also known as: MSH—MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli); HNPCC; HNPCC1; MSH3—mutS homolog 3 (E. coli); DUP; divergent upstream protein; mismatch repair protein 1; MRP1; MSH4—mutS homolog 4 (E. coli); MSH5—mutS homolog 5 (E. coli); MSH6—mutS homolog 6 (E. coli); GTBP Definition: MSH genes are a class of genes that are normally involved in deoxyribonucleic acid (DNA) mismatch repair but can be mutated in many types of cancer. Normal cellular function: DNA mismatch repair is the process whereby errors in DNA replication are recognized and repaired by proteins in the cell. If the mismatch repair machinery is defective, either by mutation of the genes encoding the proteins or by altering the expression levels of the proteins, errors are no longer repaired. Relevance to cancer: Cells that contain defects in DNA mismatch repair show mutation rates that are one hundred to one thousand times higher than normal cells. Most mutations may not have negative effects, but if mutations are made in genes required to regulate cell growth and proliferation, this can lead to cancer. A readout of this increased mutation rate is microsatellite instability (MSI). Microsatellites are repetitive DNA sequences that are prone to replication errors, and cells that are defective in mismatch repair show variability in the length of these sequences. One of the genes in this class, MSH2, is among the most frequently mutated genes in hereditary nonpolyposis colorectal cancer (HNPCC). Inheriting a mutation in this gene causes a genetic predisposition to cancer. In addition, MSH genes are often mutated in noninherited forms of cancer such as skin cancer and ovarian cancer. Other MSH genes—MSH3 and MSH6—are also mutated in cancer, but at a lower frequency than MSH2. Diagnostic and genetic testing: A number of tests are available to monitor the status of the mismatch repair machinery, which can provide diagnostic and prognostic information. DNA sequencing of the MSH2 gene can be done to look for mutations that can predispose patients to cancer. Protein levels can be measured by immunohistochemical analysis of tissue samples, and tests to monitor the MSI status of tumor cells can also be performed. Clinical implications: Because they strongly predispose people to developing cancer, patients carrying mutations
Mucinous carcinomas in mismatch repair genes should undergo frequent colonoscopy as well as screenings for endometrial cancers. In addition, levels of mismatch repair proteins as well as MSI status can be strong predictors of tumor progression and prognosis. For example, although tumors that show high MSI tend to be aggressive, the outcome is usually favorable. Further, cells defective in mismatch repair have been shown to be less sensitive to platinum-based chemotherapy as well as methylating agents, which both work by inducing DNA damage. Lindsay Lewellyn, B.S. See also Ashkenazi Jews and cancer; Cancer biology; Family history and risk assessment; Genetics of cancer; Hereditary cancer syndromes; MLH1 gene.
u Mucinous carcinomas Category: Diseases, symptoms, and conditions Also known as: Colloid carcinomas, mucinous adenocarcinomas, adenocystic carcinomas, mucoepidermoid carcinomas, gelatinous carcinomas Related conditions: Breast cancers, ductal carcinoma in situ, colon cancer, pancreatic cancer, eyelid cancer Definition: Mucinous carcinoma is a type of invasive duct cancer that occurs most frequently in the breast (MCB), although it has also been reported in the colon and pancreas. Primary mucinous carcinoma of the skin (MCS) is recognized as a rare variant of a sweat gland tumor. Risk factors: Age is the only recognized risk factor. The average age at diagnosis is sixty-seven for mucinous carcinoma of the breast and sixty-three for mucinous carcinoma of the skin. Etiology and the disease process: In all cases, the distinguishing feature is a type of mucus production called mucin. Poorly differentiated cancer cells are often completely surrounded by mucin in these tumors. The cancer spreads into the normal tissue surrounding it, although the mucin itself does not generally cause major problems. Incidence: Mucinous carcinoma of the breast is a relatively rare form that accounts for about 3 percent of all breast cancer diagnoses. It occurs most frequently in women in their sixties. Mucinous carcinoma of the skin can originate at any location on the body, although the eyelid has been reported as the most commonly affected area (41 percent of cases). There is a slight preponderance of affected males. 803
Mucosa-associated lymphoid tissue (MALT) lymphomas Symptoms: Mucinous carcinoma of the breast is usually detected as medium to large size tumors that can be felt. They are usually highly estrogen dependent and only rarely spread to local lymph nodes. Mucinous carcinoma of the skin lesions are painless gray or red nodules measuring 0.5 to 7 centimeters in diameter. Screening and diagnosis: Core needle biopsy (of the breast version) and skin biopsy (of the skin version) are usually very effective diagnostic tools. Tumor identification is most often straightforward, since the tumor cell morphology and mucin production are so characteristic of this type of cancer. Treatment and therapy: Treatment of mucinous carcinoma of the breast generally includes some combination of surgery, chemotherapy, and radiation therapy. Since lymph node involvement is rare, surgery can often be conservative (lumpectomy). Standard treatment for mucinous carcinoma of the skin is wide local excision. Prognosis, prevention, and outcomes: Mucinous carcinoma of the breast has a much better prognosis than other invasive ductal breast carcinomas because it is associated with a low risk of axillary metastases. A ten-year survival rate of more than 90 percent has been reported. Mucinous carcinoma of the skin lesions have a propensity for local recurrence and regional spread, although distant metastases are rare. One study of one hundred cases of primary mucinous carcinoma of the skin reported 29.4 percent local recurrences, 9.6 percent metastases, and an overall mortality rate of 2 percent. Jeffrey A. Knight, Ph.D. See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Breast cancers; Carcinomas; Colorectal cancer; Ductal carcinoma in situ (DCIS); Eyelid cancer; Pancreatic cancers.
Salem Health: Cancer
Disorders Linked to H. pylori Infection
• • • • • •
Stomach ulcers Duodenal ulcers Gastric cancer MALT lymphomas Possibly pancreatic cancer Possibly cardiovascular disease
Source: National Cancer Institute
trointestinal tract, usually as a result of Helicobacter pylori infection. They are solid tumors that originate from B cells in the marginal zone of the MALT. Risk factors: Gastric MALT lymphoma is frequently associated (72 to 98 percent) with the presence of H. pylori. The causes of MALT lymphoma in other parts of the body are unknown. In general, the incidence of non-Hodgkin lymphoma is two to three times higher among individuals with relatives who developed non-Hodgkin lymphoma, indicating familial clusters. In addition, a compromised immune system is a major risk factor for non-Hodgkin lymphoma development. Etiology and the disease process: MALT lymphoma starts in mucosa-associated lymphoid tissue, which is lymphatic tissue, such as the stomach, thyroid gland, and lungs. Virtually any mucosal site can be afflicted; however, colorectal involvement of MALT lymphoma is rare. MALT lymphoma is a cancer of the B-cell lymphocytes. It belongs to the group of marginal zone B-cell lymphomas. Marginal zone lymphoma can be either nodal or extranodal. In particular, MALT lymphoma is an extranodal marginal zone B-cell lymphoma.
Related conditions: Indolent non-Hodgkin lymphoma (NHL), marginal zone B-cell lymphomas
Incidence: MALT lymphoma is a relatively rare form of non-Hodgkin lymphoma. Most cases, approximately two out of three, of MALT lymphoma affecting the stomach are caused by infection with H. pylori. The disease is more common in people over sixty, but it may occur at any age from early adulthood to old age. MALT lymphoma is slightly more common in women than in men. Ethnicity may play a role in geographic differences among nonHodgkin lymphoma incidence rates. In particular, gastric lymphomas have the highest recorded incidence in northern Italy.
Definition: Mucosa-associated lymphoid tissue (MALT) lymphomas are a form of non-Hodgkin lymphoma frequently involving the MALT of the stomach and the gas-
Symptoms: The most common symptoms experienced by those with MALT lymphomas range from no symptoms to occult or gross gastrointestinal symptoms. Regardless of
u Mucosa-associated lymphoid
tissue (MALT) lymphomas Category: Diseases, symptoms, and conditions Also known as: Extranodal lymphoma, MALT lymphomas, MALTomas
804
Salem Health: Cancer
Mucosa-associated lymphoid tissue (MALT) lymphomas
organ of origin, all MALT lymphomas appear to have similar clinical, pathological, and molecular features. The symptoms exhibited depend on the site for MALT lymphoma. MALT lymphoma in the stomach may cause indigestion, bleeding into the stomach, weight loss, loss of appetite, and tiredness.
areas are affected, and whether constitutional symptoms, such as fever, night sweats, or weight loss, are present. The staging of MALT lymphoma is essential for precise prognosis and to develop an effective treatment plan. The Ann Arbor Staging System is the most widely used system for non-Hodgkin lymphoma.
Screening and diagnosis: The initial diagnosis of MALT lymphoma is typically made by esophagogastroduodenoscopy (EGD), or upper endoscopy, which is a flexible tube passed down the gullet and into the stomach. Endoscopy is used to obtain photographs of the stomach, and a small sample of cells is extracted for assessment (biopsy). Tests for H. pylori are also common when gastrointestinal MALT lymphomas are suspected. Staging is based on how extensively the cancer has spread throughout and beyond the lymphatic system, which
Treatment and therapy: When bacteria are present in the tumor tissue, biological therapy, such as intensive antibiotic treatment, often leads to a complete remission of the lymphoma. Approximately 70 to 80 percent of patients will have a complete regression of malignancy with antibiotic treatment of H. pylori when MALT lymphoma is limited to the stomach. If antibiotics do not clear MALT lymphomas or the disease spreads, other treatments are given, including radiotherapy, surgery, or chemotherapy. Some MALT lymphomas grow very slowly, especially if the site of origin is other than the stomach, and may not cause any problems for many years. In this case, treatment may not be needed immediately, and active monitoring is used instead. For MALT lymphoma affecting the lung or the bowel, the typical treatment is chemotherapy. Low-grade MALT lymphoma may transform into high-grade lymphoma, in which case it requires more intensive chemotherapy. MALT lymphoma may be removed during a surgical operation. If the lymphoma is affecting the stomach, total gastrectomy may be needed, which involves the removal of all of the stomach, along with the lower part of the gullet. The gullet is then joined directly to the small intestine. New treatments for MALT lymphoma are being researched. If patients have been treated for a lymphoma affecting the stomach, typically they will undergo regular follow-up endoscopies and biopsies of the stomach to look for signs of recurrence. Other tests may be used for people whose MALT lymphoma affects areas apart from the stomach. Side effects of non-Hodgkin lymphoma management may also vary depending on what part of the body is affected and the treatment used. The side effects of biological therapy are most often flulike symptoms, and external radiation to the abdomen may cause nausea, vomiting, and diarrhea.
A scar on the neck of a woman marks where a MALT lymphoma was removed from her salivary gland. (Dr. P. Marazzi/Photo Researchers, Inc.)
Prognosis, prevention, and outcomes: The International Prognostic Index is the most widely used prognostic system for non-Hodgkin lymphoma, and it was designed to further clarify lymphoma staging. Paradoxically, in a significant number of cases, aggressive lymphomas can be cured by chemotherapy, while indolent non-Hodgkin lymphomas generally cannot be cured. Approximately 40 percent of indolent malignancies transform into high-grade 805
Mucositis
Salem Health: Cancer
aggressive lymphomas, and the cure potential of the transformed lymphoma is less favorable than that of aggressive lymphomas without transformation. Anita Nagypál, Ph.D.
Risk factors: Mucositis is directly related to therapeutic radiation and chemotherapy. There may be genetic factors causing some people to be more sensitive or resistant to cellular damage following therapy.
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Etiology and the disease process: Radiation and chemotherapy kill cancer cells but can also damage normal tissue in the gastrointestinal tract. Endothelial cells, which make up the capillaries under the skin, and fibroblast cells, which build connective tissue, are the most sensitive to therapeutic damage. These cells produce important growth factors that maintain the epithelial cells on the surface lining of the gastrointestinal tract. Because of cell death and inflammation, ulcers form along the gastrointestinal tract.
For Further Information Ferreri, A. J., et al. “Therapeutic Management of Ocular Adnexal MALT Lymphoma.” Expert Opinion on Pharmacotherapy 8, no. 8 (June, 2007): 1073-1083. Firat, Y., A. Kizilay, G. Sogutlu, and B. Mizrak. “Primary Mucosa-Associated Lymphoid Tissue Lymphoma of Hypopharynx.” Journal of Craniofacial Surgery 18, no. 5 (September, 2007): 1189-1193. Magrath, Ian T., ed. The Non-Hodgkin’s Lymphomas. New York: Oxford University Press, 1997. Roh, Jong-Lyel, Jooryung Huh, and Cheolwon. Suh. “Primary Non-Hodgkin’s Lymphomas of the Major Salivary Glands.” Journal of Surgical Oncology 97, no. 1 (October 10, 2007): 35-39. Troch, M., et al. “Does MALT Lymphoma of the Lung Require Immediate Treatment? An Analysis of Eleven Untreated Cases with Long-Term Follow-Up.” Anticancer Research 27, no. 5B (September/October, 2007): 3633-3637. u
Other Resources
Lymphoma Information Network Mucosa-Associated Lymphatic Tissue Lymphomas http://www.lymphomainfo.net/nhl/types/malt.html Lymphomation.org MALT Lymphomas http://www.lymphomation.org/type-malt.htm See also Helicobacter pylori; Lymphomas; Non-Hodgkin lymphoma.
u Mucositis Category: Diseases, symptoms, and conditions Also known as: Oral mucositis, gastrointestinal mucositis Related conditions: In extreme cases, bacteremia and sepsis Definition: Mucositis is ulceration in the mouth (oral mucositis) and esophagus, intestines, and anus (gastrointestinal mucositis) as a side effect of radiation or chemotherapy for cancer. 806
Incidence: Up to 100 percent of patients who receive high-dose radiation treatment will develop some level of mucositis. Symptoms: Redness of the skin resulting from capiltary congestion (erythema) and swelling are early symptoms. More advanced cases develop ulcers in the mouth and intestines a few days following cancer treatment. Patients may also experience diarrhea, nausea and vomiting, a drop in blood volume (hypovolemia), dry mouth, change of taste, and loss of appetite. Ulcers can become infected, and infection can spread to the blood (bacteremia). Patients often stop eating because of the pain. Severe complications may lead to death due to blood infection (sepsis), electrolyte imbalances, and malnutrition. Screening and diagnosis: Mucositis is diagnosed by clinical observation of symptoms according to different grades established by the World Health Organization: • Grade 0: No symptoms • Grade 1: Erythema • Grade 2: Erythema, ulcers, can eat solid food • Grade 3: Ulcers, liquid-only diet • Grade 4: Ulcers, assisted (parenteral) feeding necessary Treatment and therapy: After therapy ends, mucositis will resolve without treatment. While mucositis persists, palliative treatment is given, including narcotics for pain, antibiotics for infections, and assisted feeding. Research on drugs to treat mucositis is ongoing. One drug, palifermin (Kepivance), is approved by the Food and Drug Administration for treating oral mucositis. Palifermin is related to a hormone that stimulates epithelial cells. Given before radiation therapy, palifermin strengthens and protects the oral epithelium, making it much more resistant to developing mucositis.
Salem Health: Cancer
Multiple endocrine neoplasia type 1 (MEN 1) of the small intestine). Neuroendocrine tumors (nerve-cell tumors that may produce hormones) in the pancreas and duodenum are the main cause of tumor-related death. The severity varies within families and between families. Risk factors: Because MEN 1 is hereditary, the main risk factor is having a family history of this disorder. Each child of a person with MEN 1 has a 50 percent chance of inheriting the disorder.
Etiology and the disease process: The underlying genetic cause of MEN 1 is a mutation, or a genetic change, in the MEN1 gene. MEN1 is a tumor-suppressor gene, and the protein it encodes helps stop uncontrolled cell growth and proliferation. Usually, each person has two normal copies of the MEN1 gene. Amutation in one copy Inflammatory mucositis in the mouth, developed in response to radiation treatof the gene is sufficient to cause MEN 1, ment of another part of the head. (©XVIVO LLC/Phototake—All rights rewhich is why this condition is referred to as served) autosomal dominant (autosomal means the MEN1 gene is located on one of the twentyPrognosis, prevention, and outcomes: Most patients retwo pairs of autosomes, which are the nonsex chromocover from mucositis, though a small percentage of pasomes). An affected person has a MEN1 gene mutation tients die from complications. Cancer therapy is often from the time of conception in the womb; however, sympreduced or stopped because of mucositis, which may comtoms of the disease may not manifest until later in life. promise cancer care. Most mutations are inherited from a parent, but new mutaChristopher Pung, B.S., C.L.Sp. (CG) tions do occur. See also Chemotherapy; External beam radiation therapy (EBRT); Fatigue; Gastrointestinal complications of cancer treatment; Intensity-modulated radiation therapy (IMRT); Radiation therapies; Side effects; Stomatitis.
u Multiple endocrine neoplasia
type 1 (MEN 1) Category: Diseases, symptoms, and conditions Also known as: Wermer syndrome Related conditions: Hyperparathyroidism, pituitary tumor, pancreatic tumor, duodenal tumor Definition: Multiple endocrine neoplasia type 1 (MEN 1) is a hereditary tumor syndrome characterized by endocrine and nonendocrine tumors, most of which are benign. The characteristic findings include tumors of the parathyroid glands, pituitary gland, pancreas, and duodenum (part
Incidence: Approximately 0.2 to 2 per 100,000 people have MEN 1. Symptoms: Parathyroid tumors can cause high calcium levels in the blood, nausea, fatigue, muscle pains, constipation, abdominal pain, kidney stones, and bone fractures. Symptoms of pituitary tumors vary depending on the type of hormone being made by the tumor. Tumors of the pancreas and duodenum cause many different symptoms depending on the tumor type. Screening and diagnosis: Physicians diagnose MEN 1 in a person with an endocrine tumor in two of the three tissue systems usually affected in this syndrome: parathyroid glands, pancreas, and pituitary gland. Because MEN 1 is caused by mutations in the MEN1 gene, genetic testing can be used to confirm a suspected diagnosis or to test a family member who is at risk for the disease but has no symptoms. Treatment and therapy: A combination of surgery and medication may be used to treat MEN 1 tumors. 807
Multiple endocrine neoplasia type 2 (MEN 2) Prognosis, prevention, and outcomes: Because MEN 1 is a genetic condition, its manifestations cannot currently be prevented. However, physicians recommend monitoring that includes blood testing for hormone levels and imaging of the head and abdomen. Abbie L. Abboud, M.S., C.G.C. See also Duodenal carcinomas; Endocrine cancers; Endocrinology oncology; Family history and risk assessment; Gastrinomas; Histamine 2 antagonists; Human growth factors and tumor growth; Islet cell tumors; Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Pancreatic cancers; Parathyroid cancer; Pheochromocytomas; Pituitary tumors; Thyroid cancer; Zollinger-Ellison syndrome.
u Multiple endocrine neoplasia
type 2 (MEN 2) Category: Diseases, symptoms, and conditions Also known as: MEN 2, MEN 2A, MEN 2B, Sipple syndrome, mucosal neuroma syndrome, familial medullary thyroid carcinoma Related conditions: Medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia or adenoma, mucosal neuromas of the lips and tongue, gastrointestinal ganglioneuromas Definition: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary cancer syndrome that affects the endocrine glands, which produce hormones in the body. MEN 2 is subclassified into three types: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). All three types are associated with medullary thyroid cancer (MTC, a tumor that grows from the C cells in the thyroid gland). MEN 2A and MEN 2B are also associated with pheochromocytoma (an adrenal gland tumor that releases stress hormones). MEN 2A carries an increased risk for parathyroid hyperplasia (in which the parathyroid glands become enlarged and produce too much parathyroid hormone) or parathyroid adenoma (a benign tumor), both of which cause hyperparathyroidism (increased secretion of parathyroid hormone). MEN 2B is associated with mucosal neuromas (tumors growing from a nerve) of the lips and tongue, gastrointestinal ganglioneuromas (benign growths in the intestines), and characteristic facial appearance (a slender face, with prominent, bumpy lips). The disease findings and the severity of the syndrome vary within families and between families. 808
Salem Health: Cancer Risk factors: Because MEN 2 is hereditary, the main risk factor is having a family history of this syndrome. Each child of a person with MEN 2 has a 50 percent chance of inheriting the disease. Etiology and the disease process: The underlying genetic cause of MEN 2 is a mutation, or a genetic change, in the RET gene. RET is a proto-oncogene, which means that it normally functions in cell growth and differentiation. Mutations in RET cause it to become an active oncogene, turning normal cells into cancer cells. Usually, each person has two normal copies of the RET gene. A mutation in one copy of the gene is sufficient to cause MEN 2, which is why this condition is referred to as autosomal dominant (autosomal means the RET gene is located on one of the twenty-two pairs of autosomes—the nonsex chromosomes). A person with MEN 2 has a RET gene mutation from the time of conception in the womb; however, symptoms of the disease may not manifest until later in life. Most mutations are inherited from a parent, but new mutations do occur. The age of onset for medullary thyroid cancer is usually early childhood in MEN 2B, early adulthood in MEN 2A, and middle age in familial medullary thyroid carcinoma. Mutations in different parts of the RET gene lead to the three subtypes of MEN 2. Nearly all cases of MEN 2B are caused by one specific mutation. Certain mutations are associated with a higher incidence of pheochromocytoma and hyperparathyroidism. Incidence: Approximately 1 in 30,000 people has MEN 2. Symptoms: Symptoms of medullary thyroid cancer may include a thyroid nodule (lump on the throat) and enlarged lymph nodes in the neck. Pheochromocytomas release catecholamines (stress hormones) that can cause dangerously high blood pressure levels. Hyperparathyroidism can cause high calcium levels in the blood, nausea, fatigue, muscle pains, constipation, abdominal pain, kidney stones, and bone fractures. In MEN 2B, gastrointestinal ganglioneuromas can cause constipation or megacolon (abnormally large colon). Screening and diagnosis: The criteria to diagnose MEN 2 are different depending on the subtype. MEN 2A is diagnosed by the presence of two or more endocrine tumors (in one person or in close blood relatives). MEN 2B is diagnosed in a person with mucosal neuromas on the lips and tongue, medullary thyroid cancer, and, in some cases, pheochromocytoma. Familial medullary thyroid carcinoma is diagnosed in families with four or more cases of medullary thyroid cancer without any other findings of MEN 2. Tools used to check for disease include a blood test to
Salem Health: Cancer
Multiple myeloma
Relative Survival Rates for Medullary Thyroid Carcinoma, 1988-2001 Survival Rates (%) Stage Stage II Stage III
Cases Diagnosed (%) 42.5 43.8
1-Year
2-Year
3-Year
5-Year
8-Year
10-Year
97.5 100.0
94.5 95.4
89.6 89.8
89.6 82.6
86.3 82.3
77.1 82.3
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) Note: So few cases were diagnosed at Stages I and IV that percentages and relative survival rates were not meaningful.
measure levels of calcitonin (a hormone produced by medullary thyroid cancer) and urine testing to check for catecholamines and metanephrines released by pheochromocytomas. Blood and urine testing may also be done to assess for hyperparathyroidism. Because MEN 2 is caused by mutations in the RET gene, genetic testing is a valuable tool to confirm a suspected diagnosis or to test a family member who is at risk for the disease but has no symptoms. Genetic testing detects RET gene mutations in approximately 95 percent of families with MEN 2A and MEN 2B and in approximately 88 percent of families with familial medullary thyroid carcinoma. Treatment and therapy: The only way to cure medullary thyroid cancer is to remove the thyroid gland (thyroidectomy) at a young age. A patient who has had a thyroidectomy must take thyroid hormone replacement therapy. Because the risk for cancer is so high, removing the thyroid gland is recommended for people who have a RET mutation, even if they do not yet have cancer. Surgery to remove the adrenal gland is necessary to treat patients with pheochromocytoma. Sometimes pheochromocytomas occur in both adrenal glands. All or some of the four parathyroid glands may be removed to treat hyperparathyroidism. Prognosis, prevention, and outcomes: Because MEN 2 is a genetic condition, its manifestations cannot be prevented. However, monitoring of individuals who are at risk for the disease based on their family history or who are known to have a RET gene mutation can detect problems early and lead to more effective treatment and better outcomes. Such monitoring includes yearly blood testing for calcitonin levels, yearly blood pressure checks, and yearly urine testing for catecholamines and metanephrines. The medical team caring for patients decides the age at which monitoring should start. Abbie L. Abboud, M.S., C.G.C.
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For Further Information Gertner, M. E., and E. Kebebew. “Multiple Endocrine Neoplasia Type 2.” Current Treatment Options in Oncology 5 (2004): 315-325. Gimm, O. “Multiple Endocrine Neoplasia Type 2: Clinical Aspects.” Frontiers of Hormone Research 28 (2001): 103-130. Ponder, B. A. J. “Multiple Endocrine Neoplasia Type 2.” In The Metabolic and Molecular Bases of Inherited Disease, edited by Charles R. Scriver, Arthur L. Beaudet, David Valle, and William S. Sly. 8th ed. New York: McGraw-Hill, 2001.
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Other Resources
American Cancer Society http://www.cancer.org Genetics Home Reference Multiple Endocrine Neoplasia http://ghr.nlm.nih.gov/ condition=multipleendocrineneoplasia See also Endocrine cancers; Endocrinology oncology; Family history and risk assessment; Gastrinomas; Genetics of cancer; Histamine 2 antagonists; Human growth factors and tumor growth; Islet cell tumors; Multiple endocrine neoplasia type 1 (MEN 1); Neuroendocrine tumors; Parathyroid cancer; Pheochromocytomas; Pituitary tumors; Thyroid cancer; Zollinger-Ellison syndrome.
u Multiple myeloma Category: Diseases, symptoms, and conditions Also known as: MM, myeloma, plasma cell myeloma, cancer of the bone marrow Related conditions: Multiple gammopathy of undetermined significance (MGUS), smoldering myeloma, indolent myeloma 809
Multiple myeloma
Salem Health: Cancer
Definition: Multiple myeloma is a cancer involving several clusters of cancerous plasma cells (a type of white blood cell found in the bone marrow that produces immunoglobulins to fight infection) in various bones of the body.
M-protein) present in their blood. MGUS itself is benign, but about 16 percent of individuals with the condition eventually exhibit symptoms of multiple myeloma. Patients with smoldering or indolent myeloma, often a precursor disease, exhibit higher levels of calcium and kidney dysfunction, anemia, and bone disease.
Risk factors: No one is sure what causes multiple myeloma. People who have been exposed to agricultural and other chemicals such as Agent Orange, some types of radiation, and some viruses appear to be more susceptible to multiple myeloma. People with multiple myeloma are usually diagnosed in their fifties and sixties. The disease is identified more often in men than in women and more often in African Americans than in members of other ethnic groups. Scientists have not been able to associate multiple myeloma with a genetic trait, but research suggests that chromosome 13 may be incomplete or entirely missing in myeloma cells. Patients with a condition known as multiple gammopathy of undetermined significance (MGUS) have a relatively large amount of immunoglobulin protein (the
Etiology and the disease process: Multiple myeloma occurs when abnormal plasma cells in the bone marrow multiply, accumulate, and overtake the healthy plasma cells. As the plasma cells circulate in the bloodstream, they often settle in other bones and interfere with the body’s ability to produce normal antibodies, which leads to difficulty fighting infections. Incidence: Approximately 53,000 Americans have multiple myeloma. Slightly fewer than 20,000 Americans were expected to be diagnosed with multiple myeloma in 2007. Using statistics gathered from 2002 to 2004, the National Cancer Institute estimates that 0.61 percent (1 in 165) of men and women born today will be diagnosed with multiple myeloma at some time during their lifetime.
Incidence of Multiple Myeloma per 100,000 People, by Gender 16 14
Men
14.0
Women
12 10
9.5
8
6.9
6.6 5.7
6 4.8
4.8 4.1
3.7
4
3.0
2 0 Black
Hispanic
White
American Indian/ Alaska Native
Asian/Pacific Islander
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
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Salem Health: Cancer
Multiple myeloma
Multiple myeloma in the bone marrow. (©ISM/Phototake—All rights reserved)
Symptoms: The early stages of multiple myeloma may be uneventful and indistinct from other maladies. Multiple myeloma is often marked by successive infections, weight loss, fatigue or weakness, broken bones, or bone pain, most commonly in the ribs or back. Screening and diagnosis: Kidney problems are often the first indication that something is wrong. High levels of protein in the blood can cause kidney damage, and high levels of calcium may indicate the beginning or presence of kidney problems. Symptoms of kidney problems include greater thirst and urine production, a loss of appetite, fatigue, muscle weakness, restlessness, confusion or an inability to concentrate, constipation, and nausea and vomiting. An accurate diagnosis requires consideration of the patient’s history and symptoms, a complete physical, and an evaluation of laboratory results. Adiagnosis of multiple myeloma requires blood tests to determine the amount of calcium and plasma cells in the blood and the patient’s degree of anemia. Technologists
will look for the presence of M-protein, beta-2 microglobulin (β2M), and other proteins in a blood sample and for the presence of the Bence-Jones protein (a type of Mprotein) in the urine. Additional testing will include imaging studies—X rays, computed tomography (CT) scans, or magnetic resonance imaging (MRI) studies—to examine whether bone cavities exist and whether they might be caused by a tumor. This is followed by taking a tissue sample from a large bone to examine whether myeloma cells are present in the marrow. Most clinicians use the International Staging System to categorize multiple myeloma using the following criteria: • Stage I: Serum β2M less than 3.5 milligrams/deciliter (mg/dl) and serum albumin greater than or equal to 3.5 grams/deciliter (g/dl) • Stage II: Serum β2M less than 3.5 mg/dl and albumin less than 3.5 g/dl or serum β2M 3.5 to 5.5 mg/dl • Stage III: Serum β2M greater than 5.5 mg/dl Higher serum β2M levels and lower serum albumin levels usually indicate active or advanced disease. In811
Mustard gas creased values of C-reactive protein and serum lactate dehydrogenase also may indicate active disease. Treatment and therapy: There is no cure for multiple myeloma, but several treatment options exist and new options are being developed. The aim of most therapy is to ease a patient’s symptoms and slow the progression of disease, relieve pain and discomfort, and stabilize the immune system and metabolic functions. Various combination therapies are being used to combat multiple myeloma. These include dexamethasone, either alone or in combination with thalidomide or melphalan; melphalan plus prednisone; a combination drug known as VAD (vincristine/ doxorubicin/dexamethasone); and bortezomib, either alone or in combination with other drugs such as dexamethasone, lenalidomide, or doxorubicin liposomal (Doxil). Additional therapies include the use of cyclophosphamide or etoposide. Each drug combination has advantages and disadvantages, and not all drug combinations work well in all patients. Some patients have had extremely good results using these drugs, and many have experienced disease remission. Prognosis, prevention, and outcomes: Most patients live many years after a diagnosis of multiple myeloma. Physicians may offer treatments for bone pain, infections, anemia, and fatigue or weakness, which are considered to be the most common body effects associated with multiple myeloma. Terry A. Anderson, B.S.
Salem Health: Cancer Curcumin; Hair dye; Hematologic oncology; Hemolytic anemia; Hepatitis C virus (HCV); Hypercalcemia; Immunoelectrophoresis (IEP); Interferon; Malignant fibrous histiocytoma (MFH); Melphalan; Motion sickness devices; Myeloma; Myelosuppression; Proteasome inhibitors; Protein electrophoresis; Spinal axis tumors; Waldenström macroglobulinemia (WM).
u Mustard gas Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: HD, senfgas, sulfur mustard, blister gas, s-lost, lost, Kampfstoff LOST, yellow cross liquid, yperite Related cancers: Cancers of the larynx, pharynx, upper respiratory tract, and lungs Definition: Mustard gas is a member of the sulfur mustards, which are blister-inducing agents (vesicants). Mustard gas is actually a liquid at room temperature that is clear to yellow or brown in color and is either odorless or smells like garlic, onions, or mustard. Mustard gas was originally introduced as a chemical weapon during World War I and has been used throughout the world since then. It is a powerful irritant that damages the eyes and respiratory tract and causes large blisters on exposed skin. Exposure routes: Inhalation and dermal contact
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For Further Information Anderson, Kenneth C., and Irene Ghobrial, eds. Multiple Myeloma. New York: Informa Healthcare, 2007. Brian, G., M., et al. “International Uniform Response Criteria for Multiple Myeloma.” Leukemia 20, no. 9 (2006): 1467. Dominik, D., et al. “Multiple Myeloma: A Review of the Epidemiologic Literature.” International Journal of Cancer 120, suppl. 12 (2007): 40-61. u
Other Resources
International Myeloma Foundation http://www.myeloma.org Multiple Myeloma Research Foundation http://www.multiplemyeloma.org See also African Americans and cancer; Agent Orange; Amyloidosis; Angiogenesis inhibitors; Bisphosphonates; Blood cancers; Bone cancers; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Bone pain; 812
Where found: Used during chemical warfare attacks and in research laboratories. At risk: Military personnel or civilians exposed to mustard gas during chemical warfare attacks, workers who manufacture it, and people who live near stockpiles of it or come into contact with unexploded ordnances loaded with it Etiology and symptoms of associated cancers: Because mustard gas often has no odor, people are unaware that they have been exposed to it until the onset of symptoms, which usually begin two to twenty-four hours after exposure. Symptoms include redness, itching, yellow blistering of the skin, pain, swelling and tearing of the eyes, runny nose, sneezing, hoarseness, shortness of breath, sinus pain, bloody nose, cough, abdominal pain, diarrhea, fever, nausea, and vomiting. More severe exposures can cause second-to-third-degree burns of the skin, light sensitivity in the eyes or severe pain and blindness, chronic respiratory disease, and death. Mustard gas is an alkylating agent that chemically alters
Salem Health: Cancer the nitrogenous bases in deoxyribonucleic acid (DNA). Alkylation of DNA damages it and generates mutations but can also cause chromosome breakage. Mustard-gasinduced mutations cause either cell death or transformation into a tumor cell. Therefore, mustard gas is a confirmed carcinogen in humans and animals, and exposure to it increases a person’s risk for respiratory and lung cancer. Some 25 percent of all people who get lung cancer show no symptoms, but normally, the symptoms include cough, shortness of breath, wheezing, chest pain, and coughing up blood (hemoptysis). Nonspecific symptoms include weight loss, weakness, fatigue, depression, and mood changes. The spread of the cancer decreases lung capacity, and patients die because they are unable to inspire sufficient quantities of oxygen. History: During World War I, the German army first used mustard gas in July, 1917, against British soldiers near the Belgian city of Ypres. Since then, mustard gas has been used globally, but sporadically, in modern warfare. Epidemiological studies from the 1970’s and 1980’s established that soldiers and production workers exposed to mustard gas for longer periods of time showed an increased risk of respiratory cancers. The Geneva Protocol of 1925, which was modified and extended the Chemical Weapons Convention of 1993, prohibits the development, production, and stockpiling of chemical weapons, which includes mustard gas. Michael A. Buratovich, Ph.D. See also Alkylating agents in chemotherapy; Carcinogens, known; Chemotherapy; Laryngeal cancer; Lung cancers; Melphalan; Nasal cavity and paranasal sinus cancers; Oral and oropharyngeal cancers.
u Mutagenesis and cancer Category: Cancer biology Definition: Mutagenesis is the generation of changes or mutations in the genetic material of a cell. Normally, the cells in the body maintain a critical balance between cell growth and proliferation and cell death. This balance is maintained by the action of a number of different cellular mechanisms. When mutations are made that affect the ability of a cell to maintain this balance, it can begin to proliferate uncontrollably, leading to tumor formation and ultimately cancer. Mutations can be inherited or acquired over the lifetime of an individual. In addition, certain types of cancer cells show a characteristic increased rate of mutation, known as a mutator phenotype.
Mutagenesis and cancer Mutagenesis and cancer formation: In normal cells, the processes of cell proliferation and cell death are tightly controlled by multiple redundant mechanisms. Therefore, multiple mutations are required to transform a normal cell into a cancer cell. Although the specific genes that are mutated in different tumors are highly variable, there is a common theme to the types of mutations that promote tumor formation. In general, mutations are likely to occur in two types of genes—proto-oncogenes and tumor-suppressor genes. A proto-oncogene is a gene that normally promotes cell growth, differentiation, and proliferation. When a protooncogene undergoes a mutation that promotes tumor cell formation, it is known as an oncogene. Oncogenic mutations are considered to be dominant, which means that mutation of a single copy of the gene is sufficient to confer an increased risk of tumor formation. Conversion from a proto-oncogene into an oncogene can occur by a number of different mechanisms, most of which ultimately lead to increased levels of activity of the encoded protein. For example, mutations within the coding sequence of the gene can change the structure of the protein to increase its activity or disrupt its ability to be properly regulated. Mutations outside of the coding region of the gene can affect the expression of the protein, leading to increased levels within the cell. The first identified oncogene, the protein kinase Src, was discovered in 1970 from a chicken retrovirus. In normal, nontumor cells, c-src is an enzyme that acts within a number of different signaling pathways to promote cell proliferation, cell survival, initiation of protein translation, metabolism, cell adhesion, and motility. The oncogenic form of the protein, v-src, contains a mutation that abolishes a regulatory site on the protein, leading to its constitutive activation. Cells that contain the oncogenic form of Src are able to grow in the absence of cell proliferation signals as well as without being anchored down. These properties give transformed cells a selective growth advantage over normal, nontransformed cells, which can ultimately lead to uncontrolled growth and tumor formation. The other common type of mutation found in cancer cells occurs within tumor-suppressor genes. In normal cells, tumor-suppressor genes are involved in negatively regulating cell growth and proliferation. These genes produce proteins that prevent cells from dividing when there is deoxyribonucleic acid (DNA) damage, if the cell division apparatus is compromised, and in the absence of growth signals. Mutations in tumor-suppressor genes are characterized as recessive, since both copies of the gene must be mutated. One of the most common mutations found in human cancers is within the tumor-suppressor 813
Mutagenesis and cancer gene TP53. When a cell experiences damage or stress, TP53 normally acts to suppress cell growth and proliferation, and if the damage is severe enough, promote cell death. Mutation of both copies of the TP53 gene allows cells to survive and proliferate even in the presence of DNA damage. Multiple mutations in proto-oncogenes and tumor-suppressor genes are required to transform a normal cell into a cancer cell. This idea was made famous by Alfred Knudson in 1971, who showed that the incidence of tumor formation was consistent with two mutational “hits.” For example, mutation of TP53 alone is not sufficient to induce tumor formation, since this mutation only effectively disengages the brake put on cell growth. This mutation does, however, confer on the cell a selective advantage, which will most likely cause it to produce more daughter cells than its neighbors that do not contain the mutation. Over time, progeny of this original mutant cell may accumulate an oncogenic mutation that will allow it to grow and proliferate even more and potentially form a tumor. Additional mutations can then occur that allow the cells to better survive in the harsh tumor environment, which contains very low levels of oxygen and nutrients, as well as to allow the cell to metastasize into other regions of the body. Inherited mutations: One way to acquire a mutation is to inherit it from parents. Cells in the body contain two copies of each gene—one inherited from each parent. Inheriting a mutated copy of a gene, such as a tumor suppressor, from one parent can strongly predispose a person to developing cancer. Normally, a cell must undergo mutation of both copies of a tumor-suppressor gene to abolish its function. However, if a person inherits a mutation in one copy of the gene, then the amount of time that it takes to inactivate the remaining copy of the gene is much less. Therefore, patients with inherited mutations often show increased risk and decreased age of onset of cancer. For example, inheriting one mutant copy of the TP53 tumorsuppressor gene often leads to Li-Fraumeni syndrome. LiFraumeni syndrome strongly predisposes a patient to developing cancer, which usually shows a very early age of onset, as well as formation of multiple tumors throughout the life of the individual. For example, BRCA1 is a tumor-suppressor gene encoding a protein whose normal function is to repair damaged DNA. Inheriting a mutation in BRCA1 significantly increases a woman’s risk of developing breast or ovarian cancer. This is because defects in BRCA1 function lead to the accumulation of additional mutations in the genome. Acquired mutations: In addition to inheriting mutations, an individual can acquire changes in the genetic material 814
Salem Health: Cancer over his or her lifetime. Each time a cell in the body divides, it must faithfully replicate its genetic material, which is contained in the DNA. If the DNA is not correctly replicated, then mutations can arise, which, if left uncorrected, will be passed on to all of the daughter cells that descend from that cell. Because mutations are made each time the genome is replicated, the rate of mutation within a cell depends on the fidelity of the machinery that recognizes and repairs these mutations. In addition to acquiring unrepaired mutations that may occur each time a cell replicates its genetic material, genes can become mutated because of exposure to different mutagenic agents that originate from within the cell as well as toxins originating from the environment. By-products of cellular metabolism such as reactive forms of oxygen can cause DNA mutation. Chemical carcinogens, ionizing radiation, and viruses are all environmental agents that can generate mutations. Mutagenesis in cancer cells: Cancer cells often show rates of mutation that are significantly higher than those in normal cells. This can be due to mutations in genes that are normally involved in the identification and repair of mutations. Normally, if a mutation occurs in the DNA, either during replication or as a result of another type of damage, it is recognized by a set of proteins that first signal to the cell to stop dividing and then recruit other proteins to repair the damage. If the damage is too severe, then the cell will undergo programmed cell death, or apoptosis. If DNA damage is not correctly identified and repaired, then this could lead to increased rates of mutation, ultimately leading to the accumulation of multiple genetic “hits” and development of cancer. Over time, the likelihood that mutations will occur in proto-oncogenes or tumor-suppressor genes increases. Genetic testing is available to detect mutations in some of these commonly mutated genes, and knowledge of specific mutational status can provide important insight into prognosis and treatment. Lindsay Lewellyn, B.S. u
For Further Information Hanahan, Douglas, and Robert A. Weinberg."The Hallmarks of Cancer." Cell 100 (2000): 57-70. Knudson, Alfred G. “Two Genetic Hits (More or Less) to Cancer.” Nature Reviews Cancer 2 (November 1, 2001): 157-162. Sarasin, Alain. “An Overview of the Mechanisms of Mutagenesis and Carcinogenesis.” Mutation Research 544 (2003): 99-106.
Salem Health: Cancer u
Other Resources
Gene Tests http://www.geneclinics.org Human Genome Project Information http://www.ornl.gov/sci/techresources/ Human_Genome/home.shtml National Human Genome Research Institute http://www.genome.gov See also Antioxidants; Ashkenazi Jews and cancer; Bioflavonoids; Cancer biology; Carcinogens, known; Carcinogens, reasonably anticipated; Chromosomes and cancer; Free radicals; Gene therapy; Genetic testing; Genetics of cancer; Herbs as antioxidants; Hereditary cancer syndromes; Oncogenes; Proto-oncogenes and carcinogenesis; Tumor-suppressor genes.
u Myasthenia gravis Category: Diseases, symptoms, and conditions Also known as: Familial myasthenia gravis, neonatal myasthenia gravis, congenital myasthenia gravis, juvenile myasthenia gravis Related conditions: Autoimmune disorders, thymomas Definition: The term “myasthenia gravis” comes from Latin and Greek meaning grave (severe) muscle weakness; this describes the condition very well. Although there are several forms of myasthenia gravis, the most common is a chronic autoimmune neuromuscular condition in which there is sporadic, severe weakness of the voluntary muscles of the body, especially those of the face and throat. Risk factors: Most cases of myasthenia gravis appear to be sporadic (caused by unknown factors). An elevated risk has been noted for women between the ages of twenty and forty with family history of the disease, drug ingestion, or other autoimmune disorders. Myasthenia gravis is inherited in about 5 percent of all cases, associated with specific immune system alleles (HLA-B8 and DR3). Etiology and the disease process: In myasthenia gravis, the body produces antibodies that attack its own proteins (an autoimmune response). With the exception of druginduced myasthenia gravis (D-penicillamine ingestion, for example), there is no known causative agent or pathogen that accounts for onset of the disease, which can be quite sudden. As with other cancers, the body’s regulatory
Myasthenia gravis mechanisms are not operating properly, in this case allowing antibody-producing cells that should be screened out to continue being produced. In most cases of myasthenia gravis, the antibodies produced are directed against the acetylcholine (ACh) receptor. Receptors are proteins on the cell membrane that bind to a particular class of compounds, thus triggering the cell to perform some function or action. Acetylcholine receptors are present in the motor end plate of voluntary muscles, where they are stimulated by nerves. An electrical impulse in a nerve causes acetylcholine to be released; it binds with the receptor on the muscle cell, allowing sodium and calcium to move into the cell and stimulating it to contract. The acetylcholine is then broken down by the enzyme cholinesterase (so hyperstimulation does not occur) and recycled within the nerve cell. If antibodies to the receptor are present, they bind to the receptor first, so that very little acetylcholine can bind. Thus, sodium and calcium influx is limited, and muscle contraction is limited or nonexistent. In some cases, antibodies may actually destroy the receptors on the muscle cell membranes altogether, leaving muscles unable to contract even in the presence of a strong nerve signal. The antibodies against acetylcholine receptors are produced by B cells, circulating white blood cells (leukocytes). B cells are activated by T-helper cells, which develop within the thymus. Therefore, myasthenia gravis is often associated with thymoma (tumor of the thymus), although the exact mechanism of this association is not clearly understood. A second form of antibody in some patients develops against the receptor protein muscle-specific kinase (MuSK), required for formation of the nerve-muscle junction during early development. The result is an incomplete junction, making it harder for acetylcholine to span the gap and stimulate the muscle. Incidence: The overall U.S. incidence is listed at 20 cases per 100,000 population, although many authors report it to be much higher. The discrepancy comes from the difficulty of diagnosis from initial symptoms. All ethnic groups and genders are susceptible, but there is a difference in age distribution. Generally this disease is seen in women under the age of forty, and in men and women between the ages of fifty and seventy. However, it can strike at any age including at birth (neonatal myasthenia gravis, congenital myasthenia gravis) or in children (juvenile myasthenia gravis). About 15 percent of those who contract myasthenia gravis have a thymoma. Symptoms: The primary symptom of myasthenia gravis is muscle weakness, especially those muscles that control 815
Myasthenia gravis
Drugs to Be Avoided by People with Myasthenia Gravis MG-Causing Drugs • Alpha-interferon • Botulinum toxin • D-Penicillamine Drugs That Increase Muscle Weakness • Antibiotics: particularly aminoglycosides, ciprofloxacin, telithromycin • Beta-blockers: propranolo, timolol maleate eyedrops • Calcium channel blockers • Iodinated contrast agents (for X rays) • Neuromuscular blocking agents: succinylcholine and vecuronium; only anaesthesiologists familiar with MG should use these • Quinine, quinidine, procainamide
Salem Health: Cancer Treatment and therapy: Myasthenia gravis is generally controlled through medication. The medications have two purposes: lessening muscle weakness and reducing the autoimmune response. Cholinesterase inhibitors (such as neostigmine and pyridostigmine) allow the acetylcholine to remain near the receptor for a longer period of time, thus increasing the chance that it will bind. Immunosuppresive drugs (such as prednisone, cyclosporine, or azathioprine) help reduce the antibody formation but may take weeks or months to show effects. For patients in a critical state, plasmapheresis may also be used to remove circulating antibodies from the bloodstream. Patients experiencing myasthenia gravis caused by a thymoma may have the thymoma surgically removed (thymomectomy) to prevent possible spread of cancer in the event the thymoma is cancerous; most thymomas, however, are benign.
Source: Myasthenia Gravis Foundation of America
eye and eyelid movement, chewing, talking, facial expression, and swallowing. This weakness usually increases during periods of muscle activity and decreases with periods of rest. Screening and diagnosis: Myasthenia gravis can be difficult to diagnose. The symptoms can be subtle and hard to distinguish from other neurological disorders. A thorough physical exam is the first step in diagnosis, including various tests aimed at muscle fatigability (keeping arms stretched forward for sixty seconds or looking at the feet for sixty seconds while lying on the back). Blood tests can help to identify specific acetylcholine antibodies but may be negative (due to sensitivity of the assay) in up to 50 percent of cases, especially in the early stages. Repetitive nerve stimulation (with electrical impulses) can be used to measure fatigability, as can single fiber electromyography, a sensitive test that records the electrical impulse in muscle fibers. Classification (staging) of myasthenia gravis is as follows: • Stage I: Eye muscle weakness or ptosis of any severity; no other evidence of muscle weakness • Stage II: Eye muscle weakness of any severity; mild weakness of other muscles • Stage III: Eye muscle weakness of any severity: moderate weakness of other muscles • Stage IV: Eye muscle weakness of any severity: severe weakness of other muscles • Stage V: Severe weakness leading to intubation of the airway 816
Prognosis, prevention, and outcomes: With proper treatment, patients have a normal life expectancy. However, those with malignant thymoma may experience rapid decline. Quality of life varies quite markedly, but myasthenia gravis is not a progressive disease, and therefore, some lifestyle changes can lessen the symptoms in some individuals. In some patients, symptoms come and go; for some the symptoms decrease after three to five years of treatment. Kerry L. Cheesman, Ph.D. u
For Further Information Baron-Faust, Rita, and Jill P Buyon. The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting on with Life. Chicago: Contemporary Books, 2003. Keesey, John Carl. Myasthenia Gravis: An Illustrated History. Roseville, Calif.: Publishers Design Group, 2002. National Institutes of Health. Understanding Autoimmune Diseases. NIH Publication 98-4273. Bethesda, Md.: Author, 1998. _______. Understanding the Immune System: How It Works. NIH Publication 03-5423. Bethesda, Md.: Author, 2003. _______. Questions and Answers About Autoimmunity. NIH Publication 02-4858. Bethesda, Md.: Author, 2002. Shannon, Joyce Brennfleck, ed. Movement Disorders Sourcebook: Basic Consumer Health Information About Neurological Movement Disorders. Detroit: Omnigraphics, 2003. Vincent, Angela, and Camilla Buckley. “Myasthenia Gravis and Other Antibody-Associated Neurological Dis-
Salem Health: Cancer eases.” In The Autoimmune Diseases, edited by Noel R. Rose and Ian R. Mackay. Boston: Elsevier/Academic Press, 2006. u
Other Resources
American Cancer Society http://www.cancer.org Myasthenia Gravis Foundation of America http://www.myasthenia.org National Institute of Neurological Disorders and Stroke NINDS Myasthenia Gravis Information Page http://www.ninds.nih.gov/disorders/ myasthenia_gravis/myasthenia_gravis.htm See also Lambert-Eaton myasthenic syndrome (LEMS); Mediastinal tumors; Mediastinoscopy; Surgical biopsies; Thymomas; Thymus cancer.
u MYC oncogene Category: Cancer biology Also known as: c-Myc, v-myc myelocytomatosis viral oncogene homolog (avian) Definition: First identified in humans based on its homology to the chicken viral oncogene (v-myc), MYC belongs to a family of MYC genes that codes for a transcription factor containing the basic-helix-loop-helix Leucine zipper (bHLH/LZ) domain. The MYC protein binds to the enhancer box (E-box) sequence and activates the expression of a larger number of genes. By modifying the expression of its target genes, MYC is able to activate numerous biological effects. It affects cell proliferation (downregulates CDKN1A, or p21), regulates cell growth (upregulates TP53), induces apoptosis (upregulates BCL2), and regulates differentiation (downregulates C/EBPA). Role in cancer biology: The role of MYC in influencing critical aspects of the cell cycle machinery makes it a centerpiece and key to the enigma of cancer biology. In normal cells, MYC expression is under tight regulation, with the gene being expressed only in actively dividing cells. In contrast, genetic aberrations result in the uncontrolled expression of MYC in cancer cells. Aberrant expression of MYC plays a significant role in a wide variety of human cancers: 80 percent of breast cancers, 70 percent of colon cancers, 90 percent of gynecological cancers, 50 percent of hepatocellular carcinomas, and a variety of hematologi-
Mycosis fungoides cal tumors possessing abnormal MYC signatures. An estimated 100,000 cancer deaths per year in the United States are associated with changes in the MYC gene or its expression. The clinical significance of MYC gene alterations in human cancers is best illustrated by the amplification of MYCN (N-myc) in neuroblastoma and the translocation of MYC from its normal position on chromosome 8 to chromosome 14 in Burkitt lymphoma. Inhibiting MYC: Experimental evidence shows that inhibiting MYC significantly halts tumor cell growth and proliferation; consequently MYC is an attractive target for cancer therapy. Another advantage of MYC as a therapeutic target is the fact that it is downstream of multiple converging signaling pathways that are affected by mutations in a number of genes in different cancer types. Major advances in drug development aimed at eliminating MYC include targeting it by antisense mitochondrial ribonucleic acid (mRNA) and deoxyribonucleic acid (DNA) oligonucleotides, triple-helix-forming oligonucleotides, ribozymes, porphyrins, and small interfering RNA (siRNA). Inhibition of MYC can be achieved with many of these approaches; however, for increased clinical efficacy it is probable that intervention, possibly in combination with traditional chemotherapy, will be necessary. Banalata Sen, Ph.D. See also Burkitt lymphoma; Cancer biology; Free radicals; Gene therapy; Genetics of cancer; Oncogenes; Protooncogenes and carcinogenesis; Tumor markers; Tumorsuppressor genes.
u Mycosis fungoides Category: Diseases, symptoms, and conditions Also known as: Cutaneous T-cell lymphoma (CTCL), cutaneous lymphoma, MF Related conditions: Sézary syndrome (SS), lymphomatoid papulosis, cutaneous anaplastic large-cell lymphoma, adult T-cell leukemia/lymphoma, peripheral T-cell lymphoma, lymphomatoid granulomatosis, granulomatous slack skin disease, pagetoid reticulosis Definition: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL). Mycosis fungoides was named after the mushroom-like skin tumors that were noted in the first patient diagnosed with the condition. A low-grade lymphoma that primarily affects the skin, it generally has a slow course and often remains confined to the skin. Over time, in only about 10 percent of 817
Mycosis fungoides the cases, it does slowly progress to the lymph nodes and internal organs such as the liver, lungs, and bone marrow. The cutaneous T-cell lymphomas are a group of rare skin cancers that includes Sézary syndrome, lymphomatoid papulosis, cutaneous anaplastic large-cell lymphoma, adult T-cell leukemia/lymphoma, peripheral T-cell lymphoma, lymphomatoid granulomatosis, granulomatous slack skin disease, and pagetoid reticulosis. Risk factors: The cause of mycosis fungoides is unknown. There is no supportive research indicating that this is a hereditary disease. Exposure to Agent Orange may be a risk factor for developing mycosis fungoides for veterans of the Vietnam War, but no direct cause-effect relationship has been established. Etiology and the disease process: Mycosis fungoides is a special variant of lymphoma with major involvement of the skin as well as hilar and mediastinal lymphadenopathy. It is associated with reticular nodular pulmonary lesions
Salem Health: Cancer and is often complicated by pneumonias, primarily caused by Staphlococcus aureus or Pseudomonas aeruginosa. The condition is not contagious. It is not an infection, and there are no infectious agents known to cause the disease. There has been research investigating the role of viruses, but the results are inconclusive. Incidence: In the United states, approximately 1,000 new cases of mycosis fungoides occur per year. It affects men twice as often as women and is more common in blacks than in whites. Mycosis fungoides can begin at any age, but the most common age is fifty years old. Symptoms: Mycosis fungoides progresses through four stages, which are defined by the skin symptoms, including the patch phase, skin tumors phase, skin redness stage, and lymph node stage, where mycosis fungoides begins to spread or metastasize, usually first to the lymph nodes, then to the liver, lungs, or bone marrow. Screening and diagnosis: Typically there are about six years from the onset of symptoms to the diagnosis of mycosis fungoides. Confusion with other conditions is common. A sample of the skin known as a skin biopsy is usually performed. Other laboratory tests can be done to determine the progression of the cancer. There is no cure for mycosis fungoides, so long-term survival depends on early diagnosis and treatment. Treatment and therapy: Treatments are directed at either the skin or the entire body (systemic therapy). Skindirected treatments include ultraviolet light (psoralen and ultraviolet A, or PUVA, UVB, narrow-band UVB), topical steroids, topical chemotherapies (nitrogen mustard, carmustine), topical retinoids, local radiation to single lesions, or total skin electron beam (TSEB). Systemic treatments include oral retinoids, photopheresis, photochemotherapy (also known as PUVA), fusion proteins, interferon, systemic chemotherapy (most commonly cyclophosphamide, doxorubicin, vincristine, and prednisone), and orphan drugs such as bexarotene (Targretin). These treatments may be prescribed alone or in combination.
Mycosis fungoides on a patient’s back. (©ISM/Phototake—All rights reserved)
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Prognosis, prevention, and outcomes: The course of mycosis fungoides is unpredictable, as some patients will progress slowly, some will progess rapidly, and some will not progress at all. Most patients will experience only skin symptoms, without serious complications. About 10 percent will experience progressive disease with lymph node involvement or spread to the liver, lungs, or bone marrow. Many patients live normal lives while they treat their disease, and some are able to remain in remission for long periods of time. Although there is no known cure for
Salem Health: Cancer mycosis fungoides, research has indicated that patients diagnosed with early-stage mycosis fungoides (which is 70 to 80 percent of patients) will have a normal life expectancy. Debra B. Kessler, M.D., Ph.D. u For Further Information Dummer, R. “Future Perspectives in the Treatment of Cutaneous T-cell Lymphoma (CTCL).” Seminars in Oncology 33, no. 1 (2006): S33-S36. Girardi, M., P. W. Heald, and L. D. Wilson. “The Pathogenesis of Mycosis Fungoides.” The New England Journal of Medicine 350, no. 19 (2004): 19781988. Kumar, Vinay, et al., eds. Robbins and Cotran Pathologic Basis of Disease. Philadelphia: Elsevier Saunders, 2005. u
Other Resources
Cutaneous Lymphoma Foundation http://www.clfoundation.org/ The Skin Site Mycosis fungoides http://www.skinsite.com/ info_mycosis_fungoides.htm See also Agent Orange; Cutaneous T-cell lymphoma (CTCL); Lymphomas; Sézary syndrome; Skin cancers.
u Myelodysplastic syndromes Category: Diseases, symptoms, and conditions Also known as: Myelodysplasia Related conditions: Acute myeloid leukemia Definition: Myelodysplastic syndromes characterize a range of hematological disorders in which the bone marrow stem cells either do not mature into red or white blood cells or do not function properly. This lack of healthy blood cells can lead to life-threatening conditions. Risk factors: No one is certain what causes myelodysplastic syndromes. Most researchers believe that a variety of factors will lead to different myelodysplastic syndrome subtypes, but no one has been able to pinpoint what causes their onset. Scientists believe that prior therapy for cancer and exposure to environmental toxins places individuals at great risk for myelodysplastic syndromes. The cancertreatment drugs chlorambucil, mechlorethamine, and procarbazine are all toxic to the bone marrow and seem to lead to the onset of myelodysplastic syndromes later in life.
Myelodysplastic syndromes This is particularly true when these drugs are used in combination with certain forms of radiation therapy. People who have been exposed to benzene and ionizing radiation appear to be susceptible to myelodysplastic syndromes. Benzene is found in gasoline, detergents, furniture polish, and cigarette smoke. Some researchers believe that a connection can be made between myelodysplastic syndromes and people who have had long-term exposure to certain agricultural chemicals and heavy metals. Other risk factors for myelodysplastic syndromes include the congenital disorders Fanconi anemia and Down syndrome. People who smoke cigarettes, which contain benzene and other cancer-causing substances, are also more likely to be at risk for myelodysplastic syndromes. Etiology and the disease process: Myelodysplastic syndromes rarely occur in people younger than the age of sixty, although they are appearing more often in children and adults who survive chemotherapy regimens for cancer treatment. Myelodysplasia is diagnosed more often in men than women, but there appears to be no association with ethnicity. Scientists have not been able to associate myelodysplastic syndromes with a genetic trait. Secondary myelodysplastic syndromes most often appear after treatment for acute lymphocytic leukemia, Hodgkin disease, and non-Hodgkin lymphoma, but they can also arise after chemotherapy for cancer of the breast, lung, testis, or intestinal tract, and after treatment for some autoimmune diseases. Incidence: Approximately 10,000 to 15,000 Americans are diagnosed with myelodysplastic syndromes each year. This number may be rising as the number of those who survive cancer treatment increases. Approximately 80 to 90 percent of those who receive a myelodysplastic syndrome diagnosis are the age of sixty and older. Symptoms: The early stages of myelodysplastic syndromes may be uneventful and indistinct from other diseases. Myelodysplastic syndromes are often marked by anemia, which leads to shortness of breath and fatigue during light exertion. Other symptoms may include unusually pale skin, easy bleeding or bruising, tiny red spots (petechiae) just beneath the skin, weight loss, and frequent infections. About 20 percent of patients with myelodysplastic syndromes exhibit infections or bleeding, and about 20 percent of patients have no symptoms and are diagnosed during routine blood tests. Screening and diagnosis: A complete blood count will help determine the number of platelets, red and white blood cells, and hemoglobin levels in red cells. A peripheral blood smear may help determine the shape, size, and 819
Myelofibrosis appearance of blood cells. Myelodysplastic syndromes are usually diagnosed after other diseases, such as leukemia, have been excluded. Bone marrow tests will help confirm a diagnosis of myelodysplastic syndrome. These include aspiration and biopsy to obtain bone and marrow tissues, which are then analyzed using cytochemistry, flow cytometry, immunocytochemistry, and cytogenetic profiles. Some physicians use the French-American-British (FAB) system to classify myelodysplastic syndromes into five subtypes. In the 1990’s, the World Health Organization expanded the FAB into seven subtypes on the basis of circulating blood counts or changes in the bone marrow. These subtypes are refractory anemia, refractory anemia with ringed sideroblasts, refractory cytopenia with multilineage dysplasia, refractory cytopenia with multilineage dysplasia and ringed sideroblasts, refractory anemia with excess blasts (types 1 and 2), unclassified myelodysplastic syndromes, and myelodysplastic syndromes associated with isolated del(5q) chromosome abnormality. Physicians use the International Prognostic Scoring System to assess a patient’s health. Although the system is not a precise science, it uses three factors—the percentage of blasts in the bone marrow, an assessment of the number of cell types in the circulating blood (cytopenia), and an assessment of cellular chromosomal abnormalities—each of which is assigned a score to determine a patient’s degree of health. Treatment and therapy: Most patients require a transfusion of red blood cells to help relieve anemia. Drugs such as darbepoetin and erythropoietin may help the body produce more red blood cells and thus reduce the need for transfusions. The U.S. Food and Drug Administration has approved two drugs specifically for the treatment of myelodysplastic syndromes. Azacitidine (approved May 19, 2004) and decitabine (approved May 2, 2006) are administered to stimulate blast cells to mature into healthy blood cells, but the pharmaceuticals are ineffective in some people and may cause additional problems. The only potential cure for myelodysplastic syndromes is allogeneic (donor) stem cell transplantation, but few patients are eligible for the procedure because it poses high risks. Prognosis, prevention, and outcomes: Patients with fewer bone marrow blasts and a greater number of cells in the blood and better cytogenetic profiles may demonstrate a longer median survival time, whereas patients with more blasts, fewer blood cells, and chromosome 7 abnormalities have a shorter survival time. Terry A. Anderson, B.S. 820
Salem Health: Cancer u
For Further Information Deeg, H. J., et al. Hematologic Malignancies: Myelodysplastic Syndromes. New York: Springer, 2006. Hellstr-Lindberg, E., and L. Malcovati. “Supportive Care, Growth Factors, and New Therapies in Myelodysplastic Syndromes.” Blood Reviews 22, no. 2 (March, 2008): 75-91.
u
Other Resources
Aplastic Anemia & MDS International Foundation http://www.aamds.org/aplastic Myelodysplastic Syndromes Foundation http://www.mds-foundation.org See also Acute myelocytic leukemia (AML); Anemia; Benzene; Blood cancers; Cigarettes and cigars; Down syndrome and leukemia; Fanconi anemia; 5Q minus syndrome; Ionizing radiation; Leukemias; Leukopenia; Myelosuppression; Neutropenia; Premalignancies.
u Myelofibrosis Category: Diseases, symptoms, and conditions Also known as: Agnogenic myeloid metaplasia, idiopathic myelofibrosis, aleukemic megakaryocytic myelosis, leukoerythroblastosis Related conditions: Myeloproliferative disorders, including polycythemia rubra vera (increased numbers of red blood cells) and essential thrombocytosis (overproduction of platelets in the bone marrow) Definition: Myelofibrosis is a disorder that disrupts the normal production of blood cells, leading to scarring of the bone marrow. Risk factors: Myelofibrosis is most common in patients over fifty years old. Exposure to radiation, benzene, or radioactive thorium dioxide (a chemical used during some radiology procedures) also increases one’s risk. There may also be an association between myelofibrosis and certain autoimmune diseases (in which the body attacks its own cells), leukemias and lymphomas, and other myeloproliferative disorders. Etiology and the disease process: Hematopoiesis is the process of making blood cells. It begins in the bone marrow with a hematopoietic stem cell that can develop into specialized blood cells, including red blood cells (which transport oxygen), white blood cells (which are involved in the immune system), and platelets (which form clots).
Salem Health: Cancer Myelofibrosis develops when the genetic material in a single hematopoietic stem cell changes or acquires a mutation, and then begins to replicate and affect normal blood cell production. Approximately 50 percent of patients with myelofibrosis have stem cells with mutations in the JAK kinase gene; mutations in the GATA-1 and MPL genes are less common. Mutated stem cells may affect cellular proliferation, survival, and immune responses. They may also stimulate fibroblast cells, causing them to secrete collagen that can build up scar tissue in the bone marrow. Cytokines (signals secreted from cells to affect activity of other cells), including transforming growth factor-beta (TGF-β), basic fibroblast growth factor, and platelet-derived growth factor (PDGF), may also induce bone marrow scarring. The accumulation of scar tissue may displace normal blood cells being produced within the marrow. Therefore, blood cell production may begin to occur in other parts of the body, most often the spleen and liver. However, blood cell production in those tissues is not as efficient and increases organ size. Severe anemia (a lack of red blood cells) can also occur, leading to weakness and fatigue. The abnormal hematopoietic stem cells can also spread to other organs in the body and form tumors (primarily in the adrenals, kidneys, lymph nodes, breasts, and lungs). Incidence: Myelofibrosis is rare, with an incidence rate ranging from 0.3 to 1.5 cases per 100,000 people. Among clonal hematologic disorders, myelofibrosis is the least prevalent. Symptoms: In the early stages, myelofibrosis does not cause any symptoms. However, as normal blood cell production becomes more affected, multiple signs may arise, including tiredness, weakness, shortness of breath, an enlarged liver or spleen, easy bruising and bleeding, fever, frequent infections, and bone pain. Screening and diagnosis: Screening for myelofibrosis includes blood tests to determine the number of red blood cells and their shape, because low numbers and teardropshaped cells indicate myelofibrosis. To examine enlargement of the liver and spleen, physical exams, as well as imaging tests (ultrasounds, magnetic resonance imaging, and computed tomography scans) may be performed. A bone marrow biopsy, in which a needle is used to withdraw the bone marrow from the hip bone, may be done to confirm a diagnosis. The harvested bone marrow cells can be viewed under a microscope to examine signs of scarring and the types and number of cells within the marrow. The following criteria for staging have been accepted by the World Health Organization:
Myelofibrosis
• •
A1: No other myeloproliferative disorders A2: Early clinical stage, with slight anemia and slight enlargement of the spleen • A3: Intermediate clinical stage, with moderate anemia, teardrop-shaped red blood cells, enlargement of the spleen, and no other symptoms • A4: Advanced clinical stage, severe anemia, and one or more other symptoms Treatment and therapy: There are many treatment options for myelofibrosis symptoms. Blood transfusions may improve anemia. Androgen (a hormone) or thalidomide (a drug) in combination with corticosterioids may increase red blood cell production. Hydroxyurea, a chemotherapeutic agent, can shrink enlarged spleens and may reduce bone marrow scarring. Radiation and interferon-alpha not only reduce spleen size but also may alleviate bone pain. When other treatments do not work, the spleen may be surgically removed in a process known as a splenectomy. The only way to cure myelofibrosis is through a stem cell transplant in which the patient, after being treated with high-dose chemotherapy to kill the diseased cells, is provided with healthy blood stem cells from a donor. Because this is an intensive procedure, patients must be healthy enough to undergo the process and numerous side effects may occur. Prognosis, prevention, and outcomes: The mean survival time from diagnosis ranges from 3.5 to 5.5 years. Patients with severe anemia, certain symptoms (weight loss, fatigue, night sweats, and fever), and those older than the age of sixty-five tend to have poorer mean survival rates. In approximately 15 percent of patients, myelofibrosis can progress to acute lymphocytic leukemia or lymphoma, which can be fatal. There are no known ways to prevent myelofibrosis. To alleviate or prevent symptoms of anemia, the diet should include nutrients that promote blood formation, such as iron, folic acid, and vitamin B12. Elizabeth A. Manning, Ph.D. u
For Further Information Hennessy, B. T., et al. “New Approaches in the Treatment of Myelofibrosis.” Cancer 103, no. 1 (January 1, 2005): 32-43. Spivak, J. L., et al. “Chronic Myeloproliferative Disorders.” Hematology/The Education Program of the American Society of Hematology (2003): 200-224. Tefferi, A. “The Forgotten Myeloproliferative Disorder: Myeloid Metaplasia.” Oncologist 8, no. 3 (2003): 225231. 821
Myeloma
Salem Health: Cancer
Tefferi, A., and D. G. Gilliland. “Oncogenes in Myeloproliferative Disorders.” Cell Cycle 6, no. 5 (March 1, 2007): 550-566. u
Other Resources
MayoClinic.com Myelofibrosis http://www.mayoclinic.com/health/myelofibrosis/ DS00886 MedlinePlus Primary Myelofibrosis http://www.nlm.nih.gov/medlineplus/ency/article/ 000531.htm See also Anemia; Chronic myeloid leukemia (CML); Myeloproliferative disorders; Polycythemia vera.
u Myeloma Category: Diseases, symptoms, and conditions Also known as: Multiple myeloma, plasma cell myeloma Related conditions: Non-Hodgkin lymphoma, other blood cancers Definition: Myeloma is a cancer of the plasma cells found in the bone marrow. Plasma cells produce antibodies, which fight infection. In myeloma, abnormal plasma cells in the bone marrow overproduce monoclonal immunoglobulins. Multiple myeloma occurs when there are multiple bones affected. Risk factors: As nearly all cases of multiple myeloma are diagnosed in adults over the age of forty, age is considered the most significant risk factor. It is thought, however, that myeloma is the result of several unknown factors working together. Etiology and the disease process: The definitive cause of myeloma has not been determined. However, as age is its primary risk factor, potential causes include age-related factors such as long-term exposure to carcinogens, toxins, genetic variations, and decreased immune response. Incidence: Myeloma is most commonly found in African Americans and occurs more frequently in women. Multiple myeloma is the second most common type of blood cancer (non-Hodgkin lymphoma is the first). Approximately 16,000 new cases are diagnosed each year. The average age of diagnosis is sixty-eight, and very few cases are diagnosed in people under the age of forty. 822
Myeloma in the head of the humerus. (CNRI/Photo Researchers, Inc.)
Symptoms: A common symptom is back pain, often accompanied by bone pain of the pelvis, ribs, and neck. Patients with myeloma have also reported excessive fatigue, iron deficiency, decreased immunity (frequent colds or sickness), a decrease in appetite, constipation, “pins and needles” in the feet and legs, and abnormal bleeding of the nose or gums. Screening and diagnosis: There is no standard screening for myeloma; however, patients considered at risk and exhibiting symptoms should see a hematologist (a doctor who specializes in blood disorders) and have a series of tests performed to determine a diagnosis. Blood tests, urinalysis, X rays, bone scans, and bone marrow biopsy are typically performed. There are two systems for staging myeloma: the DurieSalmon Staging System and the International Staging System. Treatment and therapy: Treatment for myeloma, like that for most cancers, depends on the stage of disease. Patients are often treated with chemotherapy and radiation, as well as additional therapies to target plasma cells.
Salem Health: Cancer Prognosis, prevention, and outcomes: Prognosis for myeloma depends on the stage at which the patient is diagnosed and the patient’s overall health. While myeloma is not curable, it can be treated and managed. Most patients survive for at least one year following diagnosis, while at least half survive an additional five years and twenty out of every hundred patients diagnosed live an additional ten years. Anna Perez, M.Sc. See also African Americans and cancer; Aging and cancer; Blood cancers; Bone cancers; Immunotherapy; Lactate dehydrogenase (LDH) test; Leukapharesis; Multiple myeloma; Non-Hodgkin lymphoma; Stem cell transplantation; Thrombocytopenia; Umbilical cord blood transplantation.
u Myeloproliferative disorders Category: Diseases, symptoms, and conditions Also known as: Blood cancers, chronic granulocytic leukemia, chronic myeloid leukemia, agnogenic myeloid metaplasia, primary myelofibrosis, myelosclerosis with myeloid metaplasia, idiopathic myelofibrosis, essential thrombocytosis Related conditions: Leukemia Definition: Myeloproliferative disorders are a group of slow-growing blood cancers, in which the bone marrow produces too many red blood cells, white blood cells, or platelets. All myeloproliferative disorders arise from an overproduction of one or more types of blood cells. Risk factors: The reason for the abnormal increase in blood cells is not well understood. Genetics and environmental factors such as overexposure to radiation may be risk factors for some of these malignancies. Some types of myeloproliferative disorders have been associated with familial clusters; one such case is marked by a mutation of the erythropoeitin receptor. Etiology and the disease process: No obvious etiology exists for myeloproliferative disorders. These malignancies begin in the bone marrow when a greater than normal number of stem cells develop into one or more types of blood cells. Normally, the bone marrow makes stem cells that develop into mature blood cells. There are three types of mature blood cells. Red blood cells are mature blood cells that carry oxygen and other materials to all tissues of the body. White blood cells are mature blood cells that fight infection and disease. Platelets are mature blood cells
Myeloproliferative disorders that help prevent bleeding by causing blood to clot. The type of myeloproliferative disorder is based on which kind of mature blood cells are overproduced. Usually one type of blood cell is affected more than the others. The disorders get worse as the number of blood cells increase. There are six types of chronic myeloproliferative disorders: • Chronic myelogenous leukemia (CML) is a slowly progressing disease of overproduction of white blood cells but not lymphocytes in the bone marrow. CML is also called chronic granulocytic leukemia and chronic myeloid leukemia. • Polycythemia vera is a disease in which too many red blood cells are produced in the bone marrow and blood, causing the blood to thicken. In polycythemia vera, the number of white blood cells and platelets may also increase. The spleen is often enlarged as the extra blood cells may collect in it. Patients with polycythemia vera may also have bleeding problems and are at high risk for blood clotting. • Chronic idiopathic myelofibrosis is a progressive, chronic disease in which the bone marrow is replaced by fibrous tissue, and blood is made in the liver and the spleen instead of in the bone marrow. The hallmark of this disease is an enlarged spleen. Chronic idiopathic myelofibrosis causes progressive anemia and is also called agnogenic myeloid metaplasia, primary myelofibrosis, myelosclerosis with myeloid metaplasia, and idiopathic myelofibrosis. • Essential thrombocythemia is an increased number of thrombocytes (platelets) in the blood. The cause of this malignancy is not known. It is also called essential thrombocytosis. • Chronic neutrophilic leukemia is a disease in which neutrophils, a type of white blood cell, are found in excess in the blood. The excess neutrophils in chronic neutrophilic leukemia may cause the spleen and liver to become enlarged. This disorder may not progress for years, or it may develop quickly into acute leukemia. • Chronic eosinophilic leukemia is a disease in which eosinophils, a type of white blood cell, are found in the tissues, bone marrow, and blood. Similar to chronic neutrophilic leukemia, chronic eosinophilic leukemia may stay the same for years, or it may develop quickly into acute leukemia. Incidence: Myeloproliferative disorders typically occur later in life. The prevalence of these diseases is low (approximately 5 per 1 million people), and they occur more commonly in men and women of East European Jewish ancestry compared with other populations. Men are more likely than women to develop polycythemia vera, primary 823
Myeloproliferative disorders myelofibrosis, and CML. However, women are 1.5 times more likely than men to develop essential thrombocytosis. Symptoms: Many individuals with myeloproliferative disorders have no symptoms when their physicians first make the diagnosis. However, as the hematocrit or platelet count increases, most patients develop symptoms including headache, blurred vision, plethora (excess of body fluid), elevated white blood cell count, and hematocrit. A sign that is common to all myeloproliferative disorders, except of essential thrombocytosis, is an enlarged spleen, which may cause abdominal pain. Other signs of myeloproliferative disorders often include fatigue, difficulty breathing, intense itching after bathing in warm water, stomach aches, purple spots or patches on the skin, nosebleeds, gum or stomach bleeding, blood in the urine, throbbing and burning pain in the skin, high blood pressure, and blockage of blood vessels. Blockage of blood vessels may cause heart disease, stroke, or tissue death of the extremities. As the disorders progress, patients may also develop cerebrovascular events, such as thrombosis. Thrombosis in small blood vessels may lead to serious events, such as cyanosis, erythromelalgia (painful vessel dilation in the extremities), ulceration, or gangrene (tissue death) in the fingers or toes. Thrombosis in larger vessels may lead to myocardial infarction, deep-vein thrombosis, transient ischemic attacks, and stroke. Screening and diagnosis: Many of the myeloproliferative disorders are discovered by primary care physicians on routine blood tests. There is no standard staging system for chronic myeloproliferative disorders. Complete blood count is necessary for proper diagnosis, which includes the number of red blood cells and platelets, the number and type of white blood cells, the amount of hemoglobin (the protein that carries oxygen) in the red blood cells, and what portion of the blood sample is made up of red blood cells. Bone marrow aspiration and biopsy via inserting a hollow needle into the hip bone or breastbone is used to look for signs of blood cancer. In addition, cytogenetic analysis is often done to look for certain changes in the chromosomes. Treatment and therapy: Treatment is based on the type of myeloproliferative disorder. Ten types of standard treatment are used: watchful waiting (monitoring a patient’s condition), phlebotomy (removal of blood), platelet apheresis (removal of platelets from the blood), transfusion therapy, chemotherapy, radiation therapy, other drug therapy, surgery, splenectomy (removal the spleen), and biological therapy. 824
Salem Health: Cancer Unfortunately, there are no known cures for most myeloproliferative disorders. However, there are treatments available that help alleviate symptoms and prevent complications associated with the disorders. The method used to alleviate symptoms depends on the type of myeloproliferative disorder. For polycythemia vera, phlebotomy is used to lower red blood cell count. In essential thrombocytosis and primary myelofibrosis, symptoms are treated with medications. Medications such as interferon may also improve survival rates of certain myeloproliferative disorders. When enlargement of the spleen becomes painful, a surgeon may perform a splenectomy to alleviate pain. Replacing the abnormal stem cells in the bone marrow with healthy stem cells may also help control the disorder. Bone marrow transplant is ideal for most patients with CML. Prognosis, prevention, and outcomes: Though myeloproliferative disorders are serious, they are most often slow to develop; therefore, patients with these conditions often live for many years after diagnosis. Some complications of myeloproliferative disorders include enlargement of the spleen and liver, gout, anemia, bleeding, kidney or liver failure, heart attacks or stroke, and infection. In particular, CML can transform into acute leukemia. The survival rates of those with myeloproliferative disorders depend on the type of disorder and symptoms. For example, the median survival rate for those with polycythemia vera is more than ten years with treatment. The major causes of death in untreated polycythemia vera patients are thrombosis and hemorrhage. Primary myelofibrosis and CML may be fatal within three to six years after diagnosis. However, if CML transforms into acute leukemia, the median survival rate may be only three months. Patients with other types of myeloproliferative disorders can live longer, especially when diagnosed early. Specifically, patients with primary thrombocythemia may have a normal life expectancy, and patients with polycythemia vera have a survival rate of between ten and twenty years. Anita Nagypál, Ph.D. u
For Further Information Hoffman, R., et al. Hematology: Basic Principles and Practice. 3d ed. New York: Churchill Livingstone, 2000. Michiels, J. J., et al. “The 2001 World Health Organization and Updated European Clinical and Pathological Criteria for the Diagnosis, Classification, and Staging of the Philadelphia Chromosome-Negative Chronic Myeloproliferative Disorders.” Seminars in Thrombosis and Hemostasis 32 (June, 2006): 307-340.
Salem Health: Cancer
Myelosuppression
Talarico, L. D. “Myeloproliferative Disorders: A Practical Review.” Patient Care 30 (1998): 37-57. Yavorkovsky, L. L., and P. Cook. “Classifying Chronic Myelomonocytic Leukemia.” Journal of Clinical Oncology 19 (2001): 3790-3792.
Cell counts often return to baseline values when treatment is stopped, reduced, or delayed.
u
Symptoms: Depending on which cell line is involved, patients may feel weak, short of breath, and tired (anemia); may be susceptible to infections and have fevers (leukopenia); or may bruise and bleed easily (thrombocytopenia).
Other Resources
The Leukemia and Lymphoma Society Myeloproliferative Disorders http://www.leukemia-lymphoma.org/ all_page.adp?item_id=311829 National Cancer Institute Myeloproliferative Disorders http://www.cancer.gov/cancertopics/types/ myeloproliferative National Cancer Institute http://www.cancer.gov/cancertopics/pdq/treatment/ myeloproliferative/patient See also Acute myelocytic leukemia (AML); Blood cancers; Chronic myeloid leukemia (CML); Cyclophosphamide; Hypercoagulation disorders; Leukemias; Melphalan; Myelofibrosis; Polycythemia vera.
u Myelosuppression Category: Diseases, symptoms, and conditions Also known as: Bone-marrow suppression, pancytopenia Related conditions: Anemia, neutropenia, leukopenia, thrombocytopenia Definition: Myelosuppression is a condition in which bone marrow function is decreased, with fewer than normal numbers of red blood cells, white blood cells, and platelets. Complete loss of bone-marrow function is called myeloablation. Risk factors: Risk factors include having had chemotherapy, radiation therapy, or bone marrow or stem cell transplants, and having myelodysplastic syndromes. Etiology and the disease process: Chemotherapy and radiation therapy for cancer destroy the rapidly dividing cancer cells as well as other rapidly dividing cells, or hematopoietic stem cells. As with anemia, leukopenia, and thrombocytopenia, hematopoietic stem cells are damaged by drugs used in chemotherapy or by radiation therapy.
Incidence: Nearly all patients who are being treated for cancer experience myelosuppression at some point and to some degree.
Screening and diagnosis: For routine monitoring during cancer therapy, myelosuppression is generally measured through blood tests. Anemia would be suspected with a red blood cell count less than 3.5 × 109 per liter in women and less than 4.3 × 109 per liter in men; leukopenia would be suspected with a white blood cell count less than 1.0 to 2.0 × 109 per liter; and thrombocytopenia would be suspected with a platelet count less than 200 × 109 per liter. Sometimes aspiration or core needle biopsy of the bone marrow is done to aid in the diagnosis of leukemia, lymphomas, and multiple myelomas, diseases associated with severe myelosuppression. Treatment and therapy: Treatment for myelosuppression depends on which cell line is involved. Simply stopping or reducing the amount of chemotherapeutic drugs or radiation therapy given may relieve the myelosuppression. Anemia may be treated with red blood cell transfusions, steroids, supplements, or erythropoiesis-stimulating proteins such as epoetin alfa (Procrit, Epogen) or darbepoetin alfa (Aranesp). Leukopenia may be treated with hematopoietic growth factors such as filgrastim (Neupogen), pegfilgrastim (Neulasta), and sargramostim (Leukine). Thrombocytopenia may be treated with platelet transfusions or with a recombinant form of interleukin (oprelvekin, or Neumega). Prognosis, prevention, and outcomes: Left untreated, myelosuppression can impair a patient’s quality of life, increase the need for hospitalization and transfusions of red blood cells or platelets or both, increase the need for intravenous anti-infectives, and increase risk of bleeding and infections. Use of hematopoietic, erythropoietic, and thrombocyte growth factors and transfusions is routine in supportive cancer treatment. MaryAnn Foote, M.S., Ph.D. See also Anemia; Chemotherapy; External beam radiation therapy (EBRT); Leukopenia; Neutropenia; Radiation therapies; Thrombocytopenia. 825
2-Naphthylamine
u 2-Naphthylamine Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: 2-Aminonaphthalene, betanaphthylamine Related cancers: Bladder cancer Definition: 2-Naphthylamine, an aromatic amine, is a yellowish crystalline solid that turns purplish-red in air and has an ammoniacal odor. Exposure routes: For the general public, exposure to 2naphthylamine comes from inhalation of emissions from burning organic matter that contains nitrogen. Two primary sources are coal furnaces and tobacco smoke. Occupational exposure occurs through inhalation by laboratory personnel doing research with 2-naphthylamine.
Salem Health: Cancer national Agency for Research on Cancer (IARC) showed its link to the increased risk of bladder cancer, its commercial production was banned in the early 1970’s. There are still a few companies in the United States that manufacture 2-naphthylamine for use in laboratory research. The last time it was imported into the United States in any significant amount was in 1967. Alvin K. Benson, Ph.D. See also Bladder cancer; Carcinogens, known; Carcinogens, reasonably anticipated; Cigarettes and cigars; Occupational exposures and cancer.
u Nasal cavity and paranasal
sinus cancers
Where found: 2-Naphthylamine is used only in laboratory research. It is still found in some dyes and rubber compounds that were manufactured before 1974. It is a byproduct of tobacco smoke and coal burning and is an impurity found in commercially produced 1-naphthylamine.
Category: Diseases, symptoms, and conditions Also known as: Nose cancers, sinus cancers
At risk: Scientists and laboratory technicians who work where 2-naphthylamine is used in research as a catalyst or an antioxidant have a high risk for 2-naphthylamine contamination. Because 2-naphthylamine is generated in tobacco smoke, people who smoke are at high risk for contamination. The general public is at risk for contamination from secondhand tobacco smoke and from the burning of organic matter that contains nitrogen, such as coal.
Definition: Nasal cavity and paranasal sinus cancers are cancers that arise in the paranasal sinuses or the nose. Many types of cancer can originate in the paranasal sinuses and nose. These include squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, lymphomas, chondrosarcoma, osteosarcoma, hemangiopericytoma, malignant melanoma, and esthesioneuroblastoma, as well as metastatic lesions from cancers of the kidney, lung, and breast. Squamous cell carcinomas arise from the epithelial (skin) cells of the sinuses and are the most common type of paranasal sinus tumor. Adenocarcinoma tends to arise in the mucus-producing glands of the upper nasal cavity. This type of nasal cavity cancer is most common in woodworkers and people working with toxic chemicals and substances. Adenoid cystic carcinomas arise out of the salivary gland tissue and have a tendency to migrate to nearby nerve tissue. These tumors are slow growing but often metastasize to distant organs. Lymphomas arise from the cells of the lymph nodes and exhibit ulceration and necrosis (tissue death) of the lymph tissue in the nasal cavity or paranasal sinuses. Chondrosarcomas are rare in the nose and sinuses and arise out of the connective tissue. Osteosarcomas are cancers of the facial bones. Hemangiopericytomas are tumors of blood vessels. They are quite rare in the nose and sinuses. Malignant melanomas arise out of the epithelial tissue of the nasal septum and the lateral na-
Etiology and symptoms of associated cancers: When 2naphthylamine is metabolized, it can be activated by liver enzymes to form adducts with blood-serum proteins, such as hemoglobin. In some cases, 2-naphthylamine can undergo additional metabolism to form reactive compounds that are transported to the bladder, where they bind to deoxyribonucleic acid (DNA) molecules. In experimental laboratory animals, 2-naphthylamine DNA adducts have been found in the bladder and in the liver. In laboratory tests on cultured human cells, 2-naphthylamine caused genetic damage that involved DNA strand breaks, changes in chromosome structure or number, addition or deletion of chromosomes, and cell transformation. History: 2-Naphthylamine was commercially produced in the United States from the early 1920’s until the early 1970’s. It was used in the production of sulfonic acids, reddye stuffs, and agrochemicals, and as a catalyst and an antioxidant in the vulcanization of rubber. After the Inter826
Related conditions: Lymphoma, melanoma, hemangiopericytoma, osteosarcoma, chondrosarcoma, adenosarcoma, squamous cell carcinoma
Salem Health: Cancer sal wall. They appear to be more common in smokers and metastasize early. Esthesioneuroblastomas arise out of the sensory epithelial cells that control olfaction (smelling) and are quite rare. Risk factors: The primary risk factor for nasal and paranasal sinus cancer is smoking. Occupational exposure to inhaled toxic substances can also put a person at risk for developing sinus cancer. These substances include dusts from wood, textiles, and leather; glues; formaldehyde; solvents; nickel and chromium dust; mustard gas; isopropyl alcohol; and radium. It is thought that heavy air pollution could lead to nasal and paranasal sinus cancers. These types of cancers do not appear to be hereditary. Etiology and the disease process: Nasal cavity and paranasal sinus cancers develop in the walls of the nose or the walls of the six sinuses. Each side of the face has a maxillary, ethmoid, and sphenoid sinus. The paranasal sinuses are actually spaces that exist within the nasal and facial bones. Cancer occurs when a single cell mutates and grows uncontrollably. This tumor tends to invade nearby structures, which causes the symptoms of this type of cancer. Incidence: Cancers of the nasal and paranasal sinuses are considered rare. Each year, only about 2,000 people in the United States develop one of these cancers. They are more common in men than in women. These cancers occur more frequently in countries other than the United States, such as Japan and South Africa. Symptoms: The symptoms of nasal and paranasal sinus cancers are much like those of chronic sinus disease. They include blocked sinuses, decreased sense of smell, frequent sinus headaches, purulent drainage from the nose, facial swelling, epistaxis (bleeding from the nose), and frequent infections. Some patients will experience more definitive symptoms, such as a growth or mass on the nose, face, or soft palate; a lump inside the nose; numbness in areas of the face or head; loosening, pain, or numbness of the teeth; continuous tearing of the eyes; trouble opening the mouth; and swelling of the eyes. Screening and diagnosis: No routine screening is performed for nasal or paranasal sinus cancers, because of their rarity. Diagnosis is achieved by physical examination, nasal endoscopy, computed tomography (CT) scan of the nose and sinuses, or magnetic resonance imaging (MRI) of the sinuses and orbits. If there is a visible mass, it is biopsied (a slice of tissue is removed for microscopic examination) to determine whether it is cancer, and if so, what type of cancer.
Nasal cavity and paranasal sinus cancers Only esthesioneuroblastomas and cancers of the maxillary sinuses, nasal cavity, and ethmoid sinuses are staged. The sinus cancers are staged using the American Joint Committee on Cancer (AJCC) staging system. This system uses the TNM (tumor/lymph node/metastasis) groupings. For esthesioneuroblastomas, the staging can be performed using one of two systems: the Kadish system or the UCLA system. Since esthesioneuroblastomas are extremely rare, these staging systems will not be discussed. For cancers of the maxillary sinus, the stages are as follows: • Stage 0 (T0, N0, M0): The cancer is confined to the epithelium and still resembles normal tissue. • Stage I (T1, N0, M0): The cancer is confined to the nasal mucosa and has not spread to other sinuses or invaded the bones of the nose. • Stage II (T2, N0, M0): The cancer has invaded the bones of the maxillary sinus, excluding the posterior wall. These bones include the hard palate and the opening into the maxillary sinus. The cancer has not spread beyond the maxillary sinus. • Stage III (T1-3, N0-1, M0): The cancer has invaded the posterior wall of the maxillary sinus or has grown through the other bones of the sinus into the skin, the eye socket, or the ethmoid sinus. It may have metastasized to a single lymph node on the same side as the tumor. The involved node is a maximum of 3 centimeters (cm) in width. • Stage IV (T1-4, any N, M0-1): The cancer has spread to the eye, the skull, the nasopharynx, or the sphenoid and frontal sinuses. There may be lymph node involvement. For a tumor to be Stage IV, there must be more than one node involved, nodes of greater than 3 cm, or involvement of nodes on the side opposite the tumor. Any maxillary cancer that has metastasized to other organs is Stage IV. The stages for nasal cavity and ethmoid cancers are as follows: • Stage 0 (T0, N0, M0): The cancer is confined to the epithelium and is very early stage. • Stage 1 (T1, N0, M0): The cancer is localized to either the nasal cavity or the ethmoid sinus and its bones. There is no presence of lymph node involvement or metastases. • Stage II (T2, N0, M0): The cancer has invaded another cavity close to the tumor, but there is no lymph node involvement or metastases. • Stage III (T1-3, N0-1, M0): Either the cancer has invaded other structures, such as the eye socket, the palate, or the maxillary sinus, and there is no lymph node involvement or metastases, or it has invaded those structures, and one lymph node is involved. This node is a maximum of 3 cm. 827
Nasal cavity and paranasal sinus cancers
• Stage IV (any T, any N, M0-1): The cancer has invaded other structures, such as the eye, skull, or the sphenoid or frontal sinuses, or the cancer has spread to two or more lymph nodes and these nodes are larger than 3 cm, or the cancer has spread to distant organs. Treatment and therapy: Nasal cavity and paranasal cancers are treated with a combination of surgical resection of the tumor, radiation therapy, and chemotherapy. The actual surgical procedure performed will depend on the location of the tumor, the stage of the tumor, and whether it can be removed en block (as one piece of tissue). Cancer cells can be left in the surgical site if the tumor is incised (cut into). Stage I and II cancers can be treated with computeraided transnasal endoscopic surgery, which is performed using an endoscope that is inserted into the nostrils and then into the sinuses. Other surgical procedures used for tumors that remain within the nasal cavity are sublabial (under the upper lip) or lateral rhinotomy (incision along one side of the nose) approaches. Surgical procedures for Stage III and IV tumors may include midfacial degloving (separating the skin, subcutaneous tissue, nerves and tendons from the facial bones), orbital exenteration (removal of the eye and orbital bones), or craniofacial resections. After the latter surgical procedures, it may be necessary to perform grafts of skin or fascia (fibrous connective tissue that separates body structures) and to insert dental, orbital, or other prostheses to reconstruct the face. Tumors that have metastasized to the brain, the spinal column, and the optic nerve, and into the cavernous sinus (bilateral large venous blood vessels that drain blood from the dura mater that covers the brain) are generally considered inoperable. Radiation therapy may be performed before or after surgery, and it may be applied internally or externally. Radiation therapy before surgery can decrease the size of the tumor and simplify tumor resection. If radiation therapy is performed after surgery, it is used to destroy any tumor cells that remain. Radiation therapy may be applied by an external beam or by radioactive objects placed within the nasal cavity, such as seeds, wires, or catheters. For radiation administered by an external beam, a mask is created to position the head precisely. Radiation beams must be carefully aimed to prevent radiation exposure of the thyroid and pituitary glands. Research is being performed on developing medications that can sensitize tumors to radiation. Nasal cavity and paranasal sinus cancers can be treated with chemotherapy either before or after surgery. Chemotherapy before surgery is performed to decrease the size of the tumor so that surgical removal is easier. Chemo828
Salem Health: Cancer therapy administered after surgery is intended to destroy any remaining cancer cells. Traditional chemotherapy drugs include cisplatin and 5-fluorouracil for paranasal sinus cancers. Vincristine (Oncovin), cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), and cisplatin are used to treat esthesioneuroblastomas. Epidermal growth factor receptor (EGFR) inhibitor drugs are also being used to treat nasal cavity and paranasal sinus cancers. These drugs interfere with the growth and division of tumor cells by inhibiting a hormone that encourages their growth. Some EGFR drugs being used are cetuximab (Erbitux), gefitinib (Iressa), and erlotinib (Tarceva). Genetic therapy is being explored and drugs tested against tumors with mutations of the TP53 (also known as p53) tumor-suppressor gene. Prognosis, prevention, and outcomes: Prognosis depends on the stage and location of the tumor and the age and condition of the patient. People with Stage I and II cancers of the nasal cavity and the paranasal sinuses often have full recovery after their treatments. For people with Stage III and IV cancers, full recovery is less likely. These patients, if they are cured, may be left with disfiguring facial changes due to surgery and radiation therapy. People who are elderly or in poor general health are less likely to survive Stage III and IV cancers. Nasal cavity and paranasal sinus cancers cannot be prevented. There are many cases with no known cause. However, avoiding risk factors can decrease the likelihood of developing one of these cancers. The outcome of a nasal cavity or paranasal sinus cancer depends on the type of tumor and the tissue from which it arises, the size of the tumor, and whether it has metastasized. Some types, like melanoma, are rapidly fatal. Other types grow slowly and may be resected successfully. The more extensive the tumor, the more likely it is that it will affect the cranial nerves and the sense of smell. More advanced tumors are quite likely to cause facial deformity as well as interference with tasting, smelling, and vision. Damage to the cranial nerves by surgery can affect the ability to open, close, and move the eyes; chew and swallow; and to change facial expressions. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Carper, Elise, Kenneth Hu, and Elena Kuzin. One Hundred Questions and Answers About Head and Neck Cancer. Sudbury, Mass.: Jones and Barlett, 2008. Genden, Eric M., and Mark A. Varvares, eds. Head and Neck Cancer: An Evidence-Based Team Approach. New York: Thieme, 2008.
Salem Health: Cancer Petruzelli, Guy, ed. Practical Head and Neck Oncology. San Diego: Plural, 2008. u
Other Resources
American Cancer Society Detailed Guide: Nasal Cavity and Paranasal Cancer http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_nasal_cavity_and_ paranasal_cancer.asp?sitearea= American Rhinologic Society An Introduction to Nasal Endoscopy http://american-rhinologic.org/ patientinfo.introendoscopy.phtml National Cancer Institute Paranasal Sinus and Nasal Cavity Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ paranasalsinus See also Air pollution; Bone cancers; Cigarettes and cigars; Head and neck cancers; Lymphomas; Melanomas; Occupational exposures and cancer; Sarcomas, soft-tissue; Squamous cell carcinomas; Tobacco-related cancers.
u National Cancer Institute
(NCI) Category: Organizations Definition: The National Cancer Institute (NCI) is a United States government organization dedicated to reducing the burden of cancer through research into prevention and treatment of the disease. It is part of the National Institutes of Health (NIH), under the Department of Health and Human Services. History: Recognizing the growing toll of cancer on the United States and the world, Congress enacted the National Cancer Institute Act on August 5, 1937. The act created the NCI and directed it to conduct research into the causes of cancer, ways it might be prevented, and means of diagnosing and treating cancer patients. The institute was also directed to aid and coordinate the research of other cancer research organizations and promote education and training related to the disease. By 1939, a research team was assembled through a merger of Harvard University’s Office of Cancer Investigations and a pharmacology division within the National Institutes of Health. In 1940 the NCI published the first issue of the Journal of the National Cancer Institute. It was the first major venue in the world to publish scientific papers exclusively
National Cancer Institute (NCI) related to cancer. Although ownership of the journal was fully transferred to Oxford University Press in 2001, it remains a peer-reviewed and highly respected source of new information about cancer research. To promote clinical trials of new cancer treatments, the NCI established the Clinical Trials Cooperative Group Program in 1955. Within three years, the program had established 17 cooperative groups, consisting of various cancer centers, researchers, and physicians, each coordinated to investigate different methods of treating cancer. By 2007, more than 1,700 institutions were involved with the program and more than 22,000 patients were participating in trials each year. In 1971 the National Cancer Act reinvigorated the National Cancer Institute. At the time, cancer was the second leading cause of death in the United States and President Richard M. Nixon vowed to change that. The act provided the institute with greater authority to coordinate national cancer activities, a significant increase in funding, and a new research facility at Fort Detrick in Frederick, Maryland, where a biological warfare laboratory was converted for cancer research purposes. By the late 1970’s, the institute began to recognize the potential of information services in the fight against cancer. In 1976, it established the Cancer Information Service, which provides information about cancer to patients and the public through a national phone service (1-800-4CANCER) and various print publications. A year later, it established the first electronic registry of cancer clinical trials. This registry, known as CLINPROT, would be the first service available through the institute’s Physician Data Query (PDQ). PDQ is available through the institute’s Web site, and in 2007 CLINPROT contained abstracts of more thab 16,000 clinical trials. In 1991 the institute’s Surveillance Epidemiology and End Results (SEER) program showed a decline in the rate of deaths caused by cancer for the first time. In 2003 the program recorded the first decline in the actual number of deaths. In 2006 the U.S. Food and Drug Administration approved a vaccine that was created using technology developed by the institute. By fighting human papillomavirus (HPV), this vaccine (marketed as Gardasil) may reduce incidence of cervical cancer by as much as 70 percent. Internal research: Research carried out within the National Cancer Institute is performed by either the Center for Cancer Research (CCR) or the Division of Cancer Epidemiology and Genetics at one of the two institute campuses. The main campus is within the National Institutes of Health, located in Bethesda, Maryland. The second 829
National Science Foundation (NSF)
Salem Health: Cancer
campus is within the Fort Detrick Army Garrison. The NCI also maintains an Advanced Technology Center at the National Institute of Standards and Technology. A combined total of about 3,200 people work in these centers, alongside about 300 principal investigators. The goal of the Center for Cancer Research is to discover better options for preventing, detecting, diagnosing, and treating cancer. Through close collaboration between basic scientific investigations and applied clinical trials, the center has found that cancer research can proceed more rapidly than was traditionally possible. By rapidly deploying innovative techniques and technologies to the scientific community, the center has made major contributions to the field.
National Cancer Institute http://www.cancer.gov
Support of external research, education, and training: In addition to the research carried out within the governmental organization, the National Cancer Institute provides funding to private research organizations, universities, hospitals, and training facilities to further the goal of reducing the burden of cancer. In 2007 the institute anticipated an investment of more than $2 billion in about five thousand research project grants. Organizations that receive these grants must first submit a detailed grant proposal that demonstrates how their research will further the goals of the NCI and maintain safety for participants. All grant proposals are peer-reviewed and carefully scrutinized by the institute. By providing educational assistance in the form of fellowships, internships, grants, and loan repayment programs, the institute also aids both predoctoral and postdoctoral students in their pursuit of education. Robert Bockstiegel, B.S.
u National Science Foundation
u For Further Information Epstein, Samuel S. Cancer-Gate: How to Win the Losing Cancer War. Amityville, N.Y.: Baywood, 2005. Jeffries, Lee P., ed. Leading Topics in Cancer Research. New York: Nova Science, 2007. Martakis, Ignatius K., ed. Cancer Research at the Leading Edge. New York: Nova Science, 2007. Pereira, Larissa S., ed. Cancer Research Perspectives. New York: Nova Science, 2008. United States Department of Health and Human Services, National Institutes of Health. The NCI Strategic Plan for Leading the Nation to Eliminate the Suffering and Death Due to Cancer. Washington, D.C.: National Cancer Institute, 2006. u
Other Resources
Association of American Cancer Institutes http://www.aaci-cancer.org 830
See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Cancer education; Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Science Foundation (NSF); Prevent Cancer Foundation; Robert H. Lurie Cancer Center.
(NSF) Category: Organizations Definition: The National Science Foundation (NSF) is a United States government organization dedicated to advancing scientific progress and promoting the health, welfare, and security of the nation by providing federal funding and support to scientific research. History: After World War II, many U.S. scientists and politicians recognized the need for sustained government support of basic scientific research if the United States was to maintain its new role as a global leader. One engineer and scientist named Vannevar Bush, then head of the wartime Office of Scientific Research and Development, was particularly instrumental in advocating for the creation of a new government agency. Bush’s 1945 report to the president, entitled “Science—The Endless Frontier,” has been called the blueprint for the National Science Foundation. Five years after the report was presented, on May 10, 1950, President Harry S. Truman signed the act, which created the NSF. After the Soviet launch of Sputnik, U.S. interest in funding science grew, and in 1958 the National Science Foundation’s budget was significantly increased. With a larger budget, however, came greater congressional oversight. In 1968 the Daddario-Kennedy amendment to the NSF charter was passed, forcing the foundation to get annual authorization of its spending from both the House and the Senate. The act also authorized the foundation to fund applied science in addition to its usual support for basic science. During the following three decades, the NSF continued to expand its budget as Congress and the nation increasingly recognized the value of investment in scientific research.
Salem Health: Cancer As the budget grew, so did the number of grants awarded. During the 1970’s, the foundation provided as few as six thousand grants, but by the 1990’s that number grew to more than ten thousand. Funding for graduate students also increased, and by the 1990’s almost thirty-four thousand graduate students were receiving federal support. By 2006 the National Science Foundation’s budget had grown to approximately $5.6 billion. It is the primary source of all federal funding for many of the nonmedical sciences and provides nearly half of all the federal support for academic nonmedical basic research. More than two hundred Nobel laureates have been funded by the foundation. Organization: The National Science Foundation is organized into two main parts: the Office of the Director and the National Science Board. Working under the director are all of the directorates for the various scientific divisions as well as several offices that provide support services. The director and all of the directorates and offices that work under the director are responsible for deciding which proposals will be funded. The twenty-four-member National Science Board provides oversight, establishes strategic policy, and approves new programs or particularly large grants. The director and members of the board serve six-year terms. They are appointed by the president of the United States and approved by the Senate. The funding process: In 2007 the National Science Foundation received more than forty-thousand grant proposals. To decide which proposals are worthy of funding, it must be determined which proposed research projects would best serve the goals of the foundation. To do this, the foundation has developed a process that begins with its staff’s participation in workshops, conferences, and symposia. By attending these gatherings, they keep in constant contact with the scientific community and identify possible areas for achievement. The NSF next publishes a solicitation for proposals to serve a specific need or to achieve a specific goal. Scientific researchers and engineers respond by submitting detailed proposals that describe their idea, request a specific amount of funding, and describe how that funding will be used. The foundation also accepts proposals that are not a response to a solicitation. Then the NSF assembles a panel of independent reviewers made up of experts in the field. For example, if a proposal seeks funding to conduct research into a new technique for studying ozone depletion, the foundation finds prominent environmental scientists. More than fifty thousand experts participate in review panels each year. These panels usually review numerous proposals at one
National Science Foundation (NSF) time and confidentially decide which proposals would best advance the goals of the foundation. This process is known as merit review. Once a proposal is accepted, the NSF will then provide funding and periodically review the progress of the research. Cancer research: The National Science Foundation does not directly fund medical research, since medical research is usually funded by other parts of the federal government, such as the National Institutes of Health. However, much of the research funded by the NSF does have applications within the medical field. Discoveries made using foundation funding are published in scientific journals and made available for scientists involved with cancer research. Often a discovery in one field will aid discovery in another. For example, in 1993 William Fenical, a foundationfunded researcher at the Scripps Institution of Oceanography in La Jolla, California, discovered a type of coral that possesses a chemical called eleutherobin. This chemical, it was discovered, binds to cellular microtubules and can prevent division of cancer cells. Like many other anticancer drugs being tested, this chemical was discovered through funding research in a completely different field. Robert Bockstiegel, B.S. u
For Further Information Jeffries, Lee P., ed. Leading Topics in Cancer Research. New York: Nova Science, 2007. Martakis, Ignatius K., ed. Cancer Research at the Leading Edge. New York: Nova Science, 2007. National Science Foundation. Overcoming the Past, Focusing on the Future. Arlington, Va.: Author, 2003. Pereira, Larissa S., ed. Cancer Research Perspectives. New York: Nova Science, 2008.
u
Other Resources
Association of American Cancer Institutes http://www.aaci-cancer.org National Science Foundation http://www.nsf.gov See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); Prevent Cancer Foundation; Robert H. Lurie Cancer Center. 831
Native North Americans and cancer
u Native North Americans and
cancer Category: Social and personal issues Also known as: American Indians, Native Americans, First Nations Definition: Native North Americans are a widely dispersed group of people made up of individuals from hundreds of different tribes throughout the contiguous United States and Alaska. According to the National Institutes of Health, cancer is the second leading cause of death among individuals of American Indian and Native Alaskan descent. Description of the population: According to the 2000 census, there were 2,475,956 individuals in the United States who identified themselves as being of American Indian or Native Alaskan descent. This included 1,233,982 men and 1,241,974 women. In 2000, 138,439 of these individuals were the age of sixty-five or older, or about 5.6 percent of the Native American and Alaskan Native population. In comparison, about 12.4 percent of the general American population were age sixty-five or older in 2000. The median household income as reported by the 2000 census of individuals who identified themselves as American Indian or Alaskan Native was $30,599 compared with a median household income of $41,994 for the American population in general. At that time, 607,734 people, or about 25 percent of American Indians and Native Alaskans, lived below the poverty line, compared with about 12 percent of the American population in general. There are 569 different American Indian and Native Alaskan tribes that are officially recognized by the United States government. American Indians and Native Alaskans speak more than three hundred different languages. Many of these individuals live on reservations, especially in the southwestern states such as Arizona and New Mexico. In total, American Indians live on nearly three hundred reservations throughout the United States, although more than half of those of American Indian or Native Alaskan heritage do not live on reservations. Incidence, death, and survival statistics: According to the United States Centers for Disease Control, in 2002 cancer was the second most common cause of death among American Indians and Native Alaskans. In 2002, 2,467 individuals self-reporting as American Indians died of cancer, accounting for about 20 percent of the total 12,415 deaths of individuals from that heritage group. For American Indian children between the ages of five and nine, cancer was the second leading cause of death, fol832
Salem Health: Cancer lowing unintentional injuries. For American Indians of both sexes between the ages of forty-five and fifty-four, cancer was the leading cause of death, as it also was for those aged fifty-five to sixty-four and those aged sixtyfive to seventy-four. For American Indians over the age of eighty-five, cancer was the second leading cause of death, following heart disease. The rates of colon and rectal cancer among Native Alaskans are higher than the rates of the same cancers among Americans who are of European heritage. Native American women who have been diagnosed with cervical cancer have a poorer prognosis than women of many other heritages. The history of the relationship between American Indians and Alaskan tribes and the United States federal government is complex and filled with problems. The result of centuries of interaction between the U.S. government and the many Native Alaskan and American Indian tribes is that the tribes have been recognized as sovereign entities. However, they are also entitled to health care and other services provided by the federal government. The Indian Health Service is a division of the federal government charged with providing health services to many American Indians and Alaskan Natives. It is a department of the U.S. Department of Health and Human Services and was founded in 1955. As of 2005 the Indian Health Service either provided service for, or covered the cost of health services for, about 1.5 million total individuals. The Indian Health Service operates mainly on recognized reservations, which means that many individuals of American Indian and Native Alaskan descent may not have access to available services because many such individuals do not live in or around reservations. Risk statistics: There are many problems that may contribute to people of American Indian and Native Alaskan descent not getting preventive health care and medical screenings that lead to early diagnosis of cancer. Many Native Alaskans and American Indians live in remote areas away from large cities where cancer centers and hospitals are often located. This can cause individuals to delay seeking treatment and to not have access to regular comprehensive medical care. Not receiving comprehensive medical care on a regular basis, including general health care and routine screenings for diseases such as cancer, is generally linked to negative health outcomes. When cancer is not detected early, it is less likely to be have a positive outcome. Many Native Alaskans and American Indians do not report receiving regular medical care and screenings that can lead to early diagnosis. According to a 2004 survey sponsored by the
Salem Health: Cancer Kaiser Family Foundation and published in the American Journal of Public Health, 26 percent of American Indians and Native Alaskans reported that they had not visited a medical doctor within the last year, compared with 20 percent of people of European heritage. Some of this dissatisfaction doubtless relates to the historic relationship between Native Americans and the Indian Health Service. Perception of the quality and effectiveness of health care services is lower among American Indians and Native Alaskans than among individuals of European descent. Some 16 percent of American Indian and Native Alaskans who sought care reported that they were not satisfied with the quality and care of the medical services that they received, compared with only 10 percent of people of European descent who reported dissatisfaction. An even larger disparity was found relating to provider communication. Some 26 percent of American Indians and Native Alaskans reported poor communication with their health care provider, compared with 17 percent of those of European descent. Lack of insurance coverage is another barrier to prevention and early diagnosis, as well as a barrier to receiving cancer care and treatment if cancer does develop. About 83 percent of Americans of European descent have access to health care through private coverage, usually through a job, while only 49 percent of American Indians and Native Alaskans have access to similar coverage. Although the Indian Health Service does provide services to many uninsured individuals, it is not available to all of them. About 35 percent of American Indians and Native Alaskans are not insured. Because a disproportionate percentage of Native Alaskans and American Indians have incomes below the poverty line, many individuals have increased cancer risks that are tied to poverty. People who live in poverty are more likely to smoke, which is a significant risk factor for many types of cancer. Individuals who live in poverty are less likely to have a well-balanced diet rich in fruits, vegetables, and whole grains, which is believed to help reduce the risk of cancer. Poor diets and concomitant obesity have historically been exacerbated by the unhealthy commodity foods provided by the U.S. government. Perspective and prospects: Many Native Alaskan and American Indian individuals have different perceptions of Western medicine, medical practitioners, and medical technology. Medical practitioners who are going to work with Native Alaskan or American Indian populations may benefit from cultural awareness training. Improving doctorpatient communication, relationships, and trust can be an important building block toward more positive cancer out-
Native North Americans and cancer comes in this population. Individuals who have a positive relationship with their health care provider are more likely to seek screenings and early treatment, which can drastically improve cancer outcomes. Although there are many barriers to prevention, early diagnosis, and effective treatment of cancer among Native Alaskans and American Indians, the outlook is improving. Many different groups and foundations have sponsored research into the health disparities faced by minorities in the United States as well as research and educational outreach programs designed specifically to help American Indians and Native Alaskans. Organizations such as the Native American Cancer Research group dedicate time and resources to providing education to American Indians about cancer, help organize research into genetic patterns of cancer inheritance among American Indians, and provide other cancer support services aimed specifically at helping reduce the incidence and mortality of cancer among the American Indian community. Helen Davidson, B.A. u
For Further Information Duran, Eduardo. Healing the Soul Wound: Counseling with American Indians and Other Native Peoples. New York: Teachers College Press, 2006. LaVeist, Thomas A. Minority Populations and Health: An Introduction to Health Disparities in the United States. San Francisco: Jossey-Bass, 2005. Metrosa, Elene V., ed. Racial and Ethnic Disparities in Health and Health Care. New York: Nova Science, 2006.
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Other Resources
National Cancer Institute Surveillance Research: Overview of Native American Initiatives http://surveillance.cancer.gov/disparities/native Native American Cancer Research http://www.natamcancer.org Native American Cancer Research Partnership http://nacrp.web.arizona.edu See also Complementary and alternative therapies; Ethnicity and cancer; Financial issues; Geography and cancer; Insurance; Poverty and cancer; Prayer and cancer support; Psychosocial aspects of cancer. 833
Nausea and vomiting
u Nausea and vomiting Category: Diseases, symptoms, and conditions Also known as: Emesis, retching, heaving, gagging, being sick to the stomach, seasickness, throwing up, butterflies in the stomach, dry heaves Related conditions: Chemotherapy, radiation therapy, food poisoning, morning sickness during pregnancy, inner ear syndrome, infections Definition: Nausea is the uneasy sensation that one is about to vomit, expelling stomach contents or undigested food through the mouth. Nausea can sometimes result in dry heaves when the stomach is empty. Risk factors: Because nausea and vomiting are symptoms of many disorders as well as cancer therapies, the risk depends on the individual patient’s medical condition and circumstances. Etiology and the disease process: Nausea and vomiting are not diseases but symptoms—a sign that something is wrong within the body. Nausea and vomiting are complex body functions coordinated by the vomiting center in the brain stem of the body’s central nervous system. Retching usually occurs after nausea and before vomiting as the body prepares to expel the stomach contents. Nausea and vomiting can occur as a reaction to many prompts, including overeating, ingesting too much alcohol or sugar, infection, viruses, inner ear disorders, irritation of the throat or stomach lining, food poisoning from contaminated food or fluids, migraine headaches, unpleasant smells or sights, stress, severe anxiety or emotional circumstances, medications, or treatments for cancer. A person experiencing a heart attack, appendicitis, or head injury with increased pressure on the brain may have nausea and vomiting. Determining the cause is critical to finding the appropriate treatment and correcting the problem. Cancer patients may experience nausea and vomiting for several reasons. Cancer treatments such as chemotherapy can affect patients by causing side effects of nausea and vomiting. Not all chemotherapy causes nausea and vomiting. The level of nausea that chemotherapy induces can range from low to severe. Factors such as the amount of the drug used or the route of administration can affect the incidence of nausea and vomiting. The characteristics of the person receiving chemotherapy—age, gender, or history of motion sickness—can influence the occurrence of nausea and vomiting. Sometimes nausea and vomiting will happen when patients enter an environment in which they have received chemotherapy because of odors or a 834
Salem Health: Cancer mental association with the setting (anticipatory nausea and vomiting). Cancer patients may have nausea and vomiting as an extension of their disease. The tumor may have spread to the gastrointestinal tract, the liver, or the brain. Also, highdose radiation treatments given for certain types of cancer can cause nausea and vomiting in the hours following therapy. Other causes for nausea and vomiting in cancer patients include bowel obstructions, infections, anxiety, and certain medicines. Usually the side effects of treatment can be controlled with medication, but if they are uncontrolled, they can result in serious metabolic dysfunction or anxiety and depression for the cancer patient and family. Incidence: Almost every person will experience nausea and vomiting at some stage of life for various reasons. Approximately 50 percent of all cancer patients have nausea and vomiting during their treatment or as their disease progresses. Some sources estimate that as many as 7 or 8 out of 10 (70 to 80 percent) cancer patients have some nausea and vomiting. Symptoms: Nausea produces a queasy feeling in the stomach and increased salivation in the mouth. Sometimes a stomachache or headache will occur before the nausea occurs. The person may experience dizziness, a fast heart rate, skin temperature changes (either feeling chilled or hot and flushed), and difficulty swallowing with nausea. Retching usually precedes vomiting as the body prepares to push out the stomach contents. However, sometimes vomiting occurs without nausea. Loss of fluids and electrolytes can leave the patient feeling drained and fatigued. Screening and diagnosis: The severity, duration, and frequency of nausea and vomiting will determine the need for further assessment and intervention by the health care provider. The key to screening and diagnosing nausea and vomiting is finding the underlying cause. Patients should review any health conditions they have that might contribute to nausea and vomiting such as migraine headaches or pregnancy (morning sickness). Health care providers can prepare cancer patients for the likely possibility of nausea and vomiting during their treatment process. The degree to which nausea and vomiting affects the patient depends on many factors. Extension of cancer with metastatic disease to vital organs can increase the incidence of nausea and vomiting. Treatment and therapy: Nausea and vomiting do not necessarily need treatment unless they continue for extended periods of time, as can occur with several types of radiation and chemotherapy. The first approach to treat-
Salem Health: Cancer
Nausea and vomiting
ment is to determine the cause. If the cause can be defined and treated successfully, the nausea and vomiting will subside. Sometimes a simple breath of fresh air can resolve the problem. Some people successfully use ginger ale, cola, or crackers to decrease the nausea. Vomiting will immediately relieve nausea but nausea may return. Simple nausea and vomiting usually respond to limiting the intake of food and fluids. Gradually patients may take clear liquids, then small amounts of dry toast or crackers. If this is well tolerated without more nausea and vomiting, patients can return to a regular diet. If the nausea and vomiting continue uncontrolled, further examination is necessary to remove or treat the cause. Over time, patients with uncontrolled nausea and vomiting will become dehydrated and may suffer an electrolyte imbalance. Patients with continuous nausea and vomiting may need antiemetics, medications that suppress these symptoms. If severe dehydration has occurred, patients may need to be given intravenous fluids by a health care provider. Dehydration and electrolyte imbalance can be serious and can even be life-threatening. Alternative or complementary therapies may help control or minimize nausea and vomiting. Nonpharmacologic therapies include biofeedback, guided imagery, attentional distraction, massage, and hypnosis. Behavior therapy such
as desensitization may be useful for anticipatory nausea and vomiting. Ginger, an herb used to decrease nausea and vomiting, can be used in food or taken in capsules. Acupressure may help some patients. Dietary approaches such as eating food with minimal smell (either cold or at room temperature) while having chemotherapy may decrease nausea and vomiting. Avoiding certain types of foods, such as high-fat, spicy, or salty foods, helps some patients. Prognosis, prevention, and outcomes: Most people experience uncomplicated nausea and vomiting at some time in their lives but can regain their health through addressing the cause and allowing the body time to heal. However, a health care provider should be notified if people have nausea and vomiting that continue for longer than forty-eight hours, experience extreme dizziness, vomit blood, or are unable to retain fluids within twenty-four hours. If people have begun taking a new medication before the onset of nausea and vomiting, they should notify their health care provider to possibly change the drug. People should consult a health care provider when they have yellowing of the skin or eyes, difficulty swallowing, mental confusion, dehydration and extreme thirst, trouble with urination, or constant or sharp pain in the chest or lower abdomen. Certain conditions when accompanied by nausea and vomiting may indicate a medical emergency, such
Medicines Used to Treat Nausea in Cancer Patients Drug
Use
Aprepitant
Used for acute and delayed nausea and vomiting
Aexamethasone
Corticosteroid, given orally and intravenously; used alone or in combination
Aiphenhydramine
Antihistamine, used for low-risk chemotherapy or when other antiemetics have failed; used in combination and also to reduce side effects from other antiemetics
Aolasetron, granisetron, ondansetron New antiemetics, given orally or intravenously Aronabinol, nabilone
Tetrahydrocannabinol (THC) is main ingredient; used when other antiemetics have failed
Haloperidol
Tranquilizer, used when other antiemetics have failed; used in combination
Lorazepam, alprazolam
Anxiety drugs; generally used in combination
Metoclopramide
Used for low-risk chemotherapy or when other antiemetics have failed; used alone or in combination
Olanzapine
Used when other antiemetics fail
Palonosetron
Used for acute and delayed nausea and vomiting; given intravenously
Prochlorperazine
Used for low-risk chemotherapy or when other antiemetics have failed; used alone or in combination
Promethazine
Used when other antiemetics have failed
Source: National Comprehensive Cancer Network
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Needle biopsies as diabetic shock, severe headache, consistent chest pain, difficulty breathing, profuse sweating, or exposure to a known allergen. At least half of all cancer patients will experience some nausea and vomiting at some point in their disease process. Using antiemetics or complementary therapies such as relaxation, massage, or meditation can sometimes produce a better outcome to the nausea and vomiting resulting from chemotherapy or radiation therapy. Education and knowledge can go a long way in helping patients help themselves. Robert W. Koch, D.N.S., R.N. u For Further Information Anderson, Greg. Cancer: Fifty Essential Things to Do. New York: Penguin Books, 1999. Donnerer, Josef, ed. Antiemetic Therapy. New York: Karger, 2003. Lyss, Alan P., and Humberto M. Fagundes. Chemotherapy and Radiation for Dummies. Hoboken, N.J.: Wiley, 2005. Tonato, M., ed. Antiemetics in the Supportive Care of Cancer Patients. New York: Springer, 1996. u
Other Resources
American Cancer Society What Can I Do About Nausea and Vomiting? http://www.cancer.org/docroot/MBC/content/ MBC_2_2X_What_Can_I_Do_About_Nausea_ and_Vomiting.asp?sitearea=MBC National Cancer Institute Nausea and Vomiting http://www.cancer.gov/cancertopics/pdq/ supportivecare/nausea/patient National Comprehensive Cancer Network Nausea and Vomiting Treatment Guidelines for Patients with Cancer http://www.nccn.org/patients/patient_gls/_english/ _nausea_and_vomiting/contents.asp See also Acupuncture and acupressure for cancer patients; Adjuvant therapy; Antinausea medications; Cachexia; Chemotherapy; Complementary and alternative therapies; External beam radiation therapy (EBRT); Gastrointestinal complications of cancer treatment; Ginseng, panax; Living with cancer; Medical marijuana; Motion sickness devices; Nutrition and cancer treatment; Radiation therapies; Side effects; Taste alteration; Weight loss. 836
Salem Health: Cancer
u Needle biopsies Category: Procedures Also known as: Fine needle biopsy, core needle biopsy, stereotactic (exact) biopsy, Mammotome biopsy, Advanced Breast Biopsy Instrumentation (ABBI) Definition: Aneedle biopsy is a procedure in which a sample of body tissue is extracted by using a hollow needle or a similar instrument. There are two types of needle biopsies: fine needle biopsy and core needle biopsy. In fine needle biopsy, a thin needle attached to a syringe is used to extract the tissue samples. In core needle biopsy, a wide-gauge needle or a special biopsy instrument, such as a Mammotome or ABBI, is used. The Mammotome and ABBI are used only to perform a breast biopsy. The core needle ranges from 0.25 to 1 centimeter in diameter. It has a special cutting edge and a spring-loaded device that suctions out the tissue samples. The Mammotome suctions in breast tissue and then cuts it with a rotating blade. The ABBI extracts a cylinder of breast tissue about the size of the tumor. Cancers diagnosed: Breast, lung, prostate, kidney, thyroid, musculoskeletal, liver, heart, and skin cancers Why performed: Needle biopsies are performed in order to obtain samples of tissue from a tumor or growth that is suspected of being cancer. Needle biopsies are considered less invasive than surgical biopsies and often can be performed as an outpatient procedure. Patient preparation: The patient preparation will depend on the tissue that is being sampled, the risk of the procedure, and the type of facility where the biopsy is to be performed. If a core needle biopsy is carried out in a physician’s office, then ultrasonic guidance is used to localize the tumor, unless it is palpable. If it is palpable, then no radiologic guidance is required. Needle biopsies that require the use of fluoroscopy, computed tomography (CT), magnetic resonance imaging (MRI), or mammography to localize the tumor or that are considered high risk are performed in an outpatient surgical center. Patient preparation may include a preoperative physical examination, blood work, and possibly an electrocardiogram (EKG). The patient needs to fast for two to four hours before the procedure. Occasionally, high-risk biopsy procedures require that the patient be admitted to the hospital for the biopsy and then stay overnight for monitoring. In this instance, patient preparation would require a preoperative physical examination, blood work, and an EKG. Also, the patient would need to fast after midnight the day of the biopsy.
Salem Health: Cancer
Needle biopsies
Steps of the procedure: The patient is positioned so that the area to be biopsied is exposed. This area is then scrubbed and disinfected. A local anesthetic is injected into the biopsy area. If the tumor is not palpable, then radiologic imaging is used to localize the tumor and to follow the progress of the needle into the tissue. This is called stereotactic localization. For a fine needle biopsy, the surgeon inserts the needle into the tumor and aspirates small samples of tissue. The needle is repositioned several times so that multiple tissue samples can be taken. Unless the tumor is superficial, for core needle biopsy, a small incision (0.25 inch in length) is made into the tissue. The core needle is then inserted into the tumor through the incision. Multiple tissue samples are taken. For core needle, Mammotome, and ABBI biopsies of the breast, the patient is positioned on her stomach with a single breast hanging through a hole in a specially designed table. This procedure uses either mammography or ultrasound guidance to localize the breast tumor. For MRI guidance, the patient is positioned on her stomach and both breasts are hanging pendent. The biopsy is performed on the hanging breast. After the procedure: If an incision was made, then either a suture (stitch) or an adhesive paper (Steri-Strip) is applied to close the edges of the incision. A sterile dressing is applied over the biopsy site. For some biopsies, a pressure dressing is applied after the biopsy procedure. Usually, the patient is monitored for at least one hour after the biopsy. The patient can remove the dressing in one to two days and should avoid vigorous physical exercise or heavy lifting for two weeks after a biopsy. Once a needle biopsy has healed, including Mammotome and ABBI, the patient is unlikely to have a scar from the procedure.
ined under a microscope. A cytologist examines the cells from a fine needle biopsy, in which the specimens consist of aspirated cells. A pathologist examines the samples from core needle biopsies, which consist of cores of tissue. This tissue must be sliced thinly and applied to a slide for examination. The surgeon will receive a pathology report that describes the cells of the tumor. It will discuss the size, shape, and activity of the cells and their nuclei, comparing them with normal cells. The report states whether the tumor is cancer and, if so, the type of cancer cells present within the tumor. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information DeVita, Vincent, Jr., Samuel Hellman, Steven A. Rosenberg, et al., eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. McPhee, Stephen J., Maxine A. Papadakis, and Lawrence M. Tierney, eds. Current Medical Diagnosis and Treatment 2008. New York: McGraw-Hill Medical, 2007. Rosen, Paul Peter, and Syed A. Hoda. Breast Pathology: Diagnosis by Needle Core Biopsy. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2006. Yang, Grace, Chia-yu Hsu, and Liang-Che Tao. Transabdominal Fine-Needle Aspiration Biopsy: A Colour
Risks: The liver and the kidney are highly vascular (have many blood vessels) and thus are at high risk of bleeding following biopsies. Lung biopsies carry a risk for causing collapse of a portion of the lung (pneumothorax). Other risks of needle biopsy are nerve damage and infection. Results: The biopsied tissue is sent to a cytologist or a pathologist to be exam-
Needle biopsy of the brain. (Custom Medical Stock Photo)
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Needle localization Atlas and Monograph. 2d ed. Hackensack, N.J.: World Scientific, 2007. u
Other Resources
Radiology Info Needle Biopsy of Lung Nodules Http://www.radiologyinfo.org/en/info.cfm?pg= nlungbiop&bhcp=1 WebMD Breast Biopsy http://www.webmd.com/breast-cancer/ guide/breast-biopsy See also Biopsy; Bone marrow aspiration and biopsy; Computed tomography (CT)-guided biopsy; Core needle biopsy; Liver biopsy; Needle localization; Pathology; Pleural biopsy; Sentinel lymph node (SLN) biopsy and mapping; Stereotactic needle biopsy; Surgical biopsies; Wire localization.
u Needle localization Category: Procedures Also known as: Wire localization, stereotactic (exact) localization Definition: Needle localization is a procedure that is used to mark a nonpalpable mass (one that cannot be felt) prior to biopsy (removal of a piece of tissue). It is most commonly associated with breast biopsies. Needle localization is performed by a radiologist or surgeon using ultrasound, mammography, or magnetic resonance imaging (MRI) to view the tumor.
Salem Health: Cancer Steps of the procedure: First, the mass is localized. When ultrasound is used, the transducer (used to transmit and receive sound waves) is held to the side of the mass while the needle is inserted. With mammography, it is necessary to use special mammography plates with a screen or a small door in them, so that the needle can be inserted while the breast is compressed. MRI imaging requires the use of a special attachment through which the needle can be inserted. A local anesthetic is injected over the tumor. Either a thin wire or a needle is then inserted into the tumor. The position of the wire or needle is verified with the radiologic imaging being used. After the procedure: The biopsy is performed either in an operating room (for a surgical biopsy) or in the biopsy room (for a core needle biopsy). The wire or needle is removed with the breast tumor. Risks: There is a slight risk of bleeding or infection after this procedure. Results: The surgeon is able to localize the nonpalpable breast tumor by the presence of the wire and then to remove it. Pathology will be performed on the tissue sample to determine whether it is cancerous. Christine M. Carroll, R.N., B.S.N., M.B.A. u
For Further Information Rosen, Paul Peter, and Syed A. Hoda. Breast Pathology: Diagnosis by Needle Core Biopsy. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2006. Rubin, Eva, and Jean F. Simpson. Breast Specimen Radiography: Needle Localization and Radiographic Pathologic Correlation. Philadelphia: Lippincott-Raven, 1998.
Cancers diagnosed: Breast cancer Why performed: Since the breast mass is not palpable, the surgeon needs a way to find the tumor in order to biopsy it. The wire serves as a marker for the tumor. Patient preparation: Needle localization is associated with surgical and core needle breast biopsy. Usually, this procedure is performed in a radiology office or a breast biopsy room. For a surgical biopsy, within a month before the procedure, the patient has a preoperative physical examination, routine blood work, and possibly an electrocardiogram (EKG). Also, she will have to fast after midnight the day of the procedure. For core needle biopsy, the patient needs to fast only for two to three hours before the procedure. 838
u
Other Resources
eMedicine Breast Needle Localization http://www.emedicine.com/Radio/topic911.htm WebMD Breast Biopsy http://www.webmd.com/breast-cancer/ guide/breast-biopsy See also Biopsy; Breast ultrasound; Magnetic resonance imaging (MRI); Mammography; Needle biopsies; Stereotactic needle biopsy; Ultrasound tests; Wire localization.
Salem Health: Cancer
u Nephroblastomas Category: Diseases, symptoms, and conditions Also known as: Wilms’ tumors Related conditions: Beckwith-Wiedemann syndrome, WAGR complex (Wilms’ tumor aniridia-genitourinary anomalies-mental retardation), Denys-Drash syndrome Definition: Nephroblastomas are the most common malignant kidney tumors of early childhood. Risk factors: Nephroblastomas may arise sporadically (in otherwise healthy children) or can be inherited. A nephroblastoma is sometimes linked to birth defects such as aniridia (absence of the iris), hemihypertrophy (enlargement of one side of the body), and genitourinary abnormalities. Birth defect syndromes associated with nephroblastoma include Beckwith-Wiedemann syndrome (tongue and internal organ enlargement and omphalocele), WAGR syndrome (Wilms’ tumor aniridia-genitourinary anomaliesmental retardation), and Denys-Drash syndrome (Wilms’ tumor, kidney disease, and pseudohermaphroditism). Children aged seven and younger are at highest risk, although older children and adults are occasionally affected. No gender or racial predilection exists. Etiology and the disease process: There is compelling evidence that genetic factors (two mutational events involving the inactivation of tumor-suppressor genes) may be responsible for tumor development. As a result, primitive embryonic cells of the kidney fail to develop and instead multiply to form a tumor.
Nephrostomy
•
Stage II: Tumor metastasis to local surrounding area, completely resectable • Stage III: Tumor metastasis to surrounding area, not completely resectable • Stage IV: Tumor metastasis to distant organs (lungs, liver, and brain) • Stage V: Tumor present in both kidneys Treatment and therapy: Treatment consists of a combination of surgery, chemotherapy, and radiotherapy. Surgery can be partial, complete, or radical nephrectomy (surgical removal of the kidney). The drugs dactinomycin, doxorubicin, vincristine, and cyclophosphamide are used for chemotherapy. Radiotherapy is usually confined to Stage III and IV nephroblastoma. Prognosis, prevention, and outcomes: The prognosis is good, with an overall survival rate of 90 percent. Outcomes for nephroblastoma patients have vastly improved since the 1970’s, thanks to concerted efforts by the National Wilms’ Tumor Study Group (NWTSG) and the International Society of Pediatric Oncology (SIOP). Ophelia Panganiban, B.S. See also Beckwith-Wiedemann syndrome (BWS); DenysDrash syndrome and cancer; Pediatric oncology and hematology; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Nephrostomy
Incidence: Annually, 450 to 500 children in the United States are diagnosed with a nephroblastoma, with 24 percent of these cases forming part of a developmental defect syndrome.
Category: Procedures Also known as: Percutaneous nephrostomy (PCN), nephropyelostomy
Symptoms: Most patients have a painless abdominal mass, usually an incidental finding by the doctor or the parent. Some complain of abdominal pain, bloody urine, nausea and vomiting, anorexia, weight loss, and constipation.
Definition: Nephrostomy is a procedure in which an opening is made and a nephrostomy tube (catheter) is placed into the kidney to drain urine to outside the body. Urine is collected into a bag attached to the nephrostomy tube. The procedure is done either through a surgical incision or percutaneously (through the skin).
Screening and diagnosis: Lab tests, a thorough family medical history, and diagnostic imaging—ultrasound, chest X ray, computed tomography (CT) scan, and magnetic resonance imaging (MRI)—will help determine the extent of tumor spread. Surgical tumor removal and tissue sampling will confirm the diagnosis. Tumor staging helps establish the treatment plan: • Stage I: Tumor confined to the kidney, completely resectable
Cancers treated: Ovarian, cervical, colon, and other cancers of the pelvic area Why performed: Tumors may cause a blockage of one or both of the ureters, the tubes that normally carry urine from the kidneys to the bladder. The blockage causes a backup of urine into the kidneys, creating a great risk of infection and kidney damage that cannot be repaired. The insertion of nephrostomy tubes prevents the backup of urine. 839
Nephrostomy Nephrostomy tubes may also be placed during a diagnostic procedure called an antegrade pyelogram, which is done to determine the location of the blockage. In some cases, the nephrostomy tubes are inserted to allow the placement of anticancer drugs directly into the kidney. Nephrostomy tubes are also used for other conditions that affect the urinary tract. Patient preparation: Nephrostomy is usually performed on hospitalized patients. Some patients may have the procedure done without admission to a hospital. Preparation for the procedure may vary depending on the patient’s condition, the physician’s practice, and the facility. Generally, the patient must not have anything to eat or drink for four to eight hours before the procedure. The physician may ask the patient to temporarily stop or adjust the dose of some medications, including aspirin, blood thinners, and diabetes medications. Laboratory tests such as a complete blood count (CBC), coagulation tests, urinalysis, and urine culture for bacteria may be done before the procedure. The physician discusses the procedure, including the type of local anesthetic used, sedation, risks, and aftercare. The patient gives the physician permission to perform the procedure by reading and signing a consent form. Before signing the form, the patient may ask the physician questions to clarify anything that the doctor has said or any part of the consent form that the patient does not understand. Steps of the procedure: An intravenous (IV) line is inserted, usually in the patient’s arm or hand, to provide fluids, antibiotics, pain medication, and sedation. Nephrostomy is generally performed in the interventional radiology department by an interventional radiologist or urologist. The patient lies on the stomach and remains awake, although medication is given that may cause drowsiness. Monitoring of blood pressure, heart rate, and oxygen level is done throughout the procedure. Imaging procedures such as ultrasound, computed tomography (CT), or fluoroscopy are used to visualize the area. These procedures are done before and during insertion of the nephrostomy tube to guide the physician in placing the tube. The site where the tube will be inserted is sterilized. A medication such as lidocaine (Xylocaine) is given to numb the skin and tissues. A small incision is made, and a needle is inserted into the kidney. Contrast dye is injected for visualization, and the nephrostomy tube is inserted. The needle is removed. A dressing is placed over the site, and the nephrostomy tube is connected to a drainage bag. The tube site is on the right or left side of the back near the waistline, depending on which kidney is blocked. If both kidneys are blocked, then the physician will insert tubes for each kidney. 840
Salem Health: Cancer After the procedure: The patient is taken to the recovery room or back to the hospital room. Anurse will monitor the patient for any changes in blood pressure, heart rate, or breathing. The nurse monitors the urine output by measuring the urine collected in the bag. The bag may be attached to the patient’s leg by use of straps that are provided. Before discharge, the physician and/or a nurse will give the patient instructions on caring for the nephrostomy site, emptying the bag, monitoring the urine output, and noting signs of complications. Patients may need others to assist them in caring for the site and emptying the bag once they are home. In addition to the urine drained through the nephrostomy tube, the patient will still need to urinate. If only one tube is placed but the other kidney works normally, then the urine from that kidney still passes into the bladder. If nephrostomy tubes are placed in both kidneys, then there may still be drainage of some urine into the bladder. Risks: The risks of nephrostomy include bleeding, infection, blood clots in the nephrostomy tube or bladder, and dislodgement of the nephrostomy tube. Results: The placement of nephrostomy tubes will alleviate the backup of urine in the kidneys or allow treatment to be given. Although their use is normally for a short time, in some cases the blockage cannot be removed and the nephrostomy tubes remain in use permanently. In these cases, the tubes are replaced periodically. Wanda E. Clark, M.T. (ASCP) u
For Further Information Berman, Joel. Understanding Surgery: A Comprehensive Guide for Every Family. Wellesley, Mass.: Branden Books. 2001. Nurse’s Five-Minute Consult: Treatments. Philadelphia: Lippincott Williams & Wilkins, 2007.
u
Other Resources
National Institutes of Health Caring for Your Nephrostomy Tube http://clinicalcenter.nih.gov/ccc/patient_education/ pepubs/percneph.pdf See also Cervical cancer; Kidney cancer; Ovarian cancers; Renal pelvis tumors; Urinary system cancers; Urologic oncology; Urostomy.
Salem Health: Cancer
Neuroblastomas
u Neuroblastomas Category: Diseases, symptoms, and conditions Also known as: Childhood autonomic nervous system tumors Related conditions: Ganglioneuroblastomas, ganglioneuromas Definition: Neuroblastomas are cancers, most often found in infants and young children, that grow from primitive, embryonic nerve cells. Two-thirds of tumors begin in the adrenal glands or the sympathetic nervous system ganglia, with growth in the abdomen. The remaining third of neuroblastomas grow in the chest, neck, or pelvis, but all evolve from sympathetic nervous system ganglia. Risk factors: Heredity may play a role in some neuroblastomas and is the only known risk factor. Infants with the familial form of neuroblastoma usually have a parent or someone in the family who had a neuroblastoma as an infant, and familial cases are usually diagnosed before one year of age. When familial neuroblastoma develops, there may be two or more tumors in various organs in the body. It is necessary to differentiate metastasis from multiorgan familial neuroblastoma.
tio of 5:4. Neuroblastoma accounts for 25 percent of cancers in children under one year of age and 7 percent of cancers in children under the age of fifteen. Symptoms: Common symptoms of neuroblastoma include fatigue; diarrhea; a swollen abdomen; difficulty breathing as the tumor gets larger or spreads to the chest area; dark circles under the eyes; pale or flushed, red skin; excessive sweating; bone pain or tenderness; rapid pulse; high blood pressure; poorly controlled movement of the extremities; or paralysis. Symptoms depend on the site of the tumor, and parents may notice or feel a mass in the abdomen, chest, or neck. Screening and diagnosis: There is no screening test for neuroblastoma. If a family has a history of neuroblastoma, it is important to tell the pediatrician at the first visit. Parents should take note of any unusual lumps, swellings, or changes in bowel or bladder patterns, as the symptoms ofneuroblastoma often manifest in this manner. The diagnosis of neuroblastoma begins with a careful physical examination, as masses may be palpated (felt) in the abdomen, chest, or neck. A twenty-four-hour urine test, blood work, and cytogenetic analysis to look for changes in chromosomes are done. A bone marrow aspiration or biopsy specimen may also undergo cytogenetic analysis and pathology review. Imaging (X-ray) studies may include ordinary X rays, computed tomography (CT) scans, ultra-
Etiology and the disease process: There is no known cause of neuroblastoma other than heredity, which is involved in only 1 to 2 percent of cases. Neuroblastoma may form before birth and is occasionally found by fetal ultrasound. Most tumors develop before five years of age. TuPossible Causative Factors for Neuroblastoma mors are generally found only as the Studies have looked at these factors as possible causes for neuroblastoma, but cancer grows and causes symptoms by so far the results have been inconclusive or contradictory. pressing on organs. The tumor has usually metastasized by the time of diagnoPregnancy-Related Factors sis, and metastasis to the bone is com• Previous miscarriage (higher risk per one study, lower per another) mon. Most tumors are fast growing, but • Fertility drug use before pregnancy in rare cases, the tumor cells may die • Alcohol use during pregnancy • Smoking during pregnancy (higher risk per one study, lower per another) spontaneously (apoptosis), and the tu• Taking certain medications during pregnancy: amphetamines, diuretics, mor disappears. Occasionally, the tutranquilizers, muscle relaxants, vaginal anti-infection drugs mor cells may quit dividing and become normal ganglia. This causes the tumor Paternal Factors to become a ganglioneuroma, which is • Father’s exposure to electromagnetic fields, pesticides, dust, rubber, paint, radiation benign. Incidence: The incidence rate of neuroblastoma in children under one year of age is 35 per million, decreasing to 1 per million between ten and fifteen years of age. Neuroblastoma is slightly more common in boys than in girls, with a ra-
Birth-Related Factors Birth defects Low birth weight
• •
Source: L. A. G. Ries et al., eds., Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program, 1975-1995, NIH Pub. No. 99-4649 (Bethesda, Md.: National Cancer Institute, SEER Program, 1999)
841
Neuroectodermal tumors sound, a magnetic resonance imaging (MRI) scan, and a positron emission tomography (PET) scan. Once a diagnosis is made, staging neuroblastoma is important to determine the treatment needed. The first step is to determine if the tumor has spread to other parts of the body. Additional tests may be indicated, including lymph node biopsy or fine needle aspiration of fluid from a lymph node as well as imaging studies with dye injection or injection of a small amount of radioactive tracer material. Four stages are used to classify neuroblastoma: Stages I, IIA and IIB, III, and IV and IVS. The higher the stage, the more extensive the disease and its spread. Neuroblastomas are categorized as low risk, intermediate risk, and high risk based on stage, with treatment determined by risk group. Treatment and therapy: Because neuroblastoma is rare, treatment in a clinical research trial is recommended by the National Cancer Institute. Treatment for neuroblastoma is multimodal, which means that surgery, radiation therapy, chemotherapy, and in rare instances watchful waiting may be used. The higher the risk group, the more aggressive the therapy. Surgery is the initial treatment of choice to remove as much of the tumor as possible and to biopsy lymph nodes. Radiation therapy may be used, especially if part of the tumor has been left behind after surgery or if distant metastases exist. Chemotherapy is used to kill any cells remaining after surgery or to attack cells that may have spread elsewhere in the body. Patients may be watched carefully until a change in their condition indicates the method of therapy. A team will make the best treatment decisions for the child based on staging, location of the tumor, and other factors. Prognosis, prevention, and outcomes: The prognosis for neuroblastoma depends on the age of the child at diagnosis, the stage of the disease, the site of the tumor, the size of the tumor, and the type of tumor cells. Infants do better than older children. Low-risk group survival at five years is 95 percent, intermediate group survival is 85 to 90 percent, and high-risk group survival is approximately 30 percent. Neuroblastoma cannot be prevented. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Maris, J. M., M. D. Hogarty, R. Bagatell, and S. I. Cohn. “Neuroblastoma.” Lancet 369, no. 9579 (June 23, 2007): 2106-2120. Nishimura, H., et al. “Proton-Beam Therapy for Olfactory Neuroblastoma.” International Journal of Radiation Oncology, Biology, Physics 68, no. 3 (July 1, 2007): 758-762. 842
Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Neuroblastoma Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ neuroblastoma/patient See also Adrenal gland cancers; Beckwith-Wiedemann syndrome (BWS); Bone marrow transplantation (BMT); Brain and central nervous system cancers; Breast cancer in children and adolescents; Childhood cancers; Horner syndrome; HRAS gene testing; Mediastinal tumors; MYC oncogene; Nasal cavity and paranasal sinus cancers; Pediatric oncology and hematology; Stem cell transplantation; Syndrome of inappropriate antidiuretic hormone production (SIADH); Tumor markers; Umbilical cord blood transplantation.
u Neuroectodermal tumors Category: Diseases, symptoms, and conditions Also known as: Primitive neuroectodermal tumors (PNETs) Related conditions: Medulloblastomas, peripheral neuroepitheliomas, central neuroblastomas, ependymoblastomas, Gorlin syndrome, nevoid basal cell carcinoma syndrome, Askin tumor (thoracopulmonary PNET), peripheral PNET/Ewing sarcoma family tumor (pPNET/ESFT), extraosseous Ewing sarcoma Definition: Neuroectodermal tumors refer to a group of cancers that were formerly thought to have a common origin from the neuroectodermal tissue layer cell line (neural crest) in the embryo. Presently, they are classified according to cell differentiation. They possess embryonic cell characteristics of brain (neuronal), neuronal support (glial), or mesenchymal cells depending on the degree of differentiation assumed. Neuroectodermal tumors may arise from bone or soft tissue (peripheral Ewing sarcoma family tumor, pPNET/ESFT), or neurons in the peripheral or central nervous system (medulloblastomas; infratentorial PNET, or iPNET; supratentorial PNET, or sPNET). Medulloblastomas represent the prototype neuroectodermal tumor. Risk factors: Neuroectodermal tumors have risk factors associated with alterations in the patient’s genome as a sporadic mutation, as part of a syndrome, or as a result of environmental exposure to a mutagen. Syndromes associated with the risk of developing iPNET include multiple-
Salem Health: Cancer tumor, autosomal dominant diseases such as Gorlin syndrome, Turcot syndrome, and Li-Fraumeni syndrome. Exposure of children to pesticides, particularly organophosphates, has been implicated in several studies as an environmental risk factor for the subsequent development of PNET. Organophosphates have been associated in at least one study with a mutation in the PON1(-108T) allele, which is responsible for expression of the organophosphate detoxification pathway (cytochrome P450/ paraoxonase) in the liver. Etiology and the disease process: The genesis of neuroectodermal tumors is associated with chromosomal changes. The most common chromosomal aberration seen in medulloblastomas is deletion of the short arm of chromosome 17 (17p13.3), seen in as many as 30 to 40 percent of medulloblastoma cases. Other gene aberrations associated with medulloblastomas may involve the TP53, PAX, and sonic hedgehog (SHH) genes and the tumor-suppression region RASSF1A, among others. The Ewing sarcoma family tumor (ESFT) is associated with the translocation t(11;22)(q24;q12), expressing the EWS-FLI1 fusion protein modulator. Incidence: The Swedish Cancer Registry reported that medulloblastomas represented 21 percent of all primary pediatric brain malignancies. The incidence of all neuroectodermal tumors is highest in children, with 0.5 medulloblastoma cases per 100,000 per year reported in the United States. Medulloblastomas represent the most common solid malignant brain tumor found in children (30 percent), with the incidence decreasing to only 1 percent of brain tumors found during adulthood. The majority of medulloblastomas occur in the cerebellum, below the tentorium (extension of the protective tissue covering the brain); only 4 percent of neuroectodermal tumors occur above the tentorium (midbrain, cerebral cortex). Neuroectodermal tumors outside the central nervous system occur in 1 percent of all sarcomas found. Symptoms: More often than not, the more common signs and symptoms relate to obstruction of cerebrospinal fluid (CSF) flow and subsequent pressure buildup and tissue compression. Symptoms of increased pressure include nausea, vomiting, morning headache, and vision changes. Brain stem compression or encroachment can manifest as irritability, lethargy, and decreased social interaction. Cerebellar signs of involvement include frequent loss of balance. Physical examination findings may include papilledema (swelling of both optic nerves); abnormal eye movements; gaze, gait, and limb incoordination; deficits in affected cranial nerves, especially those going to the
Neuroectodermal tumors throat, mouth, shoulders, and tongue; and an increase in head circumference in babies less than two years old. In other sites, neuroectodermal tumors such as pPNET/ESFT can manifest as localized bone pain, a soft-tissue mass located along the middle of long bones with fever and weight loss. Screening and diagnosis: The final diagnosis of a neuroectodermal tumor is mainly pathological, when a tissue sample is examined microscopically and with immunohistochemistry (tests determining cell markers). However, the neuroanatomical location of the tumor as suggested by clinical history, physical examination, and neuroimaging tests such as magnetic resonance imaging (MRI) can suggest a medulloblastoma. Alternatively, a computed tomography (CT) scan may reveal the tumor but has significantly less resolution than an MRI. There are no screening tests available for neuroectodermal tumors. X rays and CT of the affected limb may reveal signs of simultaneous bone destruction and remodeling (“sunburst sign”) and a periosteal reaction (disruption in the continuity of the outer bone) as well as bone infiltration. X rays and CT of the chest should also be done to find metastases. Treatment and therapy: Treatment of a neuroectodermal tumor irrespective of location includes surgical removal, radiation therapy, and chemotherapy. Surgical removal must be able to extract the entire primary tumor and probable areas of spread, and restore normal cerebral spinal fluid circulation. The latter may be achieved with the addition of a device diverting excess cerebral spinal fluid to the abdominal cavity (ventriculoperitoneal shunt). For other neuroectodermal tumors outside the nervous system, the same therapeutic principles apply. In children with limb involvement, amputation may be done because of the stunting effect of therapeutic radiation levels on growth plates. Prognosis, prevention, and outcomes: The prognosis of neuroectodermal tumors after therapy completion is good. Five-year survival rates for central nervous system tumors approach 75 percent with aggressive surgical removal, radiotherapy, and chemotherapy. pPNET/ESFT exhibits similar survival rates with the same treatment, as opposed to radiotherapy and chemotherapy alone (50 percent). Prevention of recurrence includes interval imaging and “second look” surgeries when residual disease is present. Aldo C. Dumlao, M.D. u
For Further Information Eiser, Christine. Children with Cancer: The Quality of Life. Mahwah, N.J.: Lawrence Erlbaum Associates, 2004. 843
Neuroendocrine tumors Pagé, Michel. Tumor Targeting in Cancer Therapy. Totowa, N.J.: Humana Press, 2004. Parker, James N., and Philip M. Parker, eds. The Official Parent’s Sourcebook of Ewing’s Family of Tumors. San Diego, Calif.: Icon Health, 2002. u
Other Resources
National Cancer Institute Childhood Supratentorial Primative Neuroectodermal Tumors and Pineoblastoma http://www.cancer.gov/cancertopics/pdq/treatment/ childSPNET WebMd Primitive Neuroectodermal Tumors of the Central Nervous System http://www.emedicine.com/NEURO/topic326.htm See also Brain and central nervous system cancers; Ewing sarcoma; Medulloblastomas; Pineoblastomas.
u Neuroendocrine tumors Category: Diseases, symptoms, and conditions Also known as: NET Related conditions: Multiple endocrine neoplasia (MEN) type 1 (Wermer syndrome), MEN type 2A (Sipple syndrome), MEN type 2B, carcinoid tumors, islet cell tumors, pheochromocytomas, thyroid carcinomas (medullary), parathyroid carcinomas, Zollinger-Ellison syndrome (gastrinoma), prolactinomas, Cushing syndrome, smallcell lung carcinomas Definition: Neuroendocrine tumors are a group of rare tumors affecting organs that originate embryologically from the neural crest, the layer that gives rise to the brain, spinal cord, peripheral nerves, and endocrine glands (organs that secrete hormones). These tumors mostly arise from hormone-secreting tissues; however, some tumors may not secrete hormones at all. Neuroendocrine tumors may be classified as functional or nonfunctional, or hereditary or nonhereditary. The hereditary MEN syndromes consist of two main variants, MEN 1 and MEN 2. MEN 1 has pituitary, parathyroid, and pancreas involvement. MEN 2A manifests as medullary thyroid cancer (MTC), pheochromocytoma (adrenal medulla tumor), and parathyroid hyperplasia. MEN 2B is essentially type 2A without parathyroid involvement and with the addition of mucosal neuromas and gut ganglioneuromas with a Marfanoid body habitus. Isolated 844
Salem Health: Cancer medullary thyroid cancer may also be familial but less aggressive compared to MEN-associated variants of the disease. The nonhereditary tumors include pheochromocytoma, carcinoid tumors, islet cell, small-cell, and nonfamilial medullary thyroid carcinomas. Risk factors: Although most cases involving a single organ are more sporadic, the most prominent risk factor for the development of neuroendocrine tumors is a genetic predisposition. The MEN syndromes are autosomal dominant, implying that every generation has an afflicted individual, with a 50 percent probability of offspring inheriting the disease. Exposure to leuprolide acetate and medroxyprogesterone acetate in female rats was associated with a higher incidence of pancreatic islet cell tumors. Etiology and the disease process: The genetic etiology of the heritable as well as most sporadic cases of somatic (mature, differentiated cells) cell mutations in parathyroid adenomas, gastrinomas, insulinomas, and bronchial carcinoids most commonly originates from MEN1 tumorsuppressor gene mutations, with the RET proto-oncogene implicated in sporadic medullary thyroid carcinoma cases. MEN 1 originates from one of two etiologies: a mutation within the embryonic crest cell or inactivation of the tumor-suppressor gene MEN 1, located on the long arm of chromosome 11 (11q13). In MEN 2A, MEN 2B, and familial medullary thyroid carcinoma, the origin is believed to be a mutation in the RET proto-oncogene, located on the long arm of chromosome 10 (10q11.2). Gastrinomas originate from HER2/neu (human epidermal growth factor receptor 2/neu) proto-oncogene. Incidence: The overall occurrence of neuroendocrine tumors is extremely rare, accounting for only 0.5 percent of all malignant cancers. However, an increase in the number of cases of these tumors has been observed. The gastrointestinal tract has the highest incidence of neuroendocrine tumors, accounting for 62 to 67 percent of all primary tumors, followed by the lungs (22 to 27 percent) in one study conducted in the Netherlands. Symptoms: The symptoms associated with neuroendocrine tumors vary widely and are often insidious in onset. Tumors may be found during the course of an unrelated imaging study. Some neuroendocrine tumors are related to location rather than the disease entities they mimic. For example, pancreatic tumors may manifest as poorly controlled diabetes in glucagonoma and somatostatinoma; pituitary tumors as amenorrhea in prolactinomas, unintentional skin darkening, high blood pressure, and psychosis in Cushing disease; sudden episodes of high blood pressure, cold sweats, and palpitations in pheochromocytomas;
Salem Health: Cancer or as a plethora of unrelated signs and symptoms such as flushing, abdominal cramps, diarrhea, or new-onset heart murmur in carcinoid tumors. Both nonfunctioning tumors and bulky functioning tumors can compress or infiltrate surrounding tissue or structures and cause obstructive symptoms. Screening and diagnosis: Diagnosis of neuroendocrine tumors is often difficult and missed because of misleading disease symptoms. Medullary thyroid cancer, especially when a family history is present, should initiate a comprehensive search for high calcitonin, blood and urine calcium (medullary thyroid, parathyroid), adrenocorticotropic hormone (ACTH), growth hormone, thyroid-stimulating hormone (TSH), prolactin levels (pituitary), and twentyfour-hour urine metanephrine (adrenal medulla) levels as well as computed tomography (CT) or magnetic resonance imaging (MRI) of the head, neck, chest, and abdomen, as appropriate, to look for primary as well as metastatic sites. Insulin-to-glucose ratios, chromogranin A, gastrin levels, octreoscans, endoscopy, and CT and MRI imaging studies are useful for aiding in pancreatic tumor diagnosis. Although neuroendocrine tumors have a clear genetic etiology, genetic testing for RET is reserved for patients presenting with medullary thyroid cancer. Treatment and therapy: Treatment of neuroendocrine tumors includes surgical removal, radiation therapy, and chemotherapy and is highly dependent on the tumor location and type. Precautions should be taken to stabilize the patient preoperatively for many functioning tumors. Control of blood pressure, high glucose levels, electrolyte imbalances, and gastrin excess are essential. Surgery must be able to remove the entire primary tumor and, if needed, structures susceptible to infiltration. For islet cell tumors, chemotherapy with streptozocin, doxorubicin, and 5-fluorouracil (5-FU) alone or in combination have proved beneficial (54 to 69 percent response rate). Prognosis, prevention, and outcomes: Most cases of neuroendocrine tumors have a good prognosis with radical surgery, chemotherapy, or radiotherapy. Metastatic disease at the time of diagnosis implies a poor prognosis. Gastrinomas in particular have poorer prognosis, as 60 percent are malignant; associated with MEN 1 syndrome, they have a better prognosis than gastrinoma alone. Medullary thyroid cancer and MEN 2 have a five-year survival rate of 90 percent, attributable to early treatment of medullary thyroid cancer. Observation for recurrence is needed, through periodic clinical examinations, laboratory tests for tumor markers, and CT and MRI. Genetic counseling
Neurofibromatosis type 1 (NF1) and testing are helpful in individuals with a strong family history of neuroendocrine tumors. Aldo C. Dumlao, M.D. u
For Further Information Clark, Orlo H. Endocrine Tumors. Hamilton, Ont.: BC Decker, 2003. Fossel, Michael B. Cells, Aging, and Human Disease. New York: Oxford University Press, 2004. Kelloff, Gary, Ernest T. Hawk, and Caroline C. Sigman. Cancer Chemoprevention. Totowa, N.J.: Humana Press, 2005.
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Other Resources
American Cancer Society Detailed Guide: Gastrointestinal Carcinoid Tumors http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_are_gastrointestinal_ carcinoid_tumors_14.asp Dana-Farber Cancer Institute Neuroendocrine Tumors http://research.dfci.harvard.edu/neuroendocrine/ See also Cushing syndrome and cancer; Endocrine cancers; Lung cancers; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Parathyroid cancer; Pheochromocytomas; Thyroid cancer; Von Hippel-Lindau (VHL) disease; Zollinger-Ellison syndrome.
u Neurofibromatosis type 1
(NF1) Category: Diseases, symptoms, and conditions Also known as: von Recklinghausen’s neurofibromatosis, von Recklinghausen disease Related conditions: Neurofibromas, iris Lisch nodules, optic gliomas, café-au-lait spots, freckling, learning disabilities, bone complications such as scoliosis or bone overgrowth Definition: Neurofibromatosis type 1 (NF1) is a hereditary disorder of the nervous system that affects growth and development of nerve cell tissues. This disorder is associated with neurofibromas (bumplike tumors under the skin or elsewhere in the body that develop anywhere along a nerve), café-au-lait spots (flat spots on the skin that are darker than the surrounding area), freckling in places not exposed to the sun (such as the armpit and groin), eye de845
Neurofibromatosis type 1 (NF1) velopments such as optic glioma (a tumor growing on the nerve to the eye) and Lisch nodules (harmless growths on the colored part of the eye), and bone problems such as scoliosis (curvature of the spine) or bone overgrowth. Up to 10 percent of affected individuals have malignant peripheral nerve sheath tumors (tumors that form along the protective covering around nerves located outside the brain and spinal cord), which are the most common malignant tumors associated with NF1. Although rare, malignant brain tumors do occur. Fewer than 1 percent of people with NF1 have pheochromocytomas (adrenal gland tumors that release stress hormones) that cause dangerously high blood pressure. Approximately half of individuals with NF1 have a learning disability, although it is usually mild. The severity of the disorder varies within families, between families, and even within an individual at different times during life. Risk factors: Because NF1 is hereditary, the main risk factor is having a family history of this disorder. Each child of a person with NF1 has a 50 percent chance of inheriting the disorder.
Salem Health: Cancer Etiology and the disease process: The underlying genetic cause of NF1 is a mutation, or a genetic change, in the NF1 gene. The purpose of the protein made by the NF1 gene is not fully understood, but it most likely helps stop uncontrolled cell growth and proliferation. Mutations in the NF1 gene either prevent the protein from being made or cause the protein to be made incorrectly, and the multistep process of tumorigenesis (formation or production of tumors) is left unchecked. Usually, each person has two normal copies of the NF1 gene. A mutation in one copy of the gene is sufficient to cause NF1, which is why this condition is referred to as autosomal dominant (autosomal means the NF1 gene is located on one of the twenty-two pairs of autosomes, which are the nonsex chromosomes). An affected person has an NF1 gene mutation from the time of conception; however, symptoms of the disease may be present at birth or not manifest until later in life. Nearly all individuals with NF1 have signs and symptoms of the disorder by the end of childhood. The average life expectancy of affected individuals is reduced about fifteen years.
Neurofibromas are one symptom of neurofibromatosis type 1. (Biophoto Associates/Photo Researchers, Inc.)
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Salem Health: Cancer Incidence: Approximately 1 in 3,000 people has NF1, which makes it one of the most common dominantly inherited genetic disorders. Nearly half of people with NF1 inherit the disorder from a parent. The other 50 percent have a new gene mutation, meaning the mutation occurred for the first time in those individuals. Symptoms: Symptoms vary and are usually mild to moderate and not life-threatening. Adults with NF1 may have anywhere from a few neurofibromas to hundreds or thousands, and these tumors—which continue to develop throughout life—can affect any organ in the body. Neurofibromas can cause pain and disfigurement and, more rarely, cause problems with organ function. Malignant peripheral nerve sheath tumors can cause pain, numbness, or paralysis. Optic gliomas can lead to blindness. Of the learning disabilities observed in more than half of people with NF1, visual-spatial performance and attention deficits are the most common. Screening and diagnosis: Doctors diagnose NF1 based on certain criteria, which include having two or more of the following: six or more café-au-lait spots, two or more neurofibromas or one plexiform neurofibroma (weblike neurofibroma that entwines surrounding tissues), freckling in the armpit or groin, optic glioma, two or more Lisch nodules, an unusual bone complication, or a first-degree relative (parent, sibling, or child) with NF1. Because NF1 is caused by mutations in the NF1 gene, genetic testing can be used to confirm a suspected diagnosis. However, diagnostic genetic testing is rarely needed because doctors can easily diagnose the disease based on clinical findings. Genetic testing detects more than 95 percent of NF1 gene mutations in individuals who have been clinically diagnosed by a physician. Treatment and therapy: The main focus of treatment for NF1 is controlling symptoms. Surgery can be performed to treat bone malformations or to remove tumors that cause pain or disfigurement. In the case of malignancy, the tumor is surgically removed if possible, and the patient may also have adjuvant chemotherapy and radiotherapy. Prognosis, prevention, and outcomes: The way neurofibromatosis affects a person over a lifetime varies widely. Because NF1 is a genetic condition, its manifestations cannot be prevented. However, physicians recommend that individuals with NF1 have monitoring that includes a yearly physical examination, a yearly ophthalmologic examination (eye exam) for children (less frequently for adults), regular blood pressure checks, and regular assessment of development for children. Abbie L. Abboud, M.S., C.G.C.
Neurologic oncology u
For Further Information Ferner, R. E. “Neurofibromatosis 1.” European Journal of Human Genetics. 15 (2007): 131-138. Korf, Bruce R., and Allan E. Rubenstein. Neurofibromatosis: A Handbook for Patients, Families, and Health Care Professionals. New York: Thieme Medical, 2005. Tonsgard, J. H. “Clinical Manifestations and Management of Neurofibromatosis Type 1.” Seminars in Pediatric Neurology 13 (2006): 2-7.
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Other Resources
Children’s Tumor Foundation: Ending Neurofibromatosis Through Research http://www.ctf.org Neurofibromatosis, Inc http://www.nfinc.org See also Acoustic neuromas; Astrocytomas; Ependymomas; Fibrosarcomas, soft-tissue; Gastrointestinal stromal tumors (GISTs); Gliomas; Mediastinal tumors; Medulloblastomas; Meningiomas; Pheochromocytomas; Sarcomas, soft-tissue; Schwannoma tumors; Spinal axis tumors.
u Neurologic oncology Category: Medical specialties Also known as: Neuro-oncology Definition: Neurologic oncology is a specialty practice involving the study and treatment of cancers of the brain and the peripheral and central nervous systems. Physicians who practice in this field are known as neuro-oncologists. It is a branch of medicine that studies tumors in an effort to understand their evolution, diagnosis, treatment, and prevention. The discipline of neurologic oncology has developed steadily since the 1980’s as advances in understanding of epidemiology, cellular and molecular biology, genetics, immunology, and radiobiology have come together to increase knowledge of the process of oncogenesis. Cancers treated: Brain, spine, and peripheral and central nervous system cancers Training and certification: The practice of neurologic oncology requires training and experience in two essential areas: neurology or neurosurgery to properly diagnose and assess patients based on expert knowledge of nervous system function and oncology—as it pertains to central nervous system (CNS) involvement and generic oncologic 847
Neurologic oncology management principles—for competence in the use of chemotherapeutic agents and related measures. Although no official or regulated prerequisites have been established for neuro-oncologists, all physicians practicing neurologic oncology have graduate medical degrees. Most physicians practicing neuro-oncology have backgrounds in neurology, neurosurgery, radiology/radiation oncology, or internal medicine/medical oncology. The specialty of neurology generally requires the completion of a minimum four-year residency program; the specialty of neurosurgery requires completion of a seven-year residency program. Radiologists complete a four-year residency program. Physicians trained in internal medicine complete a three-year residency program. After successful completion of a residency program, the physician assumes a fellowship in neurologic oncology for an additional two to three years, depending on whether the individual plans to engage in research and academic activities or in treating patients with brain, spinal cord, or CNS cancers. Prior board certification by the American Board of Medical Specialties (ABMS) is recommended but not required. The ABMS has twenty-four member specialty boards that certify their members through written and oral examinations and continuing education programs. Many of the physicians who study neurologic oncology have already been board certified in their original fields of study. Services and procedures performed: Neuro-oncologists provide therapy for primary and metastatic tumors of the brain, spine, and the peripheral and central nervous systems. Tumors are diagnosed using modern neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to facilitate diagnostic biopsies and appropriate treatment. The imaging studies are usually interpreted with the assistance of a neuroradiologist. Treatment may include chemotherapy, radiation therapy (conventional, brachytherapy, or radiosurgery), neurosurgery, or a combination of these treatments. Whenever possible, and especially in the case of rapidly growing, aggressive disease, neurosurgical resection of the tumor is the treatment of choice, usually followed by chemotherapy, radiotherapy, or both. In the case of inoperable cancers, a combination of chemotherapy and radiotherapy may be the treatment of choice. Chemotherapy involves the use of chemical compounds that are toxic to malignant cells. Traditional chemotherapeutic agents include carmustine (BCNU, or BiCNU), lomustine (CCNU, or CeeNU), and a combination of procarbazine, CCNU, and vincristine known as PCV. Chemotherapy may be administered orally (for exam848
Salem Health: Cancer ple, temozolomide, or Temodar, a relatively new agent, may be taken in tablet form), intravenously (most agents), or through direct surgical implantation of a chemotherapeutic wafer, usually placed in the tumor cavity after resection. Chemotherapy is typically performed in stages over time. Conventional radiotherapy alone or in combination with chemotherapy, surgery, or both may also be administered. Radiotherapy uses high-energy external X rays, gamma rays, or charged particles (electron or proton beams) to damage important biological molecules in tumor cells. If enough damage is done to the chromosomes of a cell, cell death (or apoptosis) will occur. Radiotherapy is generally administered at regular intervals over a several-week course. Brachytherapy is a type of radiotherapy in which radioactive material (most often iridium-192), usually in the form of a tiny pellet or seed, is inserted inside or next to the tumor. Brachytherapy is commonly used to treat localized cancer. Radiosurgery is a variation of radiotherapy that uses highly focused gamma rays to kill cancerous cells; radiosurgery is performed in a single session. Neurosurgery is the incision and excision of cancerous tissue. Tumors may be completely resected or partially resected, depending on their location and accessibility. The tumor may be approached via an open surgical procedure such as a craniotomy or via an endoscopic approach such as a transnasal (through the nose) route. A relatively new, but U.S. Food and Drug Administration-approved, technique is convection-enhanced delivery, which involves the implantation of a catheter into the tumor and slow infusion of a chemotherapeutic agent into the brain or tumor. Convection-enhanced delivery relies on a small, continuous gradient of pressure to infuse the chemotherapeutic agent up to several centimeters from the site of infusion. Related specialties and subspecialties: The primary care physician is often the source of the referral to the neurooncologist and thus may remain involved in some way with the patient’s care. Other comorbidities may necessitate the primary physician’s continued involvement as well as that of other physicians outside the general field of neurologic oncology. For the purposes of cancer treatment, the practice of neurologic oncology involves the cooperation of a multidisciplinary team, which, depending on the course of treatment chosen, may include neurooncology nurse specialists, medical oncologists, neurologists, neurosurgeons, radiation oncologists, neuroradiologists, neuropathologists, neuroanesthesiologists and pain management personnel, rehabilitative and cognitive physicians, neuropsychologists and psychiatrists, palliative care specialists, and hospice care providers. All team
Salem Health: Cancer members will have expertise in a neuro-related or oncologic specialty. If the treatment chosen does not involve surgery, the need for the participation of a neurosurgeon and neuropathologists will most likely be mitigated. Ideally if the course of treatment is successful, it will not be necessary for the palliative care specialists and hospice workers to play their roles. Keller Kaufman-Fox, B.A. u For Further Information Ali-Osman, Francis, ed. Brain Tumors. Totowa, N.J.: Humana Press, 2003. Lawson, C. H., et al. “Interstitial Chemotherapy for Malignant Gliomas: The Johns Hopkins Experience.” Journal of Neuro-Oncology 83 (2007): 61-70. McAllister, L. D., J. H. Ward, S. F. Schulman, and L. M. DeAngelis. Practical Neuro-Oncology: A Guide to Patient Care. 5th ed. Boston: Butterworth-Heinemann, 2001. Strother, D. R., et al. “Tumors of the Central Nervous System.” In Principles and Practice of Pediatric Oncology, edited by P. A. Pizzo and D. G. Poplack. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2002. u
Organizations and Professional Societies
American Brain Tumor Association http://www.abta.org 2720 River Road, Suite 146 Des Plaines, IL 60018 Brain Tumor Society http://www.tbts.org 124 Watertown Street, Suite 3H Watertown, MA 02472-2500 National Brain Tumor Foundation http://www.braintumor.org 22 Battery Street, Suite 612 San Francisco, CA 94111-5520 Society for Neuro-Oncology http://www.soc-neuro-onc.org 4617 Birch Street Bellaire, TX 77401-5509 u
Other Resources
American Association of Neurological Surgeons http://www.tumorsection.org
Neutropenia National Institute of Neurological Disorders and Stroke NINDS Brain and Spinal Tumors Information Page http://www.ninds.nih.gov/disorders/ brainandspinaltumors/ See also Astrocytomas; Brain and central nervous system cancers; Gliomas; Meningiomas; Pediatric oncology and hematology.
u Neutropenia Category: Diseases, symptoms, and conditions Also known as: Agranulocytosis, granulocytopenia Related conditions: Leukopenia, aplastic anemia, myelodysplastic syndromes Definition: Neutropenia is a decreased number of circulating neutrophils, which are the most abundant type of white blood cell and are an essential component of the immune response to infections, especially bacterial or fungal infections. Neutrophils are the first to respond to an infection, ingesting the microorganisms and killing them, thus preventing an infection or lessening its severity. A patient who has a significantly reduced number of neutrophils is at increased risk for infection. Normal total white blood cell counts range from 5,000 to 10,000 cells per cubic millimeter (mm3) of blood, with neutrophils making up 50 to 70 percent of the circulating white blood cells. Therefore, the normal absolute number of neutrophils is about 2,500 to 7,000 neutrophils/mm3 of blood. People are considered to have neutropenia when levels drop below 500 neutrophils/mm3 of blood. Risk factors: Because most chemotherapeutic agents work to kill fast-growing cells, including neutrophils, almost all cancer patients are at risk for neutropenia. Radiation therapy for cancer treatment can also cause neutropenia. Other factors, including age, nutritional status, and previous exposure to chemotherapy or radiation, increase the risk of neutropenia in someone undergoing chemotherapy or radiation therapy. Patients with hematologic cancers, such as leukemias or lymphomas, are also at increased risk for neutropenia. Etiology and the disease process: Four main circumstances lead to neutropenia: prolonged, severe infection; decreased survival of neutrophils; abnormal distribution of neutrophils to a body site; and decreased production of neutrophils. In the case of cancer patients, the problem is decreased production. Most anticancer drugs work to dis849
Neutropenia rupt the growth of cancer cells, which tend to grow very quickly. These drugs target cell components involved in cell division and deoxyribonucleic acid (DNA) synthesis. As a result, other fast-growing cells in the body may also be affected by the drugs. This includes the cells of the bone marrow that are precursors to blood cells. Neutrophils are short-lived (surviving two to three days) in the body, with millions of new neutrophils released every minute from the bone marrow. Therefore, the bone marrow cells that are rapidly dividing to make new neutrophils are at high risk for damage from anticancer agents. Radiation therapy can cause neutropenia if the targeted treatment area includes bones that contain productive marrow (not all marrow actively produces blood cells). Additionally, patients who need a bone marrow transplant must have the diseased bone marrow completely destroyed before the transplant. Incidence: Chemotherapy is the most common cause of neutropenia, but its incidence among patients varies. Each drug and drug combination has been shown to cause neutropenia at a different rate. For example, the cisplatin/ fluorouracil combination used to treat head and neck cancers has been shown to cause neutropenia in only 9 percent of patients. Cisplatin combined with gemcitabine to treat bladder cancer causes neutropenia in 71 percent of patients. The other risk factors, such as age, also contribute to the different incidence rates. Symptoms: Because low neutrophil counts predispose patients to infection, the first symptom is usually fever, followed by symptoms specific to the infection, including a cough, a sore throat, bronchitis, sinusitis, pneumonia, gingivitis, sores around the mouth and anus, fatigue, and frequent or unusual infections. Screening and diagnosis: A complete blood count (CBC) with differential tests for levels of the different types of cells in the blood can screen for neutropenia. The differential portion of the test tells the percentage of each type of white blood cell, including the percentage of neutrophils. From this, the absolute number of neutrophils/mm3 can be calculated to determine if a patient is neutropenic and at risk for infection. Patients with borderline levels at 500 to 1,500 cells/mm3 have a slight-to-moderate risk of infection, while patients with counts below 500 cells/mm3 (neutropenic) have a severe risk of infection. Treatment and therapy: The first priority of treatment is to address fever and underlying infection. Antibiotics or antifungals are necessary to treat the infection. The patient may also require granulocyte-macrophage colony850
Salem Health: Cancer stimulating factor (GM-CSF) or granulocyte colonystimulating factor (G-CSF). These drugs stimulate the bone marrow to increase production of neutrophils and are used following chemotherapy and following bone marrow transplantation. Additionally, changes in the chemotherapy regimen may be necessary. The physician may choose to lower the dose of medication, remove a drug from the regimen, or change the most harmful drug to a less toxic drug. Prognosis, prevention, and outcomes: A neutropenic cancer patient who acquires an infection has a mortality rate of 4 to 30 percent. To prevent neutropenia in cancer patients receiving treatment, doctors can lower the dose of chemotherapy for patients who have a documented history of neutropenia. Doctors can also use colony-stimulating factors in patients at higher risk for neutropenia, such as when a treatment regimen is known to cause neutropenia in a high percentage (greater than 40 percent) of patients. Most cases of chemotherapy-induced neutropenia resolve within two weeks of discontinuing drug treatment. Michelle L. Herdman, Ph.D. u
For Further Information Beers, Mark H., ed. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, N.J.: Merck, 2006. Mosby’s Drug Consult 2007. St. Louis: Mosby Elsevier, 2007. Tisdale, James E., and Douglas A. Miller. Drug-Induced Diseases: Prevention, Detection, and Management. Bethesda, Md.: American Society of Health-System Pharmacists, 2005.
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Other Resources
American Cancer Society http://www.cancer.org Cancer Symptoms.org Neutropenia http://www.cancersymptoms.org/neutropenia/ index.shtml Neutropenia Support Association http://www.neutropenia.ca/index.html See also Aplastic anemia; Chemotherapy; Leukopenia; Myelodysplastic syndromes; Side effects.
Salem Health: Cancer
u Nickel compounds and
metallic nickel Category: Carcinogens and suspected carcinogens RoC status: Metallic nickel, reasonably anticipated human carcinogen since 1980; nickel compounds, known human carcinogens since 2002 Also known as: Ni Definition: Nickel is a silvery white, hard, malleable, and ductile metal that forms complex compounds, most often with oxygen, sulfur, iron, and arsenic. Some nickel uptake is essential to humans but more concentrated amounts can be harmful. It remains unknown exactly which forms of nickel compounds are carcinogenic, but studies show that airborne and water-soluble compounds may be most associated with cancer risk, possibly because of greater exposure. Because nickel is widely distributed in soils, water, air, detergents, tobacco, and food, everyone is exposed to varying levels of nickel and its compounds. Food, including vegetables and chocolates, often contains larger amounts of nickel, as does tobacco. Nickel fumes or contaminants released by tobacco smoking may cause an increased risk of respiratory cancers, including those of the nose, larynx, and lungs. Contaminant levels of nickel in humans have also been linked with birth defects, including heart disorders, and have been implicated in cancerous proliferation of breast cells. In addition to being identified in the National Toxicology Program’s Report on Carinogens as carcinogenic, nickel compounds are classified by the International Agency for Research on Cancer (IARC) as Group 1 compounds, which are “causally associated with cancer in humans.” Metallic nickel is currently classified as a Group 2B compound, or “possibly carcinogenic to humans,” but will most likely be changed to category A, a known human carcinogen. Nickel and its compounds have also been identified as hazardous air pollutants in the United States’ Clean Air Act. Related cancers: Nasal, throat, lung, breast, and prostate cancer Exposure routes: Inhalation of nickel fumes from tobacco smoke and aerosols from burning of fossil fuels; ingestion of foods, especially chocolates and vegetables Where found: Earth has a solid core of nickel but this is far within the interior. Most soils typically contain trace amounts, which can be absorbed in plants and ingested by animals, including humans. Soil nickel and nickel compounds may be leached into water systems or wind driven and carried as nickel-contaminated dust in the atmosphere.
Nickel compounds and metallic nickel Small amounts of nickel and its compounds also occur in the world’s oceans and seas, where organisms can absorb it. It is a contaminant in coal and oil and is emitted into the atmosphere by powerplants and incinerators. Nickel compounds are also found in jewelry, other metals, and in everyday household items such as detergents. At risk: Everyone is at some risk. Workers in smelters that process ores containing nickel, in the electroplating industry, and in steel manufacturing are at risk of higher levels of exposure to nickel and its compounds. Smoking tobacco in all its forms also exposes heavy smokers to nickel contaminants that may increase the risk of cancer. Etiology and symptoms of associated cancers: Nasal, throat, lung, breast, and prostate cancer are all related to inhalation or ingestion of nickel compounds and metallic nickel in excess amounts. Nasal, throat, and lung cancer can affect breathing, speaking, taste, and smell. Breast cancer can be present in the form of a subdermal lump that may be painful. Prostate cancer can cause severe pain, decrease urination flow, frequency, or strength, and inhibit ejaculation. History: Nickel and its compounds are primarily used in the preparation of alloys of steel and other metal products. For example, addition of nickel to steel, copper, and other metals produces an alloy that is stronger and more resistant to heat and corrosion. Thus, nickel is important in gas turbines and rocket engines, where strength and resistance to high temperatures are factors. Nickel alloys are also used to manufacture propeller shafts of boats and piping in desalinization plants, where resistance to corrosion is important. Nickel is also used as a key ingredient in the manufacture of rechargeable nickel cadmium batteries, coinage, and in nickel plating of jewelry and other products. Nickel wire also continues to be in demand for some industrial purposes. Nickel and its compounds are recognized and listed as carcinogenic substances, especially in occupations in which workers are routinely exposed to nickel fumes. The Environmental Protection Agency (EPA) formally determined that nickel and its compounds, especially nickel subsulfides, are human carcinogens in 1984, and in 1990 the International Agency for Research on Cancer also listed nickel as potentially carcinogenic. Further regulations are possible pending ongoing reviews at federal and state levels. Dwight G. Smith, Ph.D. See also Carcinogens, known; Carcinogens, reasonably anticipated; Head and neck cancers; Laryngeal cancer; Nasal cavity and paranasal sinus cancers; Occupational exposures and cancer; Salivary gland cancer. 851
Night sweats
u Night sweats Category: Diseases, symptoms, and conditions Also known as: Sleep hyperhydrosis Related conditions: Menopause, obstructive sleep apnea, infection, low blood sugar, lymphoma and other cancers, certain medications Definition: Night sweats are excessive nighttime sweating that causes the individual to wake up and may require the individual to bathe or change nightclothes. Risk factors: There are some diseases and conditions that may be associated with an increased incidence of night sweats. Individuals who have obstructive sleep apnea, a disorder in which breathing is interrupted during sleep, are more likely to experience night sweats. Risk factors for sleep apnea, such as obesity, therefore may also be risk factors for night sweats. Women experiencing menopause are also more likely to experience night sweats. Etiology and the disease process: Night sweats can be caused by a number of underlying diseases and conditions as well as by a simple excess of bedding or an overly warm room. Some of the most common medical causes of night sweats include the changing hormone balance that occurs during menopause, obstructive sleep apnea, infection, low blood sugar, cancer (especially lymphoma), and certain medications. Other causes can include infection with the human immunodeficiency virus (HIV), tuberculosis, hyperthyroidism, epilepsy, and head injury. Incidence: There are very few significant scientific studies on the incidence of night sweats; however, they are believed to be very common. One study of night sweats found that 41 percent of the 2,267 patients who were studied reported night sweats. Many physicians report a significant percentage of individuals they see in their general practice complaining of night sweats. Symptoms: The symptoms of night sweats are waking up in the night because of excessive sweating. Night sweats are considered mild if they wake sleepers, who then remove some or all bed coverings and may turn over the pillow to use the dry side. Night sweats that make sleepers feel the need to wash the sweat off their hands or faces are considered moderate. Night sweats are considered severe when the sweating is so excessive as to cause sleepers to change their clothes or to take a shower. Some people who experience night sweats also experience excessive sweating during the day. Screening and diagnosis: The physician will typically take a history of the patient’s night sweat experiences and 852
Salem Health: Cancer perform a physical exam to see if any common causes of night sweats seem to be a likely cause. The physician may also ask a series of questions, which may involve travel history, to determine if the patient has been in any areas that increase the likelihood of becoming infected with a disease such as tuberculosis, or if there is a risk of infection with HIV. The doctor may also ask the patient’s sleeping partner about symptoms of which the individual may be unaware, such as the loud snoring that often accompanies obstructive sleep apnea. If these steps fail to determine why the night sweats are occurring, the doctor may order blood tests or additional screening procedures to test for other causes. The doctor will also ask the patient about other unusual symptoms, even those that do not seem to be related. Many diseases and conditions that can cause night sweats usually cause other symptoms as well. Types of cancer that cause night sweats are usually associated with unintentional weight loss and fever. Tuberculosis is also usually accompanied by weight loss, a cough, and a low-grade fever. Treatment and therapy: Most night sweats are treated by trying to assess the underlying cause of the night sweats and treating that disease or condition, including a possible lymphoma. Resolving the underlying problem will usually eliminate the night sweats. However, while the underlying problem is being diagnosed and treated, or if no treatable underlying cause can be found, there are some techniques that may help relieve the symptoms. Reducing the quantity of bedclothes or switching from heavy blankets made of insulating materials such as wool to lighter blankets made of fabrics such as cotton may help reduce the occurrence of night sweats or reduce their severity. Sleeping with a window open or a fan pointed toward the bed may also help to relieve the problem. Avoiding spicy food, excessive exercise before bedtime, alcohol, and tobacco may help to reduce the severity of night sweats. Prognosis, prevention, and outcomes: Sleeping in a cool room without an excess of bedding may be able to help prevent some episodes of night sweats. The prognosis for most cases of night sweats is good. Treating the underlying cause if one can be found is usually effective at eliminating the night sweats. Night sweats can be extremely frustrating as they can lead to poor quality of sleep and increased drowsiness during the day. Treating night sweats successfully can lead to a better quality of sleep, as well as an increased quantity of sleep, which can improve mood and lead to a better quality of life overall. Robert Bockstiegel, B.S.
Salem Health: Cancer u For Further Information Freedman, Jeri. Lymphoma: Current and Emerging Trends in Detection and Treatment. New York: Rosen, 2006. Souhami, Robert, and Jeffrey Tobias. Cancer and Its Management. 5th Edition. Malden, Mass.: Blackwell, 2005. Yarbro, Connie Henke, Margaret Hansen Frogge, and Michelle Goodman, eds. Cancer Symptom Management. Sudbury, Mass.: Jones and Bartlett, 2004. u
Other Resources
MedicineNet.com Eight Causes of Night Sweats http://www.medicinenet.com/script/main/ art.asp?articlekey=57394 Sleep Disorders Guide Sleep Hyperhydrosis http://www.sleepdisordersguide.com/topics/ sleep-hyperhidrosis.html See also Hormonal therapies; Hormone replacement therapy (HRT); Hot flashes; Hysterectomy; Lymphomas; Symptoms and cancer.
u Nijmegen breakage syndrome Category: Diseases, symptoms, and conditions Also known as: Berlin breakage syndrome, Seemanova syndrome II, ataxia telangiectasia variant V1 Related conditions: Bloom syndrome, Fanconi anemia, ataxia telangiectasia Definition: Nijmegen breakage syndrome is a rare autosomal recessive condition that causes chromosomal instability, sensitivity to radiation, and increased incidence of malignant lymphomas. Risk factors: A risk factor for Nijmegen breakage syndrome is the inheritance of a mutation in both copies of the NBS1 gene. Etiology and the disease process: The NBS1 gene encodes the nibrin protein, which helps heal double-stranded breaks (DSBs) in deoxyribonucleic acid (DNA) molecules. Sometimes double-stranded breaks occur as a result of DNA-severing agents or as a normal physiological process during gamete and antibody production. Without the capacity to repair double-stranded breaks, cells are unable to repair damage to DNA, make antibodies to fight infections, or produce viable gametes.
Nijmegen breakage syndrome Incidence: As of 2007, there were only 200 estimated cases of Nijmegen breakage syndrome worldwide. Symptoms: Children born with Nijmegen breakage syndrome show microcephaly (small head), growth retardation, progressive mental retardation, and characteristic facial features (birdlike face, sloping forehead, and receding jaw). The immune system is unable to fight infections, and recurrent sinus, pulmonary, and ear infections are common. More than half of Nijmegen breakage syndrome patients also show skin pigmentation irregularities. At puberty, female Nijmegen breakage syndrome patients fail to experience sexual maturation. Their ovaries are small and poorly developed (premature ovarian failure). Finally Nijmegen breakage syndrome patients show increased tendencies to develop lymphomas. Screening and diagnosis: Cytogenetic analyses, which isolate and view chromosomes from individual cells, show chromosomal instabilities that typically involve chromosomes 7 and 14. Immunologic testing shows an inability of immune cells to divide rapidly or properly synthesize antibodies in response to infections. Nijmegen breakage syndrome patients are also extremely sensitive to ionizing radiation or clastogens (substances that cause chromosome breaks). DNA sequencing of the NBS1 gene should reveal loss-of-function mutations in this gene. Treatment and therapy: Antibiotic treatments and intravenous administration of antibodies are used to treat recurrent infections that accompany immune system deficiency. Bone marrow transplants can permanently treat the immune system defects in children with Nijmegen breakage syndrome. Prepuberty female patients are treated with hormone replacement therapy to allow the development of secondary sexual characteristics and prevent osteoporosis. Cancer treatments in patients with Nijmegen breakage syndrome patients must avoid radiation and chemotherapeutic agents that damage DNA, since they can cause toxic complications. Prognosis, prevention, and outcomes: Prophylactic antibiotics are prescribed to prevent recurring infections, and vitamin E supplements are recommended to ameliorate chromosome instability. The long-term prognosis for Nijmegen breakage syndrome patients is typically quite poor. Most patients die from aggressive malignancy or complications from infections. Michael A. Buratovich, Ph.D. See also Ataxia telangiectasia (AT); Childhood cancers; Chromosomes and cancer; Fanconi anemia. 853
Nipple discharge
u Nipple discharge Category: Diseases, symptoms, and conditions Also known as: Breast discharge Related conditions: Galactorrhea, mastitis, papilloma, Paget disease of breast intraductal breast carcinoma Definition: Nipple discharge refers to secretions from either one (unilateral) or both (bilateral) breasts. Discharge can be spontaneous or appear only when expressed through squeezing and “milking” the nipple, and it can be occasional or constant. It can be clear, milky, brown, green, yellow, pink, or deeply bloody. Risk factors: Nipple discharge is more likely to be the result of underlying malignancy when it is a unilateral discharge, occurs in a woman past reproductive age, is associated with a mass, or contains blood. Older women with nipple discharge are much more likely to have a malignancy than younger women.
Salem Health: Cancer Etiology and the disease process: High levels of the hormone prolactin can cause galactorrhea, which is a milky discharge. Galactorrhea is the most common nipple discharge. Medications that commonly cause galactorrhea include psychotropics, oral contraceptives, and antiemetics. Incidence: Nipple discharge is very common and usually benign. As many as 80 percent of women are able to express fluid with manual manipulation. Although it is far more common in women, men may occasionally exhibit nipple discharge. Symptoms: Discharge may be spontaneous or occur only with manual expression, or “milking,” of the nipple. It may be a few drops of fluid or a continual leakage. Screening and diagnosis: A clinical breast exam includes taking a history of breast nipple discharge and examination of the nipples with gentle squeezing to see if fluid is expressed. Milky fluid in breast-feeding women is of no concern as long as the woman does not have symptoms of infection (breast is painful to the touch, redness is present, milk has a foul odor or has changed color), and many women continue to express milk long after they stop breast-feeding. Other testing includes cytologic examination of the discharge, mammography, and ductoscopy. Treatment and therapy: Often discharge will resolve if all stimulation of the breast is ceased; this means the woman must avoid the urge to check to see if the discharge is still occurring. Sometimes drugs that cause increased prolactin need to be adjusted, and any nipple discharge that is suspicious in terms of malignancy must be evaluated. Nipple discharge can also be a symptom of disorders in other hormone-producing glands, and those conditions may need to be treated. Prognosis, prevention, and outcomes: Prognosis and outcomes depend on the type of discharge. Prevention can often be managed by decreasing medications that increase prolactin and avoiding a cycle of stimulation of the nipple. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP)
A woman examines her breasts, checking for possible signs of cancer, such as nipple secretions. (Phanie/Photo Researchers, Inc.)
854
See also Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Clinical breast exam (CBE); Comedo carcinomas; Duct ectasia; Ductal carcinoma in situ (DCIS); Ductogram; Estrogen-receptor-sensitive breast cancer; HER2/neu protein; Invasive ductal carcinomas; Invasive lobular carcinomas; Lobular carcinoma in situ (LCIS); Mammography.
Salem Health: Cancer
Non-Hodgkin lymphoma
u Non-Hodgkin lymphoma Category: Diseases, symptoms, and conditions Also known as: Lymphoma, non-Hodgkin’s lymphoma, NHL Related conditions: Hodgkin disease, autoimmune disorders Definition: Non-Hodgkin lymphoma describes a group of cancers that originate in the lymphatic system, a part of the immune system. This system, which fights disease and infection, consists of the lymph nodes, spleen, bone marrow, and other organs throughout the body. Non-Hodgkin lymphoma develops in white blood cells called lymphocytes, of which there are two main types: B cells and T cells. Most lymphomas (85 to 90 percent) start in B cells. More than thirty types of non-Hodgkin lymphoma exist, with many subtypes. Non-Hodgkin lymphomas are classified by cell type; tumor size, shape, and pattern (nodular or diffuse); and growth rate (low grade, which are slow growing and indolent, and high grade, which are fast growing and aggressive). All lymphomas except Hodgkin disease are classified as non-Hodgkin lymphomas.
Hodgkin lymphoma can start almost anywhere and tends to be widespread, although slower growing types may be confined to one place. Typically, non-Hodgkin lymphoma begins in the lymph nodes and spreads to other parts of the lymphatic system. Occasionally, non-Hodgkin lymphoma also invades organs outside the lymphatic system, including the stomach, brain, and lungs. Incidence: Non-Hodgkin lymphoma is the fifth most common type of cancer among adults, and its rapidly increasing incidence in the United States is primarily unexplained (rates have nearly doubled since the 1970’s). According to the National Cancer Institute, in 2008, an estimated 66,120 non-Hodgkin lymphoma cases will be diagnosed and 19,160 deaths will be attributed to nonHodgkin lymphoma. A person’s risk of getting non-Hodgkin lymphoma is 1 in 50. The disease is more common among whites than African Americans or Asian Americans. Non-Hodgkin lymphoma occurs in all age groups, but the risk of developing the disease increases with age (95 percent of cases occur in adults age forty and older). Some subtypes are more common in certain age groups. In children, non-Hodgkin lymphoma is most commonly diag-
Risk factors: Some known and potential risk factors for non-Hodgkin lymphoma include age (over sixty); gender (more common in men); a compromised immune system (such as from drugs and other treatments or acquired immunodeficiency syndrome, AIDS); autoimmune disorders, such as rheumatoid arthritis and Sjögren syndrome; history of infection, such as with Epstein-Barr virus (increases risk of Burkitt lymphoma), Helicobacter pylori, and possibly hepatitis C virus; radiation exposure; and chemical exposure (such as pesticides and fertilizers). Despite the list of known and suspected risk factors for non-Hodgkin lymphoma, most people diagnosed have no known risk factors, and many who have risk factors never develop the disease. Etiology and the disease process: For most patients, the exact cause of non-Hodgkin lymphoma is unknown. One suspected cause is the activation of certain abnormal genes that allow uncontrollable lymphocyte division and growth. This uncontrolled growth causes lymph nodes and other lymphatic tissues to swell. Because lymphatic tissue is in various locations throughout the body, non-
This patient with non-Hodgkin lymphoma has a swollen lymph node in the center of the chest.(Zephyr/Photo Researchers, Inc.)
855
Non-Hodgkin lymphoma
Salem Health: Cancer
Incidence of Non-Hodgkin Lymphoma per 100,000 People, by Gender 30
Men 25
Women
24.1
20
19.2 18.1 17.0 15.7
15
14.2 11.9
11.2
11.6 9.5
10
5
0 White
Hispanic
Black
Asian/Pacific Islander
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
nosed between the ages of seven and eleven, and some types of non-Hodgkin lymphoma are among the most common childhood cancers. Symptoms: Symptoms vary depending on the area of the body in which the tumor originated and the areas to which the cancer has spread. Swollen, painless lymph nodes in the neck, underarms, stomach, or groin are commonly the only sign of non-Hodgkin lymphoma in early stages. Generalized symptoms include fever, unexplained weight loss, fatigue, excessive sweating, night sweats, chills, easy bruising, itchiness, and unusual infections. Tumors in the stomach can cause pain and swelling, which can lead to loss of appetite, constipation, nausea, and vomiting. Tumors in the thymus or chest lymph nodes can cause coughing and shortness of breath. Lymphoma of the brain can cause headaches, personality changes, and seizures. Screening and diagnosis: Many tests are used to diagnose non-Hodgkin lymphoma and assess the spread of the dis856
ease. Diagnosis begins with a medical history and physical examination, which commonly focuses on the lymph nodes, liver, and spleen. Blood and urine tests may be performed to help rule out infections and other diseases that cause swollen nodes. A biopsy is the best way to definitively diagnose lymphoma and determine the subtype. Lymph node biopsy from the neck, armpits, or groin is most common. Bone marrow biopsy may be performed to establish whether the disease has spread. Imaging tests such as X rays, magnetic resonance imaging, and computed tomography scanning may be used to detect the presence of non-Hodgkin lymphoma, determine the size of tumors, and determine the extent to which the cancer has spread. Staging helps to determine treatment. A system commonly used to stage non-Hodgkin lymphoma is the Ann Arbor staging system. This system classifies lymphoma into four stages: • Stage I: Lymphoma is limited to a single region, usually one lymph node or one lymph node region in the body.
Salem Health: Cancer
• Stage II: Lymphoma involves two or more regions, usually an affected lymph node or lymphatic organ and a second affected area, that are next to each other and on the same side of the diaphragm. • Stage III: Lymphoma has spread to both sides of the diaphragm. • Stage IV: Widespread disease has affected nonlymphatic organs. A lettering system is commonly used in combination with the stage to indicate the presence of symptoms. An “E” indicates involvement of organs outside the lymph system; a “B” indicates the presence of weight loss, night sweats, or unexplained fever; and an “A” indicates the absence of symptoms. Treatment and therapy: Treatment of non-Hodgkin lymphoma depends on the type and stage of the disease, symptoms, and the patient’s age and overall medical condition. Three main treatments are used: chemotherapy, radiation therapy (RT), and immunotherapy (also called biological therapy). Surgery is rarely used to treat the disease but may be used to relieve problems caused by nonHodgkin lymphoma, such as bowel obstruction and spinal cord compression. Chemotherapy is the primary treatment for non-Hodgkin lymphoma. It may be used alone or in combination with other treatments. Intermediate- and high-grade lymphomas and advanced low-grade lymphomas are commonly treated with multiple agents; single-drug therapy may be used for early-stage, low-grade disease. The exact medications, routes, doses, and duration of treatment depend on the stage and type of lymphoma. A common chemotherapy regimen for the initial treatment of non-Hodgkin lymphoma includes cyclophosphamide, doxorubicin, vincristine, and prednisone. Patients are usually treated on an outpatient basis unless problems arise. Radiation therapy is used to kill or shrink cancer cells. In some cases of Stage I and II non-Hodgkin lymphoma, curative treatment with radiation therapy is possible. Sometimes, radiation therapy is used with chemotherapy to treat intermediate-grade tumors or tumors in specific sites, such as the brain. However, it is typically ineffective against more advanced lymphomas. Radiation therapy may also be used to ease symptoms. Immunotherapy is an evolving treatment in which substances naturally made by the immune system are used to kill lymphoma cells or slow their growth. Investigational immunotherapies for non-Hodgkin lymphoma include monoclonal antibodies and interferons. Rituximab is a monoclonal antibody approved by the Food and Drug Administration for the treatment of B-cell non-Hodgkin lym-
Non-Hodgkin lymphoma phoma. It is commonly used in combination with chemotherapy. Some forms of radioimmunotherapy, in which monoclonal antibodies are attached to radioactive substances, are also used to treat non-Hodgkin lymphoma. Examples include ibritumomab and tositumomab. Because of their life-threatening side effects, these drugs are used only after other treatments have failed. If non-Hodgkin lymphoma recurs, treatment with highdose chemotherapy, total-body or total-lymph node irradiation, or bone marrow or stem cell transplantation may be necessary. Prognosis, prevention, and outcomes: The one-year relative survival rate for non-Hodgkin lymphoma is 81 percent; five-year, 63 percent; and ten-year, 49 percent. Rates vary depending on the person, type of lymphoma, and stage of disease. As with most other cancers, the earlier the diagnosis, the greater the chances for successful treatment. Typically, the type of tissue involved is a better prognostic predictor than cancer stage. The International Prognostic Index (IPI) is used to help predict lymphoma growth and patient response to treatment. Based on patient age, cancer stage and spread, patient function, and lactate dehydrogenase levels, the IPI is mainly used in patients with aggressive lymphomas. Low-grade non-Hodgkin lymphomas tend to be advanced when diagnosed. Although they usually respond well to treatment, they may also recur. High-grade nonHodgkin lymphomas sometimes require intensive chemotherapy. These lymphomas are often curable (some have 60 to 80 percent cure rates). However, if the cancer does not respond to chemotherapy, the disease can rapidly cause death. Because most people who have non-Hodgkin lymphoma have no known risk factors and the cause of the cancer is unknown, prevention is elusive. Jaime Stockslager Buss, M.S.P.H., ELS u
For Further Information Adler, E. M. Living with Lymphoma: A Patient’s Guide. Baltimore: Johns Hopkins University Press, 2005. American Cancer Society and National Comprehensive Cancer Network. Non-Hodgkin’s Lymphoma Treatment Guidelines for Patients. Atlanta: Author, 2005. Holman, Peter, Jodi Garrett, and William Jansen. One Hundred Questions and Answers About Lymphoma. Sudbury, Mass.: Jones and Bartlett, 2004. u
Other Resources
Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org 857
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Salem Health: Cancer
Lymphoma Research Foundation http://www.lymphoma.org
u Nonsteroidal anti-
National Cancer Institute http://www.cancer.gov
Category: Chemotherapy and other drugs ATC code: M01A
See also Agent Orange; Anthraquinones; Antimetabolites in chemotherapy; Azathioprine; Biological therapy; Blood cancers; Burkitt lymphoma; Childhood cancers; Cutaneous T-cell lymphoma (CTCL); Dioxins; Elderly and cancer; Epstein-Barr virus; Hair dye; Helicobacter pylori; Hepatitis C virus (HCV); HIV/AIDS-related cancers; Hodgkin disease; Immune response to cancer; Klinefelter syndrome and cancer; Lambert-Eaton myasthenic syndrome (LEMS); Lymphomas; Mantle cell lymphoma (MCL); Mucosa-associated lymphoid tissue (MALT) lymphomas; Myeloma; Oncogenic viruses; Pediatric oncology and hematology; Pesticides and the food chain; Primary central nervous system lymphomas; Radiopharmaceuticals; Richter syndrome; Simian virus 40; Splenectomy; Veterinary oncology; Virus-related cancers; Waldenström macroglobulinemia (WM).
inflammatory drugs (NSAIDs) Definition: Nonsteroidal anti-inflammatory drugs, or NSAIDs, are a large, heterogeneous group of medications intended to treat pain, fever, and inflammation. Cancers treated: NSAIDs are used to treat all types of pain and discomfort associated with cancer, arthritis, gout, and dysmenorrhea (painful or difficult menstruation). They have an inhibitory effect on bone tumor growth and may promote centrally mediated analgesia. Subclasses of this group: NSAIDs are weak organic acids. Subclasses include salicylates, propionic acids, pyrrolealkonic acid derivatives, phenylalkanones, indolic acids, pyrazolone derivatives, and phenyl-naphthyl-acetic acids. Delivery routes: These drugs are generally administered orally as a suspension in a liquid or in capsule or tablet
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Drug
Brands
Subclass
Delivery Mode
Aspirin
Anacin, Bayer, Excedrin, Bufferin Acetylsalicylic acid
Oral
Celecoxib
Celebrex
Sulfonamide pyrazole
Oral
Diclofenac/misoprostol Arthrotec
Carboxylic acid
Oral
Diclofenac sodium
Voltaren
Phenylacetic acid
Oral
Difunisal
Dolobid
Salicylic acid derivative
Oral, topical ointment
Etodolac
Lodine
Acetic acid derivative
Oral
Flurbiprofen
Ansaid
Difluoro-propionic acid
Oral
Ibuprofen
Motrin, Advil, Nuprin
Phenylpropionic acid
Oral, IV
Indomethacin
Indocin
Indole acetic acid
Oral, ophthalmic, epidural
Ketorolac
Toradol
Pyrrolizine-carboxylate
Oral, IV, intramuscular, ophthalmic
Meclofenamate sodium Meclomen
Meclofenamic acid
Oral
Meloxicam
Mobic
Enolic acid
Oral
Nabumetone
Relafen
Naphthylalkanone (only nonacid NSAID)
Oral
Naproxen
Anaprox, Naprosyn, Aleve
Naphthylpropionic acid
Oral, topical, ophthalmic
Piroxicam
Feldene
Oxicam
Oral
Sulindac
Clinoril
Sulfinyl acetic acid
Oral
Tolmetin sodium
Tolectin
Pyrrolealkanoic acid
Oral
858
Salem Health: Cancer form. Certain drugs can be given intravenously, as an intramuscular injection, as a rectal suppository, as a topical ointment, or in an ophthalmic solution. How these drugs work: NSAIDs inhibit cyclooxygenase enzyme activity, resulting in decreased synthesis of prostaglandins (hormones that produce inflammation and pain). Cyclooxygenase 2 (COX-2) inhibitors perform the same function but mediate the metabolic pathway by selectively blocking the COX-2 enzyme. Side effects: Common complaints from NSAID use include headache, dizziness, gastrointestinal symptoms (nausea, stomach cramps, gastric ulceration, and diarrhea), tremor, insomnia, skin rash, and platelet dysfunction. An anaphylactic (allergic) response to a particular NSAID can present as hives, rash, intense itching, and respiratory difficulties. This condition can be life threatening, and immediate emergency treatment is required. The COX-2 inhibitors Vioxx and Bextra were pulled from the U.S. market by the Food and Drug Administration (FDA) in the early 2000’s. Over an extended period of use (more than eighteen months), they place patients at significantly increased risk for heart attack and stroke. Only Celebrex remains on the market, but with significant warnings attached to its use and potential risks. John L. Zeller, M.D., Ph.D. See also Breakthrough pain; Cyclooxygenase 2 (COX-2) inhibitors; Opioids; Pain management medications; Phenacetin.
u Nuclear medicine scan Category: Procedures Also known as: Radionuclide scan, positron emission tomography (PET) scan, single photon emission computed tomography (SPECT) imaging Definition: A nuclear medicine scan detects electromagnetic radiation, usually gamma rays, emitted from an injected radioactive tracer than has been taken up by an organ in the body to be studied, with the goal of producing an image. The most common radioisotope used is technetium 99m, known as the workhorse of nuclear medicine, whose gamma rays are absorbed by a sodium iodide crystal detector. Interaction of the gamma rays with the crystals results in production of a pulse of fluorescent light proportional in intensity to the energy of the gamma ray. The light is
Nuclear medicine scan amplified and converted into an electrical signal by the photomultiplier tubes. The electrical signal is then fed to a computer, which analyzes the pulse height and generates an image of the distribution of the radiotracer in the body or organ under study. An array of these crystal detectors attached to a collimator, along with the photomultipliers and computer, is called a gamma camera. The gamma camera is used to scan the patient. The pattern of uptake of radiotracer in the organ or whole body under study varies depending on the disease process. Multiple gamma cameras are sometimes used to generate a three-dimensional view of an organ; this particular type of nuclear medicine scan is called single photon emission computed tomography (SPECT) imaging. The exceptions to the use of technetium in nuclear medicine scanning include gallium scanning, which uses gallium as the radionuclide; some thyroid imaging that uses radioactive iodine; indium-labeled white cell studies and cerebral perfusion scans; some cardiac imaging that uses thallium; the Schilling test, which uses cobalt-labeled vitamin B12; and PET scanning, which uses antimatter or positron emission instead of a gamma emitter. PET imaging utilizes fluorodeoxyglucose (FDG) labeled with F-18, a positron emitter. The F-18-labeled FDG is preferentially taken up by cancer cells because of their increased metabolic rate and therefore increased need for sugar compared to normal cells. The scanner used in PET imaging is not the gamma camera but a separate scanner based on coincidence detection of the annihilation photons resulting from positron decay. PET scanning is often combined with computed tomography (CT) performed at the same time. Cancers diagnosed: All types of cancers, both primary and secondary (metastatic), can be diagnosed using nuclear medicine scans; for PET scans, the cancers more commonly diagnosed are lymphoma (Hodgkin and nonHodgkin), esophageal cancer, lung cancer, head and neck cancers, colorectal cancer, pancreatic cancer, renal cancer, breast cancer, thyroid cancer, and melanoma. Most cancers are identified as a result of their increased uptake of the radiotracer. Others are identified as a result of their lack of uptake, called photopenia, as can be seen in some liver tumors evaluated with HIDA or sulfur colloid. For HIDA scans, differentiation among primary hepatic tumors is performed because of increased uptake seen in focal nodular hyperplasia but not hepatic adenoma, which appears photopenic. In sulfur colloid liver-spleen scans, hepatic adenoma is again seen as a cold defect because of the lack of Kupffer cells (the phagocytic or “sweeper” cells in the liver that form part of the reticuloendothelial 859
Nuclear medicine scan
Salem Health: Cancer mocytomas are diagnosed with iodine-labeled metaiodobenzylguanidine (MIBG).
A patient undergoes a nuclear medicine scan. (Digital Stock)
system) compared with focal nodular hyperplasia, which has either normal or increased colloid uptake as a result of the presence of Kupffer cells. Macrophages in the spleen function similarly. A type of benign hepatic tumor known as a cavernous hemangioma is often diagnosed by increased uptake of radiotracer on red blood cell scans in a pattern that is virtually pathognomonic. For bone scans, metastatic disease from prostate and breast as well as osteosarcoma and osteiod osteoma are most commonly diagnosed as a result of increased radiotracer activity from osteoblastic activity of the cancer cells (that is, increased bone turnover caused by the cancer cells). Multiple myeloma, on the other hand, is photopenic on bone scans. For iodine scans, thyroid cancer of both primary and secondary types is identified because of the increased uptake of radioiodine. In some cases, such as thyroid cancer, the scan and the treatment can be combined using radioactive iodine. Carcinoid tumor and medullary carcinoma of the thyroid are diagnosed with somastatin receptor imaging called indium DTPA-labeled octreotide, and pheochro860
Why performed: Nuclear medicine scans (bone scan, iodine scan, HIDA scan, red blood cell scan, sulfur colloid scan, octreotide scan, PET scan) are used to diagnose primary and secondary cancer. They are also used to diagnose various ailments depending on the type of scan, including but not limited to the following: acute and chronic cholecystitis and evaluation for postoperative leaks following cholecystectomy (HIDA or DISIDA scan); gastrointestinal bleeding (red blood cell pertechnetate scan); goiter, hypothyroidism versus hyperthyroidism, and evaluation for ectopic thyroid tissue (thyroid scan); hyperparathyroidism caused by parathyroid adenoma (parathyroid scan); Meckel’s diverticulum (Meckel’s pertechnetate scan); pernicious anemia and malabsorption as a result of sprue (Schilling test); testicular torsion, testicular trauma, orchitis, and epididymitis (testicular pertechnetate scan); bone fractures, Paget disease, prosthesis evaluation, reflex sympathetic dystrophy, bone infarction, and bone infection (bone scan); kidney obstruction, renal transplant rejection, and renal artery stenosis (renal scan); infectious and inflammatory disorders of the lungs, abdomen, pelvis, genitourinary tract, and bone, including acquired immunodeficiency syndrome (AIDS), sarcoidosis, and fever of unknown origin, among others (gallium scan); infection (indium-labeled white blood cells); cardiomyopathymyocarditis and ejection fraction of the heart, often performed after doxorubicin chemotherapy for breast cancer (MUGA scan); coronary artery disease, coronary artery bypass graft surgery evaluation, valvular heart disease, and risk stratification following myocardial infarction (myocardial perfusion imaging, radionuclide ventriculography, cardiac SPECT, cardiac PET); pulmonary embolus (lung or V/Q scan); gastrointestinal bleeding, portal hypertension, and gastric emptying (sulfur colloid scan); normal pressure hydrocephalus, cerebral spinal fluid leaks, and surgical shunt patency (indium-labeled DTPA cisternography); evaluation for brain death (DTPA cerebral blood flow study); stroke (HMPAO cerebral perfusion imaging with SPECT); identification of seizure focus, evaluation for Alzheimer’s disease versus other forms of dementia and depression, Parkinson’s disease, and drug addiction (brain SPECT and brain PET). Patient preparation: Patients are asked to fast at least four hours prior to most scans, especially DISIDA scans and PET scans. For thyroid imaging, patients should stop thyroid medication (synthroid) and avoid CT contrast intravenous dye for one month prior to the scan, as both synthroid and CT contrast dye will interfere with the scan
Salem Health: Cancer results. Cisternography requires the injection of indiumlabeled DTPA radiopharmaceutical into the lumbar subarachnoid space by lumbar puncture, also called spinal tap, prior to scanning. The Schilling test requires the patient to collect urine for twenty-four hours after injection of the radiotracer labeled vitamin B12, and the urine is then evaluated. The patient also receives an intramuscular injection of nonlabeled vitamin B12 as part of the test, prior to the urine collection. Steps of the procedure: The radioisotope is prepared by the technologist and injected into a peripheral vein by the radiologist or nuclear medicine physician. For white blood cell scans and some red blood cell scans, a small amount of blood is withdrawn from the patient and labeled with the radioisotope and is then reinjected prior to scanning. The patient is then placed on the back on a table under a gamma camera connected to a computer. Scan time is variable depending on the procedure but usually takes about one hour. After the procedure: The scan is generated by the computer attached to the detector and read by the radiologist the same day. The patient will need to contact his or her doctor for the radiology report and for follow-up treatment. Risks: Minor pain or bruising at the injection site may occur. If the patient is pregnant, then the scan should be avoided if possible, since the radiation dose, although small in most cases, is not negligible. Radioactive iodine should not be administered to a pregnant patient because of the risk to the fetus as the radioiodine crosses the placenta with significant exposure to the fetal thyroid, causing cretinism. Radioiodine is also excreted in human breast milk, and nursing should be stopped following diagnostic or therapeutic studies performed using radioiodine. Results: The results of a nuclear medicine scan are dependent on the type of scan performed and the reason for the study. Their use in detecting tumors helps the cancer care team stage the cancer and develop a treatment plan. Debra B. Kessler, M.D., Ph.D. u For Further Information Mettler, Fred A., Jr., and Milton J. Guiberteau. Essentials of Nuclear Medicine Imaging. 5th ed. Philadelphia: Saunders/Elsevier, 2006. Sandler, Martin P., R. Edward Coleman, and James A. Patton, eds. Diagnostic Nuclear Medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Wahl, Richard L., ed. Principles and Practice of Positron Emission Tomography. Philadelphia: Lippincott Williams & Wilkins, 2002.
Nutrition and cancer prevention See also Brain scan; Cold nodule; Gallium scan; Imaging tests; Positron emission tomography (PET); Radionuclide scan; Thyroid nuclear medicine scan; X-ray tests.
u Nutrition and cancer
prevention Category: Lifestyle and prevention Definition: Everyday eating habits are increasingly associated with cancer incidence, prevention, and management. According to the National Cancer Institute, 80 percent of cancers are caused by environmental factors that are within people’s control. It is estimated that the types of foods people eat directly cause 35 to 50 percent of environmental cancers. Studies show that diet and lifestyle changes can prevent and reduce the risk and recurrence of most cancers. Epidemiology: As a rule, the human immune system is able to stop carcinogens from damaging cells within the body. However, sometimes cell deoxyribonucleic acid (DNA) is attacked and altered, causing cancer cells to begin to develop and multiply. Studies show that most cancers can be prevented through lifestyle choices (a healthful diet, avoidance of tobacco and excessive alcohol use, and adequate physical activity) and changes in the environment. Strong associations link diet to some cancers, but many other factors contribute as well. Genetics, infectious agents, some viruses, and exposure to radiation, chemicals, and some carcinogenic substances in the air, water, and soil also play a role. The American Cancer Society reported that 23.1 percent of deaths in the United States in 2004 were due to cancer. Nutrition risk factors: Studies find populations that eat a diet rich in fatty foods, especially animal fats, have higher rates of cancer than populations that eat a plantbased diet high in whole grains, vegetables, fruits, and legumes. Increased death rates from breast, prostate, and colon cancers are associated with high-fat diets. Higher rates of cancer have also been linked with the consumption of low-fiber diets and excessive alcohol. Being overweight or obese is also strongly linked with cancer. Overweight people are more likely to develop breast (postmenopausal women), colon, endometrial, esophageal, and kidney cancers. Obese individuals are also at risk for developing cervical, gallbladder, ovarian, pancreatic, thyroid, and colorectal cancers; Hodgkin disease; multiple myeloma; and aggressive forms of prostate cancer. These findings are of particular concern as west861
Nutrition and cancer prevention
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creased dramatically in the United States because of the popular belief that they prevent aging and illness. Research shows that antioxidants, carotenoids, and phytochemicals do have some protective effects against free radicals, which are cell-damaging molecules arising from normal biological functions and the environment. Free radical cell destruction is believed to cause aging and many diseases in humans. However, although some studies show benefits from including antioxidants, carotenoids, and phytochemicals in the diet, other studies actually show that they cause harm. In two studies in which high doses of beta-carotene supplements were taken to prevent lung cancer, former cigarette smokers experienced increased lung cancer death. However, when beta-carotene was conResearch findings: A number of different food compounds, minerals, and vitamins are thought to protect sumed via food sources (not supplements), cancer risk was reduced. against some cancers. Some of those that have become Coffee, aspartame, saccharin, and sugar have been suswell known are antioxidants, carotenoids, and phytochempected of causing cancer, but studies have not concluicals, substances or nutrients found in foods. Antioxidants sively linked them to cancer. An increased cancer risk has include vitamins C and E and the mineral selenium; carotbeen associated, however, with the consumption of highly enoids include lycopene, lutein, and beta-carotene; and salted, preserved, or smoked meats and those cooked at phytochemicals include a number of plant-based comhigh temperatures (fried, broiled, and grilled). Many expounds, such as resveratrol (found in red wine), catechin perts recommend limiting consumption of these types of (found in teas), and allium (found in garlic). The use of meats. dietary supplements containing these substances has inStudies regarding concerns over the effects of bioengineered and irradiated foods, fish contaminated with mercury, food additives, fluoride in dental products and water, and pesticide residue on foods have not shown any increased risk for cancer. There is no evidence to date that distinguishes organic foods from conventional foods in terms of a cancer risk. However, some studies have shown that the phytochemical content of organic fruits and vegetables may be higher than that of conventionally grown crops. This finding leads some to think that this might convey some level of protection against cancer. Soy, calcium, and vitamin D are thought by some to help prevent cancers. Soy is an excellent source of protein and phytochemicals, but very little data supports the premise that soy lowers the risk of cancer. Soy contains compounds called phytoestrogens (plant estrogens), which closely resemble the hormone estrogen and may actually increase the risk of estrogenVegetables are an important part of a cancer-prevention diet. (PhotoDisc) ernized societies are experiencing increasing rates of obesity. Excessive alcohol intake, defined as more than two drinks per day for men and more than one drink per day for women (one serving equals 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of liquor), is clearly associated with cancers of the mouth, throat, larynx, esophagus, liver, and breast. No known nutrition factors are associated with brain cancer, leukemia, and lymphoma. However, some cancers related to diet may result in secondary tumors or metastatic disease in these areas.
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A Healthful Diet The U.S. Department of Agriculture, in its Dietary Guidelines for Americans, 2005, gave these broad guidelines for a diet that would be healthful for most Americans.
• • •
Centers on fruits, vegetables, whole grains, nonfat or low-fat dairy products. Contains some lean meats, poultry, fish, beans, eggs, and nuts. Has minimal amounts of saturated fats, trans fats, cholesterol, salt, and added sugar.
responsive cancers, such as breast and endometrial cancers. It may also reduce the effectiveness of tamoxifen drug treatments. Therefore, some researchers recommend that soy foods and products containing soy isoflavones should be limited to two servings per day and that dietary soy supplements should be avoided. Patients taking tamoxifen should avoid all soy products. The connection between soy and cancer, however, remains unclear. Calcium has been associated with a lower incidence of colorectal cancers, but there is also evidence that calcium supplements may increase prostate cancers, especially the aggressive form. Because of this, calcium recommendations remain at 1,000 milligrams per day for people between the ages of nineteen and fifty and 1,200 milligrams per day for people older than fifty. Nonfat or low-fat dairy sources of calcium and some leafy green vegetables are preferable to supplements as sources of calcium. Vitamin D is also increasingly thought to protect against colon, prostate, and breast cancer. The existing recommendations for intake of vitamin D, between 200 and 600 International Units (IU) daily, may not be sufficient to provide protection against cancers, especially for those living in northern climates, the elderly, people with dark skin, and exclusively breastfed babies. However, more research is needed before these recommendations can be changed. In the meantime, many researchers suggest exposing the skin (without sunscreen) to sunlight for 15 minutes every day and balancing the diet to include foods fortified with vitamin D. Many more studies need to be done to verify diet and cancer connections, but the best way for people to lower their cancer risk appears to be eating a balanced, low-fat diet that includes a variety of fruits and vegetables daily. Dietary recommendations: Research points to a number of dietary recommendations that should be followed to lower the risk for developing cancer or having it recur. The
Nutrition and cancer prevention following recommendations are from the American Cancer Society: • Maintain a healthy weight throughout life: People are advised to lose weight if they are overweight or obese, avoid excessive weight gain, and balance food intake with physical activity. • Adopt a physically active lifestyle: Adults are advised to exercise at least 30 minutes a day (ideally 45 to 60 minutes a day), five or more days of the week. Children and adolescents are advised to exercise at least 60 minutes per day, five or more days per week. • Eat a healthy diet, with an emphasis on plant sources: People are advised to eat five or more servings of vegetables and fruits every day, choose whole grains, and include legumes for protein. Also, they are to limit intake of processed and refined foods, sugars, red meat, and processed meats. A simple way to make sure the diet has the right emphasis is to fill one-fourth of the plate with a protein source, one-fourth with whole grains, and one-half with colorful vegetables. One serving of fruit is one-half cup of canned fruit, three-quarters cup of 100 percent juice, or a small to medium-sized piece of fresh fruit. One serving of vegetables is one-half cup of cooked or one cup of raw vegetables. • Limit consumption of alcoholic beverages: Women should not exceed one drink per day, and men, two drinks per day. Alice C. Richer, R.D., M.B.A., L.D. u
For Further Information American Institute for Cancer Research. Diet and Health Recommendations for Cancer Prevention: Healthy Living and Lower Cancer Risk. Washington, D.C.: Author, 2006. Awad, Atif B., and Peter G. Bradford, eds. Nutrition and Cancer Prevention. Boca Raton, Fla.: CRC, Taylor & Francis, 2006. Kushi, Lawrence H., et al. “American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention.” Cancer: A Cancer Journal for Clinicians 56 (2006): 254-281. McTiernan, Anne, ed. Cancer Prevention and Management Through Exercise and Weight Control. Boca Raton, Fla.: Taylor & Francis, 2006.
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Other Resources
American Institute of Cancer Research Recommendations for Cancer Prevention Http://www.aicr.org/site/PageServer?pagename= dc_home_guides 863
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The Cancer Project Cancer Prevention and Survival http://www.cancerproject.org/survival/cancer_facts/ factors.php National Cancer Institute Cancer Prevention Overview http://www.cancer.gov/cancertopics/pdq/prevention/ overview/healthprofessional Prevent Cancer Foundation http://www.preventcancer.org See also Aflatoxins; Alcohol, alcoholism, and cancer; Antioxidants; Beta-carotene; Bioflavonoids; Calcium; Carotenoids; Cartilage supplements; Chemoprevention; Coenzyme Q10; Complementary and alternative therapies; Cruciferous vegetables; Dietary supplements; Fiber; Folic acid; Fruits; Garlic and allicin; Ginseng, panax;
Green tea; Herbs as antioxidants; Indoles; Isoflavones; Lutein; Lycopene; Macrobiotic diet; Nutrition and cancer treatment; Obesity-associated cancers; Omega-3 fatty acids; Phytoestrogens; Poverty and cancer; Prevention; Resveratrol; Saw palmetto; Soy foods; Sun’s soup; Wine and cancer.
u Nutrition and cancer
treatment Category: Lifestyle and prevention Definition: Cancer treatments often affect people differently, and side effects can range from minor to severe. Eating well and following good nutrition habits before and during treatment help maintain strength, prevent body tis-
Effects of Cancer Treatments on Nutrition Treatment
Common Nutrition Problems
Nutrition-Related Side Effects
Surgery
May slow digestion; affect proper function of mouth, throat, stomach; increase healing and recovery needs
• May be unable to eat normally and require liquid nutrition • Chewing, swallowing, digestion functions may be impaired
Radiation therapy
Affects healthy tissues and may affect digestive system
Head, neck, chest, breast cancer treatments may cause: • dry or sore mouth • difficulty swallowing • changes in food taste • dental problems • phlegm production Stomach or pelvis cancer treatments may cause: • nausea, vomiting • diarrhea • cramps, bloating
Chemotherapy
May affect the digestive system and desire or ability to eat
• nausea, vomiting • loss of appetite • diarrhea • constipation • sore mouth or throat • weight gain or loss • changes in food taste
Hormonal therapy
May affect ability and desire to eat
• nausea, vomiting • diarrhea • sore or dry mouth • severe weight loss • changes in food taste • fatigue, muscle aches, fever
Immunotherapy May increase appetite and how the body handles fluid
864
• change in appetite • fluid retention
Salem Health: Cancer
Nutrition and cancer treatment
Tips for Managing Nutritional Side Effects of Treatment Side Effect
Suggestions for Managing Effect
Side Effect
Constipation
• Eat high-fiber foods (whole grains, fresh fruits and vegetables) • Add unprocessed wheat bran to foods • Get daily exercise • Drink a hot beverage about one-half hour before usual time for bowel movement • Discuss fiber supplements with doctor
Dry mouth
Diarrhea
• Avoid: beans, onions, strong spices greasy, fried, and fatty foods raw vegetables, fruits, nuts high-fiber vegetables (broccoli, corn, beans, cabbage, cauliflower, peas) alcohol dairy only if it increases diarrhea very cold or hot liquids/foods • Try: rice or noodles hot wheat cereal well-cooked eggs bananas pureed or soft-cooked vegetables canned/cooked fruits (no skin) white bread skinless chicken/turkey soft or ground beef fish mashed potatoes clear liquid diet during first 24 hours • Eat foods high in sodium and potassium (bananas, peaches, apricot nectar, potatoes)
Difficulty swallowing
• Take deep breaths before swallowing • Exhale or cough after swallowing • Try thick liquids or gelatin • Mash foods to thin or pureed consistency • Drink room-temperature fluids between meals • Use a straw or spoon to eat • Avoid very hot or cold foods • Work with a speech therapist on safe swallowing techniques
sue breakdown, rebuild tissues, defend against infection, cope with side effects, and make some treatments more effective. Cancer treatments: There are five main treatments used to fight cancer: surgery, radiation therapy, chemotherapy,
Suggestions for Managing Effect • Avoid: salty or tart foods and beverages • Try: ice pops, sugar-free gum, hard candy, thick nectars sip water every few minutes • Discuss products that protect your mouth with doctor or dentist
Food aversion • Avoid favorite foods until treatment over Mouth or throat pain, tooth decay
• Avoid: citrus fruit and juices spicy and salty foods rough and dry foods hot spices alcohol • Try: bananas, applesauce, watermelon, canned fruits peach, pear, and apricot nectars cottage cheese, yogurt, and milkshakes mashed potatoes macaroni and cheese custards, puddings, gelatin scrambled eggs hot cooked cereals pureed or mashed vegetables and meats foods cooked until tender and then cut up or pureed stews and casseroles • Mix food with margarine, gravy, or sauces • Use a straw to drink liquids • Eat foods and drink liquids cold or at room temperature
(continued on page 866)
hormone therapy, and immunotherapy. Surgery is used to remove tumors and cancer cells that have not spread to surrounding body tissues. It is often combined with other treatment methods. After surgery, the protein content and number of calories in the diet need to be increased to assist in wound healing and the recovery process. Eating health865
Nutrition and cancer treatment
Salem Health: Cancer
Tips for Managing Nutritional Side Effects of Treatment (continued) Side Effect
Suggestions for Managing Effect
Side Effect
Suggestions for Managing Effect
Nausea
• Avoid: fatty, greasy, fried, spicy foods sweets (candy, cake, and so on) foods with strong odors or warm or strong-smelling rooms • Try: toast, crackers, pretzels yogurt sherbet, ice pops angel food cake canned fruits skinless chicken (baked or broiled) hot cooked cereals clear liquids (apple juice, broth) ice chips • Eat small amounts often and slowly • Sip cool or chilled liquids throughout the day, except at meals • Eat room temperature or cool foods • Do not eat favorite foods • Always sit upright when eating • Rest after meals for at least one hour • Eat dry toast or crackers before getting up if nauseated in the morning • Wear loose-fitting clothes • Do not eat 1-2 hours before treatment • Keep track of which foods cause nausea • Eat biggest meal of the day when hungry • Discuss antinausea medications with doctor
Vomiting
• Do not drink or eat while vomiting • Sit upright after vomiting for at least an hour • When feeling better, try small amounts of clear liquid, such as apple juice, flat ginger ale, or room temperature broth, drinking 1 teaspoon every 10 minutes as tolerated, gradually increasing to 2 tablespoons every 30 minutes • When able to tolerate clear liquids without vomiting, increase to full liquids (hot wheat cereal, ice cream, broth, gelatin, milk, custard, pudding, and so on)
Weight gain, fluid retention
• Avoid salty foods, add less salt to foods • Drink at least 3-4 glasses of water daily and when thirsty • Exercise as much as is realistic • Meet with a registered dietitian
Weight loss, poor appetite
• Maintain normal activities as much as possible • Do not hurry meals and stay calm when eating • Eat whenever hungry • Keep nutritious snacks available • Try new foods or restaurants • Eat favorite foods • Use candlelight or favorite music at mealtimes, or change timing of meals • Meet with a registered dietitian
Taste changes
• Choose and eat foods that look and smell good • Try different foods • Marinate meats, fish, poultry, or try different spices • Try tart foods • Eat foods at room temperature • Maintain good oral hygiene
fully following surgery also helps the patient feel better by maintaining strength, energy, and a stable weight while maintaining the body’s stores of nutrients. Good nutrition is essential for the healing process, to decrease risk of infection, and to increase tolerance to side effects from other treatments used. Any surgery involving the gastrointestinal tract must be carefully monitored, as it can lead to malnutrition. 866
Radiation therapy directs radiation at the affected body area, preventing cancer cells from multiplying and spreading. Although healthy tissue is affected along with the cancer cells, it usually recovers after treatment ends. Radiation can be used alone or combined with other treatments. Treatments are usually given five days a week and last from two to nine weeks. Nutrition side effects depend on the length of treatment and the area to which the radiation is directed.
Salem Health: Cancer Chemotherapy requires the use of strong drugs to disrupt the cancer cells’ ability to grow and multiply. Chemotherapy drugs are either taken orally or injected and may be used alone or combined with other treatments. Chemotherapy affects the entire body, not just the cancer site. As a result, healthy tissue is affected. The digestive tract is very susceptible to side effects from this treatment. Hormone therapy uses drugs to block hormone production by the body. Hormones that influence the growth of some cancers, such as breast and prostate cancers, are targeted. Hormone therapy can also involve the removal of hormone-producing organs, which is thought to end or slow tumor growth by removing the source of the hormones on which these tumors thrive. Hormone therapy can affect the ability and desire to eat. Immunotherapy, also called biological therapy, enlists the body’s immune system to stimulate natural defenses to help fight the offending cancer. It can be used alone but is usually combined with other therapies. This type of therapy can affect fluid retention and may actually increase the appetite. Nutrition suggestions during treatment: Eating a healthy diet is very important during treatment. This often requires that patients plan ahead, enlist the help of family and friends, and be ready to try different foods and preparation techniques. When experiencing nutrition-related side effects during active treatment, patients are advised to eat foods and liquids that are well tolerated. All patients undergoing treatment should be encouraged to drink plenty of fluids throughout the day and visit with a registered dietitian to ensure proper eating habits. Alice C. Richer, R.D., M.B.A., L.D.
Nutrition and cancer treatment u
For Further Information Bloch, Abby, et al., eds. Eating Well, Staying Well During and After Cancer. Atlanta: American Cancer Society, 2004. Elliott, Laura, Laura L. Molseed, and Paula Davis McCallum, eds. The Clinical Guide to Oncology Nutrition. 2d ed. Chicago: American Dietetic Association, 2006. Keane, Maureen, and Daniella Chace. What to Eat If You Have Cancer: Healing Foods That Boost Your Immune System. 2d ed. New York: McGraw-Hill, 2007.
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Other Resources
American Cancer Society Handling the Side Effects of Treatment Http://www.cancer.org/docroot/MBC/MBC_6_1_ what_to_do_about_side_effects.asp American Institute of Cancer Research Nutritional Effects of Cancer Treatment Http://www.aicr.org/site/PageServer?pagename= dc_cr_treatment#nutrition National Cancer Institute Eating Hints for Cancer Patients: Before, During, and After Treatment http://www.cancer.gov/cancertopics/eatinghints/page3 See also Anthraquinones; Antioxidants; Cancell; Carotenoids; Cartilage supplements; Coenzyme Q10; Complementary and alternative therapies; Curcumin; Delta-9tetrahydrocannabinol; Dietary supplements; Electroporation therapy; Essiac; Gerson therapy; Ginseng, panax; Green tea; Herbs as antioxidants; Integrative oncology; Laetrile; Mistletoe; PC-SPES; Phenolics; Saw palmetto; Sun’s soup.
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Obesity-associated cancers
u Obesity-associated cancers Category: Diseases, symptoms, and conditions Related conditions: Many types of cancer Definition: Obesity is an increase in body weight through an accumulation of fat in the body such that people exceed their ideal weight (taking into account height, sex, age, and body build) by 20 percent or more. The National Institutes of Health define obesity as a body mass index of 30 and above; 40 and above is generally considered severely obese. (A BMI of lower than 18.5 is underweight, 18.5 to 24.9 is healthy, and greater than 25.0 is overweight.) Body mass index, which relates a person’s height and weight, is calculated by multiplying the person’s weight in pounds by 703, then dividing that number by the person’s height in inches, squared. Another important measurement that relates to obesity is a person’s waist measurement. A woman with a waist measurement of more than 35 inches and a man with a measurement of more than 40 inches are considered to be at higher risk for disease. Even if a person’s BMI falls within a healthy range, the risk of developing health problems is greater if body fat is concentrated mainly in the waist area.
Salem Health: Cancer Obesity has long been connected with the risks of developing many disorders, including diabetes, arthritis, stroke, and respiratory and heart disease. Years of research have shown that obesity has a significant effect on the development of cancer and its prognosis after treatment. The cancers that are known to be affected by obesity include breast (postmenopausal), endometrial, ovarian, esophageal, colon, prostate, testicular, kidney, pancreatic, nonHodgkin lymphoma, multiple myeloma, and gallbladder. Further research may find links to other cancers as well. Risk factors: Obesity is primarily caused by poor diet (excessive intake of calories) and physical inactivity. Weight gain may be caused in part by the abundance of readily available high-calorie food choices and the lack of physical exertion in modern lives, psychological factors such as stress or depression, physical conditions such as hypothyroidism, and certain medications including migraine medications and antidepressants.
Etiology and the disease process: Many researchers have studied obesity and its relationship to an increased incidence of certain cancers. It is believed that fat cells in the body produce hormones and other substances that affect cell growth. Obese people have significantly increased levels of these compounds because of the increased number of fat cells, which can have potentially important effects on cellular growth and planned cellular death, perhaps allowing damaged cells to survive and grow into tumors. The roles of estrogen, insulin, insulinlike growth factor-1 and insulin-like growth factor-binding protein-3, leptin, and cytokines, as well as other substances and growth factors, are being examined for their relationship to obesity-associated cancers. An example of these actions by fat tissue can be found in postmenopausal breast cancer, which is known to have a 50 percent incidence rate in obese women. Estrogen, important in the reproductive cycle, is produced by fat tissue in addition to being produced by the ovaries. After menopause, when the ovaries stop producing hormones, fat tissue becomes the most important estrogen source. In obese women, postmenopausal estrogen levels are 50 to 100 percent higher than in women who are not overweight or obese. As a result, estrogensensitive tissues in obese women are overexposed to estrogen stimulation, leading to A body mass index of 30 or greater indicates obesity, a cancer risk factor. a more rapid growth of estrogen-responsive (PhotoDisc)
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Obesity-associated cancers
Body Mass Index 59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
91 96 100 105 110 115
94 99 104 109 114 119
97 102 107 112 118 123
100 106 111 116 122 127
104 109 115 120 126 131
107 113 118 124 130 135
110 116 122 128 134 140
114 120 126 132 138 144
118 124 130 136 142 148
121 127 134 140 146 153
125 131 138 144 151 158
128 135 142 149 155 162
132 139 146 153 160 167
136 143 150 157 165 172
140 147 154 162 169 177
144 151 159 166 174 182
148 155 163 171 179 186
152 160 168 176 184 192
156 164 172 180 189 197
119 124 129 134 138
124 128 133 138 143
128 133 138 143 148
132 137 143 148 153
136 142 147 153 158
141 146 152 158 163
145 151 157 163 169
150 156 162 168 174
155 161 167 173 179
159 166 172 178 185
164 171 177 184 190
169 176 182 189 196
174 181 188 195 202
179 186 193 200 208
184 191 199 206 213
189 197 204 212 219
194 202 210 218 225
200 208 216 224 232
205 213 221 230 238
142 148 153 158 162 167 172 177 181 186
148 153 158 163 168 173 178 183 188 193
153 158 163 168 174 179 184 189 194 199
158 164 169 174 180 185 190 195 201 206
164 169 175 180 186 191 196 202 207 213
169 175 180 186 191 197 203 208 214 220
174 180 186 192 197 204 209 215 221 227
180 186 192 198 204 210 216 222 228 234
186 192 198 204 210 216 223 229 235 241
191 198 204 211 217 223 230 236 242 249
197 203 210 216 223 230 236 243 249 256
203 209 216 223 230 236 243 250 257 263
209 216 222 229 236 243 250 257 264 271
215 222 229 236 243 250 257 265 272 279
221 228 235 242 250 258 265 272 279 287
227 235 242 250 257 265 272 280 288 295
233 241 249 256 264 272 280 287 295 303
240 248 256 264 272 279 287 295 303 311
246 254 263 271 279 287 295 304 312 320
191 196 201 205 210 215 220 224 229 234
198 203 208 212 217 222 227 232 237 242
204 209 215 220 225 230 235 240 245 250
211 217 222 227 232 238 243 248 254 259
218 224 229 235 240 246 251 256 262 267
225 231 237 242 248 254 259 265 270 278
232 238 244 250 256 252 267 273 279 285
240 246 252 258 264 270 276 282 288 294
247 253 260 266 272 278 284 291 297 303
255 261 268 274 280 287 293 299 306 312
262 269 276 282 289 295 302 308 315 322
270 277 284 291 297 304 311 318 324 331
278 285 292 299 306 313 320 327 334 341
286 293 301 308 315 322 329 338 343 351
294 302 309 316 324 331 338 346 353 361
302 310 318 325 333 340 348 355 363 371
311 319 326 334 342 350 358 365 373 381
319 327 335 343 351 359 367 375 383 391
328 336 344 353 361 369 377 385 394 402
Overweight
25 26 27 28 29
Obese
30 31 32 33 34 35 36 37 38 39
Extremely Obese
40 41 42 43 44 45 46 47 48 49
——————————————— Weight (pounds) ———————————————
58
Normal
Height (inches) BMI 19 20 21 22 23 24
Source: National Heart, Lung, and Blood Institute
breast tumors. Researchers believe that the fat cells stimulate surges of hormones, insulin, proteins, and the other substances mentioned above that may, in turn, cause reactions that initiate uncontrollable growth among certain cell types. Incidence: According to the American Cancer Society, the risk of cancer from obesity is similar to the risk from using tobacco. Obesity has reached epidemic proportions and affects the entire population, regardless of age, gender, race, or ethnicity. In the United States, obesity has been increasing at an alarming rate. In 1980, about 15 percent of adults were classified as obese; by 2004, that number had more than doubled to about 33 percent; and, be-
tween 1986 and 2000, the number of adults classified as severely obese had increased from about 1 in 200 to 1 in 50. Estimates from the Centers for Disease Control associate about 112,000 deaths per year with obesity. Childhood obesity has been at the forefront of concern because of the staggering numbers of overweight children and the projected long-term health effects. From 1994 to 2000, the number of overweight children between the ages of two and five increased by more than 40 percent; overweight children aged six to eleven doubled in number between 1980 and 2002; and overweight adolescents aged twelve to nineteen more than tripled between 1980 and 2002. Overweight and obesity are most common among black and Mexican American women, 869
Obesity-associated cancers with the same patterns seen for children and adolescents in these groups. Studies have increasingly linked obesity and cancer. Many studies show that the greater the degree of obesity, the stronger the association with cancer. In one study of more than 900,000 adults, the death rates from all cancers combined were 52 percent higher in men and 62 percent higher in women who were classified as severely obese. In another study, obesity links were found in an estimated 51 percent of women and 14 percent of men with newly diagnosed cases of cancer. The studies also show a higher recurrence rate after radical prostatectomy for prostate cancer in obese men and an incidence rate of 50 percent and decreased survival rate in obese women with postmenopausal breast cancer. By applying the current levels of overweight and obesity, Graham Colditz, a physician with the Harvard School of Public Health, estimated the number of cancer cases that could be avoided if no one were overweight or obese. His estimates of avoidable cancer cases included 49 percent of endometrial cancers, 39 percent of esophageal cancers, 31 percent of kidney cancers, 20 percent of nonHodgkin lymphoma cases, 17 percent of multiple myeloma cases, 14 percent of pancreatic cancers, 14 percent of colon cancers, and 11 percent of breast cancers. Symptoms: There are no symptoms that are specific to obesity-associated cancers. Screening and diagnosis: Screening for obesity-associated cancers includes annual physical examinations to calculate BMI and take waist measurements as well as annual laboratory tests, such as serum lipid panel, fasting glucose level, and thyroid function tests. In addition, people can essentially screen themselves by monitoring their own weights. There are no specific tests for obesity-related cancers; testing is done when patients exhibit other symptoms. Staging is specific to the type of cancer that develops. Treatment and therapy: Treatment for obesity-associated cancer is specific to the type of cancer. However, based on data obtained during various studies, patients must also reduce their weight to avoid the increased risk that obesity places on successful treatment. Patients must set weight-loss goals and obtain assistance from a registered dietitian or weight-loss program for in-depth counseling. Many reputable commercial and community programs exist for obesity treatment. Desirable programs should include diets that meet the United States recommended daily allowance for nutrients, exercise counsel870
Salem Health: Cancer ing, behavior modification, and provision for long-term maintenance. The National Institutes of Health guidelines suggest nonpharmacologic treatment for six months and then consideration of medication if weight loss is unsatisfactory in those with a BMI greater than 30 or a BMI greater than 27 with associated risk factors. Patients with severe obesity (BMI greater than 40) may also be considered for gastric bypass or gastroplasty procedures. Prognosis, prevention, and outcomes: Long-term maintenance of weight loss is extremely difficult. If the patient is not motivated, successful weight loss is unlikely. Obesity can be prevented by educating children and adults in healthy dietary habits and exercise requirements, but only if individuals choose to follow the guidelines and do not have physical causes for the excess weight. Weight reduction can have a significant impact on a person’s risk for developing obesity-associated cancers. Dorothy P. Terry, R.N. u
For Further Information Calle, E. E., et al. “Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults.” New England Journal of Medicine 348, no. 17 (April 24, 2003): 1625-1638. Giovannucci, E., and D. Michaud. “The Role of Obesity and Related Metabolic Disturbances in Cancers of the Colon, Prostate, and Pancreas.” Gastroenterology 132 (May, 2007): 2208-2225. Polednak, A. P. “Trends in Incidence Rates for ObesityAssociated Cancers in the U.S.” Cancer Detection and Prevention 27 (2003): 415-421.
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Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Obesity and Cancer: Questions and Answers http://www.nci.nih.gov/cancertopics/factsheet/Risk/ obesity See also Appendix cancer; Bile duct cancer; Breast cancers; Cervical cancer; Comedo carcinomas; Craniopharyngiomas; Endometrial cancer; Gallbladder cancer; Gynecologic cancers; Hepatomegaly; Klinefelter syndrome and cancer; Leiomyosarcomas; Medulloblastomas; Nutrition and cancer prevention; Pancreatic cancers; Paraneoplastic syndromes; Rectal cancer; Risks for cancer; Stomach cancers; Urinary system cancers; Uterine cancer.
Salem Health: Cancer
u Occupational exposures and
cancer Category: Social and personal issues Definition: Cancers or malignancies can be partly or entirely caused by exposure to chemicals, physical agents, biological agents, or industrial processes at a person’s place of work or in a person’s occupation. Related conditions: Cancers linked to occupational exposure include leukemia, lymphoma, and cancers of the lung, breast, bladder, skin, larynx, nose, throat, prostate, pancreas, liver, scrotum, and soft tissue. Workers at risk: The International Agency for Research on Cancer (IARC) has identified fifty known and about one hundred suspected occupational carcinogens. Certain workplaces and jobs carry a greater risk of exposing workers to substances that may increase their chance of cancer. The workplace may be indoors, as with restaurant or factory workers, or outdoors, as with landscapers or construction workers. Because the effects of exposure to occupational toxins usually do not surface until years after exposure, linking the cancer to the workplace is sometimes difficult. However, one in five workers is exposed to and at an increased risk for cancer from toxins in the workplace. The World Health Organization (WHO) reported that of the seven million deaths from cancer each year, about 40 percent could be prevented by dedicated efforts to reduce workplace toxins. Occupational cancer claims more lives (32 percent) than any other work-related disease (circulatory disease claims 26 percent) or even work accidents (17 percent). The incidence of occupational cancers is from 4 to 20 percent of all cancers but may be higher, as many go unreported. In the United States, each year about 20,000 people die of cancers attributed to occupational toxins and about 40,000 people are newly diagnosed with cancers due to occupational causes. Globally, an estimated 609,000 workers are affected yearly. Lung cancer: Lung cancer has been linked to occupational exposure to numerous substances. Lung cancer, particularly mesothelioma, is high in people exposed to asbestos and can develop years after the exposure. If the person exposed to asbestos is a smoker, that person is 50 to 90 times more likely to be diagnosed with lung cancer compared with the average person. Asbestos has been used to strengthen the walls of buildings; as insulation for walls, boiler pipes, and steam pipes; and as soundproofing. In 1989, the United States Environmental Protection Agency (EPA) banned most asbestos-containing prod-
Occupational exposures and cancer ucts. Although the ruling was overturned in a 1991 appeal, some asbestos-containing products remain prohibited, and all nonhistorical, or new, uses are banned. Therefore, automobile parts manufacturers still use asbestos in brake shoes and clutch linings. Some products contain substances that may be contamined with asbestos, such as vermiculite (in garden products) and talc (in crayons). Asbestos often is present in the ceiling or floor tiles in older buildings. Workers who remove asbestos-containing materials from old buildings need to use protective masks to avoid inhalation and cover their clothes so they do not take asbestos dust home with them. Other industries where employees can be exposed to asbestos are railroads, insulation factories, and shipbuilders. Lung cancer risk is increased for people who work in places where they are exposed to secondhand smoke, such as bars, casinos, bowling alleys, or restaurants; tin miners and refining industry workers who are exposed to toxins such as arsenic, nickel, or chloromethyl ether; and quarrying, stone industry, and glass-manufacturing workers exposed to silica dust. Radon, a natural radioactive gas that causes lung cancer, is present at harmful levels in one in fifteen homes by the EPA’s estimate. Chemicals inhaled by painters, chemists, and printers increase their risk of lung cancer. Formaldehyde, a chemical used to disinfect surgical rooms and dialysis units and also found in carpet and furniture glues, diesel fumes, and embalming fluid, is believed to cause respiratory cancers. Bladder cancer: Bladder cancer has been linked to exposure to dyes containing benzine and naphthylamine. IARC found a small increased risk of developing bladder cancer among barbers and male hairdressers. However, some cancer-causing coloring agents were removed from dyes in the 1970’s, and the study was unable to determine if the risk was caused by past or present exposure to carcinogens. Employees who work with rubber, paint, or leathers may also be at greater risk of developing bladder cancer. Skin cancer: Skin cancers such as melanomas are more common in workers who are exposed to the ultraviolet (UV) radiation from the sun. Workers at greater risk include construction workers, farmworkers, landscapers, roofers, and fishing boat workers. Asphalt and diphenyls as well as reflections from water, sand, concrete, snow, and any light-colored surface increase the harmful effects of UV rays. Other cancers: Workers exposed to herbicides and pesticides have an increased risk of lymphomas. Farmers and others working with these chemicals demonstrate a higher 871
Occupational exposures and cancer
Salem Health: Cancer
A historical image of an asbestos thread-making machine in an asbestos mill. (Centers for Disease Control and Prevention)
incidence of prostate cancer. Pancreatic cancer is associated with pesticides, dyes, and gasoline. Health care workers can be exposed to occupational toxins as well as body fluids that harbor hepatitis B and C viruses, which can cause liver cancer. Prevention and policy: Occupational exposures to carcinogens can be limited and in many cases are preventable. Removing the risk or the toxin from the workplace is the primary way to prevent occupational cancer. When the carcinogen cannot be removed from the environment, as in the case of UV rays, workers can use protective clothing and sunscreens, and work practices can be altered to minimize exposure (such as providing a shady place for breaks and lunches). The WHO’s Global Occupational Health Network offers the following steps to prevent occupational cancers: • Develop regulations and an enforcement process for monitoring carcinogens in the workplace. • Avoid use of known carcinogens in the workplace. • Replace known toxins with safe substitutes. 872
•
Educate workers about primary prevention of workrelated cancers. • Implement a health surveillance program for workers exposed to occupational toxins. Several other approaches can decrease the risk of occupational cancer. These include testing of new chemicals before they are placed on the market, keeping hazardous toxins in an enclosed area with adequate ventilation, and using protective masks and clothing. Workers are advised to avoid smoking, as the incidence of occupational cancer increases with tobacco use. All workers must examine and weigh the risk that each occupation brings, as few jobs are risk-free, but some involve more exposure than others. The prevention of occupational cancer is directly related to legislation as laws are needed to control the use of carcinogens and to provide workers with adequate protection from exposure. Legislators, politicians, lobbyists, unions, and grassroots occupational health groups have brought pressure on the various industries to introduce protective laws and stricter inspections. Robert W. Koch, D.N.S., R.N.
Salem Health: Cancer
Occupational therapy
u For Further Information Blanc, Paul D. How Everyday Products Make People Sick: Toxins at Home and in the Workplace. Berkeley: University of California Press, 2007. Bozzone, Donna M. Causes of Cancer. New York: Chelsea House, 2007. Landrigan, Phillip J. “Prevention of Occupational Cancer.” CA Cancer Journal for Clinicians 46 (1996): 67-69. Raffle, P. B., et al., eds. Hunter’s Diseases of Occupations. 8th ed. Boston: Arnold, 1994. Rapp, Doris J. Our Toxic World: A Wake Up Call. New York: Environmental Medical Research Foundation, 2004. Veys, C. A. “ABC of Work Related Disorders: Occupational Cancer.” British Medical Journal 313 (1996): 615-619.
u Occupational therapy
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Cancers treated: All
Other Resources
Hazards Magazine Occupational Cancer/Zero Cancer http://www.hazards.org/cancer National Institute for Occupational Safety and Health http://www.cdc.gov/niosh World Health Organization Occupational Health http://www.who.int/occupational_health See also Agent Orange; 4-Aminobiphenyl; Arsenic compounds; Asbestos; Benzidine and dyes metabolized to benzidine; Beryllium and beryllium compounds; Bladder cancer; Blood cancers; Bone cancers; Breast cancer in men; 1,3-Butadiene; 1,4-Butanediol dimethanesulfonate; Cadmium and cadmium compounds; Cancer clusters; Cancer education; Carcinogens, known; Carcinogens, reasonably anticipated; Carcinomatosis; Case management; Chlorambucil; 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); Chromium hexavalent compounds; Coke oven emissions; Dioxins; Electromagnetic radiation; Epstein-Barr virus; Ethylene oxide; Formaldehyde; Head and neck cancers; Lung cancers; Lymphomas; Melanomas; Mesothelioma; 2-Naphthylamine; Nasal cavity and paranasal sinus cancers; Organochlorines (OCs); Pesticides and the food chain; Polycyclic aromatic hydrocarbons; Radon; Rehabilitation; Report on Carcinogens (RoC); Risks for cancer; Salivary gland cancer; Silica, crystalline; Surgical oncology; Ultraviolet radiation and related exposures; Urinary system cancers; Vinyl chloride; Wood dust.
Category: Medical specialties Definition: Occupational therapy is a medical specialty that helps patients function more successfully in their everyday lives. Occupational therapy is not limited to skills that are necessary for a job but rather can include any skills that are needed for daily living or participating in regular activities, which can range from work and school to hobbies. Occupational therapists can work with cancer patients during all periods of cancer treatment and afterward to help patients maintain participation in daily life and pleasurable activities, or to help patients return to their normal activities as completely as possible. Subspecialties: Pediatric occupational therapy, geriatric occupational therapy, palliative occupational therapy
Training and certification: Occupational therapists receive specialized training in a number of fields, including biology, physiology, behavioral science, and specific training in the skills necessary to assess patient needs and meet them effectively. Occupational therapists could be qualified with only a bachelor’s degree until 2007, when the licensing requirements for all new occupational therapists were raised to completion of at least a master’s degree. In addition to education, occupational therapists must fill many other requirements to practice. They must successfully complete at least six months of closely monitored work in the field and must pass a national certification exam, administered by the National Board for Certification in Occupational Therapy. After passing the certification exam, occupational therapists must apply to be licensed in the state or territory in which they plan to practice. States and territories may have their own additional licensing requirements. Because of the high cost of health care, many health care companies are encouraging licensed occupational therapists to delegate work to occupational therapy assistants and aides, who are paid less. Although the licensed occupational therapist oversees the treatment, much of the hands-on work can be done by the assistants and aides. Generally, an occupational therapist assistant must complete either an associate’s degree in occupational therapy or a certification course. Occupational therapist aides do not usually have to complete a degree or certification program but may instead receive the majority of their training in occupational therapy while on the job. Services and procedures performed: The occupational therapist provides different services and uses varying tech873
Occupational therapy niques according to the specific needs of the patient. The therapist starts by meeting with the patient and sometimes the patient’s family to determine what the needs of the patient are. This may include gathering information about what kinds of activities the patient performed on a daily basis before the cancer diagnosis and what kinds of activities are most important to the patient to be able to participate in at present. These can include work, hobbies, or activities such as spending time with the family or coaching a children’s softball team. Activities of daily living can be a primary concern for the occupational therapist and the patient. If there are activities such as eating, bathing, or dressing that the patient is unable to do without help, the therapist will gather information about these as well. After gathering information about the patient’s normal activities, the therapist can work with the patient to develop realistic goals. These goals will then enable the therapist to determine which therapeutic activities will be most effective. If treatment has not yet begun, the first therapies may focus on techniques that will help the patient get through treatment as successfully as possible, such as techniques for energy conservation.
Salem Health: Cancer If treatment has been completed successfully, the occupational therapist may focus on helping the patient regain old skills or adjust to any permanent changes resulting from the cancer and its treatment. The goals for this type of therapy may range from regaining the full function present before the cancer and treatment, to regaining the skills to allow a return to a job, to functioning in the most independent way possible. If the treatment was not successful, the occupational therapist may focus on palliative care and therapy intended to help the patient maintain independence and a range of desired skills and abilities for as long as possible. The techniques used by occupational therapists to help cancer patients depend on a wide variety of factors such as the desired skills, the location in which the therapy is being performed, and the age of the patient. Much occupational therapy is done on an outpatient basis, although it is also provided in a hospital setting. Occupational therapy for children often focuses on play, sometimes even making skills useful for daily living into play activities. For adults, therapy may focus on practicing a skill, such as dressing. The occupational therapist can provide adaptive equip-
Occupational therapists help cancer patients function better during and after treatment. (Custom Medical Stock Photo)
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Salem Health: Cancer ment, if it is available, to help with the needs of the patient and spends time helping the patient learn to use the equipment in the most effective way. Therapists may visit a workplace to help determine if adaptive equipment or a change of duties may help a patient return to work. In the home, an occupational therapist may be able to recommend changes to make it more comfortable for the patient or easier to negotiate effectively. Therapists can also help patients come up with productive alternatives for activities that may be especially difficult or can no longer be done, such as helping patients who can no longer drive find alternative modes of transportation. Related specialties and subspecialties: The occupational therapist is one of many members of the health care team who help individuals with cancer have as positive an experience as possible during treatment and afterward. An integral part of this process is helping the individual perform as many of the activities that are normally a part of the daily routine as possible. Depending on the type of cancer and the procedures used to treat it, the other members of the health care team who will work with the occupational therapist to meet this goal will vary. A physical therapist may work with the patient to increase muscle tone, flexibility, and balance. A speech therapist may work with the patient if speech and language abilities have been adversely affected by the cancer. If an amputation has been necessary, the prosthetisist works with the occupational therapist and the physical therapist to help choose the prosthetic that will best meet the patient’s needs and to help the patient develop the skills to properly use it. Therapists who work with cancer patients may be involved in helping patients work through any emotional problems that are interfering with their ability to function as normally as possible. Of course, the patient’s doctor and other members of the cancer care team will be involved to ensure that the treatment has the best possible outcome with the least negative effect on the patient’s daily life. Helen Davidson, B.A. u
For Further Information Christiansen, Charles H., and Kathleen M. Matuska, eds. Ways of Living: Adaptive Strategies for Special Needs. Bethesda, Md.: American Occupational Therapy Association, 2004. Cooper, Jill, ed. Occupational Therapy in Oncology and Palliative Care. Hoboken, N.J.: Whurr, 2006. Marcil, William Matthew. Occupational Therapy: What It Is and How It Works. Clifton Park, N.Y.: Thomson Delmar, 2007.
Oligodendrogliomas Ross, Joanna. Occupational Therapy and Vocational Rehabilitation. Hoboken, N.J.: John Wiley and Sons, 2007. Taylor, M. Clare. Evidence-Based Practice for Occupational Therapists. Malden, Mass.: Blackwell, 2007. u
Organizations and Professional Societies
American Occupational Therapy Association http://www.aota.org 4720 Montgomery Lane P.O. Box 31220 Bethesda, MD 20824-1220 National Board for Certification in Occupational Therapy http://www.nbcot.org 12 South Summit Avenue, Suite 100 Gaithersburg, MD 20877-4150 National Cancer Institute http://www.cancer.gov/ National Institutes of Health Building 31, Room 11A48 31 Center Drive Behesda, MD 20892-2590 u
Other Resources
American Cancer Society http://www.cancer.org Occupational Therapist.com http://www.occupationaltherapist.org See also Aids and devices for cancer patients; Cancer care team; Cancer education; Cognitive effects of cancer and chemotherapy; Electrolarynx; Esophageal speech; Home health services; Insurance; Karnofsky performance status (KPS); Limb salvage; Living with cancer; Orthopedic surgery; Psychosocial aspects of cancer; Rehabilitation; Relationships; Transitional care.
u Oligodendrogliomas Category: Diseases, symptoms, and conditions Also known as: Glial brain tumors, OD Related conditions: Elevated intracranial pressure, personality changes, neurological deficits Definition: Oligodendrogliomas are a type of glial tumor arising in the brain in which the oligodendroglial cell is the predominant cell type. There are several kinds of glial 875
Oligodendrogliomas
Salem Health: Cancer
Relative Survival Rates of Adults with Oligodendroglioma by Race, 1988-2001 Survival Rates (%) Years
Whites
Blacks
1 2 3 5 8 10
89.1 81.7 77.9 68.8 58.7 52.2
79.6 71.9 63.1 50.2 37.6 28.5
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
cells in the central nervous system, but each functions in support of the nerve cells (neurons). The oligodendrocytes are glial cells that coat the axons in the central nervous system with an insulating membrane called myelin. Without myelin, the nerve impulses flowing down the axon lose efficiency. The third most common of the glial neoplasms, oligodendrogliomas usually originate in the cerebral hemispheres (predominantly the frontal lobe) but on rare occasions can arise in the cerebellum, brain stem, and spinal cord. Although they are typically considered a rare neoplasm, newer diagnostic techniques such as genotyping indicate that the condition is more common than once thought. Oligodendroglioma neoplasms often contain anaplastic cells, primitive, undifferentiated cells that are a distinguishing feature of emerging embryonic cells and are often seen in malignant neoplasms. Tumors with anaplastic cells are called anaplastic oligodendrogliomas. Risk factors: There are no known causes or risk factors for oligodendroglioma. The problem occasionally clusters in some families, but this is unrelated to any mechanisms of inheritance. The disease strikes men about twice as often as women, with the risk equally distributed among the races. Although the median age of diagnosis is between forty and fifty years, oligodendroglioma can occur at any age. The anaplastic variant usually occurs between the ages of sixty and seventy. Children are less frequently affected, accounting for 6 percent of oligodendroglioma cases. Etiology and the disease process: Oligodendrogliomas evolve from primitive precursor glioma cells. The tumor 876
begins as a slow-growing, mixed tumor, combining elements of astrocytes (another type of glial cell), neurons, and oligodendroglial cells. The tumor consists of poorly defined anaplastic components, mature oligodendroglial cells, or a mixture of the two. It is impossible to predict how long it will take for patients to experience symptoms because although oligodendrogliomas usually grow quite slowly, they can quickly evolve into an aggressive malignancy and shorten the crisis point from upwards of thirty years to only a few months. When the neoplasm exhibits features of oligodendroglioma cells with astrocytic components, it is called oligoastrocytoma, but this is less common. Incidence: Intracranial tumors are second only to stroke as the most common neurological cause of death. In the United States, the incidence of oligodendrogliomas compared with all intracranial tumors may be as high as 19 percent, and they may represent 20 to 54 percent of all gliomas. Oligodendrogliomas may account for 4 percent of all brain tumors, with an annual incidence in the United States of 0.3 per 100,000 people. Symptoms: Symptoms depend on the size, location, invasiveness, and rate of growth of the tumor. Warning signs will vary but may include seizures, vomiting, fatigue, headache, numbness, pain, ataxia, paralysis, sensations of tingling or burning, hearing or vision deficits, and changes in temperature and taste sensitivity. The most common first symptom is a seizure, representing half of all patients. Screening and diagnosis: Imaging studies and biopsy examination are central to a diagnosis of oligodendroglioma. Laboratory tests are useful only in excluding other causes and determining overall health. Magnetic resonance imaging (MRI) is performed with and without the radiocontrast medium gadolinium. Computed tomography (CT) scans are helpful in revealing some details missed in MRI studies, and sometimes immunohistochemical markers further help in establishing the diagnosis. However, ultimately, only biopsy will result in a definitive diagnosis. Following biopsy, most pathologists will simply grade oligodendrogliomas according to the presence or absence of anaplastic features. Treatment and therapy: Treatment depends on the patient’s symptoms and the location and nature of the tumor. As with most cancers, the three mainstays of treatment are chemotherapy, radiation, and surgery. Chemotherapy using a combination of procarbarazine, lomustine, and vincristine has been used in the earliest diagnosed stage of the tumor, but typically relapses occur between eighteen
Salem Health: Cancer months and two years. Newer treatments in combination with radiation may prolong the time until relapse, but the classic treatment for oligodendroglioma remains surgical resection. Often, however, the tumor is poorly defined, making complete resection impossible. In the past, when surgery completely removed the tumor, further treatment was believed unnecessary. However, several years following total resection, almost all patients suffer recurrence of the tumor at the surgical site. Regardless of whether resection is complete or incomplete, typically no further treatment is given until relapse occurs. In the event of relapse, chemotherapy is the treatment of choice; radiation is reserved for patients not responding to chemotherapy. Prognosis, prevention, and outcomes: The prognosis depends on the growth rate of the tumor, its location, and its pressure effects inside the cranium. Some specific prognostic indicators have been noted: Older age at the time of diagnosis, the presence of a neurological deficit, or a central location in a child’s brain usually results in a shorter survival time. From the time of diagnosis, the median survival time ranges between three and seventeen years. Five-year survival rates range from 39 to 75 percent and ten-year rates from 19 to 59 percent, but ultimately all patients will die of the disease. Richard S. Spira, D.V.M. u
For Further Information Baumann, Nicole, and Danielle Pham-Dinh. “Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System.” Physiological Reviews 18, no. 2 (2001): 871-927. Central Brain Tumor Registry of the United States. Primary Brain Tumors in the United States: Statistical Report, 1992-1997. Chicago: Author, 2000. Ellis, T. L., V. W. Stieber, and R. C. Austin. “Oligodendroglioma.” Current Treatment Options in Oncology 4, no. 6 (2003): 479-490. Kleihus, P., and W. K. Cavenee. Pathology and Genetics of Tumours of the Nervous System. New York: Oxford University Press, 2000. Mason, W. P. “Oligodendroglioma.” Current Treatment Options in Neurology 7, no. 4 (July, 2005): 305-314. Ohgaki, H., and P. Kleihues. “Population-Based Studies on Incidence, Survival Rates, and Genetic Alterations in Astrocytic and Oligodendroglial Gliomas.” Journal of Neuropatholy and Experimental Neurology 64, no. 6 (June, 2005): 479-489. Van den Bent, M. J. “Advances in the Biology and Treatment of Oligodendrogliomas.” Current Opinion in Neurology 17, no. 6 (December, 2004): 675-680.
Omega-3 fatty acids u
Other Resources
The Brain Tumor Foundation Tumor Types: Oligodendrogliomas http://www.braintumorfoundation.org/ Oligodendrogliomas.php National Cancer Institute Adult Brain Tumors Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ adultbrain/Patient See also Brain and central nervous system cancers; Carcinomatous meningitis; Gliomas; Meningeal carcinomatosis.
u Omega-3 fatty acids Category: Lifestyle and prevention Also known as: Polyunsaturated fatty acids (PUFAs) Definition: Omega-3 fatty acids are essential polyunsaturated fats that must be obtained from food, particularly cold-water fish, fish oil, flaxseeds, soybeans, walnuts, green leafy vegetables, and canola oil. Three forms of omega-3 fatty acids exist: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Cancers treated or prevented: Colon cancer, breast cancer, prostate cancer, pancreatic cancer Delivery routes: Oral by food, capsule, or liquid How this substance works: Omega-3 fatty acids are highly concentrated in the brain and appear to play an important role in cognitive and behavioral functions, as well as normal growth and development. Research indicates that these acids are important in numerous physiological functions, particularly muscle contraction and relaxation, movement of calcium and other material into and out of cells, regulation of blood clotting, and secretion of substances including hormones and digestive enzymes. They also play a role in controlling cell division and fertility, indicating their possible importance in protection against certain types of cancer. Omega-3 fatty acids seem to reduce inflammation and retard tumor growth. On the other hand, omega-6 fatty acids, which are found in sunflower oil, safflower oil, and most saturated fats and vegetable oils, promote inflammation and feed tumor growth. An appropriate balance between omega-3 and omega-6 fatty acids is necessary to promote good health. Some research indicates that omega-3 fatty acids help 877
Ommaya reservoir to prevent certain chronic diseases, including heart disease and some cancers. EPA appears to be important in cancer prevention by affecting the production of cytokines and the tumor necrosis factor (TNF). Other research indicates that omega-3 fatty acids may play an adverse role in treating some cancers. If the latter is true, then these acids still play an indirect role in cancer prevention if cold-water fish, such as salmon, halibut, and tuna, are substituted for red and processed meats, which are known to increase the risk of colon and prostate cancers. Side effects: The consumption of omega-3 fatty acids and cancer incidence have had unfavorable associations in some case studies. One study on skin cancer and another on lung cancer showed that these fatty acids increased the risk for developing these cancers. A study on prostate cancer showed that ALA increased its risk, while EPA and DHA reduced the risk. More specific case studies need to be conducted in order to build a significant statistical database. Alvin K. Benson, Ph.D. See also Alopecia; Chemoprevention; Dietary supplements; Thyroid cancer.
u Ommaya reservoir Category: Procedures Also known as: Implanted intrathecal device, intraventricular device Definition: An Ommaya reservoir is a device surgically placed under the scalp that allows administration of drugs, such as chemotherapy, directly into the cerebrospinal fluid (CSF), bypassing the blood-brain barrier. It may also be used to sample CSF. Cancers treated: Brain and related nervous system lesions, any brain metastasis Why performed: Blood vessels that provide blood to the brain filter out drugs and other substances, preventing them from reaching the brain and cerebrospinal fluid. This blood-brain barrier also blocks chemotherapy from reaching cancer cells in the brain and CSF. With the surgical placement of an Ommaya reservoir under the scalp, drugs may be delivered directly to tumors or metastases. In some cases, the Ommaya reservoir has been used to drain cystic lesions in the brain. Patient preparation: The Ommaya reservoir, a small dome-shaped device with an attached tube, is placed by a 878
Salem Health: Cancer neurosurgeon during surgery. The patient is under general anesthesia, so there is no pain. An area of the head is shaved and an incision is made in the skin. The tube, or catheter, is inserted through a small hole made in the skull and threaded into a hollow space, or ventricle, which holds CSF. Steps of the procedure: After the surgical site heals, a physician or specially trained nurse may access the device to remove CSF or to administer chemotherapy or other drugs. This procedure may be done in the hospital or specialty outpatient clinic. Accessing the device is a sterile procedure. The skin over the device is cleansed, and then a sterile needle is used to pierce the dome and instill the chemotherapy or drug. The needle is withdrawn and pressure is applied to the needle site to control any bleeding. After the procedure: The patient should report any symptoms such as headache, unusual sleepiness, stiff neck, nausea, and vomiting immediately. Any usual side effects of chemotherapy administration may occur. It is important to observe the area over the Ommaya reservoir for signs of infection, such as redness and warmth at the needle site. Patients may go home between treatments with the device in place and may continue normal activities. Risks: The risks associated with an Ommaya reservoir are generally related to blockage of the tube or infection. Results: The patient may expect that chemotherapy and other drugs reach the necessary site of action with minimum pain. Patricia Stanfill Edens, R.N., Ph.D., FACHE See also Chemotherapy; Infusion therapies; Medulloblastomas.
u Oncogenes Category: Cancer biology; carcinogens and suspected carcinogens Also known as: Proto-oncogenes Related cancers: Leukemias, lymphomas, most sarcomas (of bone and muscle), carcinomas (of epithelial origin) Exposure routes: Inherited as genetic information Where found: Proto-oncogenes are genes found within the chromosomes of all eukaryotic (nucleated) cells and organisms. At risk: Proto-oncogenes are universal among all eukaryotic cells and organisms, which include humans and all an-
Salem Health: Cancer imals. Congenital mutations in some of these genes are associated with a significantly increased risk for certain cancers. Definition: Oncogenes are variations of cellular proto-oncogenes that normally function in the regulation of cell division. Mutations in these genes may result in the cell becoming cancerous. The term “proto-oncogene” refers to the normal cell copy of the gene, while the term “oncogene” refers to a mutated, or activated, form of the same gene that results in disruption of cell regulation. Most oncogenes have a three-letter name based on their initial identification or the type of cancer with which they were first found to be associated. For example, the SRC gene was first identified in the Rous sarcoma virus. The RAS oncogene was first identified as a gene in rat sarcomas.
Oncogenes
Selected Oncogenes and Tumor-Suppressor Genes and Their Related Cancers Gene
Associated Cancers
APC BCL2 BRC-ABL1 BRCA1, BRCA2 EWSR1 (EWS) HER2/neu (ERBB2) MLH1, MSH2 MYC (c-myc) MYCN (N-myc) RB1 TP53 (p53)
Colorectal cancer B-cell lymphoma Chronic myelogenous leukemia Breast, ovarian Ewing sarcoma Breast, ovarian Colorectal Burkitt lymphoma, others Neuroblastoma Retinoblastoma, others Brain, skin, lung, head and neck
Source: American Cancer Society
Etiology and symptoms of associated cancers: More than one hundred proto-oncogenes have now been recognized in cells. Most are involved in regulating movement through the cell cycle (regulation of chromosome replication followed by cell division). The cell cycle is characterized as having four phases: G1, which regulates events leading to deoxyribonucleic acid (DNA) replication; S, in which cell chromosomes replicate; G2, which regulates events leading to cell division; and mitosis, the period in which the chromosomes separate and the cell divides. Each phase is regulated by specific enzymes, signals, and other molecules, as well as suppressors that prevent movement through the phase. Many of the regulatory proteins involved in these events are encoded by proto-oncogenes. Not all proto-oncogenes are expressed in every cell, and the type of cancer that potentially develops is related to the particular oncogene that has undergone a mutation. Proto-oncogenes are subdivided into four categories, each of which represents a particular set of steps that regulate the cell cycle: growth factors, growth factor receptors, signal mechanisms, and tumor suppressors/regulators of apoptosis (cell death). Growth factors are small proteins that bind specific cell surface receptors and set in motion events that will result in cell division. Overproduction of growth factors may result in repeated cell division, setting the stage for development of cancer. For example, the PDGFB (commonly known as sis) oncogene, originally isolated from the simian sarcoma virus, encodes one of the protein chains that make up the platelet-derived growth factor. PDGFB is secreted by platelets and binds receptors on certain
fibroblast cells. Overproduction of PDGFB may induce uncontrolled cell division, resulting in a sarcoma. Growth factor receptors are cell surface proteins that bind specific growth factors. Each cell type expresses a particular form or forms of receptors, and the ability of any growth factor to stimulate a cell depends on expression of these surface molecules. Some of these receptor proteins are actually enzymes that, when activated, begin a series of signals within the cell, resulting in cell division. Certain mutations in the genes that encode these receptors may, in effect, cause a “short circuit” in regulation, resulting in loss of control and continuous movement of the cell through the cell cycle. One example of such a receptor mutation is that of the HER2/neu (also known as ERBB2) receptor protein expressed on certain breast cells. The HER2/neu protein is similar in its amino acid sequence to the human epidermal growth factor receptor molecule and is an example of a transmembrane enzyme that begins the signal transmission in the cell. A mutation in the HER2/neu proto-oncogene converts it into the HER2/neu oncogene (named for the neuroblastoma in which it was first identified). Overexpression of the HER2/neu protein is associated with the aggressive nature of certain forms of breast cancer. The basis for the chemotherapeutic action of Herceptin is its ability to inhibit the activity of the HER2/neu protein. Signal mechanisms represent a series or cascade of enzymatic reactions that move the cell through the cell cycle and regulate cell division. At the molecular level, intermediates in this pathway are enzymes that activate DNAbinding proteins (DBPs), inducing gene expression. The RAS supergene family and the greater than one hundred 879
Oncogenes proteins its members encode are examples of such inducers. RAS proteins are also called G proteins, reflecting their utilization of guanosine triphosphate (GTP) for their activity. Mutations in these genes may result in a continuous activating signal within the cell and uncontrolled cell division. Certain forms of colon and bladder cancers are the result of such mutations, and some forms of mutations are associated with mutations in the DNA-binding protein substrates for these RAS proteins. RAS gene mutations have been observed in nearly one-third of all cancers. Tumor suppressors/regulators of apoptosis control steps at the end of the cell cycle. The proto-oncogenes that regulate apoptosis can either promote or inhibit cell death. The BCL2 gene family produces proteins that are pro-apoptosis and anti-apoptosis (the BCL2 gene itself inhibits apoptosis, and its overexpression has been implicated in cancers such as lymphoma). Proto-oncogenes and tumor suppressors provide the cell with the means not only to block division if chromosome replication is incomplete or if a mutation has occurred that could cause the cell to become cancerous but also to actually cause the cell to die. Tumor suppressors promote apoptosis and therefore are usually inactivated in cancers. The first of the tumor suppressors to be discovered was the retinoblastoma RB1 protein, isolated in the 1980’s. The RB1 protein regulates the steps that allow DNA replication to begin in the cell. The TP53 protein, named for its size, detects mutations that have occurred in DNA and induces repair of the DNA site or, if the mutation is too extensive, induces steps that culminate in the death of the cell. As is true for other genes that regulate cell division, mutations in the genes associated with tumor suppression are associated with certain forms of cancer. For example, mutations in the RB1 gene may predispose the person for retinoblastoma. Mutations in the TP53 gene have been found in nearly 50 percent of all forms of cancer. The ability of oncogenic viruses such as hepatitis B, the etiological agent for hepatocarcinoma, or the human papillomavirus, the agent for cervical carcinoma, to initiate cancer is related to their abilities to inactivate tumor suppressors. At least two dozen types of tumor suppressors were identified in the first decade of the twenty-first century. Mutations at these sites may be caused as a result of infection by certain viruses or by exposure to carcinogens, most of which are also mutagens, chemicals that induce DNA mutations. In some cases, the mutation is congenital, the individual having been born with that specific mutation. Childhood retinoblastoma, for example, results from congenital mutations in the RB1 gene. In some cases, it is not “simply” a point mutation in a 880
Salem Health: Cancer proto-oncogene that leads to a cancer. Certain forms of the disease are known to result from chromosomal breaks and translocations, the movement of pieces of chromosomes from one site to another in the cell chromatin. The DNA in patients suffering from chronic myelogenous leukemia was found to possess a specific type of translocation. What became known as the Philadelphia chromosome is characterized by translocation of the ABL1 oncogene, on chromosome 9, into the region of the BCR oncogene on chromosome 22. The combined gene product disrupts the normal signaling mechanism in these cells, resulting in uncontrolled cell division. Inhibition of this activity is the basis of action for at least one type of antileukemic drug, imatinib mesylate (Gleevec), lending further support to this mutation as being the actual cause of chronic myelogenous leukemia. Cancer, however, generally is not the result of any individual mutation. The molecules previously described regulate cell division, The difference between a benign growth and a true malignancy is the result of accumulated mutations over time. For example, a malignancy would require not only a mutation in the signal pathway but also, at a minimum, additional mutations in tumor-suppressor genes or in steps that inhibit cell death. History: The evidence for existence of oncogenes dates to the early history of retroviruses, viruses with genomes of ribonucleic acid (RNA), which are copied into DNA following infection and which were found to be etiological agents for some forms of cancer. In the late nineteenth century, leukemia in animals was demonstrated to be transmissible using extracts from cells. However, leukemia was not considered to be a true cancer at the time. It was only when Peyton Rous demonstrated in 1911 that solid tumors in chickens—sarcomas—could be transmitted using cell-free extracts that scientists began to believe cancer, at least in animals, was associated with infectious agents. Eventually what became known as the Rous sarcoma virus (RSV) was isolated and identified with this disease in chickens. As an increasing number of such tumor viruses, in which RNA was shown to be the genetic material, were isolated by the 1950’s, the question that followed was how these viruses could change, or transform, cells from normal to cancerous. In 1958 Howard M. Temin and Harry Rubin demonstrated that single virus particles could transform chicken cells. Further work by Temin indicated that it was possible to disrupt viral replication and transformation by adding inhibitors acting at the level of DNA. Temin proposed that such viruses act using a DNA intermediate and that they encode an enzyme that copies RNA
Salem Health: Cancer into DNA, allowing what has become viral DNA to integrate into the cell chromosome. By the late 1960’s Temin and David Baltimore independently discovered an enzyme, popularly known as reverse transcriptase, that carries out this function. Viruses that encode the enzyme have become known as retroviruses and include the RNA tumor viruses. Temin and Baltimore were each awarded the Nobel Prize in Physiology or Medicine in 1975. The seemingly simplistic genetic structure of the RNA tumor viruses lent itself to determining which viral genes are associated with cancers. The discovery of a temperaturesensitive mutation in one of these genes led to the identification of the SRC gene in the Rous sarcoma virus, the first such oncogene to be discovered. The SRC gene was shown to be required for transformation by the Rous sarcoma virus. However, strains of the virus that lacked that gene were found to replicate normally, suggesting the SRC gene was superfluous for the virus and may even have originated as genetic material extraneous to the virus. In 1976 J. Michael Bishop and Harold Varmus provided the answer. Creating DNA probes from transformation defective mutants of the Rous sarcoma virus, they found that normal avian cells contained cellular homologs of the viral SRC gene—that is, a cellular proto-oncogene. The proto-oncogene product of the gene was subsequently shown to be an enzyme critical in the signaling pathway that regulates cell division. Through the 1980’s, an increasing number of cellular proto-oncogenes were identified, and evidence for their association with cancers was increasingly demonstrated. When carcinogens were used to transform cells growing in laboratory cultures, mutations were found in protooncogenes carried by these cells. Indeed, the only difference found between proto-oncogenes in normal cells and oncogenes expressed in cancer cells was often a mutation at a single site. For example, the RAS oncogene found in cases of bladder cancer differed from its counterpart in a normal cell at only one amino acid position, suggesting the origin of the cancer was a mutation at that site. The RAS product, as was the SRC product described above, was shown to be involved in the signaling pathway within the cell. Richard Adler, Ph.D. u
For Further Information Bishop, J. Michael. How to Win the Nobel Prize. Cambridge, Mass.: Harvard University Press, 2003. Coffin, John, et al. Retroviruses. Plainview, N.Y.: Cold Spring Harbor Laboratory Press, 1997. Cooper, Geoffrey. Oncogenes. 2d ed. Sudbury, Mass.: Jones and Bartlett, 1995.
Oncogenic viruses Pelengaris, Stella, and Michael Khan. The Molecular Biology of Cancer. Malden, Mass.: Blackwell, 2006. Vogelstein, Bert, and Kenneth Kinzler. The Genetic Basis of Human Cancer. New York: McGraw-Hill, 2002. u
Other Resources
American Cancer Society Oncogenes and Tumor Suppressor Genes http://www.cancer.org/docroot/ETO/content/ ETO_1_4x_oncogenes_and_tumor_suppressor_ genes.asp CancerQuest Important Oncogenes http://www.cancerquest.org/index.cfm?page=181 See also Angiogenesis; Ataxia telangiectasia (AT); Biological therapy; BRAF gene; Breast cancer in pregnant women; Breast cancers; Cancer biology; Carcinomas; Chromosomes and cancer; Craniosynostosis; Cytogenetics; Endocrine cancers; Free radicals; Gene therapy; Genetics of cancer; Giant cell tumors (GCTs); Hemangiosarcomas; HER2/neu protein; HIV/AIDS-related cancers; HRAS gene testing; Hypercalcemia; Mesothelioma; Mitochondrial DNA mutations; Monoclonal antibodies; Multiple endocrine neoplasia type 2 (MEN 2); Mutagenesis and cancer; MYC oncogene; Myelofibrosis; Neuroendocrine tumors; Oncogenic viruses; Parathyroid cancer; Protooncogenes and carcinogenesis; RhoGD12 gene; SCLC1 gene; Tumor-suppressor genes; Viral oncology; Virusrelated cancers.
u Oncogenic viruses Category: Carcinogens and suspected carcinogens Also known as: Oncoviruses Related cancers: Cancers of the cervix, skin, uterus, penis, nasopharynx, and liver; adenocarcinoma; Kaposi sarcoma; Burkitt lymphoma; non-Hodgkin lymphoma; adult T-cell leukemia Definition: An oncogenic virus is a virus that infects normal cells, alters the cells’ properties, and transforms them into cancer cells. Oncogenic viruses can cause cancer in a variety of animals, including humans. These viruses can have either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) as their genetic material. Exposure routes: Sexual, blood-to-blood contact; exchange of bodily fluids Where found: Ubiquitous 881
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At risk: People who are in contact with others
u Oncology
Etiology and symptoms of associated cancers: Etiology depends on whether the genetic material is DNA or RNA. DNA viruses include the Epstein-Barr virus (EBV), human papillomavirus (HPV), human herpesvirus 8 (HHV-8), hepatitis B virus (HBV) and RNA viruses include the human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV). The Epstein-Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), has been strongly linked to nasopharyngeal cancer and certain forms of Burkitt lymphoma that are endemic in central Africa. EBV is also suspected of causing some cases of Hodgkin disease. Human herpesvirus 8 (HHV-8) is linked to Kaposi sarcoma. The hepatitis B virus (HBV) is suspected of causing liver cancer, and adenoviruses are suspected of causing cancer of glandular epithelial tissues, a disease known as adenocarcinoma. Human papillomavirus (HPV) can cause various conditions from benign warts to malignant cancers such as carcinomas of the cervix, uterus, and penis. Some cancers of the lung, larynx, and esophagus may be related to HPV. Although there are more than one hundred recognized types of HPV, only a few are known to cause cancer. Upon entering a cell, viral DNA may integrate into the host genome and express its viral genes, the oncogenes, which cause tumors. Sometimes the virus integrates next to a cellular gene and causes cancer by inducing an overexpression of that cellular gene. The RNA viruses associated with human cancers are human T-cell lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2), which cause adult T-cell leukemia and hairy cell leukemia, respectively; the hepatitis C virus (HVC); and the human immunodeficiency virus (HIV), which is suspected of causing lymphomas. When an RNA tumor virus enters the cell, a DNA copy of its RNA is made in a process known as reverse transcription. The DNA copy may integrate into the host genome and express the viral gene that causes cancer. Alternatively, the integrated DNA can cause cancer by inducing the overexpression of a cellular gene.
Category: Medical specialties Also known as: Cancer medicine
History: In 1911, Peyton Rous discovered that sarcomas in chickens were caused by viruses. By the late 1970’s it had become clear that certain viruses also caused cancer in humans. Charles L. Vigue, Ph.D. See also Cancer biology; Oncogenes; Proto-oncogenes and carcinogenesis; Viral oncology; Virus-related cancers. 882
Definition: Oncology is a word derived from the Greek word for lump. It is the medical specialty that studies tumors, focusing on their causes, their development, and means of treating them. Although tumors may be cancerous (malignant) or noncancerous (benign), oncologists are largely concerned with the malignant type because they are more life-threatening and present greater medical challenges than benign tumors. Subspecialties: Biochemistry, radiology, radiation and cancer biology, radiation physics, chemotherapy, genetics, surgery, hematology Cancers treated: All Training and certification: Several subspecialties exist under the broad umbrella term “oncologist.” Minimally, those pursuing oncological training and certification must possess a recognized medical degree or, in the case of oncological nurses, must be registered nurses. Among the basic fields in which oncologists practice is surgical oncology, in which board-certified surgeons take special training in biopsy, tumor staging, and tumor resection or removal by surgical means. Another distinct field is pediatric oncology and hematology, in which board-certified pediatricians take special training that focuses on various malignancies frequently found in babies or in children. Medical oncology is a field that attracts internists who complete special oncological training. Yet another field is radiation oncology, which is staffed by radiologists who complete special training directed toward the radiological diagnosis and treatment of malignancies. Gynecological oncology is studied by board-certified gynecologists and obstetricians, while board-certified hematologists may continue their studies with an emphasis on cancers of the blood, such as leukemia. Specific training in oncology usually involves a residency of two to four years, generally pursued at a recognized cancer center. Such training follows the residency in each candidate’s special field, such as surgery, pediatrics, or radiology. Certification is granted by such regulatory agencies as the Accreditation Council of Graduate Medical Education, the American Board of Radiology, and the American Board of Pediatrics. Specific oncological training may focus on clinical research, on the integration of oncological training with other medical specialties, on clinical practice, or on a combination of these activities.
Salem Health: Cancer Once physicians have received initial certification in their specific fields, they usually must renew this certification at regular intervals. Such renewals may require them to take refresher courses or to pass qualifying examinations in the field. Although it is seldom necessary to withhold the renewal of certification, practicing oncologists must keep abreast of their fields to assure themselves that they will qualify for recertification. Services and procedures performed: Although cancer is the broad term used to describe the runaway proliferation of malignant cells within the body, this catch-all term is too broad to describe the many types of malignancies that oncologists encounter and are called on to treat. Cancer occurs when masses of tissue, termed neoplasms, behave abnormally, when their growth is out of control to the extent that it poses the possibility of spreading to other organs, a process know as metastasis. Because a metastasized cancer is more difficult to control than one that is confined to a small area, physicians urge patients to seek immediate medical intervention if any sign of a malignancy is detected. Cancers caught in the early stages usually can be controlled and possibly eliminated through radiation, chemotherapy, surgery, or a combination of these procedures. Early detection is key to controlling and eliminating malignancies. Oncologists in all subspecialties of oncology are fundamentally concerned with attempting to understand how normal cells mutate into malignant cells. Their research is concentrated on determining the process through which malignancies develop so that they can find means of thwarting such abnormal development. As oncologists come to understand the process through which normal somatic cells are transformed into malignant cells, they are better equipped than ever before to deal with the inroads of cancer. As knowledge of the molecular biology of cancer proliferates, oncologists have been increasingly able to develop biochemical and genetic means of not only treating malignancies but also anticipating them in patients who are at risk genetically of developing cancer. Certainly the most effective treatment of cancer is anticipatory and preventive. A family history of cancer may substantially increase the likelihood that a patient will eventually develop cancer, so oncologists can provide preventive treatment to lessen or eliminate such a possibility. Cancer genes are essentially of two types. Dominant oncogenes, as they are called, are relatively rare. Of the more than thirty thousand human genes that have been identified, less than one hundred are oncogenes. Such genes increase the ability of cells to divide. When they
Oncology grow uncontrolled in organisms, they result in both malignant and benign tumors. Anti-oncogenes are designed to suppress tumors. They sometimes undergo a mutation that thwarts the cell’s ability to develop its means of suppressing such tumors. Through mutation, dominant oncogenes and antioncogenes can both serve to cause the generation of cells that are difficult to control. Great progress has been made in understanding the basic molecular factors involved in the development of cancer, giving oncologists the tools, both genetic and biochemical, that they require to diagnose the behavior of neoplasms, or abnormal new cells, and to find ways to treat such cellular growth effectively. With medical advances and an increased understanding of the role that genetics plays in cellular growth, oncologists have developed sophisticated means of treating abnormalities in the growth of cells, particularly of malignant cells. With the unraveling of some of the mysteries of how deoxyribonucleic acid (DNA) determines cellular growth, oncologists have come to realize that the four nucleotides found in cells (adenine, guanine, cytosine, and thymine) occur in various sequences and that they contain the genetic information required to comprehend the development and configuration of cellular organisms. The genes provide cells with the information they need to develop the cellular sequence of amino acids needed to build the proteins, the building blocks, required for cells to develop and grow. Dominant oncogenes can distort the division of cells so that instead of an orderly production, a runaway production of cells takes place, resulting in tumors. Oncologists strive to understand the genetic activities of cells and to bring under control any cellular activity that thwarts or threatens the orderly production of cells and causes tumors to form. Although the primary goal of oncologists is to evaluate malignancies and work either to eliminate them or to greatly reduce their size, an important secondary goal is to offer reassurance to patients and their families and to work assiduously to make patients as comfortable and pain-free as possible in the course of their treatment. Ongoing research in oncology has proliferated greatly in the twentyfirst century. Oncologists necessarily strive to keep abreast of it. Whereas major surgery was often indicated for malignancies in the 1980’s or 1990’s, much treatment of comparable malignancies has become either noninvasive or minimally invasive. Prolonged radiation therapy with all of its side effects has, in many cases, been replaced by much more benign procedures such as the implantation at the site of the malignancy of radioactive seeds that provide an uninterrupted but much reduced dose of radiation. Such procedures pro883
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vide a constant bombardment of malignant cells with radiation but reduce substantially the side effects that accompany a more extensive radiological procedure. These means of treating malignancies often permit patients to engage quite normally in their day-to-day activities.
sequent treatment. In cases that are clearly terminal, oncologists may help patients obtain hospice care so that they will be looked after either in their homes or in facilities that are less forbidding and less costly than hospitals. R. Baird Shuman, Ph.D.
Related specialties and subspecialties: Initially, many of the patients who consult oncologists do so because they have been referred by internists or family physicians to whom they turned when symptoms begin to appear. Oncologists to whom such patients are referred generally keep in contact with the referring physician, who often continues to see such patients on a regular basis. Most of the work oncologists do is highly collaborative. Ideally it is carried out at large medical centers staffed by specialists in each of the many subspecialties of oncology. Regardless of the site of a malignancy, a radiation oncologist is necessarily involved in helping determine the extent of radiological treatment and in plotting its course. Oncologists working together make diagnoses and determine the stage of a malignancy, with stages ranging from I to IV. The two higher numbers indicate a malignancy that has metastasized or spread to organs outside the original site of the growth. Increasingly Stage IV malignancies, once considered death sentences, are being treated successfully. Some such growths have been eliminated altogether through radiation or chemotherapy, sometimes combined with surgical intervention. In such cases, the oncologist works closely with radiologists, physical oncologists, geneticists, and surgeons, all of whom have had special training in oncology, to determine an effective course of treatment that can result in eliminating or controlling the malignancy. Even in cases in which there is no cure, the quality and extent of a patient’s life can be considerably enhanced by oncological treatments devised by various specialists in the field. Cancers exist in so many forms that specialists from many fields, some only ancillary to the medical profession, may be called on to be involved in their treatment. As research increasingly indicates that diet may substantially affect the growth of cancer cells, nutritionists have become involved in working collaboratively with oncologists. Since 1911, when American pathologist Peyton Rous first detected an oncogenical virus in a malignant tumor that grew in a chicken, virologists have worked with oncologists to identify viruses that may be associated with cancer. Oncologists may also refer patients and those close to them to mental health professionals and social workers to help them cope with the depression and uncertainties that frequently accompany diagnoses of cancer and their sub-
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For Further Information De Vito, Vincent T., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott Williams and Wilkins, 2005. Langhorne, Martha E., Janet S. Fulton, and Shirley E. Otto, eds. Oncological Nursing. 5th ed. St. Louis: Mosby Elsevier, 2007. Leibel, Steven A. Textbook of Radiation Oncology. 2d ed. Philadelphia: Saunders, 2004. Pappas, Alberto S., ed. Pediatric Bone and Soft Tissue Sarcomas. New York: Springer, 2006. Parker, Robert G. Radiation Oncology for Cure and Palliation. New York: Springer, 2003. Pazdur, Richard, ed. Medical Oncology: A Comprehensive Overview. Huntington, N.Y.: PRR, 1995. Pollock, Raphael E., ed. Surgical Oncology. Boston: Kluwer Academic Press, 1997. Rizzo, Phillip A., and David G. Poplack, eds. Principles and Practice of Pediatric Oncology. Philadelphia: Lippincott Williams and Wilkins, 2002. Tomlinson, Deborah, and Nancy E. Kline, eds. Pediatric Oncology Nursing: Advanced Clinical Handbook. New York: Springer, 2005. Vasilev, Steven A., ed. Perioperative and Supportive Care in Gynelogic Oncology: Evidence-Based Management. New York: Wiley-Liss, 2000.
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Organizations and Professional Societies
American Board of Internal Medicine (ABIM) http://www.abim.org 613 New York Ranch Road Jackson, CA 95642 American Board of Obstetrics and Gynecology (ABOG) http://www.abog.org 2915 Vine Street Dallas Texas, 75204 American Board of Pediatrics (ABP) https://www.abp.org/ABPWebSite/ 111 Silver Cedar Road Chapel Hill, NC 27514
Salem Health: Cancer American Board of Radiology (ABR) http://www.theabr.org/index.htm 5441 East Williams Boulevard, Suite 200 Tucson, AZ 85711 American Board of Surgery (ABS) http://www.absurgery.org 1617 John F. Kennedy Boulevard #860 Philadelphia, PA 19103 American Society for Therapeutic Radiology and Oncology (ASTRO) http://www.astro.org Post Office Box 631567 Baltimore, MD 21263 American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 u
Other Resources
American Academy of Hospice and Palliative Medicine http://www.aahpm.org National Comprehensive Cancer Network http://www.nccn.org Oncology Nursing Society http://www.ons.org See also Dermatology oncology; Endocrinology oncology; Gastrointestinal oncology; Gynecologic oncology; Hematologic oncology; Immunocytochemistry and immunohistochemistry; Medical oncology; Molecular oncology; Neurologic oncology; Ophthalmic oncology; Pediatric oncology and hematology; Pharmacy oncology; Psycho-oncology; Radiation oncology; Surgical oncology; Urologic oncology; Veterinary oncology; Viral oncology.
u Oncology clinical nurse
specialist Category: Medical specialties Also known as: Oncology nurse specialist, cancer nurse specialist, advanced practice oncology nurse specialist Definition: An oncology clinical nurse specialist is a registered nurse who has a master’s degree and extensive
Oncology clinical nurse specialist training to provide specialized consultation and care for cancer patients and families. Subspecialties: The oncology nurse clinical specialist may choose to specialize in a particular cancer practice working with a selected population of patients. Examples of specialties include medical hematology oncology, hematology oncology, outpatient radiation, outpatient hematology oncology, outpatient pediatric oncology, and palliative care. Cancers treated: Depends on area of specialty Training and certification: The oncology clinical nurse specialist completes a bachelor’s degree in nursing and a master’s degree in nursing with appropriate clinical practicum from an accredited graduate nursing program. Education programs will vary, but the master’s degree generally takes about two years to complete and requires at least five hundred hours of clinical practicum. Required courses for a master’s degree vary from school to school. Courses included in these programs are advanced physiology and cancer pathophysiology, pharmacology, cancer genomics, epidemiology, disease and symptom management, palliative care, nursing research, nursing and medical ethics, public policy, leadership, health care financing, health program planning and evaluation, technology use, and advanced nursing concepts. Practicum hours are usually accrued in the nurse’s chosen specialty. Additional training and skills necessary to effectively practice in the role of oncology clinical nurse specialist include crisis management, in-depth knowledge of the chosen clinical cancer specialty, maturity to take responsibility for patients’ lives, understanding of medical ethics, teaching proficiency, and expertise in interpersonal relations to work with the patient, caregivers, and multidisciplinary health care team. Oncology clinical nurse specialists must have valid nursing licenses issued by the boards of nursing in their states. In some states, oncology clinical nurse specialists must also receive certification by successfully completing examinations in their specialty. In other states, attaining certification status is voluntary. Proficiency is validated through examination based on predetermined standards and given by a nongovernment agency. The Oncology Nursing Certification Corporation provides several different certifications for nurses working with cancer patients. The Advanced Oncology Certified Clinical Nurse Specialist (AOCNS) certification examination is available to professional nurses who hold a current, active license that is nonrestricted, have completed a master’s degree or 885
Oncology clinical nurse specialist higher from an accredited school of nursing, and have completed a minimum of five hundred hours of supervised clinical practice in oncology nursing. Documentation of the supervised clinical practicum hours is required and verified before certification is granted. AOCNS certification is valid for four years. The AOCNS nurse can renew certification by earning 125 points (at least 75 in oncology nursing) through activities such as continued academic education, nursing continuing education, publication, precepting, presentation, or volunteer service. Services and procedures performed: Oncology clinical nurse specialists can work in a variety of settings, including hospitals (acute care), clinics, long-term care or elder care homes, home care or hospice agencies, and private and joint practices. They can also work as consultants. The oncology clinical nurse specialist recognizes and values the expanding and evolving nature of cancer care and remains current with complex services, procedures, and treatments. The services and procedures performed depend on the setting and function of the nurse’s specific role. Some oncology clinical nurse specialists work as clinicians and provide direct care for patients and caregivers. They often work alongside other health care professionals such as physicians, nurses, and therapists to plan and evaluate patient care. These nurse specialists schedule and coordinate diagnostic and therapeutic procedures or tests for oncology patients. They will monitor the test results and revise the cancer patient’s care plan based on individual and changing needs. At a cancer care clinic or oncology hospital unit, the oncology clinical nurse specialist may perform the initial admission assessment for new patients and develop the plan of care. This nurse will monitor the plan of care and make adjustments as indicated for the individual cancer patient. The nurse assists with discharge planning to include referrals for other community resources or establish follow-up appointments to physicians’ offices or cancer care clinics. Oncology clinical nurse specialists often function as teachers. In clinical settings, these nurses keep abreast of current research and new therapies. They use their expanded knowledge of cancer and cancer treatment to teach new concepts or treatment modalities to staff members and members of the multidisciplinary health care planning team. In the hospital cancer unit or cancer care clinic, oncology clinical nurse specialists help assess current staff education, develop new educational strategies, coordinate educational agendas, and revise teaching programs. Educational programs are provided as in-service programs or as clinical practicums. They serve as advisers to staff and 886
Salem Health: Cancer other professionals. The goal of this education is to organize and implement an educational strategy that trains professional caregivers to provide the best possible cancer care for patients and their caregivers. Cancer care education is critical for the cancer patient, family, and caregivers to live life to the fullest. The oncology clinical nurse specialist builds a relationship with the cancer patient and caregivers and provides individualized patient teaching. Cancer patients need accurate and up-todate information about their disease and treatment options to make decisions about their care. The highly educated and informed oncology clinical nurse specialist is often the person who spends time with the patient and family, teaching them necessary components of self-care and disease management. Even after discharge from the hospital cancer care unit, the patient and caregivers may contact the oncology clinical nurse specialist with questions and concerns. The positive relationship developed during hospitalization often carries over to the home setting as the oncology clinical nurse specialist fills the role of consultant and educator. Administrative functions are sometimes part of the services delivered by oncology clinical nurse specialists. They monitor the medication regimen of the cancer patient and suggest changes when needed for improved patient outcomes. Sometimes they manage the research protocol as primary investigator for grants and clinical studies. Oncology clinical nurse specialists are stewards in fiscal management of resources by keeping an eye on cancer care costs, noting where services can be delivered more efficiently. Related specialties and subspecialties: Oncology clinical nurse specialists can work in a number of subspecialties depending on their interests and the positions available in the nurses’ area. Roles are evolving and diverse, as the oncology nurse clinical specialist contributes many skills to the health care team. Some assume administrative roles and perform in high levels of leadership within the cancer care settings. For example, oncology clinical nurse specialists can become nurse managers over specialized hospital oncology units or serve as directors of community cancer care centers, or they might become health care administrators for managed care or insurance companies and consult with key decision makers about covered services for cancer care patients. Oncology clinical nurse specialists can pursue further education and receive a doctorate degree in various academic fields. One example is the oncology clinical nurse specialist who completes a doctorate and enters the field of cancer research. Another nurse might earn a doctorate in
Salem Health: Cancer nursing science or a doctorate in education and join a university graduate faculty to teach others to become oncology clinical nurse specialists. As faculty, these nurses can work as consultants and mentors to undergraduate nursing students to help them become proficient in cancer care. Some pursue additional education to function in the dual role of oncology clinical nurse specialist and nurse practitioner. Still others assume an entrepreneurial spirit and use their knowledge and skills in creative and innovative private and joint practice. Marylane Wade Koch, M.S.N., R.N. u For Further Information Carper, E., and M. Hass. “Advanced Practice Nursing in Radiation Oncology.” Seminars in Oncology Nursing 22, no. 4 (November, 2006): 203-211. Skilbeck, J., and S. Payne. “Emotional Support and the Role of Clinical Nurse Specialists in Palliative Care.” Journal of Advanced Nursing 43, no. 2 (September, 2003): 521-530. Zuzelo, Patti R. Clinical Nurse Specialist Handbook. Sudbury, Mass.: Jones and Bartlett, 2007.
u
Organizations and Professional Societies
National Association of Clinical Nurse Specialists http://www.nacns.org 2090 Linglestown Road, Suite 107 Harrisburg, PA 17110 Oncology Nursing Certification Corporation http://www.oncc.org/publications/options.shtml 125 Enterprise Drive Pittsburgh, PA 15275 Oncology Nursing Society http://www.ons.org 125 Enterprise Drive Pittsburgh, PA 15275 See also Cancer care team; Counseling for cancer patients and survivors; Dermatology oncology; Endocrinology oncology; Ewing sarcoma; Gastrointestinal oncology; Gynecologic oncology; Hematologic oncology; Medical oncology; Neurologic oncology; Pediatric oncology and hematology; Radiation oncology.
Oncology social worker
u Oncology social worker Category: Medical specialties Also known as: Cancer social worker, certified social worker in health care, C-SWHC Definition: Oncology social workers provide psychosocial support, emotional counseling, and referrals for cancer patients and their caregivers. Subspecialties: Oncology social workers may support patients with diverse types of cancer or specialize in the care of patients with a certain type of cancer. An example is a social worker who is employed in a setting dedicated to women’s cancers, such as breast, ovarian, or uterine cancers. Specialization may also be based on the age of the patients such as pediatric oncology. Cancers treated: Depends on the social worker’s specialization Training and certification: An oncology social worker is a medical social worker with a master’s in social work (MSW). This program generally requires two years of course study and about nine hundred hours of supervised clinical work. Classes include subjects such as human growth and development, social research, social policy, and methods of practice. Licensure varies from state to state. Oncology social workers receive cancer care training through continuing education, in-service education courses, and on-the-job training. Certification is voluntary through the National Association of Social Workers (certified social worker in health care, or C-SWHC). Services and procedures performed: Oncology social workers serve a key role in the multidisciplinary cancer care team. They provide support and referral services tailored to the needs of cancer patients and caregivers. Oncology social workers are the liaison between the cancer patient and the health care system. They support the cancer patients as whole human beings with diverse roles in their daily lives. Some of the support services oncology social workers can provide are as follows: • Help the patient understand the cancer diagnosis and deal with the emotional aspects • Provide case management and discharge planning • Maximize insurance coverage • Mobilize community services • Access financial resources for equipment, medications, and support services • Assist in applying for disability and social security benefits 887
Oophorectomy
• Make important referrals to community agencies and support groups Related specialties and subspecialties: Oncology social workers practice in many settings. Hospitals that provide cancer care services usually employ oncology social workers. Freestanding cancer care centers, clinics, and oncology physician offices may provide oncology social workers for their patients and caregivers. Hospice services use oncology social workers in their residential or home care services. Nursing homes may contract with an oncology social worker to assist patients and families. Marylane Wade Koch, M.S.N., R.N. See also Cancer care team; Case management; Counseling for cancer patients and survivors; Family history and risk assessment; Gastrointestinal oncology; Hematologic oncology; Home health services; Medical oncology; Medicare and cancer; Oncology; Otolaryngology; Palliative treatment; Pediatric oncology and hematology; Psychooncology; Throat cancer; Transitional care.
u Oophorectomy Category: Procedures Also known as: Ovariotomy, ovariectomy, bilateral oophorectomy, preventive or prophylactic bilateral oophorectomy (PBO), prophylactic oophorectomy, laparoscopic oophorectomy Definition: Oophorectomy is the surgical removal of both ovaries as a treatment for ovarian cancer or metastasized cancer. The two ovaries are the part of the female reproductive system that produces egg cells (ova) and releases hormones, including estrogen. Both ovaries may be removed as a preventive measure for women with a high risk of ovarian cancer or breast cancer. Oophorectomy may be used for patients with estrogen-sensitive breast cancer to prevent its recurrence. Cancers treated: Ovarian cancer, metastasized cancer, preventive treatment for patients at high risk for ovarian or breast cancer, treatment for estrogen-sensitive breast cancer Why performed: Both ovaries are removed with an oophorectomy to help treat ovarian cancer. Most ovarian cancers develop in the epithelial cells that cover the outside of the ovary. Ovarian cancer can also develop in the germ cells (the cells that produce eggs) or in the stromal cells (the cells inside of the ovary that produce estrogen and progesterone). 888
Salem Health: Cancer Ovarian cancer can spread to other parts of the body. Other parts of the female reproductive system such as the Fallopian tubes, which transport eggs to the uterus for fertilization, may be removed in a surgery termed a bilateral salpingo-oophorectomy. Oophorectomy is used to treat metastasized cancer that originated elsewhere in the body and has spread to the ovaries. Women with the BRCA1 or BRCA2 gene mutations have a high risk for breast cancer and gynecologic cancer. A preventive bilateral oophorectomy (PBO) is used to remove both ovaries of women with a family history and high risk of ovarian cancer. A PBO is usually performed after a woman has experienced childbirth or at about the age of thirty-five. Research has shown that PBO does reduce the risk of ovarian cancer for high-risk women. Research shows that PBO before the age of forty can significantly reduce the risk of breast cancer for women with the BRCA1 or BRCA2 gene mutations. Oophorectomy may also be used as a preventive treatment for premenopausal women with estrogen-sensitive breast cancer. Removing both ovaries removes the main source of estrogen in the body and can help to prevent estrogensensitive cancer cells from growing. Patient preparation: Patients receive laboratory and blood tests prior to surgery. X rays or ultrasound images may be taken to help plan the procedure. Patients should eat a light dinner and not eat or drink after midnight on the day prior to the surgery. In some cases, preparations may be used to empty the colon. Steps of the procedure: Oophorectomy for the treatment of cancer uses general anesthesia and an open surgical method. A vertical incision is made on the abdomen. The abdominal muscles are spread apart to allow the surgeon access to the ovaries. The vertical incision allows the surgeon to view the abdominal cavity for disease or cancer. After both ovaries are removed, the incision is closed and bandaged. A horizontal incision may be used to remove both ovaries if cancer is not present. A horizontal incision is associated with less scarring and bleeding. A laparoscopic oophorectomy may also be used if cancer is not present, in cases of preventive surgery. Laparoscopic oophorectomy is guided by images produced by a laparoscope, a narrow tube with a light, viewing instrument, and miniature camera. The laparoscope is inserted through small incisions in the abdomen. Surgical instruments are inserted through the laparoscope to remove the ovaries. Because laparoscopic surgery is minimally invasive and uses only small incisions, it is associated with less pain, less bleeding, fewer complications or
Salem Health: Cancer infections, a shorter hospital stay, and a quicker recovery time. After the procedure: The patient remains in the hospital for three to five days and returns to regular activity levels in about six weeks. Patients receiving open surgery may experience discomfort from having the abdominal muscles moved during the procedure. Patients receiving laparoscopic surgery may remain in the hospital for a night or two and resume regular activities sooner. Patients who have both ovaries removed are no longer able to become pregnant and therefore experience “surgical menopause.” Those without cancer may receive hormones to help ease the risk of medical complications and menopausal symptoms. Symptoms of menopause may be greater in women experiencing surgical menopause than in women with naturally occurring menopause. Patients with ovarian cancer usually receive chemotherapy following oophorectomy. Chemotherapy uses medication, or a combination of medications, delivered over a period of time to help kill any remaining cancer cells. Radiation therapy is rarely used. Risks: The surgical risks of oophorectomy include infection, bleeding, blood clots, and damage to other organs. Some women experience decreased sex drive and decreased orgasm. Bilateral oophorectomy increases the risk of cardiovascular disease, osteoporosis, and thyroid cancer. Hormone therapy can help reduce the risk. Results: Normal results are removal of both ovaries without complications and no findings of cancer. Abnormal results include removal of both ovaries with findings of cancer, metastasized spread, or complications. Mary Car-Blanchard, O.T.D., B.S.O.T. u For Further Information Fader, A. N., and R. G. Rose. “Role of Surgery in Ovarian Carcinoma.” Journal of Clinical Oncology 25, no. 20 (July 10, 2007): 2873-2883. Kauff, N. D., and R. R. Barakat. “Risk-Reducing Salpingooophorectomy in Patients with Germline Mutations in BRCA1 or BRCA2.” Journal of Clinical Oncology 25, no. 20 (July 10, 2007): 2921-2927. Parker, W. H., et al. “Elective Oophorectomy in the Gynecological Patient: When Is It Desirable?” Current Opinion in Obstetrics and Gynecology 19, no. 4 (August, 2007): 350-354.
See also BRCA1 and BRCA2 genes; Breast cancers; Fallopian tube cancer; Gynecologic oncology; Hormonal therapies; Hot flashes; Hysterectomy; Hystero-oophorectomy; Salpingectomy and salpingo-oophorectomy.
Ophthalmic oncology
u Ophthalmic oncology Category: Medical specialties Also known as: Cancer of the eyes Definition: Ophthalmic oncology is a medical specialty that deals with the diagnosis and treatment of cancers of the eye. Subspecialties: Ophthalmic oncologists often specialize in one particular type of cancer, such as retinoblastoma or intraocular melanoma. Cancers treated: Intraocular melanoma (sometimes called uveal melanoma), primary intraocular lymphoma, retinoblastoma, medulloepithelioma Training and certification: Training to be an ophthalmic oncologist requires many years of specialized medical training. After receiving a medical degree from an accredited school, ophthalmic oncologists then complete a residency program. This residency is usually in ophthalmology, although during this time the individual will also often receive training in surgery and oncology. After successful completion of a residency program, the individual can apply to be board certified in ophthalmology. Board certification is a long and difficult process that requires at least one and one-half years to two years to complete. Candidates for board certification must apply to take the first test. Candidates whose applications are approved are allowed to take a five-hour written exam. Those candidates who pass are invited to take an extensive oral exam. Only after successful completion of all these steps is the candidate board certified. The individual must take extensive ongoing steps to retain board certification. Board certifications completed after 1992 must be renewed every ten years. During the board-certification process and afterward, most ophthalmic oncologists complete one or more additional fellowships or other training programs. These fellowships last one or more years and provide the doctor additional training and expertise in the chosen field. Often these fellowships are very specialized. Ophthalmic oncologists often receive training during their residencies, fellowships, training programs, or at other times in research and clinical trials. Research is continuously being conducted to develop new methods, procedures, and drugs to help with the diagnosis and treatment of cancers of the eye. Clinical trials are experiments designed to determine the effectiveness and safety of newly developed procedures, methods, drugs, and other treatments that have not yet been accepted into common practice. Individuals who have cancer may be asked by 889
Ophthalmic oncology
Salem Health: Cancer The Anatomy of the Human Eye
Sclera Choroid
Retina
Lens capsule
Iris Pupil
Cornea Aqueous humor
Optic disk (blind spot)
Optic nerve
Ciliary muscle Fovea
Vitreous humor
their oncologist or other doctor if they wish to participate in a clinical trial. Clinical trials have varying possible risks and benefits, and the decision of whether to participate should be discussed carefully with the cancer care team. Services and procedures performed: Cancers of the eye are relatively rare. According to the American Cancer Society, about 2,340 people were likely to be newly diagnosed with primary eye cancer in 2007. Most of these eye cancers are intraocular melanomas. Many ophthalmic oncologists specialize in treating only one type of eye cancer or in a certain type of treatment. Before ophthalmic oncologists can begin to treat an eye cancer, they must determine that the eye cancer does in fact exist and, if so, what type of cancer it is. A patient may be referred to an ophthalmic oncologist because of a suspicious finding during a routine vision screening or because of a visit to a primary care physician with symptoms that indicate a possible eye cancer. To diagnose eye cancer, the ophthalmic oncologist will use a specialized tool called an ophthalmoscope that al890
lows the doctor to look inside the patient’s eye. The ophthalmic oncologist will look for any abnormalities inside the eye such as spots, discoloration of the pupil, or cloudiness of the gel inside the eye. The ophthalmic oncologist will also ask the patient about any signs or symptoms, such as pain, problems with vision, seeing flashes of light or floating spots that are not really there, or other abnormalities. The ophthalmic oncologist may also examine the eye to see if there are any problems such as the eyeball moving abnormally, bulging, or seeming out of place. In many cases, further diagnostic procedures are necessary. In some cases a biopsy of the suspected tumor may be done, although this is often avoided if possible because performing a biopsy has some risk of damaging the eye. Technology such as an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI) may also be performed to help the ophthalmic oncologist get a better picture of the eye. Additional scans or tests may be done to determine if the cancer has spread outside the eye. Once the cancer has been diagnosed, the ophthalmic oncologist will work with the patient and the health care
Salem Health: Cancer team to develop a plan of treatment. The four main types of treatment for eye cancers are surgery, radiation therapy, laser therapy, and chemotherapy. New technologies and procedures are being developed all the time, and different treatments are appropriate for different types and stages of eye cancer. Surgery is often the treatment of choice for eye cancers. During the procedure, the ophthalmic oncologist will remove the cancerous area. In some cases vision out of the affected eye will still be possible after the surgery, and in others it may be diminished or gone altogether. In very severe cases the best option may be to remove the cancerous eye completely and replace it with a prosthetic. Radiation therapy and chemotherapy are used to treat many forms of eye cancer. Radiation therapy is targeted as specifically as possible so that it affects as little of the healthy area of the eye as possible. Chemotherapy is not specifically targeted to an area of the eye but instead is put into the blood intravenously or is given by mouth. The chemotherapy drugs then travel in the bloodstream to the eye. The fourth type of treatment that some ophthalmic oncologists use is laser therapy. The laser may use infrared light or a high-energy light beam to kill the cancer cells. One positive aspect of laser therapies is that lasers can be focused into a very thin beam of light that allows a high degree of accuracy, generally affecting fewer of the surrounding cells than other treatment methods. After the cancer has been successfully treated, many patients return regularly to see their ophthalmic oncologist to check for any side effects and to ensure that the cancer has not returned. Related specialties and subspecialties: There are many doctors and other health care team members who assist or work closely with an ophthalmic oncologist. An ophthalmologist is a doctor who specializes in the diagnosis and treatment of eye diseases and conditions. This can include things as diverse as eye surgery or prescribing corrective lenses. It is important for people to visit an ophthalmologist regularly for vision screening and a general checkup of their eye health. It is during this kind of routine screening that many eye problems, including cancer of the eye, are first suspected or diagnosed. There are many other members of the allied health professions who may be part of the cancer care team for someone with eye cancer. The specific individuals who will work with the ophthalmic oncologist will differ depending on the kind of cancer and the type of treatment. The team
Ophthalmic oncology may include specialists in administering radiation or chemotherapy, nutritionists, medical technologists, and nurses specializing in the care and treatment of cancer patients. The ophthalmic oncologist may also be called on to be part of a larger oncology team involving oncologists who specialize in cancer of other areas of the body if the cancer has metastasized from another area of the body to the eye. Helen Davidson, B.A. u
For Further Information Albert, Daniel M., and Arthur Polans, eds. Ocular Oncology. New York: Marcel Dekker, 2003. Denniston, Alastair K. O., and Phillip I. Murray. Oxford Handbook of Ophthalmology. New York: Oxford University Press, 2006. Shields, Jerry A., and Carol L. Shields. Intraocular Tumors: Atlas and Textbook, 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2008.
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Organizations and Professional Societies
American Board of Ophthalmology http://www.abop.org/index1.asp 111 Presidential Boulevard, Suite 241 Bala Cynwyd, PA 19004-1075 International Council of Ophthalmology http://www.icoph.org 945 Green Street San Francisco, CA 94133 European Organization for Research and Treatment of Cancer http://www.helsinki.fi/laak/silk/oog Ophthalmic Oncology Group Avenue Mounierlaan, 83/11 Brussel 1200 Bruxelles, Belgium u
Other Resources
Eye Cancer Network http://eyecancer.com Retinoblastoma International http://www.retinoblastoma.net See also Eye cancers; Eyelid cancer; Gonioscopy; Lacrimal gland tumors; Neurofibromatosis type 1 (NF1); Orbit tumors; Retinoblastomas; Rothmund-Thomson syndrome; Sjögren syndrome.
891
Opioids
Salem Health: Cancer
u Opioids Category: Chemotherapy and other drugs Also known as: Narcotics Definition: Opioids are controlled drugs prescribed for the management of moderate to severe pain. Opioids include natural alkaloids (opiates) such as morphine and codeine, which are extracted from the seedpod of the poppy plant, as well as semisynthetic derivatives and fully synthetic forms. ATC code: N02A Cancers treated: Various Subclasses of this group: Phenanthrenes, phenylpiperidines, diphenylheptanes, benzomorphans Delivery routes: Oral administration is preferred because it is the least invasive and least costly route. If a patient has difficulty swallowing or suffers from nausea or vomiting, then other options may include rectal, transdermal, and transmucosal administration or injection under the skin or into the vein or spinal area. Patient-controlled access pumps that deliver opioids to these areas are also available. Opioids are produced in both long-acting and immediaterelease forms and are often used with other pain medications for enhanced analgesia.
How these drugs work: Opioids mimic the body’s natural painkillers (for example, endorphins) by binding to receptors on the surfaces of cells in the central nervous system and gastrointestinal tract. Full agonists, the largest group of opioids, stimulate the receptors, blocking the release of neurotransmitters and interfering with the transmission of pain signals to the brain. They also alter the perception of pain. Partial agonists produce weaker effects and may also block the analgesic action of other opioids. Side effects: Adverse events are common across opioids and include sedation, nausea and vomiting, constipation, respiratory depression, dry mouth, itching, sexual dysfunction, and urinary retention. Because of the wealth of opioid receptor sites in the central nervous system, cognitive effects such as hallucinations, euphoria, and depression may also occur. Tolerance and physical dependence may develop, although psychological addiction is rarely associated with opioid use by cancer patients. Judy Majewski, M.S. See also Acupuncture and acupressure for cancer patients; Bone pain; Breakthrough pain; Brief Pain Inventory (BPI); Brompton cocktail; Cordotomy; Do-not-resuscitate (DNR) order; End-of-life care; Hospice care; Medical marijuana; Nonsteroidal anti-inflammatory drugs (NSAIDs); Pain management medications; Palliative treatment.
Common Opioids
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Drug
Brands
Subclass
Delivery Mode
Codeine
Tylenol Codeine, Empirin
Phenanthrenes
Oral
Fentanyl
Actiq, Duragesic, Fentora, Sublimaze
Phenylpiperidines
Oral, transmucosal, buccal, transdermal
Hydrocodone
Vicodin, Vicodin ES, Norco, Lorcet, Anexsia
Phenanthrenes
Oral
Hydromorphone
Dilaudid, Hydrostat
Phenanthrenes
Oral, rectal, IV, subcutaneous
Levorphanol
Levo-Dromoran
Phenanthrenes
Oral, IV, subcutaneous
Methadone
Dolophine, Methadose
Diphenylheptanes
Oral, rectal, IV, subcutaneous
Morphine
MS Contin, Avinza, MSIR, Duramorph, Roxanol IR, Kadian, Oramorph SR
Phenanthrenes
Oral, IV, epidural, intrathecal, intraventricular
Oxycodone
Oxycontin, OxyIR, OxyNorm, Percocet, Percodan, Roxicodone
Phenanthrenes
Oral
Oxymorphone
Numorphan, Opana, Opana ER
Phenanthrenes
Oral, rectal, IV, subcutaneous
Salem Health: Cancer
u Oral and maxillofacial surgery Category: Procedures Also known as: Mouth surgery, maxillectomy, laryngectomy, neck dissection Definition: Oral surgery and maxillofacial surgery are general terms for surgery of the mouth (oral) and of the upper jaw and face (maxillofacial). Specially trained dentists, known as oral and maxillofacial surgeons, perform this type of surgery. Otorhinolaryngologists (ear, nose, and throat specialists) also perform certain oral and maxillofacial surgeries, as do cosmetic, or plastic, surgeons. Surgeons use oral and maxillofacial surgery to treat a wide range of injuries, defects, and diseases. Cancers treated: Oral or mouth cancer, including cancer of the lips, mouth, gums, salivary glands, tongue, face, neck, jaws, and hard and soft palates (roof of the mouth) Why performed: In treating cancer, doctors use oral and maxillofacial surgery most often to destroy or remove cancerous tumors. In some cases, doctors use oral and maxillofacial surgery to repair or reconstruct parts of the jaw and other boney structures of the face and throat to help patients speak or swallow better, or to restore a patient’s appearance following surgery or an injury. Patient preparation: What happens before oral and maxillofacial surgery to remove or destroy a tumor depends on its location. Patients who are undernourished because chewing or swallowing is difficult, owing to the site of the tumor, receive fluids intravenously to build up their strength before the operation. Generally, patients are instructed not to eat or drink anything eight hours before the procedure. Because various general and local anesthetics are used during the surgery, patients should inform their doctors of substances to which they are allergic. Surgeons sometimes perform oral and maxillofacial surgery in an operatory, so patients need to arrange for a ride home after the procedure. Nurses help hospital patients prepare for their surgery. Steps of the procedure: Because tumors can develop in so many sites in the mouth and face, and because surgeons may either destroy or remove the tumor, surgical procedures vary widely. For example, surgeons remove earlystage tumors of the tongue with a laser instrument operated directly through the mouth. In cases where the cancer has spread to the neck lymph nodes, a common occurrence, surgeons remove the affected lymph nodes, a procedure know as a neck dissection. Following this primary surgery, surgeons may have to perform additional operations
Oral and maxillofacial surgery to restore normal function to the patient’s neck, shoulder, or other nearby parts of the body. In some cases, surgeons perform secondary surgery to restore nerve function. In many cases, oral and maxillofacial surgery disfigures the patient’s face or neck. When that happens, surgeons perform restorative, or reconstructive, surgery to restore the patient’s appearance. Such secondary surgery includes the use of tissue flaps to restore soft tissue, skin grafts, bone grafts, and prostheses (metal or plastic parts to replace original body parts). Whatever the type of surgery, patients receive, as needed, a combination of anesthetics, medicines that put the patient to sleep, relax the patient, and block pain. After the procedure: Following surgery, care varies for each patient depending on the type of surgery and the location and extent of the cancer. Some patients may return home several hours after surgery. Others may have to stay in the hospital for several days. Postoperative care and rehabilitation may include additional surgery, speech therapy, dietary guidance, and psychological counseling. Risks: The risks from oral and maxillofacial surgery include harmful reactions to anesthetics and medications, wound infection, excessive bleeding, and slow healing, which are common to most surgeries. More specifically, oral and maxillofacial surgery can adversely affect a variety of body functions, including speaking, chewing, swallowing, and controlling the flow of saliva. These risks depend on the size and location of the tumor. Sometimes when destroying or removing a tumor, surgeons destroy or remove surrounding tissue or structures in the mouth. In addition, some patients disfigured by oral and maxillofacial surgery experience psychological problems because of the change in their appearance. Coupled with a severe illness or aggressive treatment, a changed look creates mental and social problems for some patients. Results: Typically, the earlier oral cancer is detected and treated, the better the chances of survival. When a tumor is destroyed or removed in the early stages of the cancer and the cancer has not spread, the five-year relative survival rate for patients is about 81 percent; the five-year relative survival rate for all stages of oral cancer is about 59 percent, according to the American Cancer Society. This does not mean, however, that five-year survivors are cancerfree or that the cancer will not reappear. Wendell Anderson, B.A. u
For Further Information Hupp, James R., Edward Ellis, and Myron R. Tucker. Contemporary Oral and Maxillofacial Surgery. 5th ed. Philadelphia: Elsevier Health Sciences, 2008. 893
Oral and oropharyngeal cancers Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Lip and Oral Cavity Cancer. San Diego, Calif.: Icon Health, 2005. Wray, David, et al. eds. Textbook of General and Oral Surgery. New York: Churchill Livingstone, 2003. u
Other Resources
American Association of Oral and Maxillofacial Surgeons http://www.aaoms.org Oral Cancer Foundation http://www.oralcancerfoundation.org See also Cordectomy; Electrolarynx; Erythroplakia; Esophageal speech; Glossectomy; Laryngeal cancer; Laryngectomy; Oral and oropharyngeal cancers; Throat cancer.
u Oral and oropharyngeal
cancers Category: Diseases, symptoms, and conditions Also known as: Mouth cancer, tongue cancer, salivary gland cancer, gum cancer, throat (instead of oropharyngeal) cancer Related conditions: Neck cancer, esophageal cancer
Salem Health: Cancer tasize to other organs, knowledge of the location of lymph nodes in this area is crucial for understanding oral and oropharyngeal cancer. The lymph nodes that supply the head and neck run parallel to the jugular veins and can be classified into five levels: Level I, which refers to the submental and submandibular lymph nodes; Level II, which includes the upper jugular lymph nodes; Level III, which refers to the mid-jugular lymph nodes; Level IV, containing the lower jugular lymph nodes; and Level V, which refers to the lymph nodes of the posterior triangle. Risk factors: Risk factors include cigarette smoking, chewing tobacco, excessive alcohol intake, extensive exposure to ultraviolet light, denture irritation, leukoplakia (white spots on the tongue or inside the cheeks), erythroplakia (red patches inside the mouth that bleed readily when bruised), and infection with human papillomavirus (HPV). Infection with HPV has been linked to one in five oral cancers. One study conducted at the Johns Hopkins University concluded that HPV infection is a stronger risk factor for oropharyngeal squamous cell carcinoma than tobacco and alcohol use. Gastroesophageal reflux disease (GERD), in which stomach acids enter the esophagus and destroy the esophageal lining, also contributes to the risk of throat cancer. Etiology and the disease process: Oral and oropharyngeal cancers appear to be caused by deoxyribonucleic acid (DNA) damage in the cells in the mouth and throat. This DNA damage can occur from exposure to too much ultraviolet light from the sun, or from cigarette smoking, tobacco chewing, or excessive alcohol intake. Most oral
Definition: Oral cancer is a collective term that encompasses cancers of the lips, mouth, tongue, gums, and salivary glands. Oral cancers mostly occur on the lips, tongue, or floor of the mouth but may also occur inside the cheeks, in the gums, or on the roof of the mouth. The oropharynx or throat is situated between the soft palate and the hyoid bone. The top of the oropharynx connects with the oral cavity and, further up, with the nasopharynx. The bottom of the oropharynx connects with the supraglottic larynx and the hypopharynx. The oropharynx consists of the base of the tongue (including the pharyngoepiglottic folds and the glossoepiglottic folds), the tonsillar region, the soft palate (including the uvula), and the pharyngeal walls. Practically all oral and oropharyngeal cancers are squamous cell carcinomas (SCCs), which refer to cancers that originate in squamous cells. Because the lymphatic system is one of A malignant tumor of the edge of a tongue. (John Radcliffe Hospital/Photo Researchers, Inc.) the major ways that tumors spread or metas894
Salem Health: Cancer
Oral and oropharyngeal cancers
Incidence of Cancer of the Oral Cavity and Pharynx per 100,000 People, by Gender 20 18
Men
Women
17.2 15.7
16 14 12
10.5 9.7
10
9.4
8 6
5.9
6.1
5.4
4.9 3.6
4 2 0 Black
White
Asian/Pacific Islander
American Indian/ Alaska Native
Hispanic
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
and oropharyngeal cancers are carcinomas of the squamous cells, the flat cells that make up the mucosal epithelium, the layer of cells lining the inside of the mouth, nose, larynx, and throat. Less common are lymphomas, lymphoepitheliomas, and minor salivary gland carcinomas. A rare type of oral cancer is verrucous carcinoma, which usually does not metastasize but can penetrate deeply into nearby tissue. Incidence: According to the American Cancer Society, there are approximately 30,990 new cases of oral and oropharyngeal cancer annually in the United States, with an estimated 7,430 deaths from oral and oropharyngeal cancer each year. The incidence is higher in men than in women. Oropharyngeal cancer is still a relatively rare type of cancer, and both oral and oropharyngeal cancer rates have been decreasing since 1975 in the United States. Symptoms: Symptoms of oral and oropharyngeal cancer include lumps of white, red, or dark patches inside the mouth that do not recede with time, mouth sores that do not heal or that enlarge over time, lumps in the neck, persistent
pain in the mouth, thickening of the cheek, swelling or pain in the jaw, soreness in the throat or a feeling that something is caught in the throat, difficulty chewing or moving the tongue (late-stage symptom), difficulty moving the jaw (late-stage symptom), pain around the teeth, loosening of the teeth, numbness of the tongue or mouth, and changes in the voice. Screening and diagnosis: Frequent oral examinations are the best way to detect signs of oral and throat cancer. When a tumor is detected, it is graded or staged to determine how benign or aggressive it is. The TNM (tumor/lymph node/ metastasis) staging system is a standard way of classifying tumors. T stands for the size of the primary tumor and which tissues of the oral cavity or oropharynx the tumor has spread to, if any. N refers to the extent of spread to regional lymph nodes. M is used to denote whether the tumor has metastasized to other organs. The most common metastatic site is the lungs, followed by the liver and the bones. Within each of these designations, there are several subcategories. 895
Oral and oropharyngeal cancers Following TNM staging, the tumor is classified as Stage 0, I, II, III, or IV. Stage 0 refers to a tumor that is confined to the outer layer of oral or oropharyngeal tissue and has not penetrated deeper or metastasized. Stage I tumors are 2 centimeters (cm) or smaller in diameter and have not metastasized. Stage II tumors are between 2 cm and 4 cm in diameter and have not metastasized. Stage III tumors are larger than 4 cm in diameter and have not metastasized, although they may have invaded one of the nearby lymph nodes. Stage IV is further divided into three substages: Stage IVA, in which tumors have spread to nearby sites and may or may not have invaded one or more nearby lymph nodes, Stage IVB, in which tumors may or may not have spread to nearby sites but have spread to one or more lymph nodes, and Stage IVC, in which tumors have metastasized to distant organs. Treatment and therapy: Primary care physicians will often refer patients to specialists, including oral and maxillofacial surgeons, otolaryngologists (ear, nose, and throat doctors), medical oncologists, radiation oncologists, and plastic surgeons. At specialized cancer treatment facilities, several of these specialists often work together to provide tailored care for patients. Treatment options include radiation therapy, oral chemotherapy, and surgery, as well as combinations of these treatments. The most commonly used treatment is a combination of radiation therapy and chemotherapy with the drug cisplatin. In some cases, surgery may be necessary to remove the cancer cells from a localized region. The surgery is often followed by radiation therapy to destroy any remaining cancer cells. Chemotherapy is sometimes given before other treatments to potentially enhance effectiveness of the follow-up treatment. In addition, treatments for symptoms and the side effects of therapies are often administered concomitantly. Radiation therapy can take the form of external radiation from specialized equipment or internal radiation, when radioactive substances are placed in seeds, needles, or plastic tubes and inserted in the tissue. A newer form of radiation therapy, intensity-modulated radiotherapy, focuses radiation to more selectively kill the tumor instead of the surrounding healthy tissue. Surgery can be performed to remove tumors in the mouth or throat, or lymph nodes in the neck. In addition to radiation, chemotherapy, and surgery, targeted therapies are also available. These include cetuximab (Erbitux), docetaxel (Taxotere), and angiogenesis inhibitors. Cetuximab is a monoclonal antibody directed at a protein that is abundant on cancer cells in this region. In a phase III clinical trial conducted at multiple locations in the United States and Europe (lead author 896
Salem Health: Cancer James A. Bonner, of the University of Alabama at Birmingham), treatment with cetuximab combined with radiation therapy was shown almost to double the median survival of patients with nonmetastatic head and neck cancer. Another phase III study showed that patients with inoperable head and neck cancer who were administered multidrug chemotherapy that included docetaxel, followed by radiation therapy, survived four months longer with fewer side effects compared with patients on standard therapy. Another study involved 358 patients with inoperable head and neck cancer that had metastasized to lymph nodes in the neck. These patients were randomly selected to receive either standard chemotherapy with cisplastin and 5-fluorouracil, or cisplastin, 5-fluorouracil, and docetaxel. Both groups received radiation therapy after chemotherapy. The group treated with docetaxel had a longer median survival time and progression-free survival (time during which the cancer does not progress)—18.6 months and 12.7 months, respectively—compared with the group that was treated with standard chemotherapy—14.5 months and 8.4 months, respectively. Docetaxel was also associated with fewer side effects such as vomiting, nausea, and mouth sores. This provides support for the rationale of targeted therapy, which is expected to affect normal healthy tissues less than more nonspecific chemotherapy drugs. Before starting any treatment, it is important for patients to ask their physicians about the treatment length and procedure, risks, side effects, and the results that may be expected. Prognosis, prevention, and outcomes: The prognosis is good if detected and treated early. However, oral and throat cancers are often not diagnosed until they are late stage, often because they may be painless at early stages or cause minor pains similar to a toothache. The stage of cancer will also determine the type of treatment to use. After treatment, the cancer may reappear (recur or relapse). The recurrence can occur in the mouth or throat (local recurrence), in the lymph nodes (regional relapse), or in a distant site in the body, often the lungs (distant recurrence). A relapse is associated with a poorer prognosis. The fiveyear relative survival rate is a statistic that calculates the survival of cancer patients relative to the expected survival for people without cancer. This statistic can be used as a guide, but other factors, such as age, health, and tumor properties, must be considered before arriving at a complete prognosis. By studying patients treated between 1985 and 1991, the five-year relative survival rate for oral cavity cancer was calculated to range from 83 percent for Stage I cancer to 47 percent for Stage IV tumors. The oneyear survival rate for all stages was 84 percent. The five-
Salem Health: Cancer year relative survival rate for oropharyngeal cancer ranges from 57 percent for Stage I cancer to 30 percent for Stage IV cancer. Ing-Wei Khor, Ph.D. u For Further Information Bonner, J. A., et al. “Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck.” New England Journal of Medicine 354 (2006): 567578. D’Souza, G., et al. “Case-Control Study of Human Papillomavirus and Oropharyngeal Cancer.” New Enland Journal of Medicine 357 (2007): 1944-1956. Genden, Eric M., and Mark A. Varvares, eds. Head and Neck Cancer: An Evidence-Based Team Approach. New York: Thieme, 2008. Lydiatt, William M., and Perry J. Johnson. Cancers of the Mouth and Throat: A Patient’s Guide to Treatment. Omaha, Neb.: Addicus Books, 2001. Nikolakakos, Alexios P., ed. Oral Cancer Research Advances. New York: Nova Biomedical Books, 2007. Vermorken, J. B., et al. “Cisplatin, Fluorouracil, and Docetaxel in Unresectable Head and Neck Cancer.” New England Journal of Medicine 357 (2007): 16951704. u
Other Resources
Orbit tumors cer; Laryngeal nerve palsy; Laryngectomy; Laryngoscopy; Leukoplakia; Lip cancers; Oral and maxillofacial surgery; Salivary gland cancer; Throat cancer; Tobaccorelated cancers.
u Orbit tumors Category: Diseases, symptoms, and conditions Also known as: Eye socket tumors, rhabdomyosarcomas, dermoid cysts, capillary hemangiomas, lymphoid tumors, cavernous hemangiomas, neurofibromas, schwannomas, optic gliomas, skin cancers of the eyelids, osteomas Related conditions: Arteriovenous malformations, gene mutations, trauma, systemic diseases, congenital anatomic defects, chronic inflammation or infection, metastasis from adjacent or distant primary tumors Definition: Orbit tumors are tumors found in the orbit, also known as the eye socket, which encases the eyeball, optic nerve, extraocular muscles, blood vessels, and soft tissue. Orbit tumors can be primary, in which the tumor originates from the orbit, or metastatic, in which the tumor develops from adjacent or distant tissue and invades the orbit. Most orbit tumors are benign but, because of their space-occupying nature, are readily conspicuous.
American Cancer Society Detailed Guide: Oral Cavity and Oropharyngeal Cancer Http://www.cancer.org/docroot/CRI/CRI_2_3x .asp?rnav=cridg&dt=60.
Risk factors: The presence of an invasive tumor in adjacent tissue may increase the risk of developing an orbit tumor. There are no other clearly identifiable risk factors for developing orbit tumors.
Cancer Research UK Types of Mouth and Oropharyngeal Cancer. Http://www.cancerhelp.org.uk/help/default .asp?page=13033
Etiology and the disease process: The etiology of orbit tumors varies and encompasses the etiologies of arteriovenous malformations, gene mutations, trauma, systemic diseases (such as amyloidosis or lymphoma), congenital anatomic defects, chronic inflammation or infection, and metastasis from adjacent or distant primary tumors.
MayoClinic.com Oral and Throat Cancer Http://www.mayoclinic.com/health/oral-andthroat-cancer/DS00349 National Cancer Institute Oral Cancer http://www.cancer.gov/cancertopics/types/oral See also Candidiasis; Chewing tobacco; Cigarettes and cigars; Coal tars and coal tar pitches; Cordectomy; Electrolarynx; Endoscopy; Epidemiology of cancer; Epidermoid cancers of mucous membranes; Epstein-Barr virus; Erythroplakia; Esophageal speech; Glossectomy; Head and neck cancers; Hypopharyngeal cancer; Laryngeal can-
Incidence: Orbit tumors can develop in children and adults, with different incidence rates depending on tumor type. In children, rhabdomyosarcoma is the most common malignant orbit tumor and accounts for 3 percent of orbit tumors; capillary hemangioma, which occurs in 1 to 4 percent of infants, is the most common benign pediatric tumor. The most common orbit tumors in adults are lymphoid tumors, cavernous hemangioma, and metastatic tumors, which respectively make up 4 to 13 percent, 4 percent, and 8 percent of all orbital neoplasms. Other orbit tumors include dermoid cysts, neurofibromas, schwannomas, optic gliomas, skin cancer of the eyelid, and osteomas. 897
Orchiectomy Symptoms: The most common symptom is proptosis (forward displacement of the eye). Eye pain, visual abnormalities such as double vision or even visual loss, orbital edema, and eye redness are other symptoms of orbit tumors. Screening and diagnosis: The diagnosis of orbit tumors relies on a meticulous patient history, thorough physical exam, and magnetic resonance imaging (MRI) or computed tomography (CT) scans. The diagnosis is confirmed by performing a tissue biopsy, either by fine-needle aspiration biopsy (FNAB) or by open biopsy of the orbit (orbitotomy). Histological analysis will determine the type of orbit tumor and lay the groundwork for a treatment plan. Treatment and therapy: Treatment depends on the tumor type. Surgical removal is usually the best option, especially with disfiguring, massive lesions. Some tumors require external beam radiotherapy or adjuvant chemotherapy. In pediatric patients, dermoid tumors are best treated by surgical excision, while capillary hemangiomas spontaneously regress, therefore not requiring any intervention. In adults, radiotherapy is the treatment of choice for lymphoid tumors, while surgery effectively treats cavernous hemangioma. Prognosis, prevention, and outcomes: The prognosis and outcomes depend on the type of tumor. Most primary orbit tumors are benign and therefore have a good prognosis. Metastatic orbit tumors (with a primary source of cancer elsewhere in the body) usually signify a poor prognosis. Ophelia Panganiban, B.S. See also Eyelid cancer; Gonioscopy; Lacrimal gland tumors; Neurofibromatosis type 1 (NF1); Ophthalmic oncology; Retinoblastomas; Rhabdomyosarcomas; RothmundThomson syndrome; Sjögren syndrome.
u Orchiectomy Category: Procedures Also known as: Radical orchiectomy, inguinal orchiectomy, bilateral orchiectomy, unilateral orchiectomy, orchidectomy Definition: Orchiectomy is a surgical procedure to remove one or both of the testicles in men with testicular or prostate cancer. Cancers treated: Testicular cancer, prostate cancer Why performed: Orchiectomy is used to remove one or both testicles as a treatment for testicular cancer. The testi898
Salem Health: Cancer cles are the male sex organs that produce sperm and the hormone testosterone. The testicles are located in the scrotum. Nearby lymph nodes may also be removed at the time of orchiectomy. Artificial testicles may be placed at the time of surgery or in a later reconstructive procedure. Radiation therapy and chemotherapy for treatment of testicular cancer may follow orchiectomy. Orchiectomy may be the only treatment needed to cure early-stage testicular cancer. A radical or inguinal orchiectomy includes removing one or both testicles and the spermatic cord. The spermatic cord is removed to prevent the cancer from spreading to the lymph nodes and the kidneys. An inguinal orchiectomy involves removing the testicles through an incision in the groin area, rather than directly through the scrotum. Orchiectomy may be used to remove both testicles in men with prostate cancer. The growth of prostate cancer cells requires testosterone, and removing the testicles eliminates the source of this hormone. Without testosterone, the prostate tumor decreases in size, and symptoms are relieved. Orchiectomy does not cure prostate cancer, but it can help prolong the lives of men with advanced prostate cancer. Patient preparation: Patients having both testicles removed will not be able to father children after orchiectomy. Patients with one testicle should be able to do so. Patients can choose to bank their sperm in case they wish to father children in the future. It is recommended that men with one testicle consider sperm banking as a precaution in case the second testicle needs to be removed in the future. Orchiectomy can be an outpatient or inpatient procedure. It can be performed at an outpatient surgical center, urology clinic, or hospital surgery department. General anesthesia is most frequently used, in which the patient is not awake. Epidural anesthesia may be used, in which the patient is awake but does not feel anything from the waist down. Prior to surgery, the patient receives standard blood and urine tests. The patient is advised not to take bloodthinning medications in the two days before the surgery and should not eat or drink for eight hours before the procedure. The patient uses a special antibacterial soap to wash his genitals and groin before surgery. Orchiectomy takes about forty-five minutes to an hour. Steps of the procedure: The patient lies on his back on the surgical table. The patient is anesthetized, and vital signs are monitored throughout the surgery. The surgeon makes a 3- to 4-inch incision in the lower abdomen. The surgeon moves the testicles up through the inguinal canal and out through the incision. After removal of the testicles and
Salem Health: Cancer spermatic cord is complete, the area is closed with sutures and bandaged. After the procedure: The patient is observed in a recovery area until he is alert. He may stay overnight in the hospital or have another person drive him home. The patient receives medication for mild to moderate pain. Bed rest is recommended for a day. The patient should wear a jock support or support briefs for two to three days and should not participate in strenuous activities for two to four weeks. Pain may be experienced in the abdomen or scrotum for several weeks. The patient should contact his doctor if he experiences increased pain, bleeding, or signs of infection. Risks: Orchiectomy is considered a low-risk procedure. The risks include infection, bleeding, abscess formation, nerve injury, bladder damage, and the general risks associated with anesthesia. Removing both testicles causes changes in testosterone levels that increase the risk of hot flashes, erectile dysfunction, loss of sexual interest, loss of muscle mass, gynecomastia (enlarged breasts), and osteoporosis.
Organ transplantation and cancer Pectasides, D., D. Farmakis, and M. Pectasides. “The Management of Stage I Nonseminomatous Testicular Germ Cell Tumors.” Oncology 71, nos. 3/4 (July 17, 2007): 151-158. Sheinfeld, Joel. Testicular Cancer: An Issue of Urologic Clinics. Philadelphia: Saunders, 2007. Sokoloff, M. H., G. F. Joyce, and M. Wise. “Urologic Diseases in America Project: Testis Cancer.” Journal of Urology 177, no. (June, 2007): 2030-2041. u
Other Resources
American Cancer Society http://www.cancer.org See also Cryptorchidism; Prostate cancer; Sertoli cell tumors; Testicular cancer.
u Organ transplantation and
cancer Category: Diseases, symptoms, and conditions
Results: Removing a cancerous testicle cures the cancer in the testicle. In the case of prostate cancer, removing the testicles prevents the cancer cells from using testosterone and slows the growth of the cancer while reducing symptoms. Mary Car-Blanchard, O.T.D., B.S.O.T. u
For Further Information Bohle, A. “Long-Term Followup of a Randomized Study of Locally Advanced Prostate Cancer Treated with Combined Orchiectomy and External Radiotherapy Versus Radiotherapy Alone.” International Brazillian Journal of Urology 32, no. 6 (November/December, 2006): 739. Cheung, W. Y., et al. “Appropriateness of Testicular Cancer Management: A Population-Based Cohort Study.” Canadian Journal of Urology 14, no. 3 (June, 2007): 3542-3550. Mikkola, A., et al. “Ten-Year Survival and Cardiovascular Mortality in Patients with Advanced Prostate Cancer Primarily Treated by Intramuscular Polyestradiol Phosphate or Orchiectomy.” Prostate 67, no. 4 (March 1, 2007): 447-455. Ondrus, D., et al. “Nonseminomatous Germ Cell Testicular Tumors Clinical Stage I: Differentiated Therapeutic Approach in Comparison with Therapeutic Approach Using Surveillance Strategy Only.” Neoplasma 54, no. 5 (2007): 437-442.
Related conditions: Immune suppression, Kaposi sarcoma, nonmelanoma skin cancer, lymphoma Definition: When organs are transplanted, there is a potential to mechanically transmit diseases from the donor to the patient. Infections, malignant conditions, and autoimmune diseases are examples of easily transmittable conditions. Patients who receive transplanted organs must use long-term immunosuppressive therapy, drugs used to prevent organ rejection by suppressing the immune function of the body. If the immune system is weakened, the chance of developing cancer increases. Cancer risk is high for patients on dialysis for end-stage renal disease, often a precursor to kidney transplant. Risk factors: Those having undergone organ transplantation are at risk for developing cancers. Etiology and the disease process: An organ such as a liver, lung, or kidney can contain malignant cells or a tumor at the time of transplantation into a patient. Coupled with immunosuppressive therapy, which weakens the immune system, a cancer transplanted with an organ is generally aggressive and difficult to manage. As organs are more difficult to locate for transplant, older donors and donors with health issues may be used, increasing the risk for cancer transmission from a transplanted organ to the patient. Although the immune system is most effective at fight899
Organ transplantation and cancer ing infection, it does protect against cancer to a lesser degree by recognizing cells that are abnormal and attempting to control them. When the immune system is suppressed by drugs to prevent organ rejection, the body loses its ability to fight infection and abnormal cells. Cancers with a viral etiology are most encouraged by immunosuppressive therapy. Kaposi sarcoma, tumors just under the skin, may be transmitted by organ donation from donors infected with human herpesvirus 8 (HHV-8) but also may develop in patients with a preexisting infection when the immune system cannot help the body fight the infection. Lymphoma is most likely to occur in the first year after transplant or when treatment for organ rejection is started. The most common cancer in transplant patients is skin cancer. Cancer usually occurs in the first few years following a transplant. Incidence: The incidence of developing cancer after transplant is 1 to 2 percent higher than it is in the normal population, and there is a fifteen- to twentyfold higher incidence of some cancers. Patients on immunosuppressive therapy have a much greater risk of developing cancer than the normal population. The cumulative probability for cancer after transplant is approximately 15 percent. Nonmelanoma skin cancers account for 90 percent of skin cancers in transplant patients, and skin cancer in the transplant group has a rate 100 times higher than that of the normal population. In a study by the United Network for Organ Sharing, malignancies caused 26 percent of deaths in kidney patients surviving at least ten years. Liver recipients had a 24 percent death rate from cancer at one year after transplant, and 21 percent of deaths in cardiac recipients in the first two years were from cancer. Kaposi sarcoma develops in organ recipients at a rate 500 times that of the normal population. Breast, colorectal, and cervical cancer risks are also increased after transplant. Symptoms: Symptoms depend on the cancer type that develops after transplantation. Skin cancers may be visible on the surface of the skin. Screening and diagnosis: Transplant patients need to receive routine screenings for cancer according to recommended cancer screening guidelines and have routine physician visits as part of follow-up care. Patients should inspect their skin monthly for any changes that could indicate skin cancer. An annual examination by a dermatologist is recommended. There is discussion that better screening of donors before organ donation should be a priority to prevent cancer transmission from affected organs. When symptoms present, diagnosis may include radiology tests, laboratory tests, and physical examination. Staging de900
Salem Health: Cancer pends on the cancer diagnosed and the status of the tumor, lymph nodes, and presence or absence of metastasis at diagnosis. Treatment and therapy: Careful dosing of immunosuppressive therapy to prevent organ rejection without totally depressing the immune system is critical. Some cancers may respond to changing the drugs and doses used in immunosuppressive therapy. If cancer is diagnosed, the treatments depend on the disease but generally include chemotherapy, radiation, and surgery. Prognosis, prevention, and outcomes: The prognosis for patients developing cancer after transplant varies by the type of cancer. Patients should avoid sun exposure because of the high risk of skin cancer. Screening patients and donors carefully before transplant may prevent some cancers. Lower doses of immunosuppressive therapy may contribute to preventing cancer. There are newer types of immunosuppressive drugs that may decrease the incidence of cancer, including one that reverses the presence of skin cancers. Approximately one-third of all organ transplant patients die from cancer. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Kauffman, H. M., et al. “Deceased Donors with a Past History of Malignancy: An Organ Procurement and Transplantation Network/United Network for Organ Sharing Update.” Transplantation 84, no. 2 (July 27, 2007): 272-274. Niederwieser, D., et al. “Transmission of Donor Illness by Stem Cell Transplantation: Should Screening Be Different in Older Donors?” Bone Marrow Transplant 34, no. 8 (October, 2004): 657-665. Serraino, D., et al. “Risk of Cancer Following Immunosuppression in Organ Transplant Recipients and in HIV-Positive Individuals in Southern Europe.” European Journal of Cancer 43, no. 14 (September, 2007): 2117-2123. u
Other Resources
National Cancer Institute http://www.cancer.gov National Marrow Donor Program http://www.marrow.org United Network for Organ Sharing http://www.unos.org/qa.asp See also Azathioprine; Blood cancers; Bone marrow transplantation (BMT); Childhood cancers; Colony-stimulating
Salem Health: Cancer
Organochlorines (OCs)
factors (CSFs); Cyclosporin A; Denys-Drash syndrome and cancer; Graft-versus-host disease (GVHD); Stem cell transplantation; Umbilical cord blood transplantation.
which are chemically stable and viscous, with low volatility. From agriculture to office buildings, automobiles, and homes, PCBs have caused widespread contamination. Major environmental sources of PCBs include manufacturing wastes, careless waste disposal, and dumping.
u Organochlorines (OCs)
Related cancers: Liver and testicular cancer
Category: Carcinogens and suspected carcinogens Also known as: Environmental, occupational, developmental, neuro-, and reproductive toxicants Definition: Chlorination of hydrocarbons produces organochlorines, which are chemically stable, fatty, and toxic. OCs accumulate in fat and thus are transported via the food chain to top carnivores, including fish, birds, mammals, and humans. OCs are common contaminants of food, air, water, soil, and breast milk. They comprise diverse subgroups, members of which cause various types of health effects ranging from acutely fatal to chronically toxic over generations. Many OCs cause liver hypertrophy and cancer; neurotoxic, embryotoxic, reproductive, developmental, and immunotoxic effects; and various types of cancers in the pubescent children of exposed mothers. OCs are produced by the chlorination of some of the petroleum hydrocarbons and can remain in the environment decades after being introduced. They are used in insecticides, fungicides, herbicides, miticides, polychlorinated biphenyls (PCBs), flame retardants, metal cleaners, drycleaning solvents, polyvinyl chloride (PVC) and other plastics, paints, dyes, synthetic intermediates, refrigerants, rayon and cellulose manufacturing, detergents, degreasers, disinfectants, halothanes, soft PVC surgical equipment, medicines—some eleven thousand common products contain them or use them in the manufacturing process. The manufacture, use, and disposal of OCs create environmental and health problems. For example, for only one polymer, PVC, the downstream export of products from its synthesis amounts to 1,229 million metric tons. In another example, pulp and paper industries in North America produce 100 million tons of OCs. The waste by-products that pose the most serious health and ecosystem risks of the manufacturing process include PCBs, polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated diphenyl ethers (PCDEs). Other notorious OCs include the pesticides dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE), cyclodiene insecticides, Mirex, hexachlorobenzene, hexachlorocyclohexanes, and various solvents. PCBs are mixtures of various congeners and isomers,
Exposure routes: Food, air, water, mother’s milk Where found: Air, water, food, breast milk At risk: Those at highest risk for cancers associated with organochlorines (OCs) include embryos, fetuses, suckling newborns, and adults who are occupationally exposed to or living in the vicinity of the sources of release. Etiology and symptoms of associated cancers: Organochlorines constitute one of the most diverse groups of cancer-causing chemicals considering their volume, categories of use, and persistence. OCs exert both specific and broad-spectrum effects. Out of all known effects, dioxinlike effects are the most serious cause of public concern: estrogenic effect leading to breast cancer; testosterone degradation leading to male infertility; nervous system damage leading to neurobehavioral deficits in offspring of mothers exposed to OCs; immunosuppression issues; development problems (lower birth weights, shorter gestation, birth defects); and occurrence of other types of cancers. Both U.S. and European farmworkers exposed to OC pesticides have a six-times higher risk of getting testicular cancer. Many workers involved in the manufacture of 2,6-di-tert-butyl-p-cresol (DBPC; commonly used as a food preservative) have high OC concentrations in their bodies, low sperm count, and no children. Twenty-two OCs are endocrine disruptors, mimic estrogens (xenoestrogens), and induce an enzyme that degrades testosterone. An estimated 220 million pounds of farm pesticides per year in the United States act as xenoestrogens, which can also lead to breast cancer and other hormonal effects. In the United States, DDE residues in women’s fat can be transferred to the fetus or to a baby through breast milk and cause testicular cancer in their sons. OC effects are elevated in the womb and just after birth due to fat mobilization. Nursing infants get 4 to 12 percent of their lifetime’s dioxin exposure via the intake of breast milk. The stunning rise in breast cancer since the 1950’s has been suspected to be related to only a few OCs. DDE, PCBs, and DDT are suspected of being involved in human breast cancer and are found in the fat and serum of women with breast cancer. In Copenhagen the risk of breast cancer appeared to be twice as high and aggressive in women with 901
Orthopedic surgery the highest serum concentration as compared with those with the lowest concentration of dieldrin. DDT is regarded as a possible human carcinogen, while PCBs are labeled as probable human carcinogens. PCB-180 and DDE may also be linked to non-Hodgkin lymphoma. History: Organochlorines do occur, although very rarely, in nature, and are usually associated the high-temperature events such as forest fires and volcanoes. The use and manufacture of OCs by people started in the late 1800’s. They were heavily introduced into the environment with the beginning of widespread use of pesticides, particularly DDT, in 1939. Several billion tons of OCs have been used since World War II, and their residues are present in both humans and the environment. Rachel Carson’s 1962 best seller Silent Spring sounded the alarm for the general public about the dangers of pesticides in the environment. Production and usage of OC pesticides started declining in the 1970’s, and those suspected to be carcinogens were banned in the United States and later throughout much of the world, although some countries continued to use them. Millions of tons of OCs per year were still being produced in the early twenty-first century. Organochlorine residues remain in the environment (air, water, land) and thus in human food and breast milk for decades. Residues of pesticides banned in the 1970’s were still present in the food supply in the early twentyfirst century. More OCs were targeted to be banned globally in the May, 2001, Stockholm Convention on Persistent Organic Pollutants; however, the George W. Bush administration did not ratify the treaty for the United States. Although many OCs have been banned over the years, others are still registered for use. M. A. Q. Khan, M.D., Ph.D., and Samreen F. Khan, M.S. u
For Further Information Colborn, T., D. Dumanoski, and J. P. Myers. Our Stolen Future. New York: Dutton Press, 1995. Khan, M. A. Q., S. F. Khan, and F. Shutari. “Ecotoxicology of Halogenated Hydrocarbons.” In Encyclopedia of Ecology. Washington, D.C.: National Council of Science and Environment, 2007. Khan, M. A. Q., and R. H. Stanton. Toxicology of Halogenated Hydrocarbons. New York: Pergamon Press, 1980. Tenenbaum, D. J. “POPS in Polar Bears: Organochlorines Affect Bone Density.” Environmenal Health Perspectives 112, no. 17 (2004): A1011. Thornton, J. Environmental Impacts of Polyvinyl Chloride 902
Salem Health: Cancer (PVC) Building Materials. Washington, D.C.: Healthy Building Network, 2002. U.S. Environmental Protection Agency. The Effects of Great Lakes Contaminants on Human Health. Report to U.S. Congress. EPA 95-R-95-107. Chicago: Author, 1995. u
Other Resources
Department of Health and Human Services Agency for Toxic Substances and Disease Registry http://www.atsdr.cdc.gov International Agency for Research on Cancer http://www.iarc.fr/index.html U.S. Department of Labor Occupational Safety and Health Administration (OSHA) Hazardous and Toxic Substances http://www.osha.gov/SLTC/ hazardoustoxicsubstances/index.html See also Dioxins; Pesticides and the food chain.
u Orthopedic surgery Category: Medical specialties Definition: Orthopedic surgery is the branch of medicine concerned with restoring and preserving the normal function of the musculoskeletal system. It focuses on bones, joints, tendons, ligaments, and muscles. Over the last half century, surgeons and investigators in the field of orthopedics have increasingly recognized the importance that engineering principles play both in understanding the normal behavior of musculoskeletal tissues and in designing implant systems to model the function of these tissues. Orthopedic surgery encompasses the entire process of caring for the surgical patient, from diagnosis to the preoperative evaluation and through the postoperative and rehabilitation period. Although the surgical procedure may be the key step in helping the patient, the preliminary and follow-up care regimens can determine whether the surgery is successful. Subspecialties: Hand surgery, shoulder and elbow surgery, total joint reconstruction (arthroplasty), pediatric orthopedics, foot and ankle surgery, spine surgery, musculoskeletal oncology, surgical sports medicine, orthopedic trauma Cancers treated: Tumors of the musculoskeletal system, soft-tissue and bone sarcomas, osteosarcoma, synovial cell sarcoma
Salem Health: Cancer Training and certification: Orthopedic surgeons must first graduate from medical school, then complete a general surgery internship and a five-year orthopedic residency program. After residency training, a certification process is initiated. The initial process is a two-step evaluation. Successful completion of a written examination qualifies the candidate to undergo an oral examination based on surgical case studies. Certification is based on the successful completion of both exams. Since 1986, the American Board of Orthopedic Surgery has issued timelimited certificates, requiring recertification every ten years. The ten-year Maintenance of Certification (MOC) process requires: • 120 orthopedic-related continuing medical education (CME) credits in each of two consecutive three-year cycles, totaling 240 credits over six years • A minimum of 20 credits of scored and recorded selfassessment examinations within the total 120 CME credits required for each three-year cycle • Completion of a cognitive examination Services and procedures performed: Orthopedics is a broad-based medical and surgical specialty. Services and procedures are based on the following: • Medical history • Physical examination: investigation of symptoms and complaints • Use of laboratory studies: biopsy, blood, and urine • Imaging diagnostics: X ray, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine • Staging and classification: of injury, fracture, metabolic condition, or tumor Treatment protocols are based on selective data. Often treatment of sarcomas requires surgical excision, limb salvage or amputation, joint reconstruction, and the concomitant use of adjuvant therapies (drugs, chemotherapy, and radiation). Rehabilitation (physical and occupational therapies) is also part of orthopedic treatment.
Otolaryngology u
For Further Information Bernstein, J., ed. Musculoskeletal Medicine. Rosemont, Ill.: American Academy of Orthopedic Surgeons, 2003. Canale, S. Terry, ed. Campbell’s Operative Orthopaedics. 9th ed. St. Louis, Mo.: Mosby, 1998. Green, W. B., ed. Netter’s Orthopedics. Philadelphia: Saunders/Elsevier, 2006. Menendez, L., ed. Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, Ill.: American Academy of Orthopedic Surgeons, 2002. Miller, M., and M. Brinker, eds. Review of Orthopedics. 4th ed. Philadelphia: W. B. Saunders, 2004. Skinner, H. B., ed. Current Orthopedics: Diagnosis and Treatment. 4th ed. New York: Lange Medical Books/ McGraw-Hill, 2006. Weinstein, S. L., and J. A. Buckwalter, eds. Turek’s Orthopaedics: Principles and Their Application. Philadelphia: Lippincott Williams & Wilkins, 2005. Wold, L. E., C. Adler, F. Sim, and K. Unni, eds. Atlas of Orthopedic Pathology. 2d ed. Philadelphia: Saunders, 2003. u
Organizations and Professional Societies
American Academy of Orthopedic Surgeons (AAOS) http://www.aaos.org 6300 North River Road Rosemont, IL 60018 American Board of Orthopedic Surgery (ABOS) http://www.abos.org 400 Silver Cedar Court Chapel Hill, NC 27514 See also Amputation; Giant cell tumors (GCTs); Hematologic oncology; Limb salvage; Liposarcomas; Medical oncology; Pediatric oncology and hematology.
u Otolaryngology Related specialties and subspecialties: Orthopedics, which is dedicated to the prevention, evaluation, and treatment of diseases and injuries of the musculoskeletal system, has become subdivided into several subspecialties: trauma, sports medicine, spine, oncology (specialized treatment of benign and malignant tumors of bones, joints, and muscles), adult reconstructive surgery, foot and ankle, hand and microsurgery, pediatrics, and musculoskeletal rehabilitation (gait, amputation, prosthetics, and orthotics). John L. Zeller, M.D., Ph.D.
Category: Medical specialties Also known as: Otolaryngology-head and neck surgery; otorhinolaryngology; ear, nose, and throat medicine Definition: Otolaryngology is the study, diagnosis, and treatment of disorders of the ear, nose, throat, and other structures of the head and neck. To emphasize the discipline’s focus on surgery, the American Academy of Otolaryngology voted to change the specialty’s name to otolaryngology-head and neck surgery in 1980. 903
Otolaryngology Subspecialties: Head and neck diseases, including treatment of tumors; facial plastic and reconstructive surgery; otology/neurotology (ear); rhinology (nose); laryngology (throat); allergy; pediatrics; sleep Cancers treated: Any cancer occurring in the head or region of the neck above the collarbone (but not the brain or eye), including the thyroid, voice box, throat, mouth, tongue, lymph nodes, bones, nerves, and base of the skull Training and certification: Otolaryngologists must complete at least five years of specialty training beyond medical school in an accredited residency program. Residency training involves one to two years of general surgery followed by four years of otolaryngology. After completing five years of residency training, doctors are eligible to become board certified in otolaryngology-head and neck surgery by passing examinations administered by the American Board of Medical Specialties or the Royal College of Physicians and Surgeons of Canada. Many otolaryngologists go on to complete one- or two-year fellowships after their residencies to become certified in an otolaryngology subspecialty. For example, some otolaryngologists may focus on head and neck surgery and treat patients with a variety of different kinds of cancers; others may focus entirely on diseases of the larynx. During their training, otolaryngologists learn general surgical techniques and gain experience performing surgery, specifically on the head and neck. They also learn diagnostic techniques for the throat and airway such as laryngoscopy, bronchoscopy, and esophagoscopy, as well as how to interpret results of magnetic resonance imaging (MRI), computed tomography (CT), and other scanning methods. Otolaryngologists must also be knowledgeable about radiotherapy and chemotherapy because these treatments may be used to treat cancer either in conjunction with or instead of surgery. Depending on their subspecialties, otolaryngologists must renew their certifications every few years. Otolaryngologists may obtain additional certification in other specialties that may be relevant to their particular area of expertise. For example, an otolaryngologist who focuses on treating cancer may also be board certified in pathology or radiation oncology. Services and procedures performed: Otolaryngologists often receive referrals from other physicians if a patient is having ear, nose, throat, or airway symptoms. Therefore, otolaryngologists are often the ones who make the initial diagnosis of cancer. They will perform and interpret tests that stage the tumor and extent of its spread. Because otolaryngologists are trained in both medicine and surgery, 904
Salem Health: Cancer patients with head or neck cancer do not need to be referred to another physician for treatment, as is often the case for other cancers. The overall goal for the otolaryngologist in treating cancer is to remove or control the cancer while also preserving to the extent possible a patient’s ability to swallow, breathe, eat, taste, smell, and hear. Because cancers of the head and neck may also involve the respiratory or digestive system, major nerves, the brain, or the eyes, otolaryngologists will often work with other specialists such as gastroenterologists, pulmonologists, ophthalmologists, radiation oncologists, and neurosurgeons in developing the best treatment plan for the patient. Otolaryngologists can often treat early-stage cancers with radiotherapy or chemotherapy alone. Late-stage cancers typically require surgery, sometimes extensive, in addition to radiotherapy or chemotherapy. Because disfigurement due to tissue loss can occur with head and neck cancer treatments, many head and neck surgeons are also skilled in performing reconstructive or cosmetic plastic surgery. Otolaryngologists are also increasingly employing minimally invasive surgical techniques such as laser endoscopy to excise tumors. Minimally invasive methods not only preserve healthy tissue but also lead to shorter hospital stays and less risk of postsurgery complications. Related specialties and subspecialties: Otolaryngologists may employ advanced practice nurses in the care of their patients. These are registered nurses who have obtained a master’s degree in nursing. Some nurses obtain board certification in otolaryngolic nursing by passing an examination administered by the Society of Otolaryngology-Head and Neck Nurses. Because the treatment of head and neck cancers can significantly impair a patient’s ability to breathe, speak, or swallow, a speech pathologist may also be involved in a patient’s care. In particular, speech pathologists work with patients who have lost their vocal cords to cancer and must learn alternative methods of voicing. The major effects head and neck cancer can have on a patient’s physical appearance and lifestyle can often cause anxiety and depression. A patient’s care team may therefore also include a social worker or psychologist who can help the patient cope emotionally with the cancer and the effects of treatment. Pamela S. Cooper, Ph.D. u
For Further Information Corbridge, Roger, and Nicholas Steventon. Oxford Handbook of ENT and Head and Neck Surgery. New York: Oxford University Press, 2006.
Salem Health: Cancer Spiegel, Jeffrey H., and Scharukh Jalisi, eds. “Contemporary Diagnosis and Management of Head and Neck Cancer.” Otolaryngolic Clinics of North America 30, no. 1 (2005). Ward, Elizabeth C., and Corina J. van As-Brooks. Head and Neck Cancer: Treatment, Rehabilitation, and Outcomes. San Diego: Plural, 2007. u
Organizations and Professional Societies
American Academy of Otolaryngology-Head and Neck Surgery http://www.entnet.org One Prince Street Alexandria, VA 22314 American Board of Otolaryngology http://www.aboto.org 5615 Kirby Drive, Suite 600 Houston, TX 77005 American Head and Neck Society http://www.headandneckcancer.org 11300 West Olympic Boulevard, Suite 600 Los Angeles, CA 90064 American Society of Head and Neck Radiology http://www.ashnr.org 2210 Midwest Road, Suite 207 Oak Brook, IL 60523 u
Other Resources
National Cancer Institute Head and Neck Cancers http://www.cancer.gov/cancertopics/types/ head-and-neck Support for People with Oral and Head and Neck Cancer http://www.spohnc.org See also Acoustic neuromas; Laryngeal nerve palsy; Oral and maxillofacial surgery; Oral and oropharyngeal cancers; Throat cancer.
u Ovarian cancers Category: Diseases, symptoms, and conditions Also known as: Cancer of the ovaries Related conditions: Abdominal cancer, colon cancer, cancer of the diaphragm, lymphatic cancer, peritoneal cancer, stomach cancer
Ovarian cancers Definition: Ovarian cancers result from the development of a malignant tumor in the ovaries and can be divided into three main types. The most common is epithelial ovarian cancer, which originates in the surface cells of an ovary. The second type, germ-cell ovarian cancer, starts in the interior cells of an ovary, where eggs are produced. A third main type, stomal ovarian cancer, begins in the connective tissue cells that hold an ovary together and generate the female hormones estrogen and progesterone. Risk factors: One of the most important risk factors involved in the development of ovarian cancers is inherited gene mutations. Inheritance of mutated breast cancer genes, BRCA1 and BRCA2, is responsible for up to 10 percent of all ovarian cancers. Other factors include having had breast or colon cancer, having a family history of ovarian cancer, not having given birth, taking fertility drugs, and using hormone replacement therapy after menopause. Age is an important risk factor. More than half of the deaths caused by ovarian cancer occur in women between the ages of fifty-five and seventy-four. Etiology and the disease process: The exact cause of ovarian cancers is still unknown. Some specialists have suggested that ovarian cancer in younger women is related to the tissue-repair process subsequent to ovulation. The formation and division of new cells at the site where an egg is released through a small tear in the ovarian follicle may produce genetic errors. Other specialists believe that the origin of ovarian cancers in younger women is related to the production of abnormal cells associated with the increased hormone levels that occur before and after ovulation. Ovarian cancers are classified according to the histology of the tumor. Between 85 and 90 percent of ovarian cancers are epithelial ovarian cancers, which are classified by cell type and graded from 1 to 3. About 5 percent of ovarian cancers are germ-cell tumors, which develop in the egg-producing cells of the ovary and generally occur in younger women. Another type of ovarian cancer develops in the stomal cells, the tissue that holds the ovary together. Ovarian cancer cells metastasize by spreading into the naturally occurring fluids in the abdominal cavity. These cells frequently become implanted in other peritoneal structures, particularly the uterus, the intestines, the omentum, and the urinary bladder. New tumor growths often occur in these areas. In rare instances, ovarian cancer cells spread through the bloodstream or lymphatic system to other parts of the body. Incidence: Ovarian cancer is the fifth leading cause of cancer-related death in women. Each year, more than 905
Ovarian cancers 20,000 women in the United States are diagnosed with ovarian cancers and about 15,000 succumb to the disease. Ovarian cancers are most common in industrialized nations. In the United States, a woman has a 1.4 to 2.5 percent chance of developing ovarian cancer in her lifetime. Symptoms: In the majority of cases, ovarian cancer produces no symptoms or only mild symptoms until it progresses to an advanced stage. Symptoms include general abdominal discomfort, such as bloating, cramps, pressure, and swelling; nausea, diarrhea, or constipation; frequent urination; loss of appetite or feeling bloated after a light meal; and the loss or gain of weight for no apparent reason. Other symptoms can include fatigue, back pain, pain during sexual intercourse, abnormal bleeding from the vagina, menstrual irregularities, shortness of breath, and fluid around the lungs. Screening and diagnosis: A medical doctor first evaluates a patient’s medical and family history, then performs, a thorough physical examination of the pelvic region. The
Salem Health: Cancer presence of any abnormal growths should be further investigated using ultrasound imaging and computed tomography (CT) scans. Ultrasound can detect the difference between healthy tissues, fluid-filled cysts, and tumors. CT scans produce detailed cross-sectional images of regions within the body. In some cases, X rays of the colon and rectum following a barium enema help identify the presence of ovarian cancers. The level of cancer antigen 125 (CA 125) should be assessed with a blood test; however, this marker identifies only about 10 percent of early ovarian cancers. The amount of four other cancer-related proteins in the blood shows some promise for diagnosing ovarian cancers. A biopsy must be performed for a definitive diagnosis of ovarian cancer. Biopsies are usually done on tumors removed during surgery, although sometimes they are done during a laparoscopy or using a needle guided by ultrasound or CT scans. If ovarian cancer is present, the stage of the disease is assessed. Staging for ovarian cancer is as follows: • Stage I: The cancer is limited to one or both ovaries.
A normal ovary (top) and a cancerous ovary. (©Carol and Mike Werner/Phototake—All rights reserved)
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Ovarian cancers
Stage at Diagnosis and Five-Year Relative Survival Rates for Ovarian Cancer, 1996-2004 Stage a
Localized Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
19 7 68 7
92.4 71.4 29.8 24.8
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
• Stage II: The cancer has extended into the pelvic region, such as the uterus or Fallopian tubes. • Stage III: The cancer has spread outside the pelvis or is limited to the pelvic region but is present in the small intestine, lymph nodes, or omentum. • Stage IV: The cancer has metastasized to the liver or tissues outside of the peritoneal cavity. These stages are further broken down into levels of seriousness from A to C. Treatment and therapy: Depending on the stage of ovarian cancer, surgery is often performed to remove the ovaries, uterine tubes, uterus, omentum, and associated lymph nodes. This process is referred to as surgical debulking. The stage of the disease determines whether additional therapy is needed. Typically, chemotherapy is employed, and if the cancer is localized, radiation therapy is sometimes used. The most effective chemotherapy drugs used in treating ovarian cancers are carboplatin and paclitaxel (Taxol), administered intravenously. The combination reduces cell division in ovarian tumors. Intraperitoneal therapy, or pumping chemotherapy drugs directly into a patient’s abdomen, extends the lives of ovarian cancer victims by an additional year or more; however, it can cause side effects such as stomach pain, numbness in the extremities, and possible infection. In January, 2006, the National Cancer Institute recommended an individualized combination of intravenous and intraperitoneal therapy for ovarian cancer patients. New chemotherapy drugs, vaccines, gene therapy, and immunotherapy treatments are being explored as options for treating ovarian cancers.
Prognosis, prevention, and outcomes: More than 60 percent of ovarian cancer patients are in Stage III or IV at the time of diagnosis, so the prognosis is not promising. The five-year survival rate for all stages of epithelial ovarian cancer is only 35 to 38 percent. With early diagnosis, aggressive surgery, and chemotherapy, the five-year survival rate is above 90 percent and the long-term survival rate approaches 70 percent. For germ-cell ovarian cancer, the prognosis is better than for epithelial ovarian cancer. Eating well, exercising, and properly managing stress help produce good overall health and reduce the risk of developing ovarian cancers. Measures that help prevent ovarian cancer include having children and breast-feeding them, using oral contraceptives (30 percent reduction), and having a tubal ligation. For women who have a high risk of developing ovarian cancers, removal of the ovaries may be the best prevention. Alvin K. Benson, Ph.D. u
For Further Information Bardos, A. P., ed. Trends in Ovarian Cancer Research. Hauppauge, N.Y.: Nova Science, 2004. Bartlett, John M. S. Ovarian Cancer: Methods and Protocols. Totowa, N.J.: Humana Press, 2000. Conner, Kristine, and Lauren Langford. Ovarian Cancer: Your Guide to Taking Control. Sebastopol, Calif.: O’Reilly, 2003. Dizon, Don S. One Hundred Questions and Answers About Ovarian Cancer. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2006. Icon Health. Ovarian Cancer: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Nathan, David G. The Cancer Treatment Revolution: How Smart Drugs and Other New Therapies Are Renewing Our Hope and Changing the Face of Medicine. New York: Wiley, 2007.
u
Other Resources
American Cancer Society Detailed Guide: Ovarian Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=33 MayoClinic.com Ovarian Cancer http://www.mayoclinic.com/health/ovarian-cancer/ DS00293 National Institutes of Health http://www.cancer.gov/cancertopics/types/ovarian/ 907
Ovarian cysts Ovarian Cancer National Alliance http://www.ovariancancer.org/ See also Cervical cancer; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Gynecologic cancers; Ovarian cysts; Ovarian epithelial cancer; Uterine cancer; Vaginal cancer; Vulvar cancer.
u Ovarian cysts Category: Diseases, symptoms, and conditions Also known as: Functional ovarian cysts, physiologic ovarian cysts Related conditions: Ovarian cancer, uterine cancer, lymphatic cancer, peritoneal cancer Definition: Ovarian cysts are growths that develop within or on the surface of an ovary. They may consist of fluidfilled sacs, semisolid material, or solid material. Fluidfilled cysts are not likely to be cancerous. Most cysts that develop during a woman’s childbearing years are not cancerous. Risk factors: No specific risk factors have been identified. Most ovarian cysts develop as part of the ovulation process. The likelihood of an ovarian cyst causing cancer increases with the size of the growth and the age of the woman. Women over the age of fifty with ovarian cysts have a higher risk of developing ovarian cancer. Etiology and the disease process: Functional ovarian cysts, which are not disease related, commonly occur during a woman’s normal menstrual cycle. Tiny cysts develop to hold the eggs. When an egg matures, the cyst breaks open to allow the egg to move through the Fallopian tube. Typically, the cyst then dissolves. When the cyst continues to grow and does not break open to release the egg, it is termed a follicular cyst. Follicular cysts usually disappear within sixty days. If follicular cysts continue to grow inside an ovary during repeated menstrual cycles, the patient is said to have polycystic ovaries. If a cyst continues to grow after the egg is released, it is called a corpus luteum cyst. This type of cyst can grow as large as four inches in diameter and will sometimes twist the ovary, causing pelvic or abdominal pain. These cysts can also fill with blood and rupture, causing internal bleeding and intense pain. Corpus luteum cysts typically disappear within a few weeks. Other types of ovarian cysts include endometriomas, cystadenomas, and dermoid cysts. If tissue from the uterine lining grows outside the uterus, a condition known as 908
Salem Health: Cancer endometriosis, it sometimes attaches to an ovary and forms a cystic growth known as an endometrioma. These growths can be very painful during menstruation or sexual intercourse. Growths that develop from the outer epithelial cells of an ovary, known as cystadenomas, typically fill with a fluid, can become twelve inches in diameter or larger, and generate much pain by twisting the ovary. Dermoid cysts form from the germ cells that produce human eggs. They can grow rather large and produce painful twisting of an ovary. They are seldom cancerous. Incidence: Virtually all women who have menstrual periods will develop ovarian cysts of one type or another. About 20 percent of women have polycystic ovaries. Up to 60 percent of women with endometriosis have endometriomas. The vast majority of ovarian cysts are not cancerous. Symptoms: Although many women experience no symptoms associated with ovarian cysts, some signs may include abdominal pressure or pain, backache, incomplete urination, unexplained weight gain, painful menstrual periods and abnormal bleeding, pelvic pain during sexual intercourse, tender breasts, and nausea and vomiting. If sudden, severe abdominal or pelvic pain occurs, or pain accompanied by fever and vomiting develops, medical attention should be sought immediately.
Dermoid Cysts
Hairs
Hairs Tooth Eminence
Sebaceous glands
Salem Health: Cancer Screening and diagnosis: Ovarian cysts are usually found during routine pelvic exams. If a cyst is found, ultrasonic imaging is used to determine its shape, size, location, and content. To determine whether the cyst is malignant, a cancer antigen 125 (CA 125) blood test is sometimes done. For some women with ovarian cancer, this protein occurs in increased levels. Functional uterine fibroids and endometriosis can also increase the CA 125 level. CA 125 tests are recommended for patients over the age of thirty-five who have a high risk for ovarian cancer. Treatment and therapy: For women still in their childbearing years who have fluid-filled cysts, the most common approach is to wait and watch. If a cyst persists, gets larger, looks unusual, causes too much pain, or the patient goes through menopause, surgical removal may be the best option. For smaller cysts that do not look abnormal in ultrasound images, a laparoscopy may be performed. Using a small incision near the navel, a scope is used to further investigate the cyst. If nothing unusual is found, the cyst is removed. For larger, suspicious-looking cysts, a laparotomy is done. Through larger openings in the stomach, the cyst is removed and tested for cancer by the pathologist. If the cyst is malignant, the doctor will proceed to remove the affected ovary and associated uterine tissues and lymph nodes. Prognosis, prevention, and outcomes: Although ovarian cysts cannot be prevented, regular pelvic examinations are important to diagnose any problems as early as possible. Any mentrual cycle changes that are abnormal or persist should be discussed with a medical doctor. For women who frequently develop ovarian cysts, a doctor may prescribe birth control pills to reduce the risk of their formation by preventing follicle formation. In most cases, fluidfilled cysts are benign. Alvin K. Benson, Ph.D. u
For Further Information Bartlett, John M. S. Ovarian Cancer: Methods and Protocols. Totowa, N.J.: Humana Press, 2000. Conner, Kristine, and Lauren Langford. Ovarian Cancer: Your Guide to Taking Control. Sebastopol, Calif.: O’Reilly, 2003. Hammerly, Milton, and Cheryl Kimball. When the Doctor Says It’s PCOS (Polycystic Ovarian Syndrome). Beverly, Mass.: Fair Winds Press, 2003. Icon Health. Ovarian Cysts: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, Calif.: Author, 2004. Reznek, Rodney, ed. Cancer of the Ovary. Cambridge, England: Cambridge University Press, 2007.
Ovarian epithelial cancer Vliet, Elizabeth Lee. It’s My Ovaries, Stupid! 2d ed. Tucson, Ariz.: Her Place Press, 2007. u
Other Resources
American Cancer Society Detailed Guide: Ovarian Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=33 MayoClinic.com Ovarian Cancer http://www.mayoclinic.com/health/ovarian-cancer/ DS00293 National Institutes of Health http://www.cancer.gov/cancertopics/types/ovarian/ Ovarian Cancer National Alliance http://www.ovariancancer.org/ See also Amenorrhea; Antiestrogens; CA 27-29 test; CA 125 test; Cervical cancer; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Gynecologic cancers; Hysterectomy; Ovarian epithelial cancer; PeutzJeghers syndrome (PJS); Uterine cancer; Vaginal cancer; Vulvar cancer.
u Ovarian epithelial cancer Category: Diseases, symptoms, and conditions Also known as: Epithelial carcinoma Related conditions: Abdominal cancer, colon cancer, lymphatic cancer, peritoneal cancer Definition: Epithelial ovarian cancer results from the development of a malignant tumor that originates in the cells on the outer surface of an ovary. Between 85 and 90 percent of all ovarian cancers are epithelial ovarian cancers. Risk factors: A history of ovarian cancer within a family—particularly in a woman’s mother, sister, or daughter—increases the risk that a woman will develop epithelial ovarian cancer. Inherited gene mutations, specifically the mutated breast cancer genes BRCA1 and BRCA2, are responsible for 5 to 10 percent of all epithelial ovarian cancer. The risk of developing epithelial ovarian cancer is higher in women who have had breast or colon cancer and is highest among women aged fifty and older. Etiology and the disease process: The exact cause of ovarian epithelial cancer is unknown but it originates in the cells of tissue that cover an ovary. Epithelial ovarian 909
Ovarian epithelial cancer cancer cells can be readily distinguished under a microscope. These cells are differentiated and classified as serous, mucinous, endometrioid, or clear cell types. Serous epithelial cancer cells are the most common. Undifferentiated epithelial ovarian cancer cells tend to grow and spread more rapidly than the four differentiated types. Epithelial ovarian cancers are classified by cell type and graded from 1 to 3. Grade 1 cells look similar to normal tissue and are less dangerous to the patient. Grade 3 cells look quite different from normal tissue and have the worst prognosis. Epithelial ovarian cancer cells often metastasize by spreading into the abdominal cavity, where they can become implanted in the uterus, the intestines, the omentum, or the bladder. Sometimes they will metastasize to the lungs. On rare occasions, epithelial ovarian cancer cells spread into the bloodstream or lymphatic system and move to many other parts of the body. Incidence: Epithelial ovarian cancer is one of the leading causes of cancer-related deaths in women. Each year, more than 18,000 women in the United States are diagnosed with ovarian epithelial cancer and about 14,000 succumb to the disease. Symptoms: Epithelial ovarian cancer is often not detected until it has progressed to an advanced stage. Symptoms include bloating, swelling, or pain in the abdominal area and gastrointestinal problems involving nausea, diarrhea, or constipation. Screening and diagnosis: If epithelial ovarian cancer is suspected, a doctor will conduct a thorough physical examination of the pelvic region. The shape, size, and position of the uterus and ovaries are assessed. If any growths or abnormal areas are found, they will be further investigated with ultrasonic imaging and computed tomography (CT) scans. The level of cancer antigen 125 (CA 125), which is raised with ovarian cancer, is measured with a blood test. Levels of other cancer-related proteins in the blood are being evaluated for diagnosing ovarian epithelial cancer. Definitive diagnosis of epithelial ovarian cancer is made through biopsy. Usually when the tumor is removed, a sample of the tissue is analyzed and the stage of the disease is assessed. The staging of epithelial ovarian cancer is as follows: • Stage I: The cancer is limited to one or both ovaries. • Stage II: The cancer has metastasized into other parts of the pelvic region. • Stage III: The cancer has spread to areas outside of the pelvis or has extended into the small intestine or omentum. 910
Salem Health: Cancer
•
Stage IV: The cancer has metastasized outside the peritoneal cavity. Depending on the degree of seriousness, these stagings are further broken down into categories ranging from A to C. Treatment and therapy: Depending on the stage of epithelial ovarian cancer, surgery is often performed to remove the ovaries, uterus, omentum, and associated lymph nodes. After recovery, the patient typically undergoes a regimen of chemotherapy. The most effective chemotherapy drugs used in treating ovarian epithelial cancers are carboplatin and paclitaxel (Taxol), adminstered intravenously. A combination of intravenous chemotherapy and intraperitoneal therapy, the pumping of chemotherapy drugs directly into a patient’s abdomen, is recommended by the National Cancer Institute in the treatment of epithelial ovarian cancer patients.
Prognosis, prevention, and outcomes: Because epithelial ovarian cancer is not usually detected until it is in an advanced stage, the prognosis is not promising. The fiveyear survival rate for all stages of epithelial ovarian cancer is 35 to 38 percent. With early diagnosis, aggressive surgery, and chemotherapy, the five-year survival rate is above 90 percent, and the long-term survival rate approaches 70 percent. The risk of developing ovarian epithelial cancer can be reduced with a good diet, exercise, and proper management of stress. Other factors that reduce the risk are bearing children and breast-feeding them if possible. Women with a high risk of developing ovarian epithelial cancer may consider removal of the ovaries as a preventive measure. Alvin K. Benson, Ph.D. u
For Further Information Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Ovarian Epithelial Cancer. San Diego, Calif.: Icon Health, 2002. Pfragner, Roswitha, and R. Ian Freshney, eds. Culture of Human Cancer Cells. Hoboken, N.J.: Wiley-Liss, 2004. Reznek, Rodney, ed. Cancer of the Ovary. New York: Cambridge University Press, 2007.
u
Other Resources
American Cancer Society Detailed Guide: Ovarian Cancer Http://www.cancer.org/docroot/CRI/CRI_2_3x .asp?dt=33
Salem Health: Cancer MayoClinic.com Ovarian Cancer http://www.mayoclinic.com/health/ovarian-cancer/ DS00293 National Institutes of Health http://www.cancer.gov/cancertopics/types/ovarian/ Ovarian Cancer National Alliance http://www.ovariancancer.org/ See also Cervical cancer; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Gynecologic cancers; Ovarian cancers; Ovarian cysts; Uterine cancer; Vaginal cancer; Vulvar cancer.
u Overtreatment Category: Social and personal issues Definition: Overtreatment of cancer patients generally refers to the aggressive treatment of cancer in a patient whose cancer is considered extremely unlikely to spread. It can also refer to the use of an unnecessarily aggressive treatment strategy. Causes: Standard procedure is to treat anyone who has cancer in the way that is believed best to destroy the cancer. Some people, however, believe that not every person who has cancer is best served by an aggressive cancer treatment plan and that in some cases it may be in the patient’s best interest not to treat the cancer at all. A growing body of evidence suggests that it is not in the best interest of every patient to aggressively treat every cancer. Treatment of prostate and breast cancers especially has come under scrutiny. Researchers have found
Overtreatment that there are a surprising number of cases in which an autopsy has revealed a case of prostate cancer but the man had no symptoms of the cancer while alive. This type of evidence is often the basis for arguments against aggressively treating every case of cancer. Some types of cancer are very slow to grow or may never grow at all and are considered extremely unlikely to spread. Therefore, an approach of watchful waiting may be more appropriate for some individuals than an aggressive treatment plan involving surgery, chemotherapy, radiation therapy, or a combination of treatments. Side effects: Cancer treatments have many side effects that can significantly decrease people’s quality of life. These can include pain, fatigue, nausea, hair loss, appetite loss, and depression. Cancer patients should discuss with their health care team all the benefits of prompt, aggressive treatment as well as the likely side effects and the possible risks of a watchful waiting approach. The elderly: The elderly may be the group most likely to be affected by the overtreatment of cancer. If a person is of a very advanced age when a slow-growing cancer is diagnosed, it may be unrealistic to assume that the person is going to have enough benefit from treating the cancer to outweigh the negative impact on daily life from the cancer treatment being considered. Instead, it may be more beneficial for the patient to make regular appointments with a doctor to check and ensure the cancer has not grown or spread. Helen Davidson, B.A. See also Advance directives; Counseling for cancer patients and survivors; Do-not-resuscitate (DNR) order; End-of-life care; Financial issues; Home health services; Hospice care; Insurance; Living with cancer; Palliative treatment; Psychosocial aspects of cancer; Watchful waiting.
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Paget disease of bone
u Paget disease of bone Category: Diseases, symptoms, and conditions Also known as: Osteitis deformans, Paget’s disease Related conditions: Metabolic and endocrine bone diseases Definition: Paget disease of bone (osteitis deformans) is a bone disorder in which excessive bone resorption is followed by excessive bone formation. The primary disturbance is an exaggeration of activity by a cell called the osteoclast, which is responsible for removing bone in the remodeling process. Frenzied osteoclastic activity results in localized bone loss followed by a period of hectic bone formation. The osteoblast cell responds by regenerating new bone that is primitive (woven), disorganized, and weaker. The resultant effect of this cycle is a net gain in bone mass; however, the newly formed bone is structurally unsound. The disease process also results in extensive vascularity (increased number of blood vessels and blood flow) and increased fibrous connective tissue within the adjacent bone marrow space. Paget disease can produce a variety of skeletal, neuromuscular, and cardiovascular complications.
Salem Health: Cancer A mosaic pattern of bone is identifiable. The new bone is coarsely thickened but soft, porous, and lacking structural stability. These microscopic aspects make the bone vulnerable to deformation and to fracture under stress. A variety of tumors and tumor-like conditions develop in the chaotic activity associated with pagetic bone. The most dreaded complication is the development of sarcomas (bone cancers), which occurs in 5 to 10 percent of patients with severe disease. The prognosis of patients who develop secondary sarcomas is exceedingly poor, but in the absence of malignant transformation, Paget disease usually follows a relatively benign course. Incidence: Paget disease usually begins in the fifth decade of life, becomes progressively more common thereafter, and has a slight male predominance. There is a striking variation in prevalence both within certain countries and throughout the world. Paget disease is relatively common in England, France, Austria, regions of Germany, Australia, and New Zealand, affecting 5 to 11 percent of the populations in these countries. In the United States, Paget disease is estimated to occur in 1 to 3 percent of people over
Risk factors: Although the exact cause of Paget disease remains unknown, being older than forty-five years and having a family history of the disease are the only known risk factors. Of patients with Paget disease, 15 to 30 percent have a family history. Family studies suggest that a person with a first-degree relative has a seven times higher risk of developing this condition. In families with earlyonset or severe Paget disease, the risk is even greater. Etiology and the disease process: Named after the nineteenth century English surgeon Sir James Paget, Paget disease was first described in 1876 as an inflammatory condition that affects the normal biological processes of bone. The exact cause or mechanism of this disease process remains unknown. Scientists have discovered several genes that appear linked to this disorder. Other investigators believe Paget is related to a viral infection in the bone cells that may be present for many years before problems appear. As living tissue, bone is engaged in a continual process of renewal; old bone is removed and replaced by new bone. This process of remodeling is disrupted in Paget disease. In the initial, or lytic, phase, old bone starts breaking down faster because of the erratic and accelerated activity of osteoclast cells. The body responds by generating new bone at a faster than normal rate. This mixed phase is devoted to osteoblastic cell activity. In the final osteosclerotic phase, the exhausted cells become quiescent. 912
Paget disease in the spine. (Custom Medical Stock Photo)
Salem Health: Cancer the age of forty-five. Paget disease is rare before the age of twenty; the estimated incidence among individuals older than eighty is 10 percent. In contrast, Paget disease is rare in the native populations of Scandinavia, China, Japan, and Africa.
Paget disease of bone
Medications Used in Treatment of Paget Disease Pain Medications • aspirin, other nonsteroidal anti-inflammatory drugs • acetaminophen Medications That Slow the Rate of Bone Turnover • calcitonin • etidronate • alendronate • pamindronate • risedronate
Bisphosphonates (help body produce normal bone) • etidronate disodium • pamidronate disodium • alendronate sodium • tiludronate disodium • risedronate sodium
Symptoms: Paget disease affects each Antibiotic person differently. Most people with • plicamycin Paget disease have no symptoms. Initial discovery may be the result of a screening X ray for other purposes. When symptoms do occur, they may be wideSources: The Arthritis Society and National Institutes of Health spread but typically arise in the areas affected by the disease, which include bones, joints, and nerves. The most common bone sites include the spine, pelvis, • X ray: The first indication of Paget disease usually is an abnormality found on an X ray. X-ray images delineate arskull, femur (involved in up to 80 percent of cases), and eas of bone reabsorption, enlargement of bones, and bone tibia. Patients will complain of bone pain characterized as deformities. constant, aching, deep, and most severe at night. Skull involvement may produce enlargement of the head (frontal • Bone scan: In some cases, bone scans can pick up Paget disease before it is seen on an X ray. In a bone scan, radiobossing). Deafness may result from disease of the tempoactive tracers are injected into the body. The tracers are ral bone or ossicles (bones of the middle ear). Involvement preferentially taken up by areas of the bone that are metaat the base of the skull can lead to compression of the brain bolically active. Areas of pagetoid bone are seen as darker stem, resulting in symptoms of ataxia (difficulty walking), than areas of normal bone. weakness, or respiratory compromise. Compression fractures of the spine can result in spinal cord injury and spinal • Bone biopsy: Biopsy of the bone provides definitive evidence of the disease. Slides of the sectioned tissue show deformity. the classic mosaic pattern of bone. Biopsy can also be useHip and knee joints are commonly affected. The cartiful in staging the disease process. lage lining the joints near affected bones is damaged. This additional factor coupled with normal wear and tear leads to accelerated osteoarthritis, which may cause joint pain, Treatment and therapy: Asymptomatic patients may not swelling, and stiffness. need treatment. Treatment is recommended when the disEnlarged bones can compress the spinal cord or the ease is active (indicated by elevated serum levels of alkanerves exiting from the brain or spinal cord. Pain resulting line phosphatase). Treatment can help alleviate pain and from nerve compression is often more severe than bone may halt the damage done to the bones. In many cases, pain. The location of the pain caused by nerve comprestreatment can cause a remission of the disease although not sion depends on the nerve that is affected. If lumbar nerves a cure. Medications, surgery, and self-care remain the esfrom the spine are compromised, this leads to radiating sential elements in most treatment regimens. pain from the lower back and into the legs (sciatica). Nerve Drug therapy incorporates the use of nonsteroidal anticompression can result in limb weakness, pain, or paralyinflammatory medications, analgesics, and muscle relaxsis. Nerve compression has been implicated in hearing and ants that lessen pain and discomfort but do not alter the vision loss along with facial weakness and numbness. natural course of the disease. The two major pharmaceuticals employed are calcitonin (a hormone that inhibits osteoclast activity and affects extent of bone resorption, Screening and diagnosis: Diagnosis depends on the folprovides relief of acute symptom, and lowers alkaline lowing tests: phosphatase levels) and the bisphosphonates, which are • Blood test: Alkaline phosphatase is a chemical subthe most effective agents in reducing bone resorption. stance produced by bone cells that are responsible for Surgery, in rare cases, may be required to stabilize a forming new bone, and its serum level is elevated in Paget fracture or to replace a damaged joint. If Paget disease afdisease. 913
Pain management medications fects the spine or skull, decompressive surgery (removal of excess bone) is needed to reduce the pressure on the nerves, thereby restoring normal neurologic function. Prognosis, prevention, and outcomes: In most cases, Paget disease progresses slowly. The condition can be managed effectively in nearly all people and is rarely fatal. A nutritional diet, regular exercise, and maintaining a healthy weight are important aspects of any treatment protocol. Certain individuals may require a corset or brace to relieve back pain and provide support. If symptoms become severe, the use of analgesics and muscle relaxants is recommended. Medical supervision and examination are necessary since major complications of this disease can include fractures, osteoarthritis, heart failure, and cancer. John L. Zeller, M.D., Ph.D. u For Further Information Kumar, V., A. Abbas, N. Fausto, and R. Mitchels, eds. Robbins Basic Pathology. 8th ed. Philadelphia: Saunders/Elsevier, 2007. Schwamm, H. A., and C. L. Millward. Histologic Differential Diagnosis of Skeletal Lesions. New York: IgakuShoin, 1996. Singer, F. “Paget’s Disease of the Bone.” In Endocrinology, edited by L. J. DeGroot. Philadelphia: W. B. Saunders, 1995. u
Other Resources
American College of Rheumatology http://www.rheumatology.org Paget Foundation http://www.paget.org See also Bone cancers; Bone pain; Bone scan; Genetics of cancer; Nuclear medicine scan.
u Pain management medications Category: Chemotherapy and other drugs Definition: Cancer pain management is a crucial aspect of supportive care of the cancer patient and may involve medication therapy, behavioral modifications, and other lifestyle adjustments. Because pain associated with cancer results from numerous sources and manifests through multiple mechanisms, treatment options are widespread. Although pain cannot always be completely relieved, oral analgesic therapy can be successful in up to 85 percent of patients. 914
Salem Health: Cancer Cancers diagnosed or treated: Medications and other therapies that control pain symptoms are used in patients with any type of cancer; types of treatment depend on the type of pain experienced, which can be determined by the type of cancer or type of treatment (chemotherapy, radiation, surgery) used. Subclasses of this group: Numerous classes of drugs are useful in the treatment of cancer pain, including nonopioid analgesics, opioid analgesics, tricyclic antidepressants, and anticonvulsants. Delivery routes: These drugs may be administered orally in tablets, capsules, or solutions; topically as patches, creams, or intranasal sprays; rectally as suppositories; submucosally as lozenges; or intravenously, intramuscularly, or subcutaneously as injectable solutions and suspensions. The drugs may be administered in outpatient, inpatient, or drop-in clinic settings. How these drugs work: Cancer pain has historically been a cause for concern in patients and caregivers alike. The treatment of pain as a whole and in cancer patients is often poorly or inadequately managed, despite numerous available treatment options. Implementation of pain management guidelines and increased awareness of health professionals about the role of pain and the importance of pain assessment in cancer therapy, however, have improved the control of many types of cancer pain. Different types of pain require different forms of treatment. Two main types of pain include nociceptive pain— resulting from actual damage to or inflammation of a tissue or organ (visceral pain) or to bone (somatic pain)— and neuropathic pain, which results from nerve damage or compression. Any source of pain may cause acute, chronic, or breakthrough pain. Nociceptive or neuropathic pain occurring in the cancer patient may result from various sources, all with differing mechanisms. Approximately 70 percent of cancer-related pain results from the tumor itself because of invasion or compression of soft tissue, bone, or nerves. Another 20 percent results from treatments such as radiation, chemotherapy, and surgical biopsy, all of which can be associated with mucositis, neuropathy, infection, and other complications. Although many options are available to control cancer pain, pharmacologic therapy is the primary, most successful method. Other options include removal of cancer in patients whose tumor compression is the pain source; neurosurgical treatments such as epidural blocks in patients whose pain is not adequately controlled with other options; complementary therapies such as relaxation tech-
Salem Health: Cancer
Pain management medications
Common Medications for Cancer Pain Drug Class
Individual Drug Examples
Brands
Delivery Mode
Primary Pain Type Treated
Anticonvulsants
phenytoin, valproate, carbamazepine, clonazepam
Dilantin, Depakote, Tegretol, Klonopin
Oral, injectable
Neuropathic pain
Benzodiazepines
midazolam, diazepam, alprazolam
Versed, Valium, Xanax
Oral, injectable
Neuropathic pain; muscle spasm or anxiety
Corticosteroids
dexamethasone, prednisone
Decadron, Sterapred
Oral, injectable
Somatic pain from swelling; neuropathic pain
Nonopioids
acetaminophen, aspirin, NSAIDs (e.g., ibuprofen, naproxen)
Tylenol, Motrin, Anaprox
Primarily oral
Mild-to-moderate chronic pain
Opioids
oxycodone, propoxyphene, hydrocodone, morphine, hydromorphone, meperidine, fentanyl
Percocet, Darvocet, Lorcet, Duragesic, Dilaudid, MS Contin, Vicodin
Oral, injectable, transdermal, submucosal, intrarectal
Moderate-to-severe or severe chronic pain; short-acting for breakthrough pain
Tricyclic antidepressants
amitriptyline, desipramine, nortriptyline
Elavil, Norpramin, Pamelor
Oral, injectable
Neuropathic pain; depression
niques, massage, and transcutaneous electrical nerve stimulation (TENS); and psychological treatments that include behavioral or lifestyle changes and support groups. Analgesic pharmacotherapy and adjuvant medications are primarily used to control cancer pain, and 75 percent of patients experience pain severe enough to require opioid analgesia. Pain falls into many categories, which then dictate treatment options. These categories include mildto-moderate pain, moderate-to-severe pain, breakthrough pain, and neuropathic pain. Most types of pain in cancer patients are considered chronic, with only breakthrough pain being an acute situation that requires quick-acting relief. Mild-to-moderate pain may be relieved with nonopioid medications; aspirin, acetaminophen, and ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs) are the primary options. Nonopioid analgesics act primarily on the peripheral nervous system to reduce pain or inflammation at the tissue, organ, bone, or incision site. The antiinflammatory activity of NSAIDs is useful in particular for bone pain, muscle compression, and some tissue pains from swelling. Moderate-to-severe pain often requires opioid analgesic therapy. Drugs in the opioid class include oxycodone,
propoxyphene, hydrocodone, morphine, hydromorphone, meperidine, and fentanyl. Opioids work in the central nervous system by binding to pain receptors, namely mu, kappa, and/or delta, to induce analgesia. Opioids fall into three categories of activity: pure agonists (such as morphine, codeine, fentanyl, hydromorphine, oxycodone, methadone), pure antagonists (such as naloxone) used to reverse opioid toxicity but without their own analgesia, and mixed or partial agonists/antagonists (such as pentazocine, butorphanol, buprenorphine) that are used in more acute settings because of limited analgesic activity. Pure receptor agonists are primarily used for the control of chronic pain. Most opioid agonists are mu or kappa receptor-selective, although individual agents may have varying amounts of activity at the two receptor subtypes and can be synergistic with each other. Because each opioid agonist interacts uniquely and to differing degrees with mu and kappa receptors, and because patient response to each drug varies, substitutions within the class should be considered before giving up on opioid therapy when pain control is incomplete. Cancer patients often require high doses of opioids for long periods of time. Important considerations in the long915
Pain management medications
Salem Health: Cancer
term management of pain using analgesic therapy are tolerance, withdrawal, addiction, inadequate control, and breakthrough pain. Psychological dependence, or addiction, is uncommon with the appropriate use of opiates, even when doses are increased in response to tolerance. Although the mechanisms driving opiate tolerance are unclear, dosage increases usually improve tolerance of a single agent and are limited only by side effects. Although withdrawal symptoms are possible as a result of physical dependence, tapering doses in reverse often ameliorates these concerns. Adequate control is difficult because of the highly subjective nature of pain. Patients respond differently to pain and to pain medications, and they often fail to report inadequate relief because of personal concerns about dependence or addiction. Hydrocodone (Vicodin) tablets. (Custom Medical Stock Photo) Communication between health care professionals and patients, however, often that are useful for malignant, advanced pain at long-term, resolves this concern, and patients become comfortable low doses and for severe, unresponsive neuropathic pain with around-the-clock pain control. at short-term, very high doses. Steroids also have nonBreakthrough pain, or pain that occurs despite existing analgesic anti-inflammatory benefits that reduce tumorpain medications, usually requires a quick-acting, shortassociated swelling. acting secondary medication (such as immediate-release morphine tablets or submucosal fentanyl) to provide relief. Side effects: Because of the varied treatments used to conFor reasons not clearly studied or understood, opioids trol cancer pain, side effects also differ. General concerns do provide confirmed relief of peripherally mediated neuinclude breakthrough pain, medication tolerance, and withropathic pain as well. Adjuvant therapies also play a large drawal symptoms. Withdrawal symptoms vary with medirole in the treatment of specific pain situations, including cation choice and length of use but include rapid breathneuropathic pain. Common adjuvant drug classes used for ing, yawning, perspiration, agitation, increased heart rate, neuropathic pain control include tricyclic antidepressants, muscle twitching, and loss of appetite. anticonvulsants, benzodiazepines, and corticosteroids. TriNonopioid analgesics are not associated with depencyclic antidepressants (such as amitriptyline, nortriptydence, tolerance, or addiction, although all have a maxiline, and desimpramine) provide established analgesic mum analgesic dose. Select concerns with these agents effects for chronic neuropathic pain through monoamineinclude liver function damage with acetaminophen and related pain-modulating systems in addition to and often gastrointestinal disturbances or damage with aspirin and prior to the separate relief of depressive symptoms by neuNSAIDs. rotransmitter alterations. Anticonvulsants (such as pheOpioid side effects include constipation (which can nytoin, valproate, carbamazepine, and clonazepam) usube prophylactically treated with stool softeners), nausea, ally provide analgesia through the reduction of neuronal vomiting, pruritis, and sedation. Respiratory depression is excitation or abnormal discharge. Benzodiazepines (such possible in patients with decreased pulmonary function. as diazepam and midazolam) have established benefits, Many side effects can limit the potential use of a particular through psychotropic and muscle-relaxant activity, in the opiate but do not rule out the entire class, because the side treatment of neuropathic pain, and they reduce anxiety and effects (like the analgesic effects) are linked to specific mu associated muscle spasm. Finally, corticosteroids (such as and kappa receptors. For example, constipation and respiratory depression are linked to mu receptor activity. dexamethasone) provide nonselective analgesic effects 916
Salem Health: Cancer Adjuvant side effects vary drastically; overlapping toxicities are a primary concern, because adjuvant medications are often combined with each other or with opioids to provide pain relief. Nicole M. Van Hoey, Pharm.D. u For Further Information Ballantyne, J. C. “Opioid Analgesia: Perspectives on Right Use and Utility.” Pain Physician 10, no. 3 (May, 2007): 479-491. Brennan, F., D. B. Carr, and M. Cousins. “Pain Management: A Fundamental Human Right.” Anesthesia & Analgesia 105, no. 1 (July, 2007): 205-221. Burton, A. W., et al. “Chronic Pain in the Cancer Survivor: A New Frontier.” Pain Medicine 8, no. 2 (March, 2007): 189-198. Fisch, Michael J., and Allen W. Burton, eds. Cancer Pain Management. New York: McGraw-Hill, 2007. u
Other Resources
Cancer.Net http://www.cancer.net/portal/site/patient See also Acupuncture and acupressure for cancer patients; Adjuvant therapy; Antinausea medications; Bone pain; Breakthrough pain; Brief Pain Inventory (BPI); Brompton cocktail; Cordotomy; Do-not-resuscitate (DNR) order; End-of-life care; Hospice care; Medical marijuana; Nonsteroidal anti-inflammatory drugs (NSAIDs); Opioids; Palliative treatment.
u Palliative treatment Category: Chemotherapy and other drugs Definition: Palliative treatment is defined as active and compassionate care primarily directed toward symptom management and improving quality of life. It is targeted toward patients who are not candidates for curative cancer therapies. Because of the proliferation of supportive treatments that can extend life, palliative care can be lengthy, lasting for months to many years. Symptom management and control: For the cancer patient, physical symptoms and discomfort may change in nature, quality, and intensity within short, unpredictable time periods, often requiring close monitoring and therapeutic modifications at regular but nonspecific time intervals. Further, possible or actual changes in mentation, functioning, and personal control may precipitate intense
Palliative treatment emotions that are unfamiliar, unwanted, and anxiety provoking. Chronicity, remissions, and exacerbations of a variety of uncomfortable symptoms; family separation; financial strain; functional limitations; and role disruptions are but a few of the issues that characterize the lives of individuals with advanced, progressive, or incurable cancer. Even for those who experience lengthy disease-free intervals, the challenge of reducing cancer’s presence in their lives can be difficult, and assistance from multiple specialists is often needed. Common symptoms that are treated and controlled or relieved by palliative care interventions can include the following: • Pain • Difficulty breathing • Loss of appetite and weight loss • Fatigue • Weakness • Sleep problems • Depression and anxiety • Confusion Palliative treatment in context: The palliative treatment experience must be examined within the context of the health care delivery system for its potential and its pitfalls to be fully understood. Treatment advances, societal attitudes, and changes in health care structure and financing have all had a dramatic impact on the delivery of palliative care and the creation of gaps between the philosophy and delivery of palliative care services. The secrecy that prevailed in the 1960’s and prohibited disclosure of a cancer diagnosis by most physicians has given way to the practice of routinely imparting the particulars of diagnosis, treatment options, and prognosis. Despite this change, it has been observed that persistent cancer-related fears and negative attitudes among health care providers have led to a discrepancy between words and actions, resulting in communication of emotionally laden information in a fashion ranging from overprotective and paternalistic to blunt and matter of fact. Further, patients who are not candidates for curative treatment often find themselves without adequate information and resources to manage their abundant physical and psychosocial problems. Discrepancies between attitude and practice have been demonstrated by clinicians who have been found to avoid clear, open discussions of topics such as prognosis and death despite consistently expressed beliefs regarding the importance of openness and honesty with all mentally competent patients. Therefore, while the prevailing attitude in health care supports disclosure of medical information and active involvement by patients in decisions that affect them, the actual behavior of health care providers re917
Palliative treatment flects a more limited improvement in patient care. Clinician concerns and personal issues can affect communication with patients at key decision-making and transition points along the continuum of palliative care. The need for clinician support and access to resources is recognized as key in helping members of the palliative care team to assist patients fully, but there is much need for improvement and more resources in this area. Psychiatric and medical comorbidity: The time during which palliative treatment is necessary has lengthened, causing an increase in the number of cases in which patients need psychiatric care alongside medical care. This phenomenon, although largely ignored, is putting inordinate stress on patients, families, professional caregivers, and the health care system at large. Psychiatric problems tend to be treated based on whether reimbursement is provided, and reimbursement occurs only when psychiatric symptoms emerge as disease states. Insurance rarely covers psychiatric interventions targeted toward symptom management and quality-of-life enhancement, although comprehensive, low-cost interventions supported by scientific evidence of their efficacy are available. Multisystem problems are generally not addressed well by the medical system, which is fragmented and oriented toward specialty care. Because recipients of palliative cancer treatment are not candidates for curative therapies, they are faced with their own mortality and are vulnerable to intense fear and psychological distress. However, the health care system is oriented toward cure and survival, and it typically places a lower priority on treating and addressing psychosocial issues. Patients receiving palliative care are often concerned about issues such as impending death, pain or other physical discomfort that cannot be relieved, disfigurement, functional decline and increasing dependency on others, loss of mental acuity and bodily functions, and the effects of their illness on their families and friends. These patients need to be closely monitored to manage changes in symptoms and functional status and to evaluate the level of relief achieved through targeted interventions. Ethical aspects: Care providers must be mindful that the psychological vulnerability of patients receiving palliative care may put some individuals at risk for unnecessary suffering, exploitation, and victimization based on the cure-oriented values inherent in modern health care. For example, an issue that repeatedly surfaces among patients, family members, and professional care providers pertains to the use of aggressive treatment protocols in the presence of progressive, incurable disease. Patients may seek or be recruited for participation in experimental protocols even 918
Salem Health: Cancer when treatment is not expected to extend their lives. Questions of ethics and the meaning of informed consent arise in regard to the participation of terminally ill subjects in experimental protocols. Some experts question whether having a particular medical conditions or status (such as being terminally ill) diminishes full participation in the process of informed consent. The need for health care professionals to establish structured dialogue with patients, family members, and care providers regarding treatment goals and expectations is essential. Treatment planning should take into account the fact that certain individuals with a terminal illness may respond to participation in an investigational treatment with increased hope of survival, regardless of their real chances of survival. These issues, however, become even more complex as changes in health care financing prohibit reimbursement for experimental therapies. Some people will be unable to undergo experimental therapies, and others may assume the cost of aggressive yet often medically futile treatments, creating compelling ethical issues and tensions. These are weighty issues that require active dialogue and debate. The combination of rapid medical and technological advances, diminishing ability to finance rising health care costs, growing numbers of chronically ill patients living longer periods of time, and an ever widening gap between the affluent and poor is adding to the problem. Patients, their families, and health care providers need to separate and clarify personal values, thoughts, and emotional reactions to these delicate issues if individualized, quality palliative care is to be provided. Psychiatric consultation-liaison nurses, psychiatrists, social workers, and chaplains can be invaluable in assisting patients, family members, and staff to grapple with these issues in a meaningful and productive manner. Dying and terminal care: Once the terminal care period has begun, it is usually not the fact of dying, but the quality of dying, that is primary for patients and families. Palliative care that continues into the terminal stage of cancer should continue to relieve physical and psychological symptoms and promote comfort and well-being until the patient dies. Often patients and families who have received palliative services in earlier stages of the illness will be more open and accepting of palliative efforts in the final stage of life. In addition, it is important that professional and family caregivers recognize that their work is emotionally draining, and they should seek guidance and support whenever possible. Professional caregivers should target therapeutic interventions toward increasing the dying patients’ sense of
Salem Health: Cancer personal control and self-efficacy within the context of their functional decline and increased dependency. It is also therapeutic in most cases to inform patients of available resources aimed at discussing and addressing any concerns regarding death and dying. From a practical standpoint, professional caregivers may help patients by inquiring about any unfinished business, including wills and conversations with family and friends, and to provide them with the necessary support and encouragement to accomplish these final goals. Factors including personal values, socioeconomic status, cultural background, and religious beliefs can influence patients’ expectations and experiences as they approach death. For example, a stoic attitude that minimizes or negates discomfort may be related to a cultural value learned and reinforced through years of family experiences. Similarly, an extremely emotional response to routine events during the terminal phase of illness does not necessarily signal mental maladjustment but rather the person’s cultural norm. Awareness of the person’s cultural, religious, ethnic, and socioeconomic background is important in the process of understanding individual behaviors and limiting value judgments. Psychiatric complications and terminal care: Delirium, depression, suicidal ideation, and severe anxiety are among the most commonly occurring psychiatric complications encountered in terminally ill cancer patients. When severe, these problems require urgent and aggressive assessment and treatment by psychiatric personnel who can initiate pharmacologic and psychotherapeutic treatment strategies. It should be stressed that psychiatric emergencies require the same rapid intervention as medical crises. In spite of the seemingly overwhelming nature of psychosocial responses in cancer patients, most of them do indeed cope effectively, and it is important to recognize that intense emotions are not one and the same as maladaptive coping. Hospice care: Hospice care involves structured programs that offer supportive and palliative care at the end of life. The patient, family, and health care team decide when hospice care should begin, but typically patients are eligible for a hospice program when they have about six months to live. Hospice care can be home or institution based. Hospice care aims to manage physical and emotional symptoms with the overriding goal of allowing patients to live their last days with dignity and as high a quality of life as possible. Most hospice programs offer family-centered care, meaning that they involve the patient and family in decision making, which reduces distress and enhances control. A hospice team usually consists of a physician, an
Palliative treatment advanced practice nurse, a bedside nurse, nursing assistants, social workers, and chaplains. Goals of hospice treatment may include increased time of survival, symptom control, and enhanced quality of life. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u
For Further Information Barnett, Laura, ed. When Death Enters the Therapeutic Space: Existential Perspectives in Psychotherapy and Counseling. New York: Routledge, 2008. Boog, Kathryn M., and Claire Tester. A Practical Guide to Palliative Care: Finding Meaning and Purpose in Life and Death. New York: Elsevier, 2008. Jacobs, Léa K., ed. Coping with Cancer. New York: Nova Science, 2008. Kuebler, Kim, Debra E. Heidrich, and Peg Esper. Palliative and End of Life Care: Clinical Practice Guidelines. 2d ed. St. Louis: Saunders/Elsevier, 2007. Lewis, Milton J. Medicine and Care of the Dying: A Modern History. New York: Oxford University Press, 2007. Lynn, Joanne, et al. Improving Care for the End of Life: A Sourcebook for Health Care Managers and Clinicians. 2d ed. New York: Oxford University Press, 2008. Werth, James L., and Dean Blevins, eds. Decision Making Near the End of Life: Issues, Development, and Future Directions. New York: Brunner-Routledge, 2008. u
Other Resources
American Academy of Hospice and Palliative Medicine http://www.aahpm.org American Hospice Foundation http://www.americanhospice.org American Pain Society http://www.ampainsoc.org American Psychosocial Oncology Society http://www.apos-society.org Americans for Better Care of the Dying http://www.abcd-caring.org National Palliative Care Research Center http://www.npcrc.org See also Acupuncture and acupressure for cancer patients; Bone pain; Breakthrough pain; Brief Pain Inventory (BPI); Brompton cocktail; Cordotomy; Do-not-resuscitate (DNR) order; End-of-life care; Hospice care; Medical marijuana; Nonsteroidal anti-inflammatory drugs (NSAIDs); Opioids; Pain management medications. 919
Palpation
u Palpation
Salem Health: Cancer
Category: Procedures Also known as: Manual examination, feeling, probing, touching, manipulation
Risks: One advantage of palpation as a means of screening for cancer and other health care problems is that there is little risk of an adverse event to the patient. Palpation usually results in minimal and/or short-term discomfort for the patient.
Definition: Palpation is the careful manual examination of the size, shape, firmness, consistency, texture, tenderness, or location of some body part or organ. Health care professionals use palpation during a physical examination for screening and diagnostic purposes.
Results: A skillful practitioner can use palpation as an effective way to screen a patient for cancer. Immediate follow-up plans can be made for further diagnostics without waiting for the return of other test results. Marylane Wade Koch, M.S.N., R.N.
Cancers diagnosed: Cancers of the breast, prostate, uterus, ovaries, liver, abdomen, pancreas, skin, bladder, lower colon and rectum, or lymph nodes
See also Breast self-examination (BSE); Clinical breast exam (CBE); Digital rectal exam (DRE); Fibroadenomas; Gynecologic cancers; Pelvic examination; Screening for cancer; Testicular self-examination (TSE).
Why performed: Despite the technological advances in health care diagnostics, health care providers still acquire valuable information through direct interaction with the patient. By providing a physical examination, providers can screen patients for possible abnormalities. Sometimes cancer can be discovered through palpation of various body parts or organs. For example, a provider can use palpation to screen for cancers of the breast, prostate, uterus, ovaries, liver, abdomen, pancreas, skin, bladder, lower colon and rectum, or lymph nodes. A woman can use palpation in her monthly breast examination to detect lumps or thickening tissue that could indicate cancer. Palpation is a noninvasive procedure that is less costly than procedures involving technology and can be a highly reliable initial step. When an abnormality is discovered, further diagnostics are performed to diagnose the cancer and determine treatment alternatives. Patient preparation: Patient preparation depends on the type of palpation procedure. The patient should receive a thorough explanation of what is involved in the examination. Any anticipated discomfort should be disclosed to the patient, and any patient questions should be answered prior to the examination. Successful physical palpation depends of the skill of the provider and a thorough preparation of the patient. Steps of procedure: The steps of the procedure depend on the area palpated during the physical examination. After the procedure: The patient should be informed of any possible discomfort, tenderness, or soreness that may occur after the examination, which is generally minimal with palpation. Though palpation does not provide a definitive diagnosis, the practitioner can provide immediate feedback to the patient about cancer possibilities and make plans for further tests. 920
u Pancolitis Category: Diseases, symptoms, and conditions Also known as: Universal colitis Related conditions: Inflammatory bowel diseases, various types of colitis Definition: Pancolitis is inflammation of the entire large intestine. Risk factors: People with inflammatory bowel disease, with specific gastrointestinal infections, or who have had abdominal or pelvic radiation therapy or cancer, are at risk for developing pancolitis. Etiology and the disease process: For unknown reasons, the immune system sometimes attacks the digestive tract, resulting in inflammatory bowel disease (IBD). The two main types of inflammatory bowel disease are ulcerative colitis (UC) and Crohn disease (CD). In these diseases, large quantities of white blood cells migrate into the colon and repeatedly damage it. This can result in inflammation of the entire colon, or pancolitis. Other causes of pancolitis include the following: • Infections of the colon with certain microorganisms that cause community-acquired colitis • Antibiotic-related pseudomembranous colitis, which is brought on by treatments with antibiotics such as clindamycin, ampicillin, or cephalsporins that kill off the common microbial occupants of the colon and allow the growth of another microorganism (Clostridium difficile) that damages the colon • Ischemic colitis, which is caused by blockage of the blood vessels that feed the colon
Salem Health: Cancer
• Radiation colitis, whereby radiation damage blocks blood flow to the colon • Cancers that spread to the colon Incidence: The incidenc of ulcerative colitis is between 35 and 100 cases per 100,000 people, and of Crohn disease, 7 cases per 100,000 people. Between 2 and 5 percent of those who receive abdominal or pelvic radiation therapy suffer from radiation colitis.
Pancreatectomy
u Pancreatectomy Category: Procedures Also known as: Pancreatoduodenectomy, Whipple procedure, distal pancreatectomy, total pancreatectomy Definition: Pancreatectomy is a surgical procedure done to remove all or part of the pancreas. Cancers treated: Pancreatic cancer
Symptoms: The hallmarks of pancolitis are blood discharge after each bowel movement, urgency to defecate, spasm of the anal sphincter (tenesmus), abdominal pain, and rapid weight loss. Screening and diagnosis: The standard means to diagnose pancolitis is a colonoscopy, which should show continuous, inflamed, bleeding ulcers on the wall of the colon. Colon biopsies are also necessary to determine the exact cause of pancolitis. X rays or computed tomography (CT) scans in which contrast is provided by a barium enema are also used to diagnose pancolitis or its complications. Treatment and therapy: Colonic inflammation is inhibited by 5-aminosalicylic acid (5-ASA) agents such as mesalamine, sulfasalazine, and balsalazide. Other immune system inhibitors, including infliximab, azathioprine, cyclosporine, methotrexate, and 6-mercaptopurine, are used if 5-ASAs are ineffective. Steroids such as prednisone, methylprednisolone, and budesonide quell active episodes. Surgical removal of the colon (colectomy) is recommended in recalcitrant cases. Prognosis, prevention, and outcomes: Untreated pancolitis is usually fatal. Inflammatory bowel diseases are usually controlled with therapy, but patients are at increased risk for colon cancer. Colectomy cures many pancolitis cases. For Crohn disease, therapy becomes less effective with time, and surgery is required in two-thirds of patients. Michael A. Buratovich, Ph.D. See also Azathioprine; Coloanal anastomosis; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Crohn disease; Enterostomal therapy; Fecal occult blood test (FOBT); Ileostomy; Immunoelectrophoresis (IEP); Inflammatory bowel disease; Premalignancies; Risks for cancer.
Why performed: Pancreatectomy is done to remove all or part of the pancreas. This procedure may be performed when trying to cure the cancer by removing all of it, or it can be done as palliative care to reduce or prevent symptoms from cancer that has already spread to other areas. Patient preparation: The first step of patient preparation is a thorough evaluation by the cancer care team to ensure that the patient is a good candidate for a pancreatectomy. It is a very difficult procedure that usually has a long recovery time, and it is not appropriate for many individuals. The procedure is appropriate only for individuals who have cancer that is expected to be fully removable by the procedure. As few as 10 percent of individuals diagnosed with pancreatic cancer are good candidates for this surgery. In some cases, pancreatectomy may also be appropriate as a palliative treatment. Some patients receive radiation or chemotherapy before pancreatectomy. This may be done in an attempt to shrink the tumor to make complete removal more likely. It may also be done before the procedure, because the high risk of complications and long recovery time often mean that necessary additional treatments cannot begin until many weeks after the surgery. In the days before the procedure, patient preparation is generally similar to that for other major surgical operations. Patients may be instructed to avoid food or liquids for a certain amount of time before the procedure or be given antibiotics or other medications to help minimize the risk of complications. Steps of the procedure: Three main types of pancreatectomy are performed. Which one is performed depends on where the cancer is located and the extent of the cancer’s spread. If the goal is palliative, then the procedure performed will depend on the symptoms being treated or prevented. The three types of procedures differ in the amount and section of the pancreas that is removed. The most common type of procedure is known as a pancreatoduodenectomy, also called the Whipple procedure. During this procedure, the surgeon removes the head of the pancreas (the part closest to the small intestine). The 921
Pancreatectomy
Salem Health: Cancer
Surgeons remove the pancreatic head, part of the duodenum, and surrounding tissue in a Whipple procedure used to treat pancreatic cancer. (©Barry Slaven, MD, PhD/Phototake—All rights reserved)
surgeon also usually removes the duodenum, the gallbladder, and part of the bile duct. In some cases, the surgeon removes part of the stomach as well. The part of the pancreas that remains is then surgically connected to the patient’s small intestine. Another procedure in which only part of the pancreas is removed is known as a distal pancreatectomy. When performing this procedure, the surgeon removes only the tail end (the thinner end) of the pancreas. In some cases, the spleen is also surgically removed at the same time. This procedure is appropriate only when the tumor is relatively small and localized in the distal end of the pancreas. When the entire pancreas is removed, the procedure is known as a total pancreatectomy. When this is done, the surgeon takes out all of the pancreas and usually the spleen. This procedure is used when the cancer is located within the body of the pancreas. After the procedure: Pancreatectomy is a major surgical procedure and usually requires a prolonged hospital stay. Most patients remain in the hospital for two or more weeks 922
after the procedure. During this time, the patient is carefully monitored to check for complications such as infection and bleeding. If the surgery was done using an open technique, then the wound requires care and monitoring. Patients who did not receive chemotherapy or radiation therapy before the pancreatectomy generally receive it as soon as it is feasible after the surgery. If the entire pancreas, or a very large portion of the pancreas, was removed, then the patient may be given a regimen of medications to take to correct insulin and other imbalances if the pancreas no longer produces sufficient quantities for good health. Risks: There are many significant risks associated with pancreatectomy. According to the American Cancer Society, when a pancreatoduodenectomy is performed by an extremely skilled and experienced surgeon at a hospital or center where the health care team is very experienced in the procedure, 2 to 5 percent of patients die as a direct result of complications of the surgery. When the procedure is performed by a less experienced surgeon at a small hos-
Salem Health: Cancer pital that may not be prepared for possible complications, up to 15 percent of patients may die. Nonfatal complications from the procedure are very common. They can include infection, bleeding, and leakage at one of the points a surgical connection was made. Results: The results from pancreatectomy vary depending on the type of procedure performed and the extent to which the cancer has spread to other areas of the body. For patients who had cancer that is considered completely removable through the pancreatectomy, the five-year rate of survival is about 20 percent. Robert Bockstiegel, B.S. u For Further Information DeVita, Vincent T., Jr., Samuel Hellman, and Steven A. Rosenberg, eds. Cancer: Principles and Practice of Oncology—Pancreatic Cancer. Philadelphia: Lippincott Williams & Wilkins, 2006. Lowy, Andrew M., Steven D. Leach, and Philip Philip, eds. Pancreatic Cancer. New York: Springer, 2008. Riess, H., A. Goerke, and H. Oettle, eds. Pancreatic Cancer. New York: Springer, 2008. Suda, Koichi, ed. Pancreas: Pathological Practice and Research. New York: Karger, 2007. u
Other Resources
American Cancer Society http://www.cancer.org Pancreatica http://www.pancreatica.org See also Alcohol, alcoholism, and cancer; Bile duct cancer; Cholecystectomy; Endocrine cancers; Endocrinology oncology; Endoscopic retrograde cholangiopancreatography (ERCP); Gallbladder cancer; Islet cell tumors; Multiple endocrine neoplasia type 1 (MEN 1); Pancreatic cancers; Pancreatitis; Percutaneous transhepatic cholangiography (PTHC).
u Pancreatic cancers Category: Diseases, symptoms, and conditions Also known as: Adenocarcinoma of the pancreas, cystadenocarcinoma Related conditions: Acinar cell carcinoma, insulinoma, gastrinoma, glucoganoma Definition: Pancreatic cancers are malignant tumors occurring anywhere in the pancreas. The pancreas is an organ behind the stomach containing exocrine and endo-
Pancreatic cancers crine glands. The exocrine glands, where most pancreatic cancer occurs, release digestive juices, which break down fats, proteins, and carbohydrates, and neutralize stomach acids. The endocrine glands produce insulin and glycogen, hormones used by the body to metabolize, or break down, sugar to use as energy. Risk factors: Factors implicated in the development of pancreatic cancer include advanced age, diabetes, cigarette smoking, chronic pancreatitis, and a family history of the disease. Some 90 percent of those who develop pancreatic cancer are older than age fifty-five, and the average age at time of diagnosis is seventy-two. Diabetes and pancreatic cancer have been linked, but it is not clear whether diabetes is a cause or a symptom of pancreatic cancer. Research indicates that 1 percent of people diagnosed after the age of fifty with type II diabetes (in which the body does not produce adequate amounts of insulin, a hormone manufactured in the pancreas) will be diagnosed with pancreatic cancer within three years of diagnosis. This suggests that initial onset of diabetes at age fifty and older may be an early symptom of pancreatic cancer. A study in the British Journal of Cancer found that people with type I, or juvenile-onset, diabetes have twice the normal risk of developing pancreatic cancer as those without the condition. According to a study of more than four hundred women who developed gestational diabetes and were followed for a mean of thirty-eight years, those who develop gestational diabetes are at increased risk of developing pancreatic cancer years later. An estimated 25 to 30 percent of pancreatic cancer cases can be attributed to cigarette smoking. The cancercausing chemicals in cigarette smoke are thought to enter the bloodstream and damage the pancreas, creating a two to three times greater risk among smokers. The role of diet in developing pancreatic cancer is inconclusive, although diets high in fat and processed meats appear to present some increased risk, and diets high in fruit, vegetables, and fiber appear to protect against cancer. Obesity and lack of physical activity are also risk factors, as is occupational exposure to chemicals and pesticides. Long-term inflammation of the pancreas, or chronic pancreatitis, is a risk factor, but the majority of people with this condition do not develop cancer of the pancreas without the presence of other risk factors. However, having a family history of pancreatitis at a young age has been implicated in the development of pancreatic cancer years later. Individuals who have had peptic ulcer surgery with a partial gastrectomy (partial removal of the stomach) may be at increased risk of developing pancreatic cancer. 923
Pancreatic cancers
Salem Health: Cancer The Pancreas
Liver
Gallbladder
Stomach
Duodenum
Head of pancreas
Etiology and the disease process: Pancreatic cancer occurs when abnormal cells grow in pancreatic tissue. The vast majority of abnormal cells occur in the ducts carrying pancreatic juices from the exocrine glands. Although the exact cause of pancreatic cancer is not known, inherited or acquired changes in DNA are believed to be behind most cases. Many pancreatic cancers are not detected until they are locally advanced and have invaded the vascular system or have spread to lymph nodes. If the tumor blocks the common bile duct and bile cannot be released into the digestive system, the patient’s skin and whites of the eyes become jaundiced and the urine may become darker. The cancer may spread and cause pain in the upper abdomen and sometimes the back.
Incidence: Pancreatic cancer is the fourthleading cause of cancer death in the United States because it grows aggressively and causes few symptoms in the initial stages. Pancreatic duct However, it is relatively rare compared with other forms of cancer. About 30,000 new cases are diagnosed each year, as compared with 200,000 new cases of breast Helicobacter pylori infection also has been linked to pancancer and 170,000 of lung cancer. According to the creatic cancer. American Cancer Society, rates of pancreatic cancer have According to the National Familial Pancreas Tumor dropped since the 1980’s. The incidence rate of pancreatic Registry (NFPTR) at Johns Hopkins University, 5 to 10 cancer is 11.4 per 100,000 men and women, although this percent of cases of pancreatic cancer are due to familial type of cancer is more prevalent among men than women. factors. Particularly among those with two or more relaThe incidence of pancreatic cancer is 50 to 90 percent tives who have had pancreatic cancer, inherited deoxyrihigher in the African American population than in other bonucleic acid (DNA) mutations are believed to play a racial or ethnic groups in the United States, probably bepart. People of Ashkenazi Jewish descent may be at greater cause of the higher rates of obesity, poverty, cigarette risk because of the presence of an inherited mutation in the smoking, and type II diabetes in this group. breast cancer gene BRCA2 (each individual inherits two such genes, one from the mother and one from the father). Symptoms: Many people do not experience symptoms of However, the presence of one defective BRCA2 does not pancreatic cancer until the tumor has spread to the lungs, increase an individual’s risk of developing pancreatic canliver, or lymph nodes. The majority (80 percent) of pancrecer in the absence of other genetic and environmental facatic cancers occur in the head of the organ, creating symptors. toms associated with blockage of this area closest to the Further, individuals with a rare hereditary disease, bile duct. One common symptom is jaundice, a yellowing Peutz-Jeghers syndrome, in which affected family memof the skin and the whites of the eyes resulting from an acbers develop polyps from the surface of the intestine, may cumulation of bilirubin in the blood. At least half of those be at increased risk of developing pancreatic cancer. Indiwith pancreatic cancer will experience jaundice. Other symptoms include nausea and diarrhea, a swollen gallviduals with hereditary nonpolyposis colorectal cancer bladder or liver, pain in the midback, fatigue, a slow me(HNPCC) also may be at increased risk of developing cantabolism, light-colored stools, and itchy skin. cer of the pancreas. Tail of pancreas
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Salem Health: Cancer The 20 percent of pancreatic cancers occurring in the tail of the pancreas often obstruct the vein draining the spleen, resulting in an enlarged spleen and pressure in varicose veins around the stomach and esophagus. An individual may experience this as pain in the midback, pain in the stomach several hours after a meal, blood clots in the legs, and loss of appetite. Tumors or cystadenocarcinoma affecting the hormone-secreting functions of the pancreas, though rare, can produce symptoms of fatigue, dizziness, chills, diarrhea, or muscle spasms. If the pancreatic cancer occurs in the islet cells, which produce insulin and other hormones, the cells may produce too much insulin, causing the affected individual to feel dizzy and weak and to experience chills, muscle spasms, and diarrhea. This type of endocrine pancreatic cancer is considered highly treatable.
Pancreatic cancers staging, and even for detecting early-stage cancer. ERCP can be used to examine the pancreatic duct while a tissue biopsy is taken to study the cancer cells. An angiogram can be used to show any blockage or impediment of blood flow in vessels caused by the tumor or abnormality of blood vessels to assess the likelihood of removing the cancer surgically. If surgery such as a laparoscopy is performed, a biopsy may be taken to determine the location and spread of the disease. Laparoscopy is a diagnostic procedure in which an incision is made in the abdomen and a laparoscope, or lighted tube, is inserted to view the pancreas. Alternatively, the physician may choose to perform a laparotomy, a diagnostic surgical procedure in which a large incision is made to examine organs in the abdomen for extent of disease. Staging for pancreatic cancer is as follows: • Stage IA: Tumor is confined to pancreas and is no larger than 2 centimeters (cm). • Stage IB: Tumor is confined to pancreas and is larger than 2 cm. • Stage IIA: Cancer has metastasized to nearby organs and tissues but not into large blood vessels or to lymph nodes. • Stage IIB: Cancer has metastasized to nearby lymph nodes and may have spread to nearby tissues and organs but not distant sites. • Stage III: Cancer has reached blood vessels near the pancreas and may have spread to lymph nodes but not distant sites. • Stage IV: Cancer, regardless of tumor size, has metastasized to distant organs, and may also be in tissues near the pancreas or in lymph nodes. Alternatively, some physicians stage the pancreatic cancer on the basis of the likelihood that the tumor can be
Screening and diagnosis: A high blood level of cancer antigen 19-9 (CA 19-9), a product released into the blood by pancreatic cancer cells, serves as a marker indicating the presence of a pancreatic tumor. However, this marker is used only to assess response to therapy and not as a screening test. Because there is no screening test for pancreatic cancer, people should report any sudden onset of abdominal pain, loss of appetite, or unexplained weight change to their physician. If pancreatic cancer is suspected, the physician will palpate for presence of an abdominal tumor and order blood tests that will indicate changes in blood sugar or the presence of anemia. However, the pancreas is hidden behind other organs and cannot be felt during a routine physical exam. A differential diagnosis should rule out any liver-related causes of jaundice. If a pancreatic tumor is present, diagnostic tests such as ultrasound, computed tomography (CT) scans, and endoscopic retrograde cholangiopancreatography (ERCP), a type Relative Survival Rates for Pancreatic Cancer by of X ray, will be ordered to stage the Stage at Diagnosis, 1988-2003 progression of the disease. An ultrasound has been shown to be more useful Survival Rates (%) than a CT scan in detecting the presence Stage 1-Year 2-Year 3-Year 5-Year 8-Year 10-Year of small tumors. A CT scan can be used 24.5 19.5 17.4 16.8 16.6 Localizeda 40.5 to guide a needle in obtaining a biopsy. Regionalb 38.0 16.7 10.5 7.2 5.7 5.3 During a positron emission tomograDistantc 10.5 4.1 2.6 1.6 0.9 0.7 phy (PET) scan, a form of sugar that is Unstaged 20.8 9.3 6.2 4.7 4.1 3.6 readily absorbed by cancer cells is inSource: Data from National Cancer Institute, Surveillance Epidemiology and End jected into the patient’s blood to assess Results, Cancer Stat Fact Sheets, 2008 the location and spread of cancer cells. a Cancer still confined to primary site b A combination PET/CT scan has been Cancer has spread to regional lymph nodes or directly beyond the primary site c found useful in detecting the spread of Cancer has metastasized cancer that surgery cannot remove, for
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Pancreatic cancers removed surgically according to the following stages: resectable (can remove entire tumor); locally advanced, unresectable (wherein complete removal of the tumor is not possible); and metastatic (where the cancer has spread and surgery would be undertaken only to relieve symptoms or complications). Treatment and therapy: The Whipple procedure, or pancreatectomy, a major surgery with a high risk of complications, is used when it is likely that surgery will cure the individual of the entire pancreatic tumor. The head of the pancreas and parts of the stomach and small intestine, bile duct, and gallbladder are removed. After this surgery, the pancreas is still able to produce insulin and digestive juices. A total pancreatectomy involves removal of the entire pancreas, part of the stomach and small intestine, the common bile duct, and the gallbladder, spleen, and nearby lymph nodes. Palliative surgery may relieve pain and complications associated with the impact of the cancer on digestion, particularly blockage of the bile duct. When surgery cannot remove the entire tumor, during the course of an ERCP, a biliary stent is placed to relieve biliary obstruction and allow vessels to move bile. Inserting an endoscopic or percutaneous biliary stent can relieve jaundice, particularly for those with cancer in the head of the pancreas. Radiation therapy may be administered five times a week for several weeks or months before surgery, after surgery, or as a primary treatment in conjunction with chemotherapy when the cancer is isolated in the pancreas but cannot be removed surgically. Chemotherapy alone, particularly gemcitabine, is often used for palliative care of metastatic pancreatic cancer that has spread distally to other organs or body parts. Gemcitabine (Gemzar) has resulted in clinical improvement in 25 percent of these patients. The use of erlotinib (Tarceva), which stops signals that instruct cancer cells to multiply, in combination with gemcitabine has proved to be more effective than using gemcitabine alone. However, patients must be healthy and functioning well enough to be able to tolerate the side effects of chemotherapy. Common side effects of chemotherapy treatment with gemcitabine include fatigue, lowered production of blood cells, increased incidence of infection, tiredness, breathlessness, and bruising. Ongoing clinical trials involve a vaccine for pancreatic cancer that is used to treat existing disease by causing an immune response to the pancreatic cancer. Prognosis, prevention, and outcomes: The mortality rate for pancreatic cancer based on National Cancer Institute data collected between 2000 and 2004 is 10.6 deaths 926
Salem Health: Cancer per 100,000 men and women. Overall five-year survival rates for this cancer are 5 percent. The majority of pancreatic cancers (52 percent) are diagnosed when they have already metastasized. The five-year survival rate following diagnosis for those with cancers of the exocrine pancreas, the most common type, is 20.3 percent when the cancer is localized. However, when it has spread to nearby organs and tissues, the survival rate falls to 8.0 percent, and 1.7 percent when the cancer has spread to distant organs. Recommendations for preventing pancreatic cancer include health education to reduce tobacco consumption and referring those at increased risk for familial reasons to genetic counseling and possibly genetic testing. Susan H. Peterman, M.P.H. u
For Further Information Hassan, M. N., et al. “Risk Factors for Pancreatic Cancer: Case-Control Study.” American Journal of Gastroenterology 102, no. 12 (August, 2007): 2696-2707. Reber, Howard, ed. Pancreatic Cancer: Pathogenesis, Diagnosis, and Treatment. Totowa, N.J.: Humana Press, 1998. Risch, H. A. “Etiology of Pancreatic Cancer, with a Hypothesis Concerning the Role of N-Nitroso Compounds and Excess Gastric Acidity.” Journal of the National Cancer Institute 95, no. 12 (July 2, 2003): 948-960. Wiederpass, E., et al. “Occurrence, Trends and Environment Etiology of Pancreatic Cancer.” Scandinavian Journal of Environmental Health 24, no. 3 (June, 1998): 165-174.
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Other Resources
American Cancer Society Detailed Guide: Pancreatic Cancer http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_pancreatic_cancer_34.asp Medical University of South Carolina Digestive Disease Center http://www.ddc.musc.edu Pancreatic Cancer Action Network http://www.pancan.org/ Pancreatica.org http://www.pancreatica.org Sol Goldman Pancreatic Cancer Research Center http://www.pathology.jhu.edu/pancreas See also Alcohol, alcoholism, and cancer; Bile duct cancer; BRCA1 and BRCA2 genes; CA 19-9 test; Cholecystec-
Salem Health: Cancer tomy; Endocrine cancers; Endocrinology oncology; Endoscopic retrograde cholangiopancreatography (ERCP); Gallbladder cancer; Islet cell tumors; Multiple endocrine neoplasia type 1 (MEN 1); Pancreatectomy; Pancreatitis; Percutaneous transhepatic cholangiography (PTHC); Peutz-Jeghers syndrome.
u Pancreatitis Category: Diseases, symptoms, and conditions Also known as: Inflammation of the pancreas Related conditions: Diabetes mellitus, alcoholism, pancreatic cancer, gallstones Definition: Pancreatitis, inflammation of the pancreas, appears in acute and chronic forms. Acute pancreatitis comes on suddenly and typically resolves quickly, but it may be severe and life-threatening. Chronic pancreatitis slowly destroys the pancreas. Risk factors: Alcohol abuse, trauma, high lipid or calcium levels are all associatted with pancreatitis. Etiology and the disease process: The pancreas is a glandular organ that lies behind the stomach. It produces hormones and digestive enzymes. Specialized pancreatic cells produce the hormones glucagon and insulin. Glucagon stimulates the liver to convert stored glycogen into glucose, raising blood glucose (sugar) levels. As blood glucose levels rise, the pancreas responds by secreting insulin. Insulin helps transport glucose into the body’s cells, where it is used for energy. Other cells located throughout the pancreas secrete digestive enzymes. These enzymes are secreted in fluid that travels from the pancreas through the pancreatic duct to the duodenum (portion of the small intestine), where they become activated and aid digestion. In pancreatitis, the flow of pancreatic enzymes becomes obstructed by gallstones or spasm and edema at the ampulla of Vater, the area where the pancreatic and liver ducts enter the duodenum, and the enzymes begin digesting the pancreas. Incidence: More than 300,000 people are hospitalized with acute pancreatitis annually; additionally, 85,000 are hospitalized with chronic pancreatitis. Symptoms: Mild pancreatitis may manifest with upper abdominal pain centered near the umbilicus. As pancreatitis progresses, abdominal pain becomes
Pancreatitis severe and persistent and may radiate to the back. It commonly occurs after eating a large meal or drinking alcohol. Other symptoms may include abdominal distension and tenderness, bruising in the flank or around the umbilicus, fever, nausea, rapid pulse, and low blood pressure. Screening and diagnosis: Physical examination, blood tests to detect elevated pancreatic enzyme (amylase and lipase) levels, and abdominal computed tomography scan confirm the diagnosis. Abdominal ultrasonography may detect gallstones. Treatment and therapy: Treatment depends on the severity of symptoms. Mild pancreatitis may abate without treatment. Severe pancreatitis requires withholding food and fluids, administering replacement fluids and electro-
Gallbladder Bile duct Pancreas
Pancreatic duct Duodenum
Bile reflux
Obstructing stone
The pancreas, showing the pancreatic duct.
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Pap test
Salem Health: Cancer
lytes intravenously, and inserting a nasogastric tube to decrease abdominal distension. Medications such as hydromorphone or morphine are commonly prescribed to control pain. Surgical drainage of a pancreatic abscess or pseudocyst may be necessary. Prognosis, prevention, and outcomes: Pancreatitis causes approximately 3,500 deaths annually. The prognosis is good when pancreatitis results from biliary tract disease but poor when it is a complication of alcoholism. Pancreatitis increases the risk for pancreatic cancer. Collette Bishop Hendler, R.N., M.S. See also Alcohol, alcoholism, and cancer; Bile duct cancer; Cholecystectomy; Endocrine cancers; Endocrinology oncology; Endoscopic retrograde cholangiopancreatography (ERCP); Gallbladder cancer; Islet cell tumors; Multiple endocrine neoplasia type 1 (MEN 1); Pancreatectomy; Pancreatic cancers; Percutaneous transhepatic cholangiography (PTHC).
u Pap test Category: Procedures Also known as: Pap smear, Papanicolaou test, gynecological exam Definition: A Pap test is the removal of microscopic cells from the cervix, the opening between the vagina and uterus in females, for laboratory evaluation. Cancers diagnosed: Cervical cancer Why performed: The Pap test is a diagnostic procedure performed for early detection of cervical cancer. The test can also detect abnormal, noncancerous cells and certain vaginal infections. Cervical cancer has been linked to certain strains of the human papillomavirus (HPV), which is sexually transmitted. These viruses can be detected with current Pap test technology. According to guidelines from the American College of Obstetricians and Gynecologists, a female patient should have the first Pap test within three years of having sexual intercourse or at age twenty-one, whichever comes first. Until age thirty, women should have annual testing. After age thirty, if the woman is in a monogamous sexual relationship and has had three consecutive normal Pap tests, testing can be done every three years. For women over the age of sixty-five with three normal tests and no abnormal tests for the prior ten years, testing may be discontinued. Women who have had a hysterectomy may stop having Pap tests, unless the hysterectomy was performed because of cancer. These are general 928
Obtaining a Pap smear. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Salem Health: Cancer
Paracentesis
guidelines for testing; individual situations must be considered by the health care provider.
detection of cervical cancer with the likelihood of successful treatment.
Patient preparation: The patient must not be menstruating at the time of testing. It is recommended that the patient avoid sexual intercourse, tampons, douching, and vaginal medications, creams, or sprays for two days before the test. The patient should empty her bladder immediately before the procedure and then undress from the waist down. A patient gown or drape will be provided.
Results: The results are generally available within one week. A normal or negative Pap test will have no abnormal cells or infectious agents present. An abnormal Pap test may show abnormal noncancerous cells, abnormal cancer cells, or infection. If a patient has an abnormal Pap test, then further evaluation is needed. A repeat Pap test may be performed in approximately three months. This time lapse is to allow possible infections to be resolved that may be the cause of the abnormal test. Other patients may have a more detailed test or a biopsy. If cancer is detected, then surgery is generally performed. Rarely, the test may give a false negative result when the test is actually abnormal. This may occur from a poor sample or from laboratory error. Amy Bull, D.S.N., A.P.N.
Steps of the procedure: The test is usually done in a health care provider’s office during a gynecological examination, which includes a breast and pelvic examination. The patient is placed in lithotomy position on the examination table. In this position, the patient is lying on her back with feet in stirrups at the end of the table and is draped with a sheet. The examiner will push the patient’s knees apart to inspect the external genital area. A plastic or metal speculum is lubricated with water or a water-based gel and is inserted into the vagina. The curved blades of the speculum are opened and the cervix is located. A thin plastic brush with an end that looks like a broom is inserted into the opening of the cervix and is rotated 360 degrees to collect endocervical cells. The patient may feel a slight pinching sensation. The collection device and the speculum are removed. The broom end is placed into a small container with preservative chemicals and is sent to the laboratory for evaluation of the cervical cells. In the past, samples of cells were obtained with a small wire brush and smeared on a glass slide and sent to the laboratory. Newer technology with the broom is more accurate than the older methods. After the Pap test, the provider will then place lubricant on two fingers and insert them into the vagina while feeling with the other hand on top of the abdomen. This is done to feel the uterus, cervix, and ovaries for any abnormalities, tenderness, or masses. Then, a rectal examination may be done in some patients. The rectal wall lies against the back of the vaginal wall. A tilted uterus may be examined during a rectal examination. After the procedure: The patient may need to remove lubricant if it is used during the test. The patient is allowed to go home immediately after the examination and resume previous levels of activity. Risks: Brief mild discomfort may occur in some patients during a Pap test. Some may experience a small amount of vaginal bleeding or spotting during or after the test. Some women may experience embarrassment during the examination. These risks are minor given the benefits of early
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For Further Information Carlson, Karen J., Stephanie A. Eisenstat, and Terra Ziporyn. The New Harvard Guide to Women’s Health. Cambridge, Mass.: Harvard University Press, 2004. Minkin, Mary Jane, and Carol V. Wright. A Woman’s Guide to Sexual Health. New Haven, Conn.: Yale University Press, 2004. Rosenthal, M. Sara. The Gynecological Sourcebook. 4th ed. New York: McGraw-Hill, 2003.
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Other Resources
National Cervical Cancer Coalition http://www.nccc-online.org National Women’s Health Information Center http://www.4women.gov/faq/pap.htm See also Antiviral therapies; Cervical cancer; Colposcopy; Conization; Diethylstilbestrol (DES); Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers; Human papillomavirus (HPV); Hysterectomy; Hysterooophorectomy; Loop electrosurgical excisional procedure (LEEP); Pelvic examination; Pregnancy and cancer; Vaccines, preventive; Virus-related cancers.
u Paracentesis Category: Procedures Also known as: Abdominal tap, abdominal paracentesis, peritoneal tap Definition: Paracentesis is the insertion of a needle or catheter through the peritoneum, the membrane that lines the abdominal cavity, to sample or drain excess fluid. 929
Paracentesis Cancers diagnosed or treated: Most metastatic cancers, especially liver cancer, mesothelioma, and ovarian cancer Why performed: Primarily a diagnostic but sometimes a therapeutic procedure, paracentesis is performed to identify new cancer cells that have metastasized to the abdomen, or to analyze the extent of an existing cancer that is causing fluid buildup (ascites) in the peritoneal space. In the latter case, physicians may perform paracentesis to remove a large amount of fluid and relieve the patient of pain in the lungs, kidneys, and bowels. Patient preparation: The physician will discuss risks, benefits, and alternatives with the patient and ask him or her to sign an informed consent form. A few days before the procedure, the patient undergoes blood tests to confirm that there are no clotting or bleeding problems in the abdomen. On the day of the procedure, a radiologist will perform an ultrasound scan of the peritoneal space to assess the size and area of the ascites. Immediately before the test, the patient must urinate to leave an empty bladder. Steps of the procedure: Non-emergency paracentesis is scheduled in an outpatient setting. The abdominal area is cleaned with an antiseptic soap, and a local anesthetic such as lidocaine is injected into the patient’s abdomen. Based on the ultrasound and percussion of the abdomen, the physician chooses the insertion site for paracentesis. Typically, the patient sits in a semi-recumbent position, so a site just below the navel is optimal for insertion and fluid aspiration. A nurse will shave this area of the abdomen if needed. When enough fluid has been removed (10 to 50 milliliters in diagnostic paracentesis and up to 10 liters in therapeutic paracentesis), the physician withdraws the needle from the abdomen and applies direct pressure to the puncture site with a sterile dressing. Large accumulations of fluid require the insertion of a vacuum-pressurized catheter through which the fluid can drain into a container. Results are sent to the laboratory for analysis right away. The entire procedure takes ten to thirty minutes.
Salem Health: Cancer rare, a range of intraprocedure complications may occur. The paracentesis needle may perforate the bladder, bowels, or blood vessels in the abdomen, causing internal bleeding or hemorrhage. Infection of the peritoneal fluid or the spread of cancer inside the abdomen are also risks associated with the paracentesis needle. The risk of external infection around the puncture site is increased if there is persistent leakage from the puncture site. Results: Patients undergo paracentesis only if they have ascites, an abnormal condition, in the abdomen. Several laboratory tests are performed on the peritoneal fluid to assess the abnormality. A high white blood cell count may indicate inflammation, bacterial perotinitis, infection, or cancer in the abdomen. High albumin protein content in the fluid, as compared to the content in the patient’s blood serum, may indicate tuberculosis, kidney disorder, pancreatitis, or cancer. Lower protein content may indicate liver cirrhosis or portal hypertension. A high level of the enzyme lactate dehydrogenase in the fluid may indicate infection or cancer. A high level of the enzyme amylase may indicate pancreatitis. A low level of glucose may indicate infection. To confirm the type of infection or cancer, cells from the fluid will undergo culture and pathology in the laboratory. A biopsy may also be performed. Bharat Burman, B.A. u
For Further Information Aziz, K., and G. Y. Wu. Cancer Screening: A Practical Guide for Physicians. Totowa, N.J.: Humana Press, 2002. Foley, K. M., et al. When the Focus Is on Care: Palliative Care and Cancer. Atlanta: American Cancer Society, 2005. Waller, A., and N. L. Caroline. Handbook of Palliative Care in Cancer. Boston: Butterworth-Heinemann, 2000.
u
Other Resources
After the procedure: The patient rests for one to four hours while vital signs, incision site, and fluid drainage are monitored. If large amounts of fluid are drained, then nurses will actively monitor the patient’s blood pressure for hypotension and shock. An intravenous (IV) line may be inserted to avoid fluid shifts in the body and prevent kidney failure. Slight fluid drainage from the puncture site may continue for one to two days. Normally, the patient does not require an overnight stay.
American Cancer Society Treatment of Mesothelioma by Stage http://www.cancer.org/docroot/CRI/content/ CRI_2_4_4X_Treatment_Options_by_stage_29 .asp?sitearea=
Risks: Paracentesis is a relatively safe procedure. Although the incidence of any particular complication is
See also Ascites; Mesothelioma.
930
National Cancer Institute Screening and Testing to Detect Cancer http://www.cancer.gov/cancertopics/screening
Salem Health: Cancer
u Paraneoplastic syndromes Category: Diseases, symptoms, and conditions Also known as: Paraneoplastic disorders Related conditions: Cushing syndrome, Lambert-Eaton myasthenic syndrome, dermatomyositis-polymyositis, malignant carcinoid syndrome, leukemoid reaction, disseminated intravascular coagulation (DIC), syndrome of inappropriate antidiuretic hormone (SIADH) Definition: Paraneoplastic syndromes are a large group of clinical symptoms that may arise from the presence of a malignancy. These symptoms, while they can be considered distinct clinical entities in themselves, are an indirect result of the biochemical by-products of the primary neoplastic entity. Risk factors: The risk factors for developing one or more paraneoplastic syndromes depend on a family history of malignant cancer and the type of primary tumor. For instance, specific tumors such as small-cell lung carcinoma are associated with a higher predilection for Cushing syndrome from adrenocorticaltropic hormone (ACTH) secretion. Etiology and the disease process: The origin of most paraneoplastic syndromes is generally attributed to the unabated production of different types of chemical messengers by tumor cells. These chemicals include cytokines, hormones and their precursors, autoantibodies, enzymes, and fetal proteins. The corresponding effect of these substances on metabolic, biochemical, and physiologic pathways can be observed clinically. Because these substances circulate through the body, the primary site of the tumor may be distant from the organ systems involved. In a similar manner, a paraneoplastic syndrome alone may herald the presence of malignancy bearing a poor prognosis. Incidence: The incidence of paraneoplastic syndromes is estimated at 10 to 15 percent in patients with malignant cancer. The exact figure may be within the range of 2 to 20 percent, as these syndromes can masquerade as nonmalignant diseases on manifestation and thus are poorly accounted for. Symptoms: Symptoms of paraneoplastic syndromes are very broad and may initially occur as nonspecific complaints such as an unexplained, persisting fever; noninduced loss of appetite; and involuntary weight loss. More specific symptoms point to an affected organ system, although the primary tumor may remain unknown. Vague joint and muscle pain may be associated with bone joint thickening
Paraneoplastic syndromes or connective tissue proliferation (scleroderma or amyloidosis). Weakness, diarrhea, and mental status changes can be attributed to electrolyte imbalances of sodium, potassium, and phosphorus; acid-base disorders caused by adrenocorticotropic hormone, antidiuretic hormone, or intestinal hormone secretion; kidney damage; or malabsorption of nutrients. Bleeding from underproduction or overactivation and depletion of coagulation components (disseminated intravascular coagulation, cryoglobulinemia), migratory sites of spontaneous intravascular clotting, or abnormal excesses of or deficits in red blood cells or white blood cell subtypes (anemia, erythrocytosis, thrombocytosis) may also be present. Itching is the most common skin complaint of cancer patients. Other skin lesions may appear and include loss or excess of hair (alopecia, hypertrichosis), stress-induced flushing, scalelike changes (icthyosis), shingles (herpes zoster), and black pigmentation of skin (acanthosis nigricans, dermic melanosis). Cushingoid symptoms (fatigue, lethargy, psychosis, buffalo hump, hypertension, purple striae, central obesity) is suggestive of excess ACTH-like molecule secretion. Muscular weakness around the pelvic girdle and scapular areas that improves throughout the day and decreased tendon reflexes are characteristic of Lambert-Eaton syndrome (LEMS). Screening and diagnosis: There is currently no screening available for paraneoplastic syndromes, as they depend on the underlying cause. Establishing the etiology of a paraneoplastic syndrome depends on clinical and confirmatory investigation of a suspected neoplasm through a combination of laboratory, imaging, and pathology studies of biopsy specimens. Bleeding disorders can often be assessed with blood tests such as complete blood counts, as well as assessments of platelet function, platelet factors, and clotting mechanisms. Multistep diagnostics such as the dexamethasone suppression test can be used to rule out a pituitary cause of Cushingoid symptoms by measuring ACTH and cortisol levels in response to low and high doses of dexamethasone if a twenty-four-hour screening for urine cortisol before testing is positive. In spite of all these investigations, a definitive “diagnosis” is truly established only once the primary tumor is located and biopsied, if not excised. Decrease in antidiuretic hormone secretion by the tumor is often resistant to changes in serum levels by withholding water intake. Autoantibodies such as anti-Hu, anti-Ri, and antibodies against amphyphysin are present in some patients exhibiting neurologic symptoms and syndromes such as neuronopathy, encephalitis, opsoclonus/myoclonus syndrome, and stiff man syndrome. Cancer-associated autoantibodies 931
Parathyroid cancer
Salem Health: Cancer
Cancers Commonly Associated with Paraneoplastic Syndromes
• • • • •
Breast cancer Gastric cancers Hepatocellular carcinoma Leukemias Lung cancer
• • • • •
Lymphomas Neural cancers Ovarian cancer Pancreatic cancers Renal carcinoma
MayoClinic.com Paraneoplastic Syndromes of the Nervous System http://www.mayoclinic.com/health/paraneoplasticsyndromes/DS00840 See also Carcinoid tumors and carcinoid syndrome; Cushing syndrome and cancer; Disseminated intravascular coagulation (DIC); Endocrine cancers; Hormonal therapies; Lambert-Eaton myasthenic syndrome (LEMS); Syndrome of inappropriate antidiuretic hormone production (SIADH).
such as the antineuronal antibody Ma2 are seen in testicular cancer. Treatment and therapy: Treatment and therapy are directed toward tumor detection and elimination. This may involve a combination of surgical, chemotherapeutic, and radiologic interventions depending on the type of tumor found. Treatment of the paraneoplastic disease itself will often fail if the location of the primary tumor is not established. In cases in which an immune-mediated etiology is present, immunosuppression may be of help. Agents used include cyclosporine, antithymocyte globulin, and prednisone. Prognosis, prevention, and outcomes: Prognosis is widely variable and depends on the clinical presentation of the paraneoplastic disease. For example, disseminated intravascular coagulation may indicate a poor prognosis while less life-threatening diseases fare better. Generally, treatment of the tumor results in resolution of the paraneoplastic disease. However, severity of the specific disease may prolong recovery. There are no preventive measures. Aldo C. Dumlao, M.D. u For Further Information Kelloff, Gary, Ernest T. Hawk, and Caroline C. Sigman, eds. Cancer Chemoprevention. 2 vols. Totowa, N.J.: Humana Press, 2004-2005. Montgomery, Hugh, Neil Goldsack, and Richard Marshall. My First MRCP Book. London: Remedica, 2003. Rose, Noel R., and Ian R. Mackay. The Autoimmune Diseases. Amsterdam: Elsevier/Academic Press, 2006. u
Other Resources
National Institute of Neurological Disorders and Stroke Paraneoplastic Syndromes Information Page http://www.ninds.nih.gov/disorders/paraneoplastic/ paraneoplastic.htm 932
u Parathyroid cancer Category: Diseases, symptoms, and conditions Also known as: Parathyroid carcinoma Related conditions: Primary hyperparathyroidism, hypercalcemia Definition: Parathyroid cancer is an uncommon endocrine malignancy of the parathyroid glands. The parathyroid glands, which are at the upper and lower poles of the thyroid gland, are usually distinguishable as four distinct glands; however, more or less than four have been found during surgeries. The parathyroid glands help normalize the body’s metabolism by regulating calcium concentrations in the blood. The hormone that is released by the parathyroid gland acts on bones, kidney structures, and tissues of the intestines. Parathyroid cancer has been known to cause increased production and activity of the glands, or hyperparathyroidism. Because of the infrequency of this form of cancer, limited studies have been made of its natural history and underlying biologic basis. Risk factors: Increased risk of parathyroid cancer is associated with hereditary hyperparathyroidism and a related condition called hyperparathyroidism-jaw tumor syndrome (HPT-JT). Previous radiation to the neck is known to be a slight risk factor for head and neck cancer. No association between gender and parathyroid cancer has been reported. Etiology and the disease process: What causes parathyroid cancer is unknown. However, a related cancerproducing gene (oncogene) has been located on chromosome 11. Also, some cases of parathyroid cancer in patients under twenty years of age indicate a genetic factor as a potential causative factor in this form of cancer. As the disease progresses, parathyroid hormone levels become elevated and as high as 10.2 times the upper limit of normal.
Salem Health: Cancer
Parathyroid cancer
Even a very small metastatic deposit may produce significant release of parathyroid hormone and cause severe increases of calcium levels. Parathyroid cancer grows slowly and metastasizes late, with the lungs being a common (20 to 40 percent) area of involvement. Other sites that may be affected include bones, the pleura, pericardial tissue surrounding the heart, and the pancreas. Because the disease is usually slow growing, most patients die of metabolic complications rather than the cancer itself. Incidence: Parathyroid cancer is one of the rarest of all human cancers, with an estimated incidence of 0.015 per 100,000 population and an estimated prevalence of 0.005 percent in the United States. The incidence of hyperparathyroidism has increased since 1974, yet studies show that the incidence of parathyroid cancer among patients with primary hyperparathyroidism is around 1 percent. Symptoms: Parathyroid cancer usually manifests with symptoms consistent with severe hyperparathyroidism. Because most of the parathyroid cancer tumors preserve the ability to produce active parathyroid hormone, hypercalcemia is a common feature. There is a greater incidence of renal and bone disease compared with patients with benign hyperparathyroidism. Hoarseness with recurrent laryngeal nerve involvement is rare. However, its presence in a patient with primary hyperparathyroidism who has not had prior neck surgery is very suggestive of parathyroid cancer. Screening and diagnosis: Diagnosis of parathyroid cancer is considered with a palpable neck mass, significant elevated calcium and parathyroid hormone (PTH) levels, and combined renal and bone disease. Hypercalcemia, the hallmark of hyperparathyroidism, is usually severe in patients with parathyroid cancer. For patients suspected to have this form of cancer, computed tomography (CT) scanning is thought to be the most useful for detecting the primary tumor, its local extent, and metastases. Ultrasonography in conjunction with CT scans and magnetic resonance imaging (MRI) may be useful in the evaluation of the disease in the neck and better detects distant metastases in the chest or abdomen. If any of these noninvasive tests is unsuccessful in local-
izing the tumor, specific venous sampling or arteriography is a useful option. Researchers Ashok R. Shaha and Jatia P. Shah have proposed a staging system, with subgroups based on tumor size and metastases, for these relatively rare tumors. Tumor size: T1 • = Primary tumor less than 3 centimeters (cm) in size • T2 = Primary tumor greater than 3 cm • T3 = Primary tumor of any size with invasion of the surrounding soft tissues • T4 = Massive central compartment disease invading the trachea and esophagus or recurrent parathyroid cancer Metastases: • N0 = No regional lymph node metastases • N1 = Regional lymph node metastases • M0 = No evidence of distant metastases • M1 = Evidence of distant metastases Stage grouping: • Stage I: T1N0M0
In this posterior view of the trachea, two small paired parathyroid glands can be seen embedded in each lobe of the thyroid gland. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Pathology
Salem Health: Cancer
Relative Survival Rates for Parathyroid Cancer by Gender, 1988-2001 Survival Rate (%) Gender
1-Year
3-Year
5-Year
10-Year
Men Women Total
93.8 94.0 94.1
93.8 93.1 94.1
89.6 93.1 93.1
71.7 88.4 81.6
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
• • • • •
Stage II: T2N0M0 Stage IIIA: T3N0M0 Stage IIIB: T4N0M0 Stage IIIC: Any T, N1, M0 Stage IV: Any T, any N, M1
Treatment and therapy: Initial therapeutic treatment for parathyroid cancer involves surgical resection of the entire tumor. Patients who are not surgical candidates, such as those in whom the tumor has invaded neck structures, undergo radiation therapy or chemotherapy; however, these therapies have met with limited success. Prognosis, prevention, and outcomes: The prognosis for individuals with parathyroid cancer varies. The best prognosis results from early detection and complete removal of the tumor during the initial surgery. The average time between the initial surgery and the first potential recurrence is around two to three years. Recurrence earlier than this is an unfavorable factor regarding prognosis. The recurrencefree survival rate is 30 percent. Complete cure is reported unlikely once the tumor has recurred, yet lengthened survival can be possible with surgery or chemotherapy or both. Radiation therapy for inoperable parathyroid carcinoma is usually ineffective. In cases of recurrence of the tumor, the five-year overall survival rate is reported to be about 50 percent and the ten-year survival rate varies from 13 to 49 percent. Jeffrey P. Larson, P.T., B.S., A.T.C. u
For Further Information Copstead, Lee-Ellen C., and Jacquelyn Banasik. Pathophysiology: Biological and Behavioral Perspectives. 3d ed. Philadelphia: Saunders, 2005. Kulkarni, P. S., and Purvish M. Parikh. “The Carcinoma of Parathyroid Gland.” Indian Journal of Cancer 41 (April 1, 2004): 51-59. 934
Wiseman, Sam M., et al. “Parathyroid Carcinoma: A Multicenter Review of Clinicopathologic Features and Treatment Outcomes.” Ear, Nose and Throat Journal 83, no. 7 (July 1, 2004): 491-494. u
Other Resources
MedlinePlus Parathyroid Cancer http://www.nlm.nih.gov/medlineplus/ency/article/ 007264.htm National Cancer Institute Parathyroid Cancer http://www.cancer.gov/cancertopics/types/ parathyroid/ See also Endocrine cancers; Endocrinology oncology; Family history and risk assessment; Giant cell tumors (GCTs); Hypercalcemia; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Nuclear medicine scan; Pheochromocytomas; Pituitary tumors; Ultrasound tests; Zollinger-Ellison syndrome.
u Pathology Category: Medical specialties Also known as: Pathobiology, anatomical pathology, clinical pathology Definition: Pathology is a science that seeks to understand the changes in function and structure of organs, tissues, cells, and body fluids that lead to disease and death. The word “pathology” comes from the Greek word pathos, meaning feeling, pain, or suffering, and the suffix ology, which signifies “the study of.” Pathologists, in concert with the scientists and technicians who assist them, investigate the nature and causes of disease in anatomical and metabolic systems at molecular and genetic levels. These molecular-level processes must be fully understood in order to diagnosis a disease. An accurate differential diagnosis is the basis for the choice of therapy and potential return to health. Anatomical pathology, the study of structural and cellular changes in disease processes, includes surgical pathology; autopsy services that identify clues for the coroner or medical examiner, who determines causes of death; and forensic pathology, which provides the scientific link between medicine and the law Clinical pathology focuses on the cellular and chemical changes in body cells and fluids that differentiate
Salem Health: Cancer health from disease and includes the disciplines of microbiology, immunology, hematology, immunohematology/ blood banking/transfusion services, and chemistry. Subspecialties: Pathology is a unique specialty in the sense that pathologists do not typically see a patient but instead consult with the patient’s physician. Pathology includes ten certifiable clinical and anatomical subspecialties at the physician level. Clinical pathology specialties are blood banking/transfusion medicine/immunohematology, chemical pathology, hematology, medical microbiology, and molecular genetics and are supported by clinical laboratory scientists and technicians. Anatomical pathology specialties are cytopathology, dermatophathology, neuropathology, pediatric pathology, and forensic pathology and are supported by pathology assistants, histologists, cytologists, and cytogeneticists. Anatomical pathology. When a patient undergoes surgery for tumor evaluation and removal, it is the surgical pathologist who advises the surgeon if the mass is cancer or not. While the patient remains under anesthesia, the surgeon passes the tissue to the surgical pathologist, who examines the specimen both by gross examination with the naked eye in its entirety and by frozen section at the time of the operation. In the case of tumor removal, it is the surgical pathologist who is looking at the margins of the excision and telling the surgeon if they are clean (free of cancer) or not. It is the surgical pathologist who informs the surgeon if the entire tumor has been removed, whether the lymph nodes are involved, and whether the tissue is metastatic, a manifestation of malignancy as a secondary growth arising from the primary tumor. In this way, the surgical pathologist plays a pivotal role in determining what the surgeon will ultimately choose as the next step. When tissue is removed, it is passed to the histology department, where histologists stabilize the tissue by fixation. The tissue is then immersed in multiple baths to dehydrate and clear it, and finally impregnate it with wax. After embedding, sectioning, and staining, the tissue is once again reviewed by the pathologist, who is often determining whether cancer or particular receptors for cancer such as HER2/neu are present. In cytopathology the anatomical pathologists work closely with cytologists who process, stain, and review all cell preparations. These specialists study cell structures, cell composition, the interaction of cells with other cells, and the larger environment in which cells exist. Cytologists look for too many of one kind of cell or note when a particular cell type is missing. Suspicious smears are referred to the pathologist.
Pathology One common cytological procedure is the PAP test, the medical screening method to detect premalignant and malignant changes in the ectocervix. The Pap smear has become a routine procedure during a woman’s annual gynecological examination. The cytologist looks at the cell structures to detect the early formation of cancer cells. Early detection leads to greater survival rates. Clinical pathology. In the clinical laboratory, thousands of medical tests are available, including those designed to diagnose and track cancer. Examples include tests for cancer antigens (CA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), lipid-associated sialic acid (LASA), prostate-specific antigen (PSA), and the Tlymphocyte cluster of differentiation (CD) markers. General chemistry and hematology tests identify cancers or may function to demonstrate the degree to which the body is tolerating therapies and provide guidance to the patient’s physician in making adjustments to treatment. As genomics and proteomics become more commercially available, the clinical laboratory will provide personalized profiles that will permit the treating physician to tailor therapies specific to the particular cancer and to the individual for more effective protocols leading to a cure. New and potentially useful markers for cancer diagnoses are continuously being discovered. Time and tedious research are required to determine which ones will result in earlier diagnoses, increasingly targeted and cost-effective treatment, and ultimately prevention. Training and certification: Although pathology departments are in the background, away from the public eye, they are complex, multifaceted operations supporting the practitioners who care for patients. Directors of full-service laboratories must be licensed physicians or individuals who have earned a doctor of philosophy degree in chemical, physical, biological, or clinical laboratory science. Certified pathologists are licensed physicians who have first graduated from an approved medical school or college of osteopathic medicine and who select specialty training in a pathology residency program that is accredited by the Accreditation Council for Graduate Medical Education or the Royal College of Physicians and Surgeons of Canada. After three or four years of graduate medical education, candidates pass an objective written and practical examination. There are three pathology certifications: anatomic pathology (AP), clinical pathology (CP), and combined anatomic pathology and clinical pathology (AP/CP). After January, 2006, new diplomates were required to renew certificates after ten years. Within the pathology department are cadres of scien935
Pathology tists and specialists in chemistry, microbiology, hematology, transfusion service, immunology, cytology, and histology with certifications that require baccalaureate and associate degrees. Services and procedures performed: In addition to performing surgical diagnostic procedures, anatomical pathologists examine tissue that is acquired through biopsy from all parts of the body. After providing a gross examination of the specimen, histologists prepare tissue slides that are then stained and reviewed for a final diagnosis by the pathologist. The clinical pathologist is responsible for the quality assurance of all the biological tests performed in the chemistry, hematology, immunology, immunohematology, and microbiology laboratories. These responsibilities include method selection, quality control, and interpretation of test results. Forensic pathologists are trained to assist law enforcement in homicide cases. They establish the cause of death, estimate the time of death, infer the type of weapon used, distinguish homicide from suicide, establish the identity of the deceased, and determine the effect of trauma or preexisting conditions to the consequential death. Related specialties and subspecialties: Pathologists, clinical laboratory scientists, cytologists, cytogeneticists, histologists, pathology assistants, and phlebotomists work together as a team to deliver diagnostic and monitoring laboratory test results to the primary care physicians who actually interact with patients and their families. Each of these professional groups has academic, certification, and continuing education requirements to support changing and emerging practice in the specialty. Clinical laboratory scientists have bachelor’s degrees, and clinical laboratory technicians have associate degrees. Both are certified to perform testing procedures in chemistry, microbiology, hematology, transfusion services, and immunology. Phlebotomists collect blood and other body fluids for analysis in the clinical laboratories and may be certified. Histologists are technologists with associate or bachelor’s degrees who are certified to process, embed, stain, and cut tissue to the thickness of a single layer for the purpose of demonstrating cellular morphology, chemical composition, and function of normal and abnormal tissue. Cytologists, cytogenecists, and pathology assistants all have obtained a bachelor’s degree and certification. Cytologists are trained to process and prepare cells for review. Suspicious cells are passed to pathologists for final identification. Cytogeneticists are trained to process cells and thus reveal information coded in the chromosomes to de936
Salem Health: Cancer scribe the heredity of the individual as this information relates to particular diseases. Pathology assistants are specifically trained to provide anatomical services under the direction of a pathologist, including the gross examination of surgical pathology specimens and autopsies. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) u
For Further Information Benson, Ellis S., Barbara F. Atkinson, and Martin Alax. Career Guide in Pathology. Chicago: American Society for Clinical Pathology, 1998. McClatchey, Kenneth D., ed. Clinical Laboratory Medicine. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2002. Pagana, Kathleen Deska, and Timothy J. Pagana. Mosby’s Diagnostic and Laboratory Test Reference. Philadelphia: Elsevier-Mosby, 2006. Sloan, Sheila B., and John L. Dusseau. Word Book in Pathology and Laboratory Medicine. 2d ed. Philadelphia: Elsevier/Saunders, 1995. Thomas, Lewis. The Fragile Species. New York: Collier Books, 1992. _______. The Lives of a Cell: Notes of a Biology Watcher. New York: Viking Press, 1974. u
Organizations and Professional Societies
American Association of Bioanalysts http://www.aab.org 906 Olive Street, Suite 1200 St. Louis, MO 63101-1434 American Association of Clinical Chemistry http://www.aacc.org 1850 K Street NW, Suite 625 Washington, D.C. 20006-2213 American Association of Pathologists’ Assistants http://www.pathologistsassistants.org Rosewood Office Plaza, Suite 300N 1711 West County Road B Roseville, MN 55113 American Board of Pathology http://www.abpath.org P.O. Box 25915 Tampa, FL 33622-5915 American Osteopathic College of Pathologists http://www.doaocp.org 142 East Ontario Street Chicago, IL 60611-8224
Salem Health: Cancer
PC-SPES
American Society for Clinical Pathology http://www.ascp.org 33 West Monroe, Suite 1600 Chicago, IL 60603
u PC-SPES
American Society of Cytopathology http://www.cytopathology.org 400 West 9th Street, Suite 201 Wilmington, DE 19801
Definition: PC-SPES is a mixture of eight herbs marketed as a dietary supplement for prostate health and as a complementary and alternative medicine (CAM) for prostate cancer. It should not be confused with SPES, a different product.
Clinical Laboratory Management Association http://www.clma.org 989 Old Eagle School Road, Suite 815 Wayne, PA 19087 College of American Pathologists http://www.cap.org/apps/cap.portal 325 Waukegan Road Northfield, IL 60093-2750 Intersociety Council for Pathology Information http://www.pathologytraining.org 9650 Rockville Pike Bethesda, MD 20814-3993 National Accrediting Agency for Clinical Laboratory Sciences http://www.naacls.org 8410 West Bryn Mawr Avenue, Suite 670 Chicago, IL 60631 National Credentialing Agency for Laboratory Personnel http://www.nca-info.org 18000 West 105th Street Olathe, KS 66061-7543 u
Other Resources
Lab Tests Online http://www.labtestsonline.org MyBiopsy.org http://www.mybiopsy.org U.S. Food and Drug Administration CLIA—Clinical Laboratory Improvement Amendments http://www.fda.gov/cdrh/clia See also Breslow’s staging; Cancer biology; Carcinomatosis; Cytology; Gleason grading system; Grading of tumors; Hematologic oncology; Immunocytochemistry and immunohistochemistry; Malignant tumors; Medical oncology; Metastasis; Molecular oncology; Needle biopsies; Staging of cancer; Stereotactic needle biopsy; TNM staging; Tumor markers; Urinalysis.
Category: Complementary and alternative therapies Also known as: PC-CARE, Ponicidin
Cancers treated or prevented: Prostate cancer Delivery routes: Oral by capsule How this substance works: PC-SPES (a name derived from the initials for “prostate cancer” and the Latin word for “hope,” spes) is a dietary supplement alleged to support prostate health and limit the growth of prostate cancer. The ingredients include eight herbs used in traditional Chinese medicine: Baikal skullcap (Scutellaria baicalensis), licorice (Glycyrrhiza glabra L. or Glycyrrhiza uralensis), reishi mushroom (Ganoderma lucidum), isatis (Isatis indigotica), ginseng (Panax ginseng or Panax pseudoginseng var. notoginseng), chrysanthemum flowers (Dendranthema morifolium), Rabdosia rubescens (Isodon rubescens), and saw palmetto (Serenoa repens). In the 1990’s, PC-SPES showed promise both in preventing cell damage and in limiting tumor growth in cases of prostate cancer. Between 1997 and 2002, PC-SPES was marketed in the United States as a dietary supplement; it therefore did not need to meet the U.S. Food and Drug Administration (FDA) standards for drug safety and efficacy and did not require a prescription. In early studies in which cancer cells from rats were mixed with PC-SPES, the mixture limited the growth of the tumor cells. When testing revealed, however, that some forms of PC-SPES illegally contained warfarin (a blood thinner), diethylstilbestrol (DES, a hormonal therapy for prostate cancer), and indomethacin (an anti-inflammatory), PC-SPES was taken off the market. Forms of PC-SPES without these drugs remain on the market but are unstandardized. How PC-SPES may work without the prescription drugs is unknown but is being studied. The herbs contain plant estrogens (phytoestrogens) that may be effective in limiting the action of testosterone, the male hormone that contributes to tumor growth. Patients respond to PC-SPES similarly to those responding to estrogen therapy using DES. The National Center for Complementary and Alternative Medicine (NCCAM) is conducting studies on drug-free forms of PC-SPES to determine its efficacy, and clinical trials may be planned once a standard formula is established. 937
Pediatric oncology and hematology Side effects: Users of PC-SPES have noted side effects including breast swelling and tenderness, loss of libido, impotence (erectile dysfunction), and, less frequently, blood clots in the legs and diarrhea. PC-SPES may also have interactions with drugs, including anticancer drugs. Christina J. Moose, M.A. See also Cartilage supplements; Chemoprevention; Complementary and alternative therapies; Dietary supplements; Diethylstilbestrol (DES); Gerson therapy; Herbs as antioxidants; Lutein; Lycopene; Nutrition and cancer prevention; Nutrition and cancer treatment; Prostate cancer; Saw palmetto; Sun’s soup.
u Pediatric oncology and
hematology Category: Medical specialties Also known as: Pediatric cancer treatment Definition: Pediatric oncology and hematology is the medical specialty for the diagnosis and treatment of childhood and adolescent cancerous diseases and blood disorders. Most pediatric oncology and hematology programs treat children and young adults from birth through age twenty. Pediatric oncology and hematology practices can be found in university medical centers, large community hospitals, specialized children’s hospitals, comprehensive cancer centers, and specialty pediatric cancer centers. Certain medical centers are designated as comprehensive cancer centers by the National Cancer Institute because they meet certain research and patient treatment criteria, including having a multidisciplinary team of professionals with expertise and training in pediatric and adolescent hematologic and malignant disorders, clinical services connected to research, clinical trials and basic laboratory research, cancer information services, and psychosocial support services. Research has shown that children and adolescents who are treated in a center with specialized cancer services and specialists have better outcomes. A child’s pediatrician or family doctor can provide a referral to a pediatric cancer program. Subspecialties: Pediatric hematology, pediatric radiation oncology, neuro-oncology, ortho-oncology Cancers treated: Many childhood and adolescent cancers, particularly leukemia, lymphoma, osteogenic sarcoma, 938
Salem Health: Cancer rhabdomosarcoma, Ewing sarcoma, neuroblastoma, nonHodgkin lymphoma, brain tumors, bone tumors, musculoskeletal and soft-tissue tumors, solid tumors of the kidney and liver, tumors of the eye, Langerhans cell histiocytosis, and Wilms’ tumor (nephroblastoma) Training and certification: In addition to having a fouryear medical degree from an accredited program and board certification from the American Board of Pediatrics, pediatric hematologists-oncologists have completed three years of postgraduate residency training in general pediatrics and at least three years of fellowship training in pediatric hematology and oncology. After completing a minimum of three years of successful training, pediatric hematologist-oncologist fellows are eligible to take a certification examination offered by the Subboard of Hematology/Oncology of the American Board of Pediatrics. Once certified, pediatric hematologistsoncologists may further their training by participating in one or more years of clinical or laboratory research. Pediatric hematologists-oncologists are trained in the basic science and clinical expression of cancer and blood diseases in children and adolescents. They are involved in patient care, medical teaching, and research. They study the etiology of cancer and its evaluation, diagnosis, and management in ambulatory and hospitalized patients. Specific areas of study include chemotherapy, oncology, hemostatis-thrombosis, hematology, sickle cell treatment, neuro-oncology, stem cell transplantation, hematopathology, clinical pathology, blood banking, and radiation oncology. Hematologist-oncologists often focus on treating patients with either cancer or blood disorders, although they receive training in diagnosing and treating both conditions. Pediatric hematology and oncology clinical practice guidelines, quality standards, and quality assurance measures have been established by these organizations: • Children’s Oncology Group (COG): A network of research groups, sponsored by the National Cancer Institute, with more than two hundred international member institutions that conduct pediatric and adolescent clinical trials to identify cancer causes and introduce new treatments that address long-term childhood cancer survival. • American Society of Pediatric Hematology/Oncology (ASPHO): A professional association for pediatric hematologist-oncologists. ASPHO established standard requirements for pediatric hematology and oncology programs. • American Academy of Pediatrics (AAP): A professional organization of more than sixty thousand pediatricians and pediatric subspecialists that creates clinical practice guidelines.
Salem Health: Cancer Services and procedures performed: A pediatric hematologist-oncologist plans and coordinates the diagnosis and treatment of newly diagnosed or recurring malignancies and blood disorders in children and adolescents. The pediatric hematologist-oncologist is part of a multidisciplinary team of pediatric cancer providers whose goals are to provide early detection; accurately diagnose the condition; offer prompt, appropriate treatment to reduce morbidity and improve quality of life and survival; reduce long-term effects of chemotherapy and radiation therapy; and provide long-term follow-up. Pediatric hematologist-oncologists are trained and skilled in chemotherapy drug indications and toxicities so they can safely administer these therapies while minimizing side effects. Related specialties and subspecialties: Pediatric hematologist-oncologists work with a multidisciplinary team that includes the primary care pediatrician and also may include pediatric surgical specialists such as urologic surgeons, orthopedic surgeons, and neurosurgeons; diagnostic radiologists; radiation oncologists; infectious disease specialists; pediatric pathologists; pediatric oncology nurses; consulting pediatric specialists; physical therapists; pediatric oncology social workers and other allied health care professionals, such as child-life specialists, educational specialists, registered dietitians, and pharmacologists. Communication between the pediatric hematologist-oncologist and the patient’s primary care pediatrician is essential to ensure the continuum of care. Laparoscopy and thoracoscopy are among the surgical techniques used by pediatric surgeons to diagnose and treat cancers in children and adolescents. Pediatric surgeons first obtain a four-year medical degree from an accredited program and board certification from the American Board of Surgery, then complete five years of residency training in an accredited general surgery program and at least two years of fellowship training in pediatric surgery. Pediatric oncology surgeons receive additional training in the surgical diagnosis and treatment of pediatric cancers. Diagnostic radiologists capture and interpret medical images for the purpose of diagnosis. They must have a four-year medical degree from an accredited program, must have board certification from the American Board of Radiology or the American Osteopathic Board of Radiology, and must have passed a licensing examination and completed at least four years of residency training in an accredited radiology program. Radiation oncologists use radiation to treat cancers. In the United States, most of them have completed residency training in their field in a program approved by the Ameri-
Pediatric oncology and hematology can Council of Graduate Medical Education or the American Board of Radiology. Infectious disease specialists are pediatricians who are experts in the diagnosis and treatment of infectious diseases. In addition to having a four-year medical degree from an accredited program and board certification from the American Board of Pediatrics, infectious disease specialists have completed three or more years of residency training and two to three years of additional training in infectious diseases. Pediatric pathologists are physicians who are experts in the pathology of hematologic malignancies and solid tumors in children and adolescents. They use immunochemistry and molecular techniques to assess malignancies. Pediatric pathologists obtain a four-year medical degree from an accredited program and board certification from the American Board of Pediatrics, then complete three or more years of residency training and one to two years of additional training in pathology. The Association of Pediatric Oncology Nurses provides a certification program for pediatric oncology nurses. The organization also facilitates the professional development of pediatric oncology nurses. Pediatric oncology nurses provide medical care, educate patients and their families, and administer medications. Pediatric oncology clinical nurse specialists are registered nurses with a master’s degree in oncology nursing. They have experience in managing complications of cancer treatment, understand pediatric protocols, and prepare and administer medications, including chemotherapy. Pediatric oncology nurse practitioners are registered nurses with a master’s or doctoral degree. u
For Further Information Altman, Arnold J., ed. Supportive Care of Children with Cancer: Current Therapy and Guidelines from the Children’s Oncology Group. Baltimore: Johns Hopkins University Press, 2004. American Academy of Pediatrics. “Guidelines for the Pediatric Cancer Center and Role of Such Centers in Diagnosis and Treatment.” Pediatrics 113, no. 6 (June, 2004): 1833-1835. Lanzkowsky, Philip. Manual of Pediatric Hematology and Oncology. 3d ed. San Diego, Calif.: Academic Press, 2000. Pizzo, P. A., and D. G. Poplack. Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. Stocker, J. T., and L. P. Dehner, eds. Pediatric Pathology. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2001. 939
Pelvic examination u
Salem Health: Cancer
Organizations and Professional Societies
American Society of Pediatric Hematology/Oncology http://www.aspho.org 4700 West Lake Avenue Glenview, IL 60025 Association of Pediatric Oncology Nurses http://www.apon.org 4700 W. Lake Avenue Glenview, IL 60025-1485 Children’s Oncology Group http://www.curesearch.org Research Operations Center 440 East Huntington Drive, Suite 400 Arcadia, CA 91006-3776 National Childhood Cancer Foundation/CureSearch http://www.curesearch.org 4600 East West Highway, Suite 600 Bethesda, MD 20814-3457 u
Other Resources
Candlelighters Childhood Cancer Foundation http://www.candlelighters.org Children’s Cancer Association http://www.childrenscancerassociation.org National Children’s Cancer Society http://www.nationalchildrenscancersociety.org Ronald McDonald House Charities http://www.rmhc.com Angela M. Costello, B.S. See also Childbirth and cancer; Childhood cancers; Endocrinology oncology; Ewing sarcoma; Family history and risk assessment; Hematologic oncology; Histiocytosis X; Juvenile polyposis syndrome; Medical oncology; Molecular oncology; Nephroblastomas; Neurologic oncology; Pregnancy and cancer; Wilms’ tumor; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer; Young adult cancers.
u Pelvic examination Category: Procedures Also known as: Female gynecologic examination, reproductive health examination Definition: A pelvic examination is a visual inspection of external female genitalia, followed by insertion of a 940
Pelvic examinations allow doctors to check for several types of cancer. (PhotoDisc)
speculum into the vagina to visualize the cervix and a bimanual examination of the uterus and adnexa (ovaries, Fallopian tubes, and uterine ligaments) for masses, tenderness, and overall impression. Cancers diagnosed: If a collection of cells for a Pap (Papanicolaou) test is done as part of the pelvic examination, then screening for cervical cancer and precursor cellular changes (precancerous conditions) is included; visual inspection of the external genitalia may reveal abnormal tissue to be biopsied for the detection of vulvar or vaginal cancer. Why performed: A pelvic examination allows for examination of internal and external genitalia as well as the collection of specimens. Some pelvic examinations include laboratory specimen collection for Pap testing (with the collection of cervical and endocervical samples either by fixed slides or the newer liquid cytologic methodology); examination of vaginal discharge for bacterial vaginosis,
Salem Health: Cancer trichomonas, or yeast vaginitis; and testing for common infections such as gonorrhea and chlamydia. Any particular pelvic examination, however, may include only some or none of these tests. It is important for patients to be aware that not all pelvic examinations include Pap testing. Exams may be performed for routine screening, including a Pap smear, or for symptomatic gynecologic problems. Patient preparation: The patient should empty her bladder prior to the exam and should have a chance to express any concerns or apprehensions. She should not douche prior to the exam. It is preferable for patients not to be menstruating when examined, although this may not be possible depending on the reason for the visit. Having the patient move down to the far end of the table relieves some pressure from the speculum.
Penile cancer
u Penile cancer Category: Diseases, symptoms, and conditions Also known as: Cancer of the penis, penile carcinoma, penile malignancies, penile carcinoma in situ (CIS), erythroplasia of Queyrat, Bowen disease Related conditions: Male reproductive cancers, urethral cancer, dermatologic malignancies, squamous cell carcinomas, human papillomavirus infections, testicular cancer, prostate cancer, recurrent balanitis, phimosis Definition: Penile cancer is cancer on the skin and deeper tissues of the penis. Risk factors: Poor hygiene, exposure to human papillomavirus (especially subtypes 16 and 18), and lack of circumcision are major risk factors for development of penile cancer. Age is also a risk, as most cases appear in men aged fifty and older. Smoking is an additional risk
Steps of the procedure: A pelvic exam involves the external examination and palpation of the genitalia, followed by insertion of a vaginal speculum, collection of specimens, and a bimanual examination with palpation of uterine and adnexal size, mobility, position, contours, presence of masses, and tenderness with palpation. After the procedure: The physician will help the patient sit up slowly when the exam is completed. Bleeding is possible following a pelvic examination but is not a cause for alarm unless excessive or prolonged. Risks: Pelvic examinations may be embarrassing and emotionally and physically uncomfortable for some patients, but they carry no known risks. Results: The results of a pelvic examination depend on visual examination and any clinical or laboratory findings. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP) See also Antiviral therapies; Cervical cancer; Colposcopy; Conization; Diethylstilbestrol (DES); Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers; Human papillomavirus (HPV); Hysterectomy; Hysterooophorectomy; Loop electrosurgical excisional procedure (LEEP); Pap test; Pregnancy and cancer; Transvaginal ultrasound; Uterine cancer; Vaccines, preventive; Vaginal cancer; Virus-related cancers; Vulvar cancer.
This penile cancer is a giant condyloma of Buschke and Löwenstein. (Centers for Disease Control and Prevention)
941
Penile cancer factor. The most important risk is phimosis, a narrowing of the opening of the prepuce that results in a foreskin that cannot be retracted. This is a painful condition in which the foreskin of uncircumcised men becomes inflamed with a chronic buildup of smegma under the foreskin, often due to lack of hygiene. Circumcision is an operation, usually done on newborns, that removes the foreskin from the penis. In the United States about two-thirds to three-quarters of newborns are circumcised, although this varies around the world, with circumcision being rare in many parts of the developing world. Etiology and the disease process: Penile cancer most commonly begins as small lesions (sores) on the skin of the glans of the penis or prepuce, the opening of the foreskin. Lesions are usually squamous cell carcinomas, which may remain on the skin, then invade deeper into the tissues and spread (metastasize) into the bloodstream and lymph nodes. Delays in seeking treatment, due to misinformation, embarrassment, and fear, result in many cases being diagnosed at an advanced stage. Penile cancer that has metastasized into the adjacent lymph nodes can cause death from sepsis or hemorrhage. Metastasis into the blood, liver, bone, and brain are rare unless the cancer has been untreated and has reached a very advanced stage. If left untreated, penile cancer is fatal for most patients within a period of about two years. Incidence: Penile cancer is quite rare in developed countries. In the United States, around 1,300 cases are diagnosed each year; however, in parts of the developing world, such as Asia, Africa, and South America, it can account for anywhere from 6 to 30 percent of cancers in men. Symptoms: Symptoms include sores, rashes, or skin growths on the penis and foul-smelling material under the foreskin of uncircumcised men. The foreskin can obscure a lesion that is not healing and may not be detected until tissue death (necrosis) produces material under the foreskin that has a foul odor. Screening and diagnosis: Screening for penile cancer is not customary, but men should have a genital examination as part of their routine physicals. Diagnosis is made from biopsy and is more likely to be performed early on a suspected lesion if patients seek care from a urologist. Staging of the cancer determines how much it has spread (invasiveness) and if lymph nodes have been affected. Biopsy of sentinel lymph nodes may also be done to determine the degree of spread to the lymphatics. Staging is generally done using the TNM (tumor/lymph node/metastasis) sys942
Salem Health: Cancer
Relative Survival Rates for Penile Cancer, 1988-2001 Years
Survival Rates (%)
1 3 5 10
87.4 76.7 71.4 62.6
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
tem, which classifies the tumor based on the presence or absence of spread, involvement of lymph nodes, and existence of more distant metastases. Treatment and therapy: Treatment for penile cancer is usually surgery to remove the cancerous area. Radiation therapy and chemotherapy may also be used to kill cancer cells. Although laser therapy can sometimes be used, most often more radical forms of surgery are necessary, although penis-sparing surgery is used whenever possible. Penectomy is surgery that removes all or part of the penis. A partial penectomy may preserve sexual function and the ability to urinate from the penis. A total penectomy completely removes the penis and creates a new outlet for urination, usually located behind the testicles. Plastic surgery to create a new penis is possible, but function may be limited. Mohs micrographic surgery is an advanced technique that uses microscopy to remove cancerous tissue and allows for maximal sparing of penile tissue. Radiation is less likely to be used than surgical treatment but may involve external beams or implantation of a radioactive source near the tumor. Chemotherapy may be locally applied or, in cases of metastatic cancer, given systemically. Prognosis, prevention, and outcomes: Prognosis depends on the time between first appearance of penile cancer and initiation of treatment, and the status of lymph nodes is the most important clinical indicator of prognosis. Occurrence of penile cancer is rare in men who have been circumcised as newborns; however, circumcision itself carries risks, and medical authorities have not agreed that there is enough evidence to support recommendations for routine neonatal circumcision. Adult circumcision does not prevent development of the disease. It is not yet known if the development of a vaccine against the human papillomavirus can reduce incidence of penile cancer.
Salem Health: Cancer Outcomes depend on state of progression (especially lymph node involvement) when the cancer is detected, treatments used, and response to treatment. Cure rates in men without lymph node involvement who have had surgical treatment may average 80 to 100 percent, whereas cure rates are 32 to 50 percent in men with lymph node involvement. In cases where penis-sparing therapies have been used, surveillance for recurrence is important. Any consideration of outcomes should address the emotional toll of the disease and necessary treatments. Clair Kaplan, R.N., M.S.N., A.P.R.N. (WHNP), M.H.S., M.T. (ASCP) u For Further Information Busby, J. E., and C. A. Pettaway. “What’s New in the Management of Penile Cancer?” Current Opinion in Urology 15, no. 5 (September, 2005): 350-357. Jemal, A., et al. “Cancer Statistics.” CA: A Cancer Journal for Clinicians 57 (2007): 43-66. McDougal, W. S. “Advances in the Treatment of Carcinoma of the Penis.” Urology 66, suppl. 5 (November, 2005): 114-117. Micali, G., M. R. Nasca, D. Innocenzi, and R. A. Schwartz. “Penile Cancer.” Journal of the American Academy of Dermatology 54, no. 3 (March, 2006): 369391.
u
Other Resources
American Family Physician Penile Cancer http://www.aafp.org/afp/20040201/617ph.html M. D. Anderson Cancer Center Penile Cancer Facts http://www.mdanderson.org/diseases/penile-cancer/ ?gclid=CMzR0b2Axo4CFQp7PAodSwLixw National Cancer Institute Penile Cancer http://www.cancer.gov/cancertopics/types/penile/ See also Bowen disease; Infectious cancers; Oncogenic viruses; Prostate cancer; Prostatectomy; Sexuality and cancer; Skin cancers; Testicular cancer; Testicular selfexamination (TSE); Urethral cancer; Urinary system cancers; Urologic oncology.
Percutaneous transhepatic cholangiography (PTHC)
u Percutaneous transhepatic
cholangiography (PTHC) Category: Procedures Also known as: Operative cholangiography, T-tube cholangiography, cystic duct cholangiography Definition: Percutaneous transhepatic cholangiography (PTHC) is a diagnostic test used to visualize the the liver or bile ducts. Although this procedure is frequently performed in the operating room at the time of exploration of the biliary tract for nonpalpable stones or tumors, it can also be performed postoperatively in the radiology suite to assess catheter patency and drainage and to evaluate for the presence of residual stones or residual narrowing or obstruction of the biliary tract. Cancers diagnosed: Bile duct carcinoma, pancreatic cancer Why performed: The main application of PTHC is to avoid common bile duct surgical exploration and to identify calculi that have escaped palpation, as well as to evaluate for the presence of biliary tract tumors or pancreatic tumors. The intrapancreatic segment of the common bile duct is often altered by pancreatic cancer, and PTHC can be used for its evaluation. Postoperative cholangiography is usually performed in the X-ray suite prior to removal of the T tube placed at the time of surgery to demonstrate the patency of the common duct, the absence of retained stones, and the free passage of bile into the duodenum. Patient preparation: This procedure is frequently performed in the operating room at the time of exploration of the biliary tract for nonpalpable stones or tumor. Therefore, patient preparation is determined by the surgeon prior to the procedure and commonly involves the usual preadmission testing performed before any surgical procedure, as well as instructions such as nothing by mouth after midnight the night before the procedure. Steps of the procedure: Radiopaque material is injected by the surgeon into the cystic duct while the patient is still in the operating room. Alternatively, after surgery, radiopaque material may be injected into the T tube by a radiologist in the radiology suite. This tube was placed in the common duct intraoperatively using sterile technique under fluoroscopic guidance. In both situations, X-ray films are then taken. In some cases, a trained interventional radiologist, under fluoroscopic control and using sterile technique, can insert a fine needle directly into the biliary tree and outline the intrahepatic ducts, the common hepatic ducts, and the common bile duct using a contrast medium. 943
Pericardial effusion After the procedure: If a T tube was placed in the common duct intraoperatively, then the procedure is performed as an inpatient procedure (during the patient’s hospital stay). Patients should consult their health care providers if they have any questions or concerns regarding the use of a Ttube cholangiogram or PTHC. Risks: Patients will consult with their health care providers regarding the need for the study, its risks, how it will be done, and what the results indicate. Results: The X-ray films taken during the procedure are read by the radiologist the same day. The patient will need to contact the doctor or health care provider for the radiology report and for follow-up therapy. Results are dependent on the reason for the study, such as exploration of the biliary tract for nonpalpable stones or tumors. Debra B. Kessler, M.D., Ph.D.
Salem Health: Cancer
Some Causes of Malignant and Nonmalignant Pericardial Effusion Causes of Malignant Pericardial Effusion Cancer of pericardium or heart muscle Cancers that have metastasized from the lung, breast, esophagus, thymus, and lymph system
• •
Causes of Nonmalignant Pericardial Effusion Acquired immunodeficiency syndrome (AIDS) Heart attack Infection of pericardium; can be a side effect of radiation therapy or chemotherapy • Injury • Lupus • Surgery • Underactive thyroid gland
• • •
Source: National Cancer Institute
See also Bile duct cancer; Gallbladder cancer.
u Pericardial effusion Category: Diseases, symptoms, and conditions Also known as: Dropsy of pericardium, malignant pericardial effusion, pericarditis, swollen heart, fluid around the heart Related conditions: Any number of cancers that have spread throughout the body Definition: Pericardial effusion is an increase in the amount of fluid between the pericardium and the heart. The pericardium is a thin layer of tissue that forms the pericardial sac, a pouch that holds the heart and the ends of the major blood vessels. The pericardium keeps the heart confined to the chest cavity and prevents it from enlarging if blood flow to the heart increases. The sac normally contains a small amount of fluid. Too much fluid puts pressure on the heart and affects its normal functioning. When the buildup of excess fluid is caused by infection of the pericardium, the condition is known as pericarditis. When the buildup is a result of inflammation or cancer it is called pericardial effusion. When the amount of fluid reaches a dangerous level, it is called malignant pericardial effusion. Effusions in cancer patients are malignant about half of the time. Risk factors: For cancer patients, the disease itself poses the greatest risk. A less serious but still common risk is earlier radiation treatments to the chest, especially for lung cancer. 944
Etiology and the disease process: The causes of effusions in patients who do not have cancer are many. The cause of malignant pericardial effusion in cancer patients is cancer that develops in the pericardium or the heart muscle, or cancer that has metastasized from almost anywhere else in the body, including the lungs, breasts, esophagus, colon, prostate, and even bone marrow (leukemia) and skin (melanoma). Cancerous cells rub against the pericardium. This irritant causes fluid to build up, much the way a blister forms under the skin. Some cancers produce little fluid but cause the pericardium to thicken and become rigid. Both conditions are serious. An effusion can be chronic (present over time) or acute (occurring suddenly). If the fluid collects slowly over time, the pericardium may stretch enough to hold it. The patient usually feels no symptoms until a large amount of fluid accumulates. When the volume of fluid reaches a critical amount or when fluid accumulates rapidly—even a relatively small amount of fluid—a condition known as cardiac tamponade occurs. At this stage, the effusion surrounds and squeezes at the heart. This interferes with the heart’s ability to effectively pump blood. Cardiac tamponade is a medical emergency that can be fatal if not promptly treated. Incidence: Because effusions develop from a number of different diseases or conditions, any patient with any of the many conditions that can produce an effusion may be stricken with one. Effusions affect both sexes, all age groups, and all racial and ethnic groups.
Salem Health: Cancer Malignant pericardial effusion is more common in cancer patients than in patients who do not have cancer. Studies have revealed that 33 percent of patients with lung cancer have an effusion caused by the spread of their cancer at the time of their death. Further, 33 percent of pericardial effusions are a result of the spread of lung cancer. Lung cancer is the most common cancer found in malignant pericardial effusions in men. Breast cancer causes 25 percent of pericardial effusions, and about 25 percent of patients with breast cancer have pericardial effusion. Breast cancer is the most common cancer found in malignant pericardial effusions in women. Cancers that affect the blood (such as leukemia and Hodgkin disease) account for 15 percent of malignant pericardial effusions.
Pericardial effusion
Fluid filled pericardial sac
Heart
Xiphoid retracted Diaphragm Subxiphoid approach
A surgical approach to treating cardiac tamponade. (LifeART© 2008 Wolters Kluwer Symptoms: Symptoms of an effusion Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.) are similar to symptoms associated with heart problems and include chest pain, rapid heartbeat, shortness of breath, diagnosis. About one-third died within the first month. In dizziness or fainting, difficulty in swallowing, cough, and 43 percent of the cases studied, pericardial effusion was low blood pressure. the first sign of cancer. Wendell Anderson, B.A. Screening and diagnosis: Spotting an effusion is relatively easy for doctors. X rays and other imaging techu For Further Information niques reveal the characteristic “water-bottle” shape of the Gornik, H., M. Gerhard-Herman, and J. Beckman. “Abswollen pericardial sac. Sometimes doctors perform a normal Cytology Predicts Poor Prognosis in Cancer pericardiocentesis, a procedure that uses a needle to withPatients with Pericardial Effusion.” Journal of Clinical draw some of the fluid. Doctors then analyze the fluid to Oncology 23, no. 22 (August 1, 2005): 5211-5216. determine the cause of the effusion. Laham, R., et al. “Pericardial Effusion in Patients with Cancer: Outcome with Contemporary Management Treatment and therapy: For cancer patients, treatment Strategies.” Heart 75, no. 1 (January, 1996): 67-71. generally involves relief of symptoms, because pericardial Moore, K., and L. Schmais. Living Well with Cancer: A effusions usually arise in the later stages of cancer, often in Nurse Tells You Everything You Need to Know About the last few week of life. Doctors use various noninvasive Managing the Side Effects of Your Treatment. New and surgical procedures to drain the fluid, thus offering the York: Putnam Publishing Group, 2001. patient some relief. In addition, doctors prescribe aspirin and anti-inflammatory drugs. u Other Resources Prognosis, prevention, and outcomes: There is no way to prevent an effusion in cancer patients. The prognosis for MayoClinic.com cancer patients with malignant pericardial effusion is poor. Pericardial Effusion: What Are the Symptoms? One study showed that of patients diagnosed with malighttp://www.mayoclinic.com/health/ nant pericardial effusions, 86 percent died within a year of pericardial-effusion/HQ01198
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Pericardiocentesis National Cancer Institute Malignant Pericardial Effusions http://www.nci.nih.gov/cancertopics/pdq/ supportivecare/cardiopulmonary/Patient/page4 See also Lactate dehydrogenase (LDH) test; Mesothelioma; Pericardiocentesis.
u Pericardiocentesis Category: Procedures Also known as: Pericardial tap, percutaneous pericardiocentesis Definition: Pericardiocentesis is the insertion of a needle or catheter through the pericardium, the membrane that surrounds the heart, to drain excess fluid. Cancers diagnosed or treated: Mesothelioma, advanced breast cancer Why performed: Primarily a therapeutic but sometimes a diagnostic procedure, pericardiocentesis is performed to remove from the pericardium excess fluid that is inhibiting the heart’s pumping action. If this pericardial effusion has accumulated rapidly, causing a life-threatening condition known as cardiac tamponade, then the procedure is performed on an emergency basis to avoid sudden death. In cases of suspected metastatic cancer, fluid buildup requires both relief and pathology. Patient preparation: A few days before the procedure, an electrocardiogram (EKG), an echocardiogram, and blood tests confirm that it is safe to perform the operation. Patients must not eat or drink for several hours beforehand. Steps of the procedure: Nonemergency pericardiocentesis is scheduled in a hospital. An intravenous (IV) line is inserted in the patient’s arm or hand for medications. The puncture site is sterilized and a local anesthetic given. With the patient’s head elevated 30 to 60 degrees, the physician, guided by an image on a video monitor, inserts a needle beneath the breastbone and into the pericardium. When enough fluid has been removed, the needle is withdrawn and direct pressure is applied. Large accumulations of fluid require the insertion of a catheter through which the fluid can drain into a bag. Extreme cases require general anesthesia and open surgery. After the procedure: The patient stays in an intensive care unit while vital signs, the incision site, and fluid drainage are monitored. Nurses especially watch for bulging of the jugular vein in the neck, which suggests problems with 946
Salem Health: Cancer blood flow. The length of the hospital stay may be as short as overnight or as long as a few days. Risks: With guided imaging, pericardiocentesis is relatively safe, with a 5 percent risk of these side effects: air embolism (air in a blood vessel, blocking blood flow); infection of the pericardial membranes (pericarditis) or at the incision site; irregular heartbeat (arrhythmia); heart attack (myocardial infarction); pneumopericardium (introduction of air into the pericardial sac); and puncture of the heart muscle (myocardium), stomach, lungs, liver, or a coronary artery. Results: Normal pericardial fluid is clear, straw-colored, and low in viscosity. High viscosity, low clarity, and the presence of blood, bacteria, abnormal cells, high levels of protein, or an excessive number of white blood cells indicate an abnormal result. The latter three conditions particularly suggest the spread of cancer to the pericardium, which is confirmed with biopsy and pathology. Christina J. Moose, M.A. See also Acupuncture and acupressure for cancer patients; Bronchoalveolar lung cancer; Mediastinoscopy; Mesothelioma; Pericardial effusion; Thoracoscopy; Thymomas.
u Peritoneovenous shunts Category: Procedures Also known as: Peritoneovenous ascites shunts Definition: Peritoneovenous shunts are surgically implanted devices used to relieve intractable cases of ascites. This condition, characterized by excess buildup of fluids in the peritoneal (abdominal) cavity, generally results from chronic liver disease but also from malignancy in one out of ten cases. The shunt—a plastic or silicone rubber tube—serves to drain fluid from the abdominal cavity into the jugular vein in the neck. Cancers treated: Ovarian, endometrial, colon, gastric, breast, and pancreatic cancers Why performed: Tumor-induced ascites is difficult to manage and is usually a manifestation of late-stage cancer. It causes abdominal swelling, nausea, loss of appetite, and shortness of breath as a result of fluid accumulation in the chest cavity. Peritoneovenous shunting carries potential risks but may be recommended to ease discomfort when medical therapy consisting of salt restriction, diuretics, repeated fluid aspirations, chemotherapy, or immunotherapy fails to reduce ascites.
Salem Health: Cancer Patient preparation: Before surgery, the patient undergoes routine laboratory tests, including a coagulation profile and liver panel, and imaging tests, such as computed tomography (CT) scan and ultrasonography, to assess the extent of ascites and the condition of the veins selected for shunting. The operation is contraindicated if an additional test shows that the ascitic fluid is infected. Steps of the procedure: The patient is given a sedative and undergoes either local or general anesthesia at the hospital. The surgeon makes a small incision and inserts a shunting tube under the skin of the chest that will run from the abdominal cavity to the jugular vein. The tube is then passed down to the superior vena cava, a large vein that returns blood to the heart. With a pump chamber and a one-way valve that prevents backflow, the shunt drains ascitic fluid into the systemic circulation. After the procedure: After surgery, the patient’s vital signs are monitored by a nursing staff, and for up to fortyeight hours the shunt is checked to make sure that it functions properly. Antibiotics and pain medication are prescribed as needed. Patients are instructed to pump the shunt daily to remove fluid from the abdomen, to take their prescribed medication, and to restrict sodium intake. Risks: Complications are common and include shunt malfunction, infection, blood clots, edema, leakage of ascitic fluid, and heart failure. Results: The procedure is deemed successful when fluid in the abdomen gradually ceases to accumulate after surgery, but frequently a blood clot or scar tissue will form around the shunt and block the valve or tube. Anna Binda, Ph.D. See also Ascites; Cytology; Gallbladder cancer; Gastrointestinal cancers; Krukenberg tumors; Mesothelioma; Pancreatic cancers; Paracentesis.
u Personality and cancer Category: Social and personal issues Definition: The question of whether certain personality traits make some people more prone to develop or die from diseases such as cancer dates back to the time of Hippocrates, the ancient Greek physician. Research: The ancient Greeks classified personality types based on humours: sanguine (blood—arrogant, impul-
Personality and cancer
Eysenck Personality Questionnaire The Eysenck Personality Questionnaire (1975) was the product of Hans Eysenck (1916-1997), a German-born English psychologist. He based his theory of personality on physiology and genetics and focused on temperament, or the part of the personality that is from nature, not nurture. He was one of the first psychologists to use factor analysis, a statistical method, in the study of personality. His first personality test, the Maudsley Medical Questionnaire (1959), focused on neuroticism/stability. With the Maudsley Personality Inventory (1959), he added extraversion/ introversion. With the Eysenck Personality Inventory (1964), he added a lie scale, which measured a person’s tendency to dissimulate. The 1975 version added psychoticism/socialization, which looked at aggressiveness and impulsivity. Eysenck’s personality tests have been widely used.
sive), choleric (yellow bile—a leader, ambitious), melancholic (black bile—depressive, creative), and phlegmatic (phlegm—unemotional, rational). Twentieth century psychologist Hans Eysenck categorized personality by examining four factors based on character traits: extraversion (social and lively), neuroticism (anxious and emotionally unstable), psychoticism (aggressive, cold, egocentric, and tough-minded), and “lie” (conforming, socially naïve, and dissimulating). Many other classification schemes exist. Multiple studies have looked at whether certain personality types or traits increase a person’s risk of developing or dying from cancer. Some studies reported an association between personality traits and risk of developing cancer or dying from cancer, while others found no association. Researcher Naoki Nakaya and his colleagues, from Tohoku University in Japan, reviewed these studies and found limitations that make it impossible to come to any conclusions about their findings. For example, one study did not assess personality traits before the cancer diagnosis, making before-and-after comparisons impossible. Further studies by Nakaya and other scientists continued to yield mixed results. Studies of Japanese men and women and Swedish twins did not find an increased risk of developing or surviving cancer among people based on personality traits. However, Nakaya’s study in a large group of Danish cancer patients did find a strong association between neuroticism and rate of survival. In 2008, Eveline M. A. Bleiker of the Netherlands Cancer Institute and her colleagues published the results of a follow-up study of about 9,700 women with breast cancer. Although the original study, in 1996, had found a weak link between antiemotionality, or a lack of emotional behavior, and a higher risk of developing breast cancer, their study thir947
Pesticides and the food chain teen years later found no connection between personality traits and an increased risk for breast cancer. Linking personality traits to cancer risk is difficult because there are so many things that may be more closely related to a person’s cancer risk, such as stress, depression, or a person’s behaviors and decisions. For example, neuroticism can lead to distress and stress, which in turn can weaken the immune system and leave people vulnerable to illness. In addition, neuroticism has been linked to depression, and studies have found an association between depression and survival from certain types of cancers. Researchers from the National Institute on Aging studied a group of men and women over seventy-one years of age and found an 88 percent higher risk of developing cancer in those who were chronically depressed (depressed for at least six years). Risky behavior: The American Cancer Society takes the position that lifestyle and behavior are better predictors than personality in assessing people’s risk for developing or dying from cancer. About 75 to 80 percent of cancer cases and deaths result from things people do, such as smoking or chewing tobacco, not exercising or not eating right, and not visiting the doctor regularly. In 2000 almost 5 million people worldwide died prematurely from a smoking-related disease. At least 30 percent of cancer deaths and 87 percent of lung cancer deaths are related to smoking. In addition, 33 percent of cancer deaths are linked to poor diet and exercise habits and being overweight or obese. Neglecting personal health ranks high on the list of risky behaviors that can and often will lead to poorer outcomes after a cancer diagnosis. Early detection and treatment of cancer can save a person’s life. Screenings and guidelines are available for breast, cervix, colon, rectum, prostate, mouth, and skin cancers through the American Cancer Society. Perspective and prospects: Research has not definitively established personality as a risk factor for cancer. The main risk factors remain behaviors and lifestyle issues (tobacco use, poor diet, physical inactivity, and obesity) along with environmental factors (carcinogens, infectious agents). Rather than an individual’s personality, that person’s mental state (chronic depression or stress) may be a better predictor of an individual’s risk of developing or surviving cancer. Christine G. Holzmueller, B.L.A. u For Further Information Bleiker, E. M., et al. “Personality Factors and Breast Cancer Risk: A Thirteen Year Follow-Up.” Journal of the
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Salem Health: Cancer National Cancer Institute 100, no. 3 (February 6, 2008): 213-218. Dalton, Susanne Oksbjerg, et al. “Depression and Cancer Risk: A Register Based Study of Patients Hospitalized with Affective Disorders, Denmark, 1969-1993.” American Journal of Epidemiology 115, no. 12 (2002): 1088-1095. Nakaya, Naoki, Pernille E. Hanson, et al. “Personality Traits and Cancer Survival: A Danish Cohort Study.” British Journal of Cancer 95 (2006): 146-152. Nakaya, Naoki, Yoshitaka Tsubono, et al. “Personality and Risk of Cancer.” Journal of the National Cancer Institute 95 (2003): 799-805. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Psychological Stress and Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ stress See also Anxiety; Complementary and alternative therapies; Depression; Ependymomas; Non-Hodgkin lymphoma; Oligodendrogliomas; Pineoblastomas; Psychosocial aspects of cancer; Self-image and body image; Singlehood and cancer; Stress management; Symptoms and cancer.
u Pesticides and the food chain Category: Carcinogens and suspected carcinogens RoC status: Dichlorodiphenyltrichloroethane (DDT), reasonably anticipated human carcinogen since 1985 Also known as: Insecticides—chlorinated hydrocarbons, organophosphates, carbamates, dinitrophenols, thiocyanates, growth regulators, inorganics (arsenicals and fluorides), microbials; herbicides—amides, acetamides, carbamates, thiocarbamates, phenoxy compounds, dinitrophenols, dinitroanilines; fungicides—dicarboximides, chlorinated aromatics, dithiocarbamates, mercurials; algicides—organotins; molluscicides—chlorinated hydrocarbons; nematocides—halogenated alkanes; rodenticides—anticoagulants, botanicals, fluorides, inorganics, thioureas Related cancers: Lymphoma, brain tumors, leukemia, cancers of the breast, skin, stomach, prostate, ovaries
Salem Health: Cancer Definition: Pesticides refer to any substance or mixture of substances intended for preventing, destroying, repelling, or lessening the damage of any pest. A pest is any living organism that could harm crops and people or other animals, or is in an undesirable location. Pesticides may be chemical, biological, or antimicrobial. They are released into the environment primarily through the spraying of insecticides on fruits and vegetables and other crops, such as corn, wheat, rice, and cotton, and by the use of herbicides on grass. Pesticides are believed to be responsible for a number of cancers. Exposure routes: Ingestion, inhalation, absorption Where found: Pesticides are found in the environment, in streams, rivers, lakes, groundwater, and the soil, including fields (where chlorophenols, particularly in the form of weed killers, build up over the years) and chemically treated lawns. DDT, banned in the United States in 1972, still exists in the soil and is stored in the fatty tissues of individuals; it may also be on products imported into the United States from countries where it is allowed. Pesticides have entered the food chain: Chemicals from pesticides get into groundwater or streams, then into the grass and other vegetation, then into carnivorous animals and then omnivorous animals such as humans. Those animals at the top of the food chain, such as humans or scavengers, fare worse than those below them, as the buildup of toxins is much greater at the top. In the aquatic food chain, chemicals from pesticides enter agricultural runoff or wastewater, then are taken up by algae and plankton, then smaller organisms, then larger fish, and finally humans. Fish containing mercury or other chemicals can be lethal to people. At risk: People who produce or distribute pesticides, agricultural workers and people living in close proximity to fields, people who use pesticides in and around their homes, and people who eat fish or pesticide-treated fruits and vegetables Etiology and symptoms of associated cancers: Studies have shown that human bodies contain hundreds more chemicals—including those contained in pesticides—than they did fifty years ago. Pesticides are linked to lymphoma, a cancer of the white blood cells. Of the two kinds of lymphoma, Hodgkin disease and non-Hodgkin lymphoma (NHL), the latter is most associated with pesticide carcinogens. Non-Hodgkin lymphoma begins when a blood cell (lymphocyte) becomes malignant and subsequently produces descendants of the single cell in which mutations (errors) have occurred. Although lymphoma can occur in any part of the body, tumors typically form
Pesticides and the food chain in the lymphatic system, meaning bone marrow, lymph nodes, the spleen, and blood. The initial symptoms are usually perceived as swelling around the lymph nodes at the base of the neck, fever, fatigue, and unexplained weight loss. Breast cancer is linked to organochlorine pesticides, which affect the endocrine system. Absorbed through ingested foods, the pesticides mimic, alter, or modulate hormonal activity and are therefore known as endocrine disruptors. Raising the activity and quality of estrogens the human body produces causes tumors to form. Pesticides are also linked to ovarian cancer, in that malignant ovarian tumors are endocrine related and hormone dependent. Atrazine, used on 96 percent of the United States corn crop, exists in most drinking water supplies in the Midwest and has been linked to birth defects in farmers’ children. Long-term exposure to atrazine has been linked to weight loss, cardiovascular damage, retina and muscle degeneration, and cancer. Organophosphate pesticides, which have largely replaced organochlorine pesticides, are connected with skin and eye problems, headaches, dizziness, nausea, vomiting, and abdominal pain. The thirty-seven compounds that make up this group destabilize a key enzyme in the brain known as cholinesterase, causing trauma to the brain and nervous system. Studies have related pesticide risk with respiratory problems, memory disorders, dermatologic conditions, cancer, depression, neurologic deficiencies, miscarriages, and birth defects. Primarily, these pesticides affect the nervous system by disrupting the enzyme that regulates acetylcholine, a neurotransmitter. Definitive proof that DDT is a human carcinogen is still lacking, but it has been associated with liver, lung, and thyroid tumors. History: More than four thousand years ago, Sumerians dusted sulfur on their crops to kill insects, and more than two thousand years ago, ancient Greeks used pesticides to protect their crops. By the fifteenth century, arsenic, mercury, and lead—highly toxic chemicals—were used on crops to eliminate insects. During the seventeenth century, farmers used nicotine sulfate, derived from tobacco leaves, as an insecticide, and in the nineteenth century, pyrethrum, extracted from chrysanthemums, and rotenone, removed from roots of tropical vegetables, were used as pesticides. In 1939 Swiss scientist Paul Müller discovered the potency of a compound made of carbon and hydrogen called dichlorodiphenyltrichloroethane (DDT), first used in World War II against typhus, plague, malaria, and dengue and yellow fevers. After the war, DDT use in the United States soared. Farmers killed pests such as boll 949
Pesticides and the food chain weevils that were devastating cotton crops, and the government used low-flying crop-dusting planes to rid the forests of gypsy moths. Other parts of the world began using DDT to combat malaria; after homes and huts were sprayed in North Africa, Asia, India, and Zanzibar, the number of malaria cases declined drastically. In 1962 Rachel Carson published Silent Spring, the product of more than four years of research, in which she maintained that pesticides were harming wildlife and the environment. Using meticulous documentation, Carson claimed that the government knew little about the dangers of pesticides. Although the book was criticized as well as praised, it spurred concerns about pesticides and other pollutants, leading to the beginning of the environmental movement and President Richard M. Nixon’s creation of the Environmental Protection Agency (EPA) in 1970. Soon the EPA targeted DDT, eventually banning it in 1972. Although time has proven Carson’s position on the harm from pesticides to wildlife correct, the idea that DDT is a human carcinogen is still being contested. In the years since its ban, DDT has been replaced by a huge array of insecticides, herbicides, and pesticides that have been tentatively linked with tumors and cancers of the lymphatic, endocrine, neurological, respiratory, and reproductive systems but have not been proven to to be carcinogens. Although studies have shown an increase in the rates of tumors or cancers in agricultural areas where large amounts of pesticides are used, scientific proof of the connection is inconclusive. Because of the gap in time between exposure and the first symptoms of illness (frequently decades) and the inability to pinpoint a particular pesticide as the carcinogen, definite scientific proof is hard to provide. Nevertheless, strict regulations are in effect: The EPA must approve any pesticide for sale or use in the United States, and the Food Quality Protection Act (1996) requires the oversight of the manufacture, distribution, and use of pesticides. Although the causal relationship between pesticides and cancer is hard to establish, pesticides have other proven health risks, and many people in the United States are trying to minimize or avoid their use. The EPA provides many suggestions on how to use pesticides more safely, and some people have turned to organically grown products as a way to avoid most pesticides. Because of the carcinogenic potential of pesticides, the organic foods industry has grown. The Organic Foods Production Act (1990) authorized national standards for the production, handling, and processing of organically grown agricultural products. Essentially, organic farming is an ecological system that avoids chemical pesticides, promotes soil conservation, and integrates the parts of the 950
Salem Health: Cancer farming system into an ecological whole. Although organic farming cannot guarantee that the soil does not contain pesticide residue, the practice follows methods designed to minimize contamination from air, soil, and water. Organic meat, poultry, eggs, and dairy products come from animals that are not given any antibiotics or growth hormones. Organic food is produced without using conventional pesticides or fertilizer made from synthetic ingredients or sewage sludge. Organic farms use cover crops, green manures, animal manures, and crop rotation to manage weeds, insects, and diseases and promote biological activity and long-term soil health. Mary Hurd, M.A. u
For Further Information Beres, Samantha. Pesticides: Critcal Thinking About Environmental Issues. Farmington Hills, Mich.: Greenhaven Press, 2002. Carson, Rachel. Silent Spring. 1962. Reprint. Boston: Mariner Books, 2007. Dunn, Jancie. “Toxic Overload: Teflon, Pesticides on Golf Courses, Plastic Bottles—An Explosion of Research Is Investigating Environmental Links and Breast Cancer.” Vogue, October, 2006, 326ff. Hemingway, Jean. “An Overview of Pesticide Resistance.” Science 5, no. 298 (October 4, 2003): 96-97. Izakson, Orna. “Farming Infertility: Country Living May Be Hazardous to Your Potency.” E/The Environmental Magazine 15, no. 1 (January/February, 2004): 40-41. Levine, Marvin J. The Toxic Time Bomb in Our Midst. Westport, Conn.: Praeger, 2007. National Research Council. Carcinogens and Anticarcinogens in the Human Diet. Washington, D.C.: National Academy Press, 1996. _______. Pesticides in the Diets of Infants and Children. Washington, D.C.: National Academy Press, 1993. Rosenberg, Tina. “What the World Needs Now Is DDT.” The New York Times, May 23, 2004, p. 8. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. Wright, Karen. “Testing Pesticides on Humans.” Discover 3, no. 12 (December, 2003): 66-69. u
Other Resources
National Cancer Institute Cancer Trends Progress Report—2007 Update: Pesticides http://progressreport.cancer.gov/doc_detail.asp?pid= 1&did=2007&chid=71&coid=713&mid=
Salem Health: Cancer
Peutz-Jeghers syndrome (PJS)
U.S. Environmental Protection Agency Pesticides http://www.epa.gov/pesticides/index.htm See also Acrylamides; Agent Orange; Aplastic anemia; Arsenic compounds; Astrocytomas; Bisphenol A (BPA); Coal tars and coal tar pitches; Coke oven emissions; Curcumin; Dietary supplements; Diethanolamine (DEA); Dioxins; Epstein-Barr virus; Erionite; Herbs as antioxidants; Macrobiotic diet; Neuroectodermal tumors; NonHodgkin lymphoma; Occupational exposures and cancer; Organochlorines (OCs); Pancreatic cancers; Premalignancies; Prevention; Richter syndrome; Risks for cancer; Vinyl chloride.
u Peutz-Jeghers syndrome (PJS) Category: Diseases, symptoms, and conditions Also known as: PJS, polyps and spots syndrome Related conditions: Unexplained hamartomatous mixed polyposis Definition: Peutz-Jeghers syndrome (PJS) is a rare disorder that causes the growth of multiple benign polyps in the stomach and small intestines. Most people with PJS have a family history of this inherited disorder, but it can also affect those without such a history. Polyps characteristic of the syndrome usually begin to develop during childhood or adolescence and have even been found in newborns. They often cause such medical problems as recurrent bowel obstructions, chronic bleeding, and abdominal pain, and they tend to become cancerous over time. PJS has also been found to increase an affected person’s risk of developing other cancers throughout the body, including breast, ovarian, uterine, pancreatic, testicular, and lung cancer. Risk factors: Peutz-Jeghers syndrome is genetically linked, meaning that it is associated with a defect, or mutation, in one or more genes. A person at increased risk of developing this disorder usually has family members with the disease. The risk factors for people who develop PJS without a familial link are unknown. In these cases, the disease appears to result from new mutations in the gene responsible for the disorder, so exposure to chemicals in the environment may also be a risk factor.
Etiology and the disease process: Peutz-Jeghers syndrome is caused by a mutation in a gene that aids in the control of cell growth and division. Normally, during conception, two copies of each gene are passed on to the child, one from the mother and one from the father. In PJS, one inherited copy of a gene called serine/threonine-protein kinase 11, or STK11, is defective and is present in all cells, disrupting the cells’ ability to control division. Research has shown that an additional gene mutation is necessary for PJS to cause cancer, either in the second copy of the STK11 gene or in another gene. Whether the person develops cancer and which organs will be affected depends on which cells are affected by the second mutation. It is believed that the defective STK11 gene is only one requirement in a process that involves mutations in other genes. Some people with defective STK11 genes do not develop cancer because the other mutations do not occur. Incidence: Peutz-Jeghers syndrome is considered a rare disorder; however, with estimates of its incidence ranging from 1 in 25,000 to 1 in 280,000 births, it is uncertain how many cases go undiagnosed. Symptoms: Individuals with Peutz-Jeghers syndrome commonly develop small, dark blue or brown spots that resemble freckles around the eyes, lips, and nostrils; inside the mouth; around the anus; and, frequently, on the hands and feet. They typically appear during infancy or early childhood and gradually fade as the person ages. Many symptoms depend on the location and extent of the polyps or cancer and can include abdominal cramps and pain,
Pigmentation on the lips of a male patient with Peutz-Jeghers syndrome. (©Watney Collection/Phototake–All rights reserved)
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Pharmacy oncology bloody urine and stools, anemia, and vomiting (possibly with blood). Gynecomastia, an abnormal enlargement of the breasts, typically precedes the development of testicular, ovarian, and uterine cancer. Other findings in a patient with PJS include ovarian cysts, benign ear tumors, rectal prolapse, intussusception (part of the bowel folds into itself), and bladder, ureteral, intestinal, bronchial, and nasal polyps. Screening and diagnosis: Screening for Peutz-Jeghers syndrome includes a blood test to look for a mutation in the STK11 gene. It is not routinely performed unless PJS is suspected or other family members have been diagnosed with the disorder. An accurate family history and extensive physical examination, including testing, are essential for the diagnosis of PJS. The syndrome is suspected when someone has a family history of PJS and the characteristic spots that accompany the disorder. Diagnostic tests should include an X ray of the abdomen, upper and lower gastrointestinal studies, stools for occult blood, mammography, testicular ultrasound, and colonoscopy or sigmoidoscopy. Staging of PJS is based on the cancers that develop. Treatment and therapy: Treatment of Peutz-Jeghers syndrome may include surgery to remove polyps that are causing chronic problems and to decrease bowel loss caused by intussusception. Repeated surgery to remove part of the intestine is common in PJS and often results in short-bowel syndrome, a condition that develops after bowel surgery, when there is not enough surface area in the bowel to absorb sufficient nutrients from food. If this occurs, special nutritional interventions are required. The primary goal in treating PJS, however, is the early identification of malignancies. Physical examinations and screening tests should be scheduled at recommended intervals to monitor polyps and detect cancers. Surveillance programs typically recommend that colon and testicular cancer screenings start between ages eight and ten and that screening for most other cancers starts by age twenty. Other treatments are specific to any cancers that may be identified. Prognosis, prevention, and outcomes: The incidence of cancer in people with Peutz-Jeghers syndrome is high; it is estimated that 93 percent will develop cancer by age sixtyfour. Breast (50 percent), colorectal (40 percent), pancreatic (35 percent), and stomach (30 percent) cancers are among the most common. Deaths result from complications of polyps, repeated surgeries, or cancer. There is no known method of preventing PJS. Dorothy P. Terry, R.N. 952
Salem Health: Cancer u
For Further Information Bourke, B., et al. “Peutz-Jeghers Syndrome and Management Recommendations.” Clinical Gastroenterology and Hepatology 4, no. 12 (December, 2006): 1550. Gunabushanam, G., et al. “Peutz-Jeghers Syndrome.” Pediatric Radiology 36, no. 8 (August, 2006): 888-889. Hearle, N., et al. “Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome.” Clinical Cancer Research 12, no. 10 (May 15, 2006): 3209-3215.
u
Other Resources
Genetics Home Reference Peutz-Jeghers Syndrome http://ghr.nlm.nih.gov/condition= peutzjegherssyndrome Peutz-Jegher’s Syndrome http://www.peutz-jeghers.com/ See also Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer screening; Family history and risk assessment; Gastric polyps; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Juvenile polyposis syndrome; Pancreatic cancers; Polyps; Sertoli cell tumors; Small intestine cancer.
u Pharmacy oncology Category: Medical specialties Also known as: Oncology pharmacy, hematology/ oncology pharmacy Definition: Pharmacy oncology is the specialized practice of pharmacy with the specific goals of reducing the cancer care burden and of promoting optimal, cost-effective, safe cancer care. According to the Board of Pharmacy Specialties, which certifies oncology pharmacists, pharmacy oncology specialists “recommend, design, implement, monitor, and modify pharmacotherapeutic plans to optimize outcomes in patients with malignant diseases.” The practice of oncology pharmacy, when incorporated into multidisciplinary care, provides cancer patients with the best access and control of treatment options. It also provides educational and research support to other members of the interdisciplinary cancer care team. Subspecialties: Community oncology pharmacy, chemotherapeutics Cancers treated: All Training and certification: Clinical, registered pharmacists with a bachelor of science in pharmacy (BSP) or doc-
Salem Health: Cancer tor of pharmacy (Pharm.D.) may be found working in hospital or clinical settings and in nontraditional community oncology settings, such as individual oncologist offices or retail pharmacies that specialize in chemotherapeutic treatments. In addition to practical experience in drug information, intravenous (IV) admixture, and patient interaction, pharmacists have structured educational opportunities to become pharmacy oncology specialists. On-site training with an existing oncology pharmacist and the oncology team is often provided to individual pharmacists in institutional or community pharmacies, and residencies and fellowships in oncology are available to newly graduated or practicing pharmacists with a doctor of pharmacy. Residency programs entail one full year of practical study in general clinical pharmacy; thereafter, students apply for a specialty residency in oncology. The specialty oncology residency requires another full year of practical study in a purely cancer-based setting. For this residency, the pharmacist is mentored by an existing specialty oncology pharmacist and participates in patient care as part of the health professional team. Examples of educational instruction topics for oncology residencies include adult medical oncology, bone marrow transplantation, pediatric oncology, palliative and pain care, surgical oncology, immunotherapy, radiation oncology, and pharmaceutical management. Residency programs typically require a doctor of pharmacy for application and, after successful completion, provide the pharmacist the necessary requirement for more intense training. For pharmacists interested in training beyond residency programs, fellowship positions in oncology are available. Such postdoctoral fellowships are generally two-year positions that provide pharmacists an opportunity to focus their knowledge in oncology topics. Fellowship programs are often highly specific and include instruction on topics such as the clinical pharmacology of chemotherapeutic and related medications, study design and analysis techniques, presentation and publication of scientific data, pharmacokinetic and pharmacodynamic modeling, therapeutic drug monitoring of individual agents, and drug information management and analysis. Deeper involvement with the oncology care team and with oncology research is provided in fellowship positions. An oncology specialty certification may be awarded by the Board of Pharmacy Specialties to pharmacists who meet the following minimum criteria: The registered pharmacist must have completed at least three years of practice, with a substantial amount of that time spent in oncology settings, or must have completed a specialty residency in oncology pharmacy plus one year of practice, with a substantial portion of that year spent in oncology settings.
Pharmacy oncology In addition, the pharmacist must pass a stringent written test, the Oncology Pharmacy Specialty Certification Examination. After meeting these criteria and applying to the Board of Pharmacy Specialties for certification, the pharmacist may be designated a board-certified oncology pharmacist (BCOP). The pharmacist may retain this title as long as recertification requirements are met every seven years, by either retaking and passing the examination or completing one hundred hours of continuing education; both the exam and education are provided by the Board of Pharmacy Specialties. Services and procedures performed: Oncology pharmacists provide numerous services to the health care team and to patients. Oncology pharmacists may be found in hospital-based or office-based oncology clinics or in standalone community pharmacies that service nearby cancer providers. Although they vary between settings, all services provided by oncology pharmacists fall into a handful of categories: educational and counseling services, drug administration and monitoring services, supportive care services, research and guidelines development services, medication safety services, and economic benefits. Oncology pharmacists regularly provide educational services to other members of the health care team and counseling services to patients. Pharmacists provide safehandling instructions to nurses who handle and administer cytotoxic drugs. They provide intravenous (IV) admixture instruction to pharmacists and technicians to prevent chemotherapy incompatibilities and provide IV administration instruction to nurses to prevent medication errors. Oncology pharmacists educate all members of the health care team about medication-error prevention, including instruction about confusing, similar-sounding or similarly written medication names. They often contribute to the development and enforcement of the institution’s best practices in cancer care. In direct interactions with patients, pharmacists provide safe handling and administration instructions of cytotoxic drugs, and they provide dosing suggestions and methods to manage medication side effects. In addition, pharmacists who counsel cancer patients have the opportunity to reinforce the treatment goals and address adherence issues or other patient concerns. In community settings especially, oncology pharmacists contribute to the continuity of care by supporting and managing even complex outpatient treatments, thus keeping patients out of the hospital for longer durations and by providing another source of communication between the patient and primary cancer care provider. Drug information services are a primary responsibility 953
Pharmacy oncology of pharmacists on the oncology care team. In addition to providing specific drug suggestions and knowledge about drug interactions and incompatibilities, side effects, and handling risks associated with chemotherapy, pharmacists are able to evaluate pharmacokinetic and pharmacodynamic effects of drugs and regimens. They interpret laboratory changes and other treatment-related problems and adjust chemotherapy regimens accordingly. By performing therapeutic drug monitoring for specific agents, pharmacists anticipate and prevent drug toxicities or subtherapeutic risks as well. In addition to providing information about chemotherapy regimens, oncology pharmacists are trained to safely perform chemotherapy admixture and can provide this service even to outpatients in a community oncologist office setting. Supportive care services offered by the oncology pharmacist include antiemetic and pain-control care. By developing and implementing antiemetic regimens according to the emetic potential of chemotherapy regimens, oncology pharmacists help minimize or even eliminate this common side effect of chemotherapy. Pharmacists often oversee the provision of pain management and palliative care with medications. Because of their extensive medication knowledge, oncology pharmacists are able to manage these cancer-related concerns and also anticipate and prevent the associated side effects or drug interactions that may occur with the drug therapy of pain or emesis. Pharmacists often contribute to the interdisciplinary team by providing access to drug-related databases and by presenting new research findings on drug therapy or updated regimens, within an institution in a brown-bag or continuing-education setting or to the larger medical field through publications in journals. In addition, oncology pharmacists play a role in developing institutional treatment guidelines for specific cancers or cancer-related health issues along with other team members and in evaluating medication use practices and offering improvements. Related to these contributions, oncology pharmacists provide medication safety services, such as reporting medication errors to MedWatch or other oversight and reporting organizations. They also ensure that cytotoxic medications are properly stored and prepared by professionals and ensure that professionals use appropriate protective measures during preparation. Lastly, oncology pharmacists reduce cancer-care costs to patients and to providers by ensuring the smooth delivery of cancer care. In particular, oncology pharmacists are able to recommend affordable treatment options, to decrease waste from incorrect medication handling, and to streamline treatment plans by removing unnecessary or replacing overly toxic medications. 954
Salem Health: Cancer Related specialties and subspecialties: Related specialties in the cancer field include medical oncology, nursing oncology, and radiation oncology. Together with oncology pharmacists, members of these fields make up a typical interdisciplinary cancer care team. Related specialties in the pharmacy field include IV admixture pharmacy, nutrition pharmacy, pain-management pharmacy, and clinical pharmacology and pharmaceutics. Pharmacists may also complete certification programs in nutrition pharmacy and in clinical pharmacology. Nicole M. Van Hoey, Pharm.D. u
For Further Information Holdsworth, M. T. “State of Oncology Pharmacotherapy.” The Annals of Pharmacotherapy 40, no. 12 (December, 2006): 2238-2239. Liekweg, A., M. Westfeld, and U. Jaehde. “From Oncology Pharmacy to Pharmaceutical Care: New Contributions to Multidisciplinary Cancer Care.” Support Care Cancer 12, no. 2 (February, 2004): 73-79. Nygren, P. “The Pharmacist and Quality of Cancer Chemotherapy.” Acta Oncologica 46, no. 6 (2007): 715716. Semaan, N. “Integration of Complementary Disciplines into the Oncology Clinic. Part III, Herbal MedicineDrug Interactions: The Role of the Pharmacist.” Current Problems in Cancer 24, no. 4 (July/August, 2000): 213-222. u
Organizations and Professional Societies
American Society of Health-System Pharmacists (ASHP) http://www.ashp.org/s_ashp/index.asp 7272 Wisconsin Avenue Bethesda, MD 20814 Hematology/Oncology Pharmacy Association (HOPA) http://www.hoparx.org 175 Wall Street Princeton, NJ 08540 u
Other Resources
Board of Pharmacy Specialties http://www.bpsweb.org Canadian Association of Pharmacy in Oncology http://www.capho.org/about.htm
Salem Health: Cancer International Society of Oncology Pharmacy Practitioners http://www.isopp.org See also Case management; Overtreatment; Palliative treatment.
u Phenacetin Category: Chemotherapy and other drugs; carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1980 Also known as: Saridon, Acetophenetidin Related cancers: Urothelial neoplasms, especially transitional cell carcinoma of the renal pelvis and bladder Definition: Phenacetin is an analgesic and antipyretic introduced in 1887. It was linked to urothelial neoplasms, especially transitional cell carcinoma of the renal pelvis and bladder, as well as interstitial nephritis in combination with renal papillary necrosis and was removed from the market in 1983. Exposure routes: Oral ingestion Where found: Sold as an analgesic and antipyretic (feverreducing) medication At risk: All who have taken medications containing phenacetin Etiology and symptoms of associated cancers: The cause and mechanism of the nephropathic change due to phenacetin in humans is unknown, but the renal lesion sometimes seen was interstitial nephritis in combination with renal papillary necrosis. When administered in the diet, phenacetin caused benign and malignant tumors of the urinary tract in mice and rats of both sexes and of the nasal cavity in rats of both sexes, according to studies by the International Agency for Research on Cancer (IARC). There is limited evidence for the carcinogenicity of phenacetin in humans because this medication was usually taken mixed with other drugs. History: Phenacetin, first introduced in 1887, was used principally as an analgesic and fever reducer. Its analgesic effects are reportedly because of its actions on the sensory tracts of the spinal cord. In addition, phenacetin acts as a negative inotrope on the heart, weakening the heart’s muscular action. Phenacetin also was once used as a stabi-
Phenolics lizer for hydrogen peroxide in hair-bleaching preparations. Many case reports provided evidence that abuse of analgesic mixtures containing phenacetin resulted in kidney cancer (cancer of the renal pelvis). It was implicated in kidney disease (nephropathy) and renal papillary necrosis due to abuse of analgesics and was withdrawn from the U.S. market in 1983. Phenacetin was first listed in the First Annual Report on Carcinogens (RoC; 1980), and analgesic mixtures containing phenacetin were first listed in the Fourth Annual Report on Carcinogens (1985). Debra B. Kessler, M.D., Ph.D. See also Adenocarcinomas; Bladder cancer; Gallbladder cancer; Gastrointestinal oncology; Kidney cancer; Renal pelvis tumors; Transitional cell carcinomas; Urethral cancer; Urinary system cancers.
u Phenolics Category: Complementary and alternative therapies ATC code: D08AE Also known as: Phenols Definition: Phenolics are a class of compounds grouped together because of their chemical structure; they are aromatic compounds (containing benzene rings), usually with hydroxyl groups. Their function varies, however, and they may have a protective role against many cancers. Subclasses of this group are benzenediols, capsaicinoids, monolignols, and phenol ethers. Cancers treated or prevented: Primarily breast cancer Delivery routes: Oral in diet, pills, or capsules How these compounds work: Phenolic acids have become the topic of much study for their protective role against many cancers. Examples of phenolics include gallic acids, curcumin, and ferulic acids. Found in abundance in many plants, phenolics in even low concentrations decrease cell proliferation, which makes them critically important in the shrinkage of cancer cells and concurrent reduction in size of tumors. Though the exact mechanisms by which phenolics work as antiproliferative substances in the treatment of cancer is unclear, a diet consisting of many fruits and vegetables seems to play an important role in cancer prevention and aids in cancer treatment by reducing tumor size and spread. Proposed mechanisms by which these phenolic acids function include antioxidant effects, steroid receptor bind955
Pheochromocytomas ing, direct interaction with intracellular elements and signaling systems, and aryl hydrocarbon receptor (AhR) binding and modification of subsequent pathways. Polyphenols and phenolic acids are rich in antioxidants, which reduce the concentration of harmful free radicals in the human body. Binding to receptor sites and inhibiting particular enzymes inhibits cell growth and prevents the inflammatory response of surrounding healthy tissues. As a result of their oxidation-reduction properties, they efficiently inactivate oxyl radicals and repair amino acid and deoxyribonucleic acid (DNA) base radicals. Phenols also induce apoptosis (scheduled cell death) and restrict the formation of new blood vessels. This active mechanism of phenolics is an important feature, since both growth and metastasis of a tumor depends heavily on angiogenesis (blood vessel formation) to provide oxygen and nutrients to the growing tumor cells. Numerous laboratory studies have shown that phenolic acids inhibit the growth of cancerous cell in vitro. Unfortunately, studies performed in vivo do not show such clear benefits. Much of this may be attributable to differences in lifestyle or genetics. One promising study, however, showed that individuals who were prescribed low doses of aspirin had a decreased risk of developing colon cancer. The main metabolite of aspirin is a phenolic acid called salicylic acid. Salicylic acid is also found in plants, where it exists as a protective hormone. Its presence in fruits and vegetables may explain their oncoprotective role when made a staple in the human diet. Many more studies are currently being conducted on this matter. Side effects: There are no known side effects of phenolics in the diet, but phenolics can be toxic at excessive levels for those who have phenol sulfotransferase (PST) deficiency, a disease that results from a difficulty in processing phenols into useful or at least nonharmful substances. In this case, phenols in the diet should be reduced or an agent used to facilitate processing. Dwight G. Smith, Ph.D. See also Angiogenesis; Antioxidants; Beta-carotene; Bioflavonoids; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Calcium; Carotenoids; Chemoprevention; Clinical breast exam (CBE); Coenzyme Q10; Complementary and alternative therapies; Cruciferous vegetables; Curcumin; Dietary supplements; Essiac; Free radicals; Fruits; Garlic and allicin; Glutamine; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Nutrition and cancer prevention; Phytoestrogens; Resveratrol; Wine and cancer. 956
Salem Health: Cancer
u Pheochromocytomas Category: Diseases, symptoms, and conditions Also known as: Chromaffin cell tumors, PCC Related conditions: Early-onset hypertension, medullary thyroid cancer, multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau (VHL) disease, neurofibromatosis type 1, and abnormalities in succinate dehydrogenase subunit B (SDHB) and succinate dehydrogenase subunit D (SDHD) Definition: Pheochromocytomas are tumors of chromaffin cells, neuroendocrine cells of the sympathetic nervous system (SNS). Their primary locations are in the adrenal medulla and sympathetic nervous system ganglia. These cells produce and secrete norepinephrine and epinephrine, vital agents in human survival that contribute to the fightor-flight stress response. Pheochromocytomas are predominantly adrenal medulla tumors but may be found in other chromaffin cell locations, including the abdomen, thorax, and neck. Extra-adrenal tumors are called paragangliomas. Pheochromocytomas and paragangliomas may be benign or malignant. Risk factors: The risk factors for the majority of the cases of pheochromocytomas are unknown. However, in cases where there is a family history of the disease, the primary risk factor is having a parent with the disease. Inheritance is by the autosomal dominant mechanism, so a person with the disease has a 50 percent chance of passing the abnormal gene and therefore the disease to his or her child. Etiology and the disease process: The majority of pheochromocytomas have no known genetic basis and are termed sporadic. However, approximately 25 percent have a genetic etiology and are associated with specific syndromes such as multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau disease, neurofibromatosis type 1 (NF1), succinate dehydrogenase subunit B (SDHB), and succinate dehydrogenase subunit D (SDHD) abnormalities. The MEN syndromes, caused by abnormalities on chromosome 10, make certain endocrine glands become overactive. MEN 2a causes pheochromocytomas, medullary thyroid cancer in early adulthood, and hyperparathyroidism, while MEN 2b manifests as pheochromocytomas, medullary thyroid cancer in early childhood, and neuromas, especially of the lips and tongue. Von Hippel-Lindau disease is characterized by angiomas in the eye, hemangioblastomas of the brain and spinal cord, renal cell cancer, and pheochromocytomas. The VHL gene located on chromosome 3 normally func-
Salem Health: Cancer
Pheochromocytomas
tions as a tumor suppressor and inhibits uncontrolled cell proliferation. Mutations result in tumor growth. Neurofibromatosis type 1 is a neurocutaneous disorder characterized by multiple café-au-lait spots and neurofibromas of the skin and nerves. Malignant connective or other soft-tissue neoplasms are common. The NF1 gene is also a tumor suppressor. Located on chromosome 17, this gene can undergo mutations that result in abnormal cell growth and tumor formation. Succinate dehydrogenase (SDH) is a component of the Krebs cycle and the mitochondrial respiratory chain. Four subunits have been identified: SDHA, SDHB, SDHC, and SDHD. SDHB and SDHD mutations correlate with extraadrenal malignant paragangliomas, SDHB more so than SDHD mutations. Metastasis is common and precludes a cure. Incidence: The rate of occurrence of pheochromocytoma is between 1 in 2,000 and 1 in 6,000 people. The annual occurrence rate is between 500 and 1,000 cases per year. Additional occurrences have been detected on autopsy. Symptoms: Symptoms are related to elevated levels of catecholamines and metanephrines. Since pheochromocytomas release these agents intermittently, symptoms are paroxysmal. The most common symptoms include autonomic disturbances such as hypertension, tachycardia, palpitations, tachypnea, and sweating. In addition headache, flushing of the face, nausea and vomiting, chest pain, anxiety, nervousness, panic, and a sense of impending doom are often noted. Screening and diagnosis: Detection of a pheochromocytoma can involve multiple and repeated testing, which can be time-consuming and expensive. The failure to detect the presence of a pheochromocytoma can be lifethreatening to the individual.
Relative Survival Rates for Malignant Pheochromocytoma, 1988-2001 Survival Rates (%) Gender
1-Year
3-Year
5-Year
10-Year
Men Women Total
83.9 85.1 84.5
73.4 72.6 73.0
67.3 62.4 64.8
29.7 58.9 44.0
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Laboratory evaluation includes urine and blood sampling. Urinary tests are done for the presence of metanephrines and vanillyl mandelic acid (VMA). Plasma measurements are done for metanephrines and catecholamines. Urine testing is less sensitive and specific. Metanephrines (normetanephrine and metanephrine) are metabolites of norepinephrine and epinephrine, the catecholamines normally secreted by the adrenal medulla but with increased levels in pheochromocytoma. A negative test reliably excludes the presence of a pheochromocytoma and avoids the sometimes false negative results obtained when plasma catecholamine values are obtained. Generally, a negative metanephrine plasma test precludes further testing. Accurate evaluation requires the avoidance of caffeine and acetaminophen before testing. When a pheochromocytoma is diagnosed by laboratory methods, radiological evaluation helps identify the location and extent of any tumors. Magnetic resonance imaging (MRI), metaiodobenzylguanidine (MIBG) scintigraphy, and dopa positron emission tomography (PET) scanning are the most reliable methods of choice. Treatment and therapy: Treatment of pheochromocytomas is by surgical removal, either through a traditional open incision or by newer laparoscopic techniques using several small incisions, a small camera, and long instruments. If only one adrenal gland is affected, typically the entire gland is removed. When bilateral involvement is present, attempts may be made to salvage the adrenal cortex. If this is not possible, lifelong adrenal medication supplementation will be required. It is possible that in the future, drugs will be developed to prevent endocrine gland overactivity and inhibition of angiogenic factors. In patients with metastatic pheochromocytomas, a regimen of chemotherapy, radiation, somatostatin analogs, and 131I-MIBG is utilized. The survival rate is poor. Prognosis, prevention, and outcomes: Since about 15 percent of patients with pheochromocytomas have a genetic basis for associated syndromes, they are candidates for genetic counseling and chromosomal analysis. Surgical removal of the pheochromocytoma alleviates symptoms associated with sympathetic nervous system involvement. Early and consistent screening for medullary thyroid cancer development leads to diagnosis and treatment in earlier stages of the disease, making a cure more possible. Total thyroidectomy prevents thyroid cancer but requires the patient to undergo lifelong thyroid medication supplementation. Malignant pheochromocytomas and paragangliomas have a mean survival rate of three years. Wanda Todd Bradshaw, R.N.C., M.S.N. 957
Pheresis u For Further Information Benn, Diana E., et al. “Clinical Presentation and Penetrance of Pheochromocytoma/Paraganglioma Syndromes.” Journal of Clinical Endocrinology and Metabolism 91, no. 3 (2005): 827-836. Neumann, Hartmut P., B. Bausch, et al. “Germ-Line Mutations in Nonsyndromic Pheochromocytoma.” New England Journal of Medicine 346 (2002): 1459-1466. Neumann, Hartmut P., A. Vortmeyer, et al. “Evidence of MEN-2 in the Original Description of Classic Pheochromocytoma.” New England Journal of Medicine 357 (2007): 1311-1315. Scholz, Tim, et al. “Current Treatment of Malignant Pheochromocytoma.” Journal of Clinical Endocrinology and Metabolism 92, no. 4 (2006): 1217-1225. u
Other Resources
National Cancer Institute Pheochromocytoma http://www.cancer.gov/cancertopics/types/ pheochromocytoma
Salem Health: Cancer Pheochromocytoma Organization http://www.pheochromocytoma.org/sys-tmpl/door/ See also Adrenal gland cancers; Antidiarrheal agents; Endocrine cancers; Endocrinology oncology; Hemangioblastomas; Medulloblastomas; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Neurofibromatosis type 1 (NF1); Nuclear medicine scan; Parathyroid cancer; Thyroid cancer; Von Hippel-Lindau (VHL) disease.
u Pheresis Category: Procedures Also known as: Apheresis, automated blood collection Definition: Pheresis is a process in which the patient’s blood is withdrawn from the body, the white blood cells or platelets are removed from the blood, and then the blood is returned back to the patient. Therapeutic pheresis is used to treat patients who have an elevated white blood count or
Here pheresis is being used to treat a patient with chronic lymphoblastic leukemia. (Antonia Reeve/Photo Researchers, Inc.)
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Salem Health: Cancer platelet count related to a cancer disease process. Pheresis is also used to collect donor platelets from healthy people to be given to cancer patients who have no platelets. Cancers treated: Hematological (blood) cancers
Photodynamic therapy (PDT) ditional medications, then the count will again rise to an unsafe level and the patient will need to receive pheresis therapy again. Katrina Green, R.N., B.S.N., O.C.N.
Why performed: Blood cancers can cause the bone marrow to malfunction and produce too many platelets or white blood cells, creating a life-threatening situation if the levels of these cells are not decreased. Oral medications can be given if levels are only slightly elevated, but for more acute cases, pheresis may be used. Specialized pheresis treatments are also performed. Photopheresis is used to treat graft-versus-host disease as well as lymphoma. Pheresis is also used to harvest stem cells for bone marrow transplantation. Therapeutic plasma exchange is used to treat the side effects of lung cancer, breast cancer, colon cancer, thymomas, and Hodgkin disease.
u
Patient preparation: Patients who have low levels of calcium may need to take a calcium supplement prior to having pheresis done. Patients may also receive calcium tablets during the procedure to help with the side effects associated with low calcium counts.
National Cancer Institute http://www.cancer.gov
Steps of the procedure: The patient is positioned for comfort, usually in a recliner or a bed. An intravenous (IV) line is placed in the arm, usually the inner elbow, to allow for the blood to be withdrawn. The blood travels from the IV through a tube and then circulates through the pheresis machine to pull out the cells. The blood is then returned into the other arm through another IV that is placed there. This procedure can take two to three hours to perform and is done in a variety of settings. Pheresis can be done at the bedside, in a clinic, or even in a mobile pheresis lab. After the procedure: After pheresis, the patient will be monitored for bleeding from the IV site. Pressure may need to be applied for five to ten minutes directly to the insertion site. Patients will also be monitored for tingling of the face and arms, which indicates low calcium levels, as well as dizziness. Cancer patients with an elevated platelet count or white blood cell count have their counts lowered to a safe level and then are placed on an oral agent or receive chemotherapy to maintain the safe levels. Risks: Bleeding and infection may occur. Rare episodes of an air embolus have occurred with the removal of access lines. Results: The patient will have the blood count lowered to a safe level in order to receive chemotherapy for the underlying cancer diagnosis. If a patient is given pheresis because the count is too high and does not follow up with ad-
For Further Information Tabuchi, T., et al. “Granulocyte Apheresis as a Possible New Approach in Cancer Therapy: A Pilot Study Involving Two Cases.” Cancer Detection & Prevention 23, no. 5 (1999): 417-421.
u
Other Resources
American Cancer Society http://www.cancer.org American Red Cross http://www.redcross.org
See also Blood cancers; Bone marrow transplantation (BMT); Breast cancers; Chronic myeloid leukemia (CML); Infection and sepsis; Lambert-Eaton myasthenic syndrome (LEMS); Leukapharesis; Lymphomas; Myasthenia gravis; Mycosis fungoides; Myeloproliferative disorders; Side effects; Waldenström macroglobulinemia (WM).
u Photodynamic therapy (PDT) Category: Chemotherapy and other drugs ATC code: 101XD Definition: Photodynamic therapy (PDT) is an emerging modality for treating local precancerous and cancerous lesions of epithelial origin. The technology relies on a class of anticancer drugs called photosensitizers that become active when exposed to specific light wavelengths, usually from a laser beam. Minimally invasive, PDT is also used to treat nonmalignant diseases, particularly the ocular condition known as wet age-related macular degeneration. Cancers treated: Esophageal cancer, lung cancer, bladder carcinoma, nonmelanoma skin cancer Subclasses of this group: Currently, most of the clinically approved photosensitizers are porphyrins, but other drugs under clinical investigation belong to the chlorin or purpurin family. Delivery routes: Intravenous or topical, depending on the drug’s chemical structure and the type of cancer and its location 959
Phyllodes tumors
Salem Health: Cancer
Common Photosensitizers Drug (Other Names)
Brands
Subclass
Aminolevulinic acid (5-aminolevulinic acid, ALA)
Levulan
Porphyrin Topical
Actinic keratosis (precancerous skin lesion)
Methyl aminolevulinate (m-ALA)
Metvix
Porphyrin Topical
Actinic keratosis, skin cancer
Porfimer sodium
Photofrin Porphyrin IV
Temoporfin Foscan (meta-tetrahydroxyphenylchlorin, mTHPC)
Chlorin
How these drugs work: The first clinical application of PDT was reported in 1903 by two German researchers, who used a topical coal tar dye called eosin in combination with visible light to treat skin cancer. The isolation of safer and more effective photosensitive dyes, called porphyrins, has propelled the field forward. Photosensitizers preferentially accumulate in abnormal tissues and cause little damage to surrounding healthy cells. PDT is a two-part process. First, a nontoxic photosensitizer is administered to the patient. The lesion site is then exposed to light that is of a suitable wavelength to excite the photosensitive drug. Activated drug molecules initiate cytotoxic reactions that destroy tumor cells. They transfer energy to molecular oxygen, which, in turn, generates reactive oxygen species (ROS), such as singlet oxygen. These active molecular species damage deoxyribonucleic acid (DNA) and cause the oxidation of proteins and lipids. As a result, cancer cells undergo necrosis or apoptosis, the natural process of cell death. Because light needed to activate most photosensitizers cannot penetrate deeply into tissue, the therapeutic potential of PDT is limited to the treatment of local superficial tumors rather than large tumors or metastases. Side effects: One side effect of PDT is increased sensitivity to light (sunburn-like reactions), which may last for several weeks after administration. Other side effects include constipation, irritation at the injection site, back pain, chest pain, fever, flulike syndrome, and general weakness. Anna Binda, Ph.D. See also Basal cell carcinomas; Bile duct cancer; Bladder cancer; Bone cancers; Bowen disease; Cutaneous breast cancer; Esophageal cancer; Keratosis; Laser therapies; Lung cancers; Skin cancers; Squamous cell carcinomas. 960
Delivery Mode Conditions Treated
IV
Barrett esophagus (precancerous lesion), esophageal cancer, cervical cancer, lung cancer, stomach cancer, superficial bladder cancer Head and neck cancer
u Phyllodes tumors Category: Diseases, symptoms, and conditions Also known as: Phylloides tumors, cystosarcoma phyllodes Related conditions: Fibroadenomas Definition: Phyllodes tumors are masses that originate in the connective tissue of the breast. The term “phyllodes” comes from a Greek word meaning leaf. The tumor is sonamed because it has leaflike projections seen on cross section. Most are benign, or noncancerous, and the rate of malignancy is estimated to be from 23 to 50 percent. A small percentage of phyllodes tumors occur in men, usually in the breast and occasionally in the stromal tissue of the prostate gland. Risk factors: Women with a history of fibroadenoma, a benign breast tumor, may be at higher risk. Etiology and the disease process: The cause of phyllodes tumors is not known. They develop in the connective, or stromal, tissue of the breast and can penetrate into ductal tissue or cystic spaces. They usually have a glandular component as well. These tumors may grow slowly for years, then enlarge rapidly over a period of weeks or months. Because of their rapid growth, most phyllodes tumors are discovered on self-examination. If left untreated, they can encompass the entire breast. Incidence: Phyllodes tumors are rare, making up less than 1 percent of breast masses, or about 1 in 100,000. The overall risk of malignancy is low, about 2 per 1 million women. Phyllodes tumors usually occur in adult women, the average age at diagnosis being forty to fifty years, though they sometimes occur in adolescents or the elderly.
Salem Health: Cancer Symptoms: The most common symptom of phyllodes tumors is a firm, moveable, rapidly enlarging breast mass. Pressure from the tumor mass can compress the skin of the breast and cause it to appear translucent or bluish with dilated blood vessels. Tumors sometimes break through the skin and cause ulceration. Some tumors are painful; others are not. Metastasis, or spread to other parts of the body, from cancerous tumors can cause pain at the site of metastasis. Screening and diagnosis: Mammograms reveal phyllodes tumors to be smooth or lobular masses with welldefined borders. Ultrasound examination or other imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), may be used to locate and size phyllodes tumors, but, because of similarities between benign and malignant phyllodes tumors and between phyllodes tumors and fibroadenomas, diagnosis is based on histology, or microscopic examination, of a tumor sample. Fibroadenomas can be diagnosed by needle biopsy and imaging studies, but these methods are not adequate for diagnosis of phyllodes tumors. Excisional or core biopsy is essential to their diagnosis. Histologic factors that help differentiate benign from malignant phyllodes tumors, and both from other tumors, include degree of cellularity, cellular atypia, and growth pattern. Immunostaining of tumor cells is useful in differentiating phyllodes tumors from fibroadenomas because of markedly increased stromal cellularity in phyllodes tumors. Phyllodes tumors are classified as benign, borderline, or malignant. Benign tumors have largely normal cell growth and differentiation. Malignant tumors have a high number of mitotic figures, or rapidly dividing cells (10 or more per 10 high power fields), infiltrating margins, and marked atypia of cells (2-3+). Borderline tumors have some features of both benign and malignant growths, with 5 to 9 mitotic figures per 10 high power fields, pushing or infiltrating margins, and 2+ cellular atypia. Even within these guidelines, phyllodes tumors are difficult to evaluate, and their growth is unpredictable. For this reason, more than one review of tumor cells is warranted in every case. Treatment and therapy: The most common treatment for phyllodes tumors is surgical excision, or removal, of the lesion. A wide margin of normal cells (1 to 2 centimeters, or cm) is removed with the tumor to reduce the chance of recurrence. Tumor size varies from about 5 to 30 cm. Mastectomy, or removal of the entire breast, may be the treatment of choice for large tumors or for any tumor that recurs. The treatment is the same for benign and malignant tumors, as chemotherapy, radiation, and hormone therapy
Phyllodes tumors have not, in most cases, been effective against cancerous phyllodes tumors. Prognosis, prevention, and outcomes: The prognosis, or most likely outcome, for phyllodes tumors varies because growth and chance of recurrence are unpredictable. Benign tumors can recur, sometimes with more aggressive or malignant growth. The recurrence rate is reported to be from 1 to 35 percent for benign tumors and 27 to 35 percent for malignant tumors. About one-fourth of malignant tumors metastasize. The lungs, bones, chest wall, and abdominal organs are the most common sites of metastasis. Metastasis is usually fatal within three years of diagnosis. Because treatment options are limited, close follow-up, even for benign tumors, is essential for the best long-term results. Cathy Anderson, R.N., B.A. u
For Further Information Beers, M. H., and R. Berkow, eds. “Cystosarcoma Phyllodes.” In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, N.J.: Merck Research Laboratories, 2004. Esposito, N. N., et al. “Phyllodes Tumor: A Clinicopathologic and Immunohistochemical Study of Thirty Cases.” Archives of Pathology and Laboratory Medicine 130, no. 10 (2006): 1516-1521. Jacobs, T. W., et al. “Fibroepithelial Lesions with Cellular Stroma on Breast Core Needle Biopsy: Are There Predictors of Outcome on Surgical Excision?” American Journal of Clinical Pathology 124, no. 3 (2005): 342354. Wang, Z. C., A. Buralmoh, J. D. Iglehart, and A. Richardson. “Genome-Wide Analysis for Loss of Heterozygosity in Primary and Recurrent Phyllodes Tumor and Fibroadenoma of Breast Using Single Nucleotide Polymorphism Arrays.” Breast Cancer Research and Treatment 97, no. 3 (2006): 301-309.
u
Other Resources
American Cancer Society What Is Breast Cancer? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_breast_cancer_5.asp American Society of Breast Disease http://www.asbd.org See also Benign tumors; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Computed tomography (CT) scan; Fibroadenomas; Imaging tests; Magnetic resonance imaging (MRI). 961
Phytoestrogens
u Phytoestrogens Category: Lifestyle and prevention Also known as: Soy isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), coumestans (coumestrol) Definition: Phytoestrogens are naturally occurring, estrogen-like chemicals found in many plants. There are three basic categories of phytoestrogens: isoflavones, lignans, and coumestans. They come primarily from food sources. Cancers treated or prevented: May mitigate breast, prostate, uterine, and possibly lung and colon cancers Delivery routes: Oral through diet, pill, or capsule
Salem Health: Cancer clover, green tea, hops, alfalfa, licorice, citrus peel, and flax seeds; herbal teas are considered longevity tonic. Phytoestrogens are also marketed in pill and capsule form as food supplements. The U.S. Food and Drug Administration (FDA) does not regulate food supplements for safety and effectiveness; these supplements are not recommended, as their safety has not been established and could increase the incidence of cancer. Phytoestrogens consumed in food are generally considered safe when taken in moderate amounts. Though some research studies have shown that phytoestrogens may protect against cancer, others dispute this effect. More studies are needed to fully assess the effect of phytoestrogens on the body chemistry. Side effects: Patients taking hormone therapies for cancer, such as tamoxifen or other antiestrogenic drugs, should seek the advice of their health care providers before taking supplementation of phytoestrogens, as these phytonutrients may interfere with drug therapy. Marylane Wade Koch, M.S.N., R.N.
How these compounds work: Phytoestrogens have been touted as natural substances that help prevent certain types of cancer, especially hormone-related cancers such as breast, prostate, and uterine cancer. Phytoestrogens can provide hormonal modulation, which naturally regulates See also Antioxidants; Beta-carotene; Bioflavonoids; hormones. Though not conclusive, some studies demonBreast cancers; Calcium; Carotenoids; Chemoprevention; strate that phytoestrogens may also provide some protecCoenzyme Q10; Complementary and alternative theration against lung and colon cancers. pies; Cruciferous vegetables; Curcumin; Dietary supplePhytoestrogens can be absorbed into the body chemisments; Essiac; Free radicals; Fruits; Garlic and allicin; try either to act as estrogens at low levels or to block the esGlutamine; Green tea; Herbs as antioxidants; Isoflavones; trogen effect at high levels. These substances can mimic a weak estrogen to stimulate or to inhibit the growth of cells. Research has shown that inFood Sources of Phytoestrogens creased exposure to certain hormones can inPhytoestrogen content of foods, from highest to lowest combined crease the risk of cancer. Phytoestrogens appear isoflavones (genistein, daidzein, glycitein, formononetin), lignans to protect the body from hormones that can pro(secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and duce cancer. coumestan (coumestrol), in micrograms per 100 grams. The best sources of phytoestrogens occur naturally in plants. More than three hundred foods Food mcg/100g Food mcg/100g contain phytoestrogens. The most common ones Flax seeds 379,380.0 Dried dates 329.5 are whole grains such as oats, wheat, and corn; Soy beans 103,920.0 Sunflower seeds 216.0 edible seeds such as flax and sesame; legumes Tofu 27,150.1 Chestnuts 210.2 such as lentils, soybeans, sprouts, black beans, Soy yogurt 10,275.0 Olive oil 180.7 and chickpeas; vegetables such as leafy greens, Sesame seeds 8,008.1 Almonds 131.1 fennel, celery, asparagus, carrots, parsley, and Flax bread 7,540.0 Green beans 105.8 Multigrain bread 4,798.7 Peanuts 34.5 seaweed; fruits such as oranges, bananas, and Soy milk 2,957.2 Onions 32.0 strawberries; olive, safflower, and pumpkin oils; Hummus 993.0 Blueberries 17.5 nuts such as pistachios, chestnuts, and walnuts; Garlic 603.6 Corn 9.0 and other sources such as garlic, onions, and red Mung bean sprouts 495.1 Coffee, regular 6.3 wine. Soy products such as tofu (bean curd), soy Dried apricots 444.5 Watermelon 2.9 milk, tempeh, and soy yogurt are well-known Alfalfa sprouts 441.4 Milk, cow 1.2 sources of isoflavone phytoestrogens. Certain herbs also contain phytoestrogens, such as red 962
Salem Health: Cancer
Pineoblastomas
Lutein; Lycopene; Macrobiotic diet; Nutrition and cancer prevention; PC-SPES; Phenolics; Prevention; Prostate cancer; Resveratrol; Soy foods; Uterine cancer; Wine and cancer.
u Pineoblastomas Category: Diseases, symptoms, and conditions Also known as: Pinealoblastomas Related conditions: Supratentorial primitive neuroectodermal tumors, pineocytomas Definition: Pineoblastomas, made up of immature cells in the pineal gland (a small organ near the center of the brain), are fast-growing, cancerous tumors that primarily affect young children. The pineal gland is made up of two main cell types: glial cells, which give it its form, and pineocytes, neural cells with photosensory and neuroendocrine functions that produce several hormones, in-
cluding melatonin, which helps to control the sleep-wake cycle. Pineoblastomas are invasive tumors that spread to nearby areas of the brain and cerebrospinal fluid and can cause bleeding into the brain’s ventricles. Pineoblastomas should not be confused with pineocytomas, which are slow-growing, benign tumors that primarily develop in middle-aged and older adults. Risk factors: The risk factors for pineoblastoma are unknown; however, some researchers believe that gene mutations may be involved. Etiology and the disease process: The cause of pineoblastomas is unknown. Researchers studying other diseases have noticed an increased incidence of pineoblastoma in patients with hereditary, bilateral retinoblastoma, caused by the retinoblastoma gene (RB1). They believe that this gene may play a role in the development of pineoblastoma in addition to affecting its response to treatment. Because of the rarity of pineoblastoma, however, research is limited and this theory has not been investigated sufficiently.
Thalamus
Stria medularis
Pineal gland Third ventricle Medial geniculate body
Superior colliculus
Lateral geniculate body Brachium of Inferior colliculus Cerebral peduncle
Inferior colliculus Trochlear nerve (IV) Superior Cerebellar Middle Peduncles Inferior
Lateral recess Rhomboid fossa Obex
Dorsal median sulcus Fasciculus gracilis Fasciculus cuneatus
Posterior view of the brain stem, showing the pineal gland (top center) along with other structures. (©F. D. Giddings/Phototake. All rights reserved.)
963
Pineoblastomas As pineoblastomas grow, they cause increased pressure in the brain and block the flow of cerebrospinal fluid, causing many neurologic symptoms. Because cells in the pineal gland produce hormones needed for normal body functions, pineoblastomas also cause changes in other body systems. In a process called seeding, they tend to produce multiple, initially small, tumors that are deposited into the cerebrospinal fluid early in the disease process. Pineoblastomas then spread through the brain and spinal cord via the cerebrospinal fluid. When they spread to other body areas, the most common sites are the bones and lungs. Incidence: After leukemia and lymphoma, brain tumors are the most common type of childhood cancer. However, pineoblastomas are extremely rare among these brain tumors, with only about a 0.4 to 1.0 percent incidence out of all brain tumors. Each year, cancer of the brain and spinal cord occurs in about 2,200 children younger than age fifteen in the United States. Of that number, only between 10 and 40 will be diagnosed with pineoblastoma. Symptoms: Pineoblastomas cause symptoms related to an increase in pressure inside the brain and blockage of cerebrospinal fluid. They can vary depending on the size of the tumor, its location, and the child’s age. Most symptoms of pineoblastomas are similar to those of other brain tumors, including nausea and vomiting, seizures, changes in personality or behavior, unusual sleepiness, headaches, double vision, and developmental delays or failure to thrive. Hydrocephalus, an excessive accumulation of fluid in the brain, and hormonal abnormalities may also occur. Screening and diagnosis: Screening for abnormal brain function takes place whenever a medical practitioner makes a physical examination of a child and takes a growth and development history. When abnormalities appear, the practitioner will typically order laboratory tests and possibly imaging studies. Laboratory tests usually include a complete blood count, electrolyte levels, and liver, thyroid, and kidney function tests. Imaging studies include a chest X ray, bone scan, magnetic resonance imaging (MRI), and computed tomography (CT) scanning. An examination of the cerebrospinal fluid, called a lumbar puncture, will be performed to look for cancer cells as well as to rule out other diseases. If the child’s condition permits, a definitive diagnosis of pineoblastoma is made during surgery, after a pathologist examines the tumor cells. For pineoblastoma, the extent of the cancer is usually described as risk groups instead of stages. The tumor is called “average risk” when the child is older than age three, most or all of the tumor was removed by surgery, 964
Salem Health: Cancer and the cancer has not spread beyond the pineal gland. It is called “poor risk” when the child is younger than age three, the tumor was near the center of the brain, some of the tumor was not removed by surgery, or the cancer has spread to other parts of the brain or body, including the spinal cord. Treatment and therapy: Treatment for pineoblastoma is based on the child’s age and risk group. When the child is younger than age three, surgical removal of most or all of the tumor is performed. If the child is considered a poor risk, chemotherapy is used after surgery. When the child is older than age three, surgery is followed by radiation treatment of the entire brain and spinal cord. Any child considered a poor risk might also be given chemotherapy. Prognosis, prevention, and outcomes: There is no known prevention for pineoblastoma. The prognosis for pineoblastomas varies with the child’s age and risk group but is typically poor, with an estimated survival time of sixteen to twenty-five months. Although some children do survive five years or more, the tumors commonly recur or develop in other parts of the body. When they do, they are almost always fatal. Dorothy P. Terry, R.N. u
For Further Information Amendola, B. E., et al. “Pineal Tumors: Analysis of Treatment Results in Twenty Patients.” Journal of Neurosurgery 102 (January, 2005): 175-179. Bruce, J. N., and A. T. Ogden. “Surgical Strategies for Treating Patients with Pineal Region Tumors.” Journal of Neurooncology 69, nos. 1-3 (August/September, 2004): 221-236. Gururangan, S., et al. “High-Dose Chemotherapy with Autologous Stem-Cell Rescue in Children and Adults with Newly Diagnosed Pineoblastomas.” Journal of Clinical Oncology 21, no. 11 (June 1, 2003): 21872191.
u
Other Resources
American Cancer Society Treatment of Specific Types of Brain and Spinal Cord Tumors http://www.cancer.org National Cancer Institute Childhood Supratentorial Primitive Neuroectodermal Tumors and Pineoblastoma http://www.nci.nih.gov/cancertopics/pdq/treatment/ childSPNET
Salem Health: Cancer See also Brain and central nervous system cancers; Childhood cancers; Cobalt 60 radiation; Computed tomography (CT) scan; Imaging tests; Lumbar puncture; Magnetic resonance imaging (MRI); Neuroendocrine tumors; Retinoblastomas.
u Pituitary tumors Category: Diseases, symptoms, and conditions Also known as: Pituitary adenomas, pituitary carcinomas, teratomas, germinomas, choriocarcinomas, Rathke cleft cysts, gangliocytomas, prolactinomas Related conditions: Multiple endocrine neoplasia type 1 (MEN 1), acromegaly, Cushing syndrome, panhypopituitarism, hypogonadism, diabetes insipidus, hyperthyroidism Definition: Pituitary tumors are found in the pituitary gland, a small organ that sits in the sella turcica (a small bony space) in the center of the brain just above the nose. Almost all pituitary tumors are adenomas, which are benign (not cancerous) glandular tumors. Malignant tumors (for example, pituitary carcinomas) are rare. Among those, teratomas, germinomas, and choriocarcinomas usually occur in children or young adults. Rathke cleft cysts and gangliocytomas of the pituitary are usually found in adults. Cancers that metastasize to the pituitary from other sites are classified by their primary site and not as pituitary tumors. Risk factors: People with multiple endocrine neoplasia type 1 (MEN 1), a hereditary condition, have a very high risk of developing tumors of the pituitary along with tumors of two other glands, the parathyroid and pancreas. About 50 percent of the children of an affected parent will inherit the defective gene that causes MEN 1. Etiology and the disease process: The pituitary gland produces hormones that regulate the functions of other glands in the body. Most pituitary tumors start in the anterior pituitary gland. Pituitary adenomas remain confined to the skull but may grow into the walls of the sella turcica and surrounding nerves, vessels, and coverings of the brain. An enlarged pituitary can damage nearby parts of the brain. For example, damage to the optic nerve can lead to vision problems or even vision loss. About 75 percent of pituitary adenomas produce hormones and are therefore termed functional, while the rest do not and are termed nonfunctional. Pituitary tumors can cause overproduction of hormones; however, damage to pituitary tissue can also lead to hormone deficiency.
Pituitary tumors Adenomas are categorized into two types: microadenomas, tumors that are smaller than 1 centimeter (cm), and macroadenomas, which are larger than 1 cm. Microadenomas generate symptoms because of hormone overproduction and rarely because of damage to surrounding tissue, whereas macroadenomas cause symptoms by both hormone overproduction and tissue damage. Adenomas are further classified by the specific hormones produced: prolactin (prolactinomas, about 43 percent of all pituitary adenomas), growth hormone (GH, about 17 percent), adrenocorticotropin (ACTH, about 7 percent), thyroidstimulating hormone (TSH, about 3 percent), and gonadotropin (which with null-cell, or nonfunctional, adenomas make up about 30 percent). About 3 percent of all pituitary tumors are caused by inherited mutations in deoxyribonucleic acid (DNA) in people with MEN 1. Some 40 percent of GH-secreting adenomas have an acquired mutation in a specific protein called Gs alpha. It is not clear yet whether abnormal genes are essential for pituitary tumor formation. However, gene alterations probably result in the loss of regulatory mechanisms for hormone production and growth of glandular cells, thereby promoting tumor growth. Incidence: In the United States, pituitary tumors represent between 10 and 15 percent of all intracranial tumors. The incidence of acromegaly, a condition produced when the body creates too much growth hormone, is approximately 3 per 1 million people and similar in men and women. Symptoms: All adenomas can cause headaches and visual problems when they grow large enough to affect nearby tissues. Macroadenomas can lead to neurologic symptoms such as double or blurred vision due to paralysis of eye movement, loss of peripheral vision, sudden blindness, facial numbness or pain, headaches, dizziness, and even loss of consciousness. The destruction of normal pituitary tissue by macroadenomas and pituitary carcinomas leads to a lack of normal body hormones such as cortisone, thyroid hormone, and sex hormones. This can result in nausea, weakness, weight loss or gain, irregular menses, erectile dysfunction, and decreased libido (mainly in men). Macroadenomas and pituitary carcinoma can also cause diabetes insipidus as a result of a lack of production of vasopressin (also called the antidiuretic hormone, ADH). If severe and untreated, this condition can lead to coma and death. GH-secreting adenomas in children can stimulate excessive bone growth, leading to gigantism. Symptoms are being very tall and experiencing very rapid growth, joint pains, and increased sweating. Adults with GH-secreting adenomas may develop acromegaly, characterized by 965
Pituitary tumors
Salem Health: Cancer
growth of the skull, hands, feet, and facial bones, leading to changes in the appearance of the face; joint pain; deepening of the voice; increased sweating; diabetes mellitus; kidney stones; heart disease; headaches; unusual hair growth; and thickening of the tongue, palate, and skin. ACTH-secreting adenomas can stimulate the production of steroid hormones by the adrenal gland and subsequently cause a condition called Cushing syndrome. The symptoms are weight gain, increased body hair, fat deposits in the neck, mood swings, irregular menses, high blood pressure, high blood sugar, osteoporosis, easy bruising, and purple stretch marks on the abdomen. Prolactin-producing adenomas (prolactinomas) are difficult to spot in children. They are most common in young women, in whom high prolactin levels can cause irregular menses and abnormal breast milk production (galactorrhea), and in older men, in whom they cause impotence or loss of libido. TSH-secreting adenomas cause hyperthyroidism, with symptoms such as an enlarged thyroid, weight loss, increased appetite, rapid heartbeat, tremor, anxiousness, sleeping problems, frequent bowel movements, and feeling warm or hot. Gonadotropin-secreting adenomas are not very com-
mon. They produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which may cause irregular menses. Nonfunctional adenomas may be the most common pituitary tumors, but they are rarely detected, as they do not cause symptoms and are typically detected by magnetic resonance imaging (MRI) or computed tomography (CT) scans taken for other reasons. Screening and diagnosis: Knowing what hormone an adenoma produces is critical in choosing the treatment and determining the prognosis. Biochemical testing for GHsecreting adenomas includes a check for excessive production of GH and insulin-like growth factor 1 (IGF-1). If both levels are very high, the patient clearly has a pituitary tumor. If the levels are only slightly increased, a glucose suppression test is done. Biochemical testing for ACTH-secreting adenomas includes measuring levels of ACTH and cortisol in blood samples and of cortisol and other steroid hormones in urine samples taken at different times during the day. These tests may be repeated after taking dexamethasone, a cortisone-like drug. These tests are also used to distinguish patients with ACTH-secreting adenomas from patients
Hormones Secreted by the Pituitary Gland and Their Functions Hormone
Functions
Adrenocorticotropic hormone (ACTH)
• stimulates adrenal glands to release cortisol, which controls blood pressure and metabolism of fat, protein, and carbohydrates • controls fight-or-flight response through adrenal glands
Antidiuretic hormone (ADH); also known as vasopressin
• increases amount of water reabsorbed into the blood by kidneys
Endorphin
• reduces the sensation of pain • helps control immune system
Follicle-stimulating hormone (FSH)
• stimulates maturation of ovarian follicles • helps support sperm cell maturation
Growth hormone (GH)
• controls growth and metabolism • stimulates muscle development and reduces fat tissue
Luteinizing hormone (LH)
• triggers ovulation • stimulates production of testosterone
Melanocyte-stimulating hormone
• governs production of melanin in the skin
Oxytocin
• contracts uterus in labor • promotes ejection of milk in breast-feeding
Prolactin
• stimulates the production of breast milk after giving birth
Thyroid-stimulating hormone (TSH)
• stimulates thyroid to control basal metabolic rate • stimulates thyroid to guide growth and maturation
966
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Pituitary tumors
with other diseases, such as adrenal gland tumors, which cause similar symptoms. Tests to measure blood levels of prolactin, TSH, LH, and FSH can identify patients with prolactinomas, TSH-secreting adenomas, or gonadotropin-secreting tumors. If tests for excessive hormone production are negative or the levels are lowered, a pituitary adenoma is considered nonfunctional. Macroadenomas and pituitary carcinomas— and particularly metastatic cancer—can damage the part of the pituitary gland that produces vasopressin, leading to diabetes insipidus. This can also occur as a side effect of the surgical treatment of pituitary tumors. Diagnosis of diabetes insipidus is made by tests to measure sodium levels and total salt concentration (osmolality) of the blood and urine. In addition, a water deprivation test may be necessary. Imaging tests (MRI and CT scans) are used to visualize tumors. Venous blood sampling may be necessary to confirm the presence of ACTH-secreting adenomas if they are too small to be detected by MRI scans. Testing of vision and visual fields also helps to detect pituitary tumors. A closer analysis of the type of tumor can be done by taking a biopsy. A pituitary tumor in the area of the optic chiasma affects a person’s peripheral No staging system exists for pituitary tuvision. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.) mors as they are nearly always benign. Pituitary carcinomas are too rare for development of a staging system. The most useful informau Other Resources tion in treating an adenoma is whether it is a macroadenoma or a microadenoma, whether it produces horNational Cancer Institute mones, and which hormones it produces. Pituitary Tumors Treatment Treatment and therapy: Pituitary tumors may be treated http://www.nci.nih.gov/cancertopics/pdq/treatment/ surgically, medically, radiotherapeutically, or with compituitary/patient/ binations of these therapies. Which therapy is used depends on the type of tumor. National Institute of Neurological Disorders and Stroke Prognosis, prevention, and outcomes: Pituitary tumors Pituitary Tumors Information Page are usually curable. Prognosis depends on the type of pituhttp://www.ninds.nih.gov/disorders/pituitary_tumors/ itary tumor and on the patient’s general health and age. pituitary_tumors.htm Nicola E. Wittekindt, Dr.Sc. (ETH Zürich) u
For Further Information Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. Nussey, S. S., and S. A. Whitehead. Endocrinology: An Integrated Approach. London: Taylor & Francis, 2001. Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, Taylor & Francis, 2007.
Pituitary Network Association http://www.pituitary.org See also Acrylamides; Amenorrhea; Cushing syndrome and cancer; Endocrine cancers; Endocrinology oncology; Family history and risk assessment; Multiple endocrine neoplasia type 1 (MEN 1); Neuroendocrine tumors. 967
Placental alkaline phosphatase (PALP)
u Placental alkaline phosphatase
(PALP) Category: Cancer biology Definition: Placental alkaline phosphatase (PALP) is one of the four isoenzymes of alkaline phosphatase, a group of enzymes that hydrolyze organic phosphate esters. Alkaline phosphatase isoenzymes associated with the liver, bone, and intestine are normally present in serum. When the serum alkaline phosphatase level is above established reference ranges, determining which fraction is elevated may be helpful in pinpointing the source of disease. PALP is normally produced by the syncytiotrophoblast of the placenta. This unique cell layer is in direct contact with maternal blood during pregnancy and is considered the source of rising PALP levels in maternal plasma during gestation, with the highest levels occurring right before delivery. PALP-like isoenzymes are similar to PALP but different enough in their biochemical and physical properties to be considered separate proteins. Several PALP-like isoenzymes have been identified, characterized, and named: Regan, Nagao, and Kasahara. Some authors refer to the PALP-like isoenzymes as germ-cell alkaline phosphatases. Related cancers: When pregnancy is not a condition of consideration, elevated levels of PALP have been associated with cancers of the testis, ovary, colorectal tract, and lung. In the 1970’s and 1980’s, researchers investigated the relationship between malignant changes in many tissues with the serum concentration of several fetal-type proteins. They pursued PALP along with alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as tumor markers. Of these, PALP and the PALP-like isoenzymes have yet to be demonstrated as useful markers for screening or monitoring cancer and related conditions. Ongoing research: Cancer researchers continue to explore a role for PALP as a tumor marker. Antibodies to detect and differentiate PALP and the related PALP-like isoenzymes are being designed and tested. Some of the antibodies are used in immunohistochemistry protocols, requiring a biopsy of the organ where the suspicious tumor is located. These tissue biopsy studies can confirm the presence of PALP and PALP-like isoenzymes, which further choracterizing the tumor and leading to a more specific diagnosis and targeted therapy. Other researchers are designing antibodies that target PALP and PALP-like isoenzymes in an individual’s plasma and thus can serve as noninvasive markers for cancer. To 968
Salem Health: Cancer date elevated concentrations of PALP and PALP-like enzymes have been found to be no better than cancer antigen 125 (CA 125) and AFP in monitoring ovarian cancer. However, there is some evidence that PALP and PALPlike isoenzymes may become useful indicators of cancer recurrence in survivors. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) See also Alkaline phosphatase test (ALP); Cancer biology; Immunocytochemistry and immunohistochemistry; Paget disease of bone; Pregnancy and cancer; Staging of cancer; Tumor markers.
u Plant alkaloids and terpenoids
in chemotherapy Category: Chemotherapy and other drugs ATC code: 101C Definition: Alkaloids and terpenoids are compounds derived from plants, some of which are shown to have anticancer activity and have been developed into useful chemotherapeutic agents. Subclasses of this group include vinca alkaloids, taxanes, podophyllotoxins, epipodophyllotoxins, camptothecins, ellipticine, and colchicine. Cancers treated or prevented: Breast cancer, ovarian cancer, lung cancer, prostate cancer, lymphomas, leukemias Delivery routes: Intravenous How these drugs work: Plants are an important source of natural products effective in treating human cancer, with several useful chemotherapeutic agents currently on the market or in clinical trials. Specifically, many plant-derived alkaloids and terpenoids have significant anticancer properties. Synthetic and semi-synthetic derivatives of alkaloid and terpenoid compounds with anticancer activity have also been developed. In plants, these compounds are produced as secondary metabolites that probably function as defense chemicals that inhibit cell division in invading pathogens. These same cytostatic compounds can be useful in cancer treatment by stopping the growth of cancer cells. Some examples of alkaloids and terpenoids used in chemotherapy are vinca alkaloids, podophyllotoxins, and taxanes. Alkaloids are naturally occurring amines produced by plants and are grouped into several classifications, usually based on the metabolic pathway through which they are generated. These classifications include indole, purine, pyridine, and isoquinoline, with terpenoids one classifica-
Salem Health: Cancer
Plant alkaloids and terpenoids in chemotherapy
Common Plant Alkaloids and Terpenoids Drug
Brands
Subclass
Delivery Mode Cancers Treated
9-Aminocamptothecin
9-AC
Camptothecin
IV
Ovarian, stomach cancers
Amsacrine
Amsidine
Epipodophyllotoxin derivative
IV
Germ-cell testicular cancer, bone and soft tissue sarcomas, adult and childhood leukemias
Colchicine
IV
Solid tumors, chronic myelocytic leukemia, other leukemias
Colchicine Docetaxel
Taxotere
Taxane diterpenoid
IV
Breast, prostate, non-small-cell lung, and other cancers
Elliptinium
Celiptium
Ellipticine
IV
Stomach, lung, and breast cancers
Etoposide
Etophos, Vepesid
Epipodophyllotoxin
IV, oral
Lung, ovarian, and testicular cancers
Irinotecan
CPT-11, Camptostart, Campto
Camptothecin
IV
Metastatic colorectal cancer, bowel cancer
Paclitaxel
Taxol
Taxane diterpenoid
IV
Metastatic breast cancer, advanced lung cancer, head and neck cancers, melanoma, ovarian cancer, lymphomas, non-small-cell lung cancer
Teniposide
Vumon, VM-26
Epipodophyllotoxin
IV
Adult and childhood leukemias, lymphomas, Hodgkin lymphoma, childhood neuroblastoma
Topetecan
Hycamtin
Camptothecin
IV
Ovarian, small-cell lung cancers
Vinblastine
Velbe
Vinca alkaloid
IV
Hodgkin disease; non-Hodgkin lymphomas; leukemia; renal, testicular, head, neck, breast, and lung cancers
Vincristine
Oncovin, Cytocristin, Vinca alkaloid Onococristin-AQ, Vincristine, Vincristine sulfate
IV
Kaposi sarcoma, non-Hodgkin lymphoma, Hodgkin disease, acute lymphocytic leukemia, small-cell lung cancer, cervical and breast cancer
Vindesine
Eldisine
Vinca alkaloid
IV
Leukemia, lymphoma, melanoma, breast and lung cancers
Vinflunine
Javlor
Vinca alkaloid
IV
Bladder, lung, gastric cancers
Vinorelbine
Navelbine
Vinca alkaloid
IV
Breast cancer, small-cell lung cancer
tion of alkaloids. Terpenoids are sometimes also referred to as isoprenoids and are classified according to the number of isoprene units that they contain. For example, monoterpenoids are made up of two isoprene units, whereas diterpenoids are composed of four isoprene units. Four structural classes of plant-derived anticancer agents of alkaloid or terpenoid origin are available in the United States: vinca alkaloids, taxanes, epipodophyllotoxins, and camptothecins. These compounds work by affecting cell division and deoxyribonucleic acid (DNA) synthesis or function.
The search for anticancer agents from plants was initiated in 1947 when podophyllotoxins from the American mayapple (Podophyllum peltatum) inhibited the growth of tumor cells in laboratory experiments. The subsequent discovery of antileukemic properties of vinblastine and vincristine, bis-indole alkaloids derived from the Madagascar periwinkle (Catharanthus roseus), spurred broad investigations of plant-derived compounds for possible anticancer activity. C. roseus was found to be a storehouse of more than seventy-five alkaloids, several of which possess anticancer activity. Among other plant species that 969
Plant alkaloids and terpenoids in chemotherapy have provided clinically useful drugs are Taxus brevifolis, the source of diterpene taxol; Ochrosia elliptica, one of the sources of the pyridocarbazole alkaloid ellipticine; and Camptotheca acuminata, which contains camptothecin. While being used to treat other conditions, the leaves of C. roseus, formerly Vinca roseus, were found to contain cytotoxic compounds. Among these compounds were two terpenoid indole alkaloids, vinblastine and vincristine, which subsequently became the first natural anticancer agents used clinically. Vinblastine and vincristine, together with a number of semi-synthetic derivatives, are collectively termed the vinca alkaloids. Although they have been in clinical usage since the 1970’s, the vinca alkaloids are still extremely useful chemotherapeutic agents with well-known antimitotic activity. Vinca alkaloids work by binding specific sites on tubulin and preventing assembly of tubulin into microtubules, which are essential for cell division. Soon after the introduction of vinblastine and vincristine, intensive chemical research was undertaken to try to develop semi-synthetic derivatives that had higher activity, lower toxicity, and broader anticancer effects. Several successful semi-synthetic derivatives were developed, including vindesine, vinorelbine, and vinflunine. Vindesine has a vincristine-like spectrum of activity and is used mainly to treat melanoma, acute lymhoblastic leukemia, and advanced non-small-cell lung cancer. Vinorelbine has reduced side effects and is now widely used in treatment of non-small-cell lung cancer and breast cancer, with utility toward other cancers, including lymphoma and esophageal and prostate cancers, under clinical investigation. Vinflunine is a semi-synthetic fluorinated derivative of vindesine and is currently in clinical trials for treatment against various cancers, including bladder, lung, and gastric cancers. Another class of plant alkaloids used in chemotherapy is the taxanes. Taxanes are derived from either the bark or the needles of some species of yew tree. Taxanes currently used as chemotherapeutic agents include paclitaxel and docetaxel. Paclitaxel is derived from the bark of the European yew tree (Taxus baccata), while docetaxel is derived from the pine needle of the Pacific yew tree (Taxus brevifolia). Paclitaxel, marketed under the name Taxol, is one of the most effective plant-derived chemotherapeutic agents. Patients with refractory ovarian cancer, metastatic breast cancer, advanced lung cancer, cancers of the head and neck, melanoma, and lymphomas respond positively to treatment with Taxol. The taxanes work by increasing the stability of microtubules, which inhibits cell division by preventing the separation of chromosomes during anaphase. Other classes of plant alkaloids used in chemotherapy 970
Salem Health: Cancer include the podophyllotoxins, camptothecins, ellipticines, and colchicine. Podophyllotoxins, or epipodophyllotoxins, are alkaloids naturally occurring in the root of the American mayapple or mandrake (Podophyllum emodi). A rare Himalayan mayapple (Podophyllum hexandrum) has also recently been found to contain active compounds, but this plant is endangered and consequently limited in supply. Efforts to obtain these compounds through recombinant technologies are under way. Some epipodophyllotoxin derivatives, etoposide and teniposide, are currently used in cancer treatment. Semi-synthetic derivatives such as amsacrine and etoposide phosphate also exist. Podophyllotoxins and their derivatives work by preventing cell division in tumor cells by keeping cells from entering the cell cycle and undergoing DNA replication. Camptothecin is a quinoline alkaloid isolated from C. acuminata. Examples of camptothecins used in chemotherapy include topotecan and irinotecan. Topotecan is currently used to treat ovarian cancer, and irinotecan is currently marketed for treatment of metastatic cancer of the colon or rectum. Another compound, 9-aminocamptothecin, is also being investigated for treatment of ovarian and stomach cancers. Ellipticine is an alkaloid isolated from an evergreen tree of the Apocyanaceae family. Ellipiticine and its derivatives, including elliptinium, are promising anticancer agents and are highly effective against several types of cancer, with limited side effects. Colchicine is a tricyclic tropane alkaloid from the autumn crocus (Colchicum autumnale) and gloriosa lily (Gloriosa superba). Cochicine has been used effectively to treat chronic myelocytic leukemia, but toxic or near-toxic doses are required for therapeutic benefit. For this reason, colchicine and its analogs are primarily used as tools to study new mitotic inhibitors rather than in chemotherapy. Although exact mechanisms of action of podophyllotoxins, camptothecins, and ellipticines still have to be elucidated, these compounds and their derivatives are believed to function as either type I or type II topoisomerase inhibitors, enzymes essential for critical steps in cell division—the transcription and replication of DNA. Colchicines prevent tubulin polymerization during the cell cycle. Side effects: Side effects of plant alkaloids and terpenoids used in chemotherapy include lowered resistance to infection, bruising or bleeding, anemia, constipation, cramps, diarrhea, nausea, peripheral neuropathy (numbness or tingling in hands or feet), headaches, tiredness, and hair loss. Mouth sores and ulcers, changes in taste, and loss of appetite can also occur. Skin rashes and allergic reactions are seen less commonly. C. J. Walsh, Ph.D.
Salem Health: Cancer u For Further Information Cutler, S. J., and H. G. Cutler. Biologically Active Natural Products: Pharmaceuticals. Boca Raton, Fla.: CRC Press, 2000. Kintzios, S. E. “Terrestrial Plant-Derived Anticancer Agents and Plant Species Used in Anticancer Research.” Critical Reviews in Plant Sciences 25 (2006): 79-113. Mukherjee, A. K., et al. “Advances in Cancer Therapy with Plant Based Natural Products.” Current Medicinal Chemistry 8 (2001): 1467-1486. Noble, R. L. “The Discovery of the Vinca Alkaloids— Chemotherapeutic Agents Against Cancer.” Biochemistry and Cell Biology 68 (1990): 1344-1351. Perry, Michael C., ed. The Chemotherapy Source Book. 4th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2008. u
Other Resources
Cancer Backup http://www.cancerbackup.org.uk National Cancer Institute http://www.cancer.gov National Center for Complementary and Alternative Medicine http://nccam.nih.gov See also Antineoplastics in chemotherapy; Antioxidants; Breast cancers; Caffeine; Complementary and alternative therapies; Dietary supplements; Green tea; Herbs as antioxidants; Indoles; Leukemias; Lung cancers; Lymphomas; Nutrition and cancer prevention; Nutrition and cancer treatment; Opioids; Ovarian cancers; Prostate cancer; Stomach cancers.
u Plasticizers Category: Carcinogens and suspected carcinogens Definition: Plasticizers are chemical substances that are used as additives during the manufacture of various polymers such as polyvinyl chloride (PVC), food packaging, food storage containers, children’s toys, and medical devices to impart flexibility, strength, and durability. Types of plasticizers: A large variety of chemicals are used as plasticizers. They are classified into various categories based on their chemical structure. The most widely used plasticizers are derived from the family of dicarboxylic esters and are commonly known as phthalates: Exam-
Plasticizers ples include di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DOP), adipates, and maleates. Chemicals from the family of organophosphates and some glycol esters are also used as plasticizers. Uses: Phthalates such as DEHP are predominantly used in the manufacture of PVC, which is one of the oldest polymers used to make pipes and various plastic containers. Phthalates are also used as plasticizers in medical devices such as dialysis bags, intravenous bags, and tubing. They are also used in detergents, lubricating oils, flooring materials, food-packaging materials, and storage containers. Environmental exposure: Plasticizers are not covalently bound to the plastic matrix, and they consequently leach out when in contact with oils, fats, and other greasy substances, especially at higher temperatures. This is especially true of phthalates, which are used in food wraps and containers. Plasticizers in food wraps have been shown to migrate into and contaminate fatty foods such as meat, cheese, and oily snacks. Plasticizers are also released into the environment directly during the manufacture of plastics and from discarded plastic containers, wraps, and pipes. As plastics have myriad uses, the plasticizers in them are ubiquitous contaminants of air, water, food, and medicines. Human exposure to plasticizers is mainly through ingesting water and food contaminated with them. Infants are exposed to plasticizers when they chew or suck on plastic toys or pacifiers or drink liquids out of plastic feeding bottles. Another source of exposure is through air, in which plasticizers such as DEHP adhere to aerosol particles. Animal studies have shown that phthalates can cross the placental barrier, and therefore, this can potentially cause prenatal exposure in humans. Toxicity and metabolism: Toxicity studies on plasticizers (especially the phthalates DEHP and DOP) have been done on rodents through various exposure routes. It has been found that the rodents metabolize phthalates readily, and the liver and kidneys are common target organs for general toxicity. The major concern about the toxicity of phthalates stems from reports from the U.S. National Toxicology Program showing several of them to be carcinogenic in rodents. The mechanism of carcinogenesis in rodents or other species is as yet unclear, and there are no clear-cut studies extrapolating the animal data to humans. Many industry groups and advocacy panels have analyzed the animal data on the toxicity of plasticizers and have failed to come to a consensus because the toxicity patterns vary greatly by species and routes of exposure. Plasticizers have been detected in breast milk and children’s blood samples, but there are no studies that 971
Pleural biopsy clearly relate childhood exposure to the risk of adult human cancers, and therefore childhood exposure to plasticizers is shrouded in controversy. There are reports in literature that indicate that plasticizers, especially the phthalates, act as hormone disrupters. Hormones are chemical messengers produced by various glands in animals and humans that travel through the bloodstream and regulate growth, reproduction, and metabolic functions in the body. This system, known as the endocrine system, is a very finely tuned mechanism in the body, and endocrine disrupters can readily throw it off balance, creating major health and cancer risks. Young animals and children are more vulnerable to exposure to such disrupters because their systems are still in the developmental stage, so there is a great concern regarding the exposure of infants and children to phthalates. Preventive measures: Because plasticizers are widely distributed environmental contaminants, there is a great deal of concern regarding cancer and other health risks to adult human populations as a result of exposure of infants and children to environmental endocrine disrupters. The conflicting conclusions from various animal studies and the lack of data extrapolating the animal exposure studies to human infants and adults underscore the complexity of the science. More studies delineating the toxicokinetics of plasticizers, especially in vulnerable subpopulations such as pregnant and lactating women, premature infants, and children, are needed. There are many ongoing studies to assess the risk of exposure to plasticizers and evaluate the potential of early childhood exposure in increasing the risk of cancer in adults. The European Union has recommended banning the use of certain phthalates. Toy manufacturers are funding research to develop newer plasticizers with greater biodegradability and lower toxicity, such as alkyl citrates and esters of vegetable oils. These environmentally benign plasticizers are being developed for use in food-packaging materials, medical devices, and children’s toys. With all the conflicting health and cancer risk data on plasticizers, it makes perfect sense for individuals and industry and government regulatory agencies to take reasonable steps to limit exposure to plasticizers. Lalitha Krishnan, Ph.D. u
For Further Information Huber, W. W., B. Grasl-Kraupp, and R. Schulte-Hermann. “Hepatocarcinogenic Potential of Di(2-ethylhexyl) Phthalate in Rodents and Its Implications on Human Risk.” Critical Reviews in Toxicology 26 (1996): 365481. 972
Salem Health: Cancer Sissell, Kara. “States, Retailers Push to Eliminate Phthalates from Toys.” Chemical Weekly 170, no. 12 (April 14-21, 2008): 29. _______. “Study Links Phthalates and Infant Care Products.” Chemical Weekly 170, no. 5 (February 11-18, 2008): 29. Voiland, Adam. “More Problems with Plastics: Like BPA, Chemicals Called Phthalates Raise Some Concern.” U.S. News & World Report, May 19, 2008, p. 54. Woodward, Kevin N. Phthalate Esters: Toxicity and Metabolism. Boca Raton, Fla.: CRC Press, 1988. u
Other Resources
Canadian Cancer Society Phthalates http://www.cancer.ca/ccs/internet/standard/ 0,3182,3172_1706523966__langId-en,00.html National Toxicology Program http://cerhr.niehs.nih.gov U.S. Environmental Protection Agency Consumer Factsheet on: Di (2-ethylhexyl) Phthalate http://www.epa.gov/OGWDW/dwh/c-soc/ phthalat.html U.S. Food and Drug Administration FDA Public Health Notification: PVC Devices Containing the Plasticizer DEHP http://www.fda.gov/cdrh/safety/dehp.html See also Bisphenol A (BPA); Carcinogens, known; Carcinogens, reasonably anticipated; Childhood cancers; Di(2-ethylhexyl) phthalate (DEHP); Organochlorines (OCs); Risks for cancer; Vinyl chloride.
u Pleural biopsy Category: Procedures Also known as: Needle biopsy of the pleura, open pleural biopsy, closed pleural biopsy Definition: A pleural biopsy is the removal of a sample of the pleura (the membrane that surrounds the lungs) so that it can be tested by a pathologist for cancer or other diseases. Cancers diagnosed: Lung cancer, metastatic pleural tumor, malignant pleural mesothelioma Why performed: This test may be used to diagnose mesothelioma, a tumor in the pleural membrane, or lung cancer.
Salem Health: Cancer It is indicated when a pleural fluid sample shows possible cancer or when a chest X ray shows a thickening or mass in the pleura. Patient preparation: Pleural biopsy may be done in a doctor’s office or in the hospital using a local anesthetic. A blood test may be required before the test to ensure that the patient does not have a prolonged bleeding or clotting time. Steps of the procedure: In a percutaneous biopsy, the doctor uses a large-bore needle. The skin around the site is cleaned and injected with a local anesthetic. The patient sits up and may be asked to hold his or her breath to prevent air from entering the chest during the procedure. The physician makes an incision and inserts the needle through the chest wall and into the pleura. Ultrasound can be used to help view the progress of the needle. When it is in place, a biopsy trocar is inserted through the needle to remove a sample of tissue. The doctor usually removes three samples, places them in fixative, and sends them to the laboratory. The procedure can take less than thirty minutes. To obtain larger specimens of the pleura, the biopsy can also be performed during a thoracoscopy, using a laparoscope (a tube with a tiny camera on the end) that the doctor inserts through the skin and into the chest, or as an open pleural biopsy, a surgery performed under general anesthesia. After the procedure: A bandage is placed over the incision. The patient is observed for respiratory distress and bleeding. After returning home, the patient should be aware of any shortness of breath. Light-headedness or an increased pulse rate might indicate internal bleeding. Risks: Potential complications from this procedure include respiratory distress, pneumothorax (presence of air in the chest outside the lung), injury to the lung, infection, and bleeding. Results: Preparation of a tissue sample and analysis by a pathologist may take several days. The pathologist can identify the presence or apparent lack of cancer cells in the tissue. Marcia Pinneau, R.N. See also Bronchoalveolar lung cancer; Lung cancers; Mesothelioma; Needle biopsies; Pleural effusion; Pleurodesis; Thoracentesis; Thoracoscopy.
Pleural effusion
u Pleural effusion Category: Diseases, symptoms, and conditions Also known as: Parapneumatic effusion, water or fluid in the chest, pleural fluid Related conditions: Lung cancer Definition: A pleural effusion is the abnormal collection of excess fluid between the layers of the pleura, the membranes lining the lungs and chest cavity. Pleural effusions are either malignant or nonmalignant. Depending on the cause of the pleural effusion, the excess fluid is either rich in protein (exudative) or proteinpoor (transudative or watery). Congestive heart failure and abnormal lung pressure are often associated with transudative pleural effusions. Certain cancers, kidney disease, pneumonia, or other lung infections are usually associated with exudative pleural effusions. Risk factors: The risk factors for pleural effusions include chemotherapy or radiation therapy of the chest, a collapsed lung, lung cancer, breast cancer, lymphoma, and leukemia. Pleural effusions may occur as a complication of abdominal or thoracic surgery or because of chest trauma. Etiology and the disease process: A small amount of fluid is normally present in the pleural cavity to lubricate the pleural surfaces. The abnormal collection of fluid in the pleural space may occur as the result of cancer treatment such as chemotherapy or radiation therapy or in the presence of a collapsed lung or certain cancers. Cancer causes about 40 percent of symptomatic pleural effusions, according to the National Cancer Institute. In addition, lung cancer, breast cancer, lymphoma, and leukemia account for approximately 75 percent of all malignancyrelated pleural effusions. In some cases, the fluid itself is malignant. Incidence: In the United States, approximately 100,000 cases of pleural effusions are diagnosed per year, and 43 cases are detected per 100,000 hospital admissions, according to the National Cancer Institute. Symptoms: Symptoms of a pleural effusion include shortness of breath, rapid or labored breathing, chest pain, and dry cough. Additional symptoms are often related to the underlying condition, such as fluid retention and swelling. In some cases, there are no symptoms, but the effusion may be discovered during a routine chest X ray or other diagnostic test. 973
Pleural effusion Screening and diagnosis: The accurate diagnosis of a pleural effusion is essential so that treatment can be targeted for malignant effusions. The first steps in the diagnosis include a medical history and physical exam, lungfunction tests, and chest X ray. Other diagnostic tests include a computed tomography (CT) scan, chest ultrasound, thoracentesis, and pleural fluid analysis (biopsy). A thoracentesis is the removal of pleural fluid by a needle inserted through the chest wall, between the ribs. The pleural fluid is then analyzed in the laboratory. Thoracoscopy (T-scope) and pleural biopsy are performed in some cases when a thoracentesis cannot be done because of the location of the effusion. A thoracoscopy is a minimally invasive surgical procedure performed with a small videoscope instrument (thoracoscope) and surgical instruments. The scope and instruments are inserted through small incisions to examine the chest cavity and remove a tissue sample or pleural fluid sample (pleural biopsy). The sample is then examined in a laboratory. Treatment and therapy: In cancer patients, not all pleural effusions are malignant but may be the result of malnutrition or the result of a comorbid condition, such as con-
Salem Health: Cancer gestive heart failure, pulmonary embolism, or pneumonia. Treatment is directed at the underlying medical condition or type of cancer causing the pleural effusion. The goals of treatment include draining excess fluid, treating infection, and fully expanding the lung. When the effusion is transudative and asymptomatic, no treatment may be needed. Treatment options include thoracentesis, use of sclerosing agents, or surgery. Thoracentesis helps reduce pressure on the lungs by removing excess fluid. It can be used as a palliative treatment to relieve symptoms of advanced cancers. Sclerosing agents such as talc, doxycycline, and bleomycin may be inserted through a chest tube during thoracentesis to prevent a recurring effusion. Sclerosing agents also may be used during pleurodesis, a procedure to close the pleural sac. Pleurodesis is usually performed for cases of recurring malignant effusions in patients with metastatic breast, ovarian, or lung cancer. Surgical options to drain excess fluid include thoracotomy (open-chest surgery) or minimally invasive videoassisted thoracoscopic surgery. Surgery is recommended for the treatment of infections or when the location of the effusion prohibits the use of thoracentesis for fluid analysis. In some cases, a pleural-peritoneal shunt is implanted to transfer fluid from the pleural cavity to the abdominal cavity, where it can drain more easily. Pleurectomy is another surgery performed under general anesthesia to remove the parietal pleura, the outermost lining around the lungs. Prognosis, prevention, and outcomes: The outcome of a pleural effusion depends on the underlying condition causing the effusion. Potential complications of a pleural effusion include an empyema (abscess in the pleural space) if the pleural fluid becomes infected and a collapsed lung if the fluid has built up for a long time. Malignant pleural effusions are often associated with advanced disease and increased morbidity and mortality. Angela M. Costello, B.S. u
Pleural effusion. (LifeART© 2008 Wolters Kluwer Health, Inc.Lippincott Williams &Wilkins. All rights reserved.)
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For Further Information Akopov, A. L., et al. “Thoracoscopic Collagen Pleurodesis in the Treatment of Malignant Pleural Effusions.” European Journal of Cardiothoracic Surgery 28, no. 5 (2005): 750-753. Colice, G. L., et al. “Medical and Surgical Treatment of Parapneumonic Effusions: An Evidence-Based Guideline.” Chest 118 (2000): 1158-1171. Maghfoor, I., D. C. Doll, and J. W. Yarbro. “Effusions.” In Clinical Oncology, edited by M. D. Abeloff et al. New York: Churchill Livingstone, 2000.
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Other Resources
American College of Chest Physicians http://www.chestnet.org National Cancer Institute Cardiopulmonary Syndrome Overview http://www.cancer.gov/cancertopics/pdq/ supportivecare/cardiopulmonary Society of Thoracic Surgeons Patient Information http://www.sts.org/sections/patientinformation/ See also Asbestos; Bronchoalveolar lung cancer; Lung cancers; Mesothelioma; Needle biopsies; Pleural biopsy; Pleurodesis; Radiofrequency ablation; Thoracentesis; Thoracoscopy; Ultrasound tests.
u Pleurodesis Category: Procedures Definition: Pleurodesis is the binding together of the pleural membranes surrounding the lungs to make breathing easier. Cancers treated: Mesothelioma, lung cancer Why performed: Pleurodesis is used to help lung cancer patients with malignant pleural effusions breathe more easily. Normally, the membranes of the pleural cavity that surrounds the lungs are coated with fluid that provides surface tension to make them adhere, causing the lungs to inflate when the diaphragm moves during inspiration. Extra fluid in this cavity (pleural effusion) makes it difficult to breathe because pleural surfaces do not stick together and also because the lungs do not have room to expand completely. During pleurodesis, the extra fluid is removed and a sclerosant (chemical irritant) such as sterile talc or an antibiotic is injected into the pleural cavity. The irritation causes inflammation in the membranes, which makes them stick together and also prevents more fluid accumulation. Alternatively, the surfaces can be mechanically irritated (scraped) during a surgical procedure. Patient preparation: Patients are typically hospitalized, although pleurodesis can also be done on an outpatient basis. Patients should report any allergies to medications or other substances, such as iodine. They may be asked to stop taking medications that can increase the risk of bleeding.
Pleuropulmonary blastomas Steps of the procedure: The skin and chest wall are injected with a local anesthetic and a chest tube is inserted into the pleural cavity (a procedure called a thoracotomy). A chest X ray is taken to ensure proper placement. Any fluid in the cavity is drained, in some cases over several days. Before injection of the sclerosant, the patient may receive an analgesic and/or sedative to prevent discomfort. Sometimes the patient is asked to rotate from side to side. Then the excess sclerosant is drained and the doctor removes the chest tube, which may take only a few hours. An occlusive dressing is applied over the opening to prevent air from entering the chest. After the procedure: Patients are observed for serious complications such as respiratory distress, a collapsed lung, or bleeding. The occlusive dressing is typically left in place for two days; if stitches are used to close the opening, then they may remain in place for a week. Additional pain medication may be needed once the anesthetic has worn off. A low-grade fever is a common response to the inflammation. Risks: The risks of pleurodesis include respiratory distress, infection, a collapsed lung, and bleeding. Patients may also have a reaction to the irritant. Results: After a successful pleurodesis, the patient will find breathing is easier. This procedure may be repeated if needed. Marcia Pinneau, R.N. See also Bronchoalveolar lung cancer; Lung cancers; Mesothelioma; Pleural biopsy; Pleural effusion.
u Pleuropulmonary blastomas Category: Diseases, symptoms, and conditions Also known as: Pneumoblastomas, mesenchymal cystic hamartomas, pulmonary rhabdomyosarcomas Related conditions: Cystic nephromas, renal tumors Definition: Pleuropulmonary blastomas are rare childhood cancers occurring most commonly in the lungs. Risk factors: A risk factor for pleuropulmonary blastoma is a familial history of childhood cancers, including lung cysts, kidney cysts, and thyroid tumors, although the specific genetic defect has not been elucidated. Children with pleuropulmonary blastoma may have other types of cancers and neoplastic diseases outside the lung, such as cystic nephroma of the kidney. 975
PMS genes Etiology and the disease process: Pleuropulmonary blastoma is almost always intrathoracic or intrapulmonary. Multiloculated or unilocular lung cysts often precede development of pleuropulmonary blastoma. In 40 percent of cases, air-filled cysts were present at diagnosis, and in 25 percent of these cases pneumothorax occurred. Pleuropulmonary blastoma is categorized into three subtypes (I, II, III), and the latter two are aggressive malignancies with metastatic potential. Metastases to contralateral or ipsilateral lung tissue develop relatively frequently. Types II and III pleuropulmonary blastoma may metastasize within or beyond the chest cavity. Metastasis in most pleuropulmonary blastoma cases occurs within twentyfour months after diagnosis but occasionally at thirty-six months and beyond. Incidence: Pleuropulmonary blastoma is a rare condition that occurs almost exclusively in children under the age of seven to eight years. Type I disease is found more often in younger children, and type III in older children. Symptoms: Symptoms of pleuropulmonary blastoma include mild to severe respiratory distress, dyspnea (shortness of breath), fever, cough, and chest or abdominal pain due to air-filled cysts or pneumothorax. Screening and diagnosis: Type I pleuropulmonary blastoma is cystic in appearance with no grossly identifiable nodular disease. Type II is cystic and has identifiable nodular disease. Type III is a nodular disease with no detectable cystic areas. The median age of diagnosing type I pleuropulmonary blastoma is eleven months. The frequency of cerebral metastasis in pleuropulmonary blastoma typically tends to be higher than in other pediatric sarcomas. Treatment and therapy: Type I pleuropulmonary blastoma patients are treated with surgery with or without adjuvant chemotherapy. Typically children with types II or III pleuropulmonary blastoma are treated with surgery, chemotherapy, or radiation. Prognosis, prevention, and outcomes: In a study, the overall survival in type I pleuropulmonary blastoma was between 65 and 90 percent. Type I may recur and progress to type II or III, and type II may progress to type III. After recurrence, type II and III pleuropulmonary blastoma has a poor prognosis. Anita Nagypál, Ph.D. See also Childhood cancers; Hereditary papillary renal cell carcinomas; Kidney cancer; Lung cancers; Renal pelvis tumors. 976
Salem Health: Cancer
u PMS genes Category: Cancer biology Also known as: PMS1 postmeiotic segregation increased 1 (Saccharomyces cerevisiae); postmeiotic segregation increased (S. cerevisiae) 1; PMS2 postmeiotic segregation increased 2 (S. cerevisiae); postmeiotic segregation increased (S. cerevisiae) 2 Definition: PMS genes, PMS1 and PMS2, encode proteins that are part of the cellular mismatch repair machinery that corrects errors made during deoxyribonucleic acid (DNA) replication. Defects in mismatch repair proteins are seen in hereditary nonpolyposis colorectal cancer, or HNPCC. Normal cellular function: Each time a cell divides, it must faithfully replicate its genetic material contained within the DNA. Due to the inherent properties of the replication machinery, a number of mutations are made each time the genome is replicated. These mutations are rarely permanent, though, because of the action of a set of proteins that recognize and repair DNA damage. One type of repair mechanism is called the mismatch repair pathway. Role in cancer: Individuals who inherit a mutation in one of the mismatch repair genes are strongly predisposed to developing certain types of cancer, including colorectal, ovarian, and endometrial. MLH1 and MSH2 are the most commonly mutated genes in this pathway, but PMS1 and PMS2 are also mutated in some cases of hereditary nonpolyposis colorectal cancer. Cells that have defects in mismatch repair proteins have a mutator phenotype; that is, because the machinery that normally corrects errors is compromised, the frequency of mutations is significantly higher than in normal cells. These cells are more likely to accumulate mutations within genes that are critical for limiting cell growth and proliferation and inducing cell death when damage has been done to the DNA, which are characteristics of cancer cells. Clinical implications: Because inheriting a mutation in one of the DNA mismatch repair genes greatly predisposes an individual to developing cancer, it is important to identify at-risk individuals so that they can be frequently screened for tumors. People with a strong family history of early-onset colorectal cancer are urged to undergo genetic testing to identify mutations in the mismatch repair genes. Once a tumor has formed, the levels of mismatch repair proteins can provide insight into the patient’s prognosis and cancer progression. In addition, knowing the levels of mismatch repair proteins within tumor cells can have implications for the method of treatment that is prescribed. Although the effects vary based on tumor type, there have
Salem Health: Cancer been data showing that the state of the mismatch repair machinery can affect the efficacy of certain types of chemotherapeutic agents. For example, patients with ovarian cancer resulting from defective mismatch repair show higher levels of cancer recurrence following treatment with cisplatin. Lindsay Lewellyn, B.S. See also Endometrial cancer; Family history and risk assessment; Genetic testing; Genetics of cancer; Hereditary cancer syndromes; Ovarian cancers; Turcot syndrome.
u Pneumonectomy Category: Procedures Also known as: Lung removal, extrapleural pneumonectomy Definition: Pneumonectomy is the surgical removal of the entire lung. Extrapleural pneumonectomy is the surgical removal of the lung, a portion of the membrane covering the heart, the membrane lining the affected side of the chest cavity, and a portion of the diaphragm. Cancers treated: Lung cancer, mesothelioma Why performed: Pneumonectomy is a surgical procedure used to treat lung cancer when the tumor cannot be removed by a less extensive procedure. It may also be performed in the presence of severe chest trauma. Rarely, pneumonectomy is used for treatment of bronchiectasis, lung abscesses, or extensive unilateral tuberculosis. Extrapleural pneumonectomy is sometimes a treatment option for those patients with malignant mesothelioma. Patient preparation: Before planning surgery, a computed tomography (CT) scan of the head and abdomen and a bone scan are typically performed to confirm that the cancer has not spread to other areas of the body. If the cancer has spread, then pneumonectomy may not be a treatment option. Before surgery, studies are performed to check for abnormalities and establish a baseline for postoperative comparison. These studies include a chest X ray, electrocardiogram (EKG), bleeding time, and blood tests to check kidney function; electrolyte, hemoglobin, and oxygen levels; and white blood cell count. Pulmonary function tests are performed to evaluate lung function and to determine whether the remaining lung is healthy enough to handle the increased workload. A blood sample is also drawn to check the patient’s blood type in case a transfusion is needed during surgery.
Pneumonectomy A week before surgery, aspirin and anti-inflammatory drugs are stopped. The patient is given special instructions about when to stop taking anticoagulants, if prescribed. The patient must not eat or drink for at least eight hours before surgery, and an intravenous (IV) catheter is inserted for the delivery of fluids and medications. An indwelling urinary catheter is also inserted so that urine output can be monitored closely during and after the procedure. Steps of the procedure: When the patient arrives in the operating suite, an arterial catheter may be inserted to monitor the patient’s blood pressure and oxygenation. An epidural catheter may also be inserted for postoperative pain control. An endotracheal tube is inserted through the nose or mouth to maintain the patient’s airway and provide oxygenation during surgery. After the patient is anesthetized, the surgeon makes an incision into the chest cavity. When the chest cavity is entered, the lung collapses. The surgeon locates and ties off the pulmonary artery supplying the lung and the pulmonary veins. The ribs are spread, and the lung is exposed for removal. In some cases, it is necessary to remove a rib. The mainstem bronchus is divided, and the affected lung is removed. The surgeon staples or sutures the bronchial stump. Chest tubes typically are not inserted into the chest; instead fluid is permitted to accumulate inside the empty chest cavity, preventing mediastinal shift. Finally, after making sure that the bronchial stump is not leaking air, the surgeon closes the chest cavity and applies a sterile dressing. When an extrapleural pneumonectomy is necessary, the surgeon removes the lung, a portion of the membrane covering the heart, the membrane lining the affected side of the chest cavity, and a portion of the diaphragm and replaces them with synthetic patches. After the procedure: The patient is transferred to the surgical intensive care unit (SICU) and attached to a monitor that displays the patient’s heart rhythm, blood pressure, and oxygen saturation. These devices help the SICU nurses monitor the patient’s condition closely. The patient may have an endotracheal tube in place and require mechanical ventilation to assist breathing. If mechanical ventilation is not necessary, then the patient will receive supplemental oxygen through a nasal cannula or facemask. The patient is encouraged to cough, deep-breathe, and use an incentive spirometer to prevent pneumonia. If the patient requires mechanical ventilation immediately after surgery, then early extubation is the goal to prevent ventilator-associated pneumonia. The head of the patient’s bed is elevated at least 30 degrees to help prevent pneumonia. The patient is turned every two hours from the back to the nonoperative 977
Pneumonectomy
Salem Health: Cancer
After lung surgery, patients are asked to exercise their lungs by using a spirometer. (Digital Stock)
side to prevent the heart and remaining lung from shifting toward the operative side. Fluids are administered conservatively through an IV infusion pump to prevent fluid overload. Sequential compression devices are attached to the patient’s legs to help prevent blood clot formation. Pain medications are administered continuously either through an epidural catheter or through an IV catheter, as needed. The patient is transferred to a medical surgical floor when considered stable, typically a few days after surgery, and then discharged to home. The patient is instructed to resume activities of daily living slowly in order to allow the remaining lung to compensate for its increased workload. Recovery commonly takes several months because shortness of breath significantly limits the patient’s ability to exercise. Some patients require lifelong supplemental oxygen therapy. Risks: The risks of pneumonectomy include surgical site infection, pneumonia, empyema (pus in the pleural space), 978
hemorrhage, pulmonary edema, myocardial infarction, cardiac arrhythmia, pulmonary embolism, and ventilatordependent respiratory failure. Rarely, stump failure results in cardiopulmonary arrest. Results: Pathologic examination of the lung specimen reveals the type of cancer. Collette Bishop Hendler, R.N., M.S. u
For Further Information Lorigan, Paul. Lung Cancer. Dana-Farber Cancer Institute Handbook. Philadelphia: Mosby, 2007. Smeltzer, Suzanne C., et al., eds. Brunner and Suddarth’s Textbook of Medical-Surgical Nursing. 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2008. Surgical Care Made Incredibly Visual! Philadelphia: Lippincott Williams & Wilkins, 2006. See also Asbestos; Bilobectomy; Bronchoalveolar lung cancer; Lung cancers; Mesothelioma; Pleurodesis; Thoracentesis; Thoracoscopy.
Salem Health: Cancer
u Pneumonia Category: Diseases, symptoms, and conditions Also known as: Pneumonitis, bronchopneumonia, community-acquired pneumonia Related conditions: Aspiration pneumonia, atypical pneumonia, viral pneumonia, walking pneumonia, Legionella pneumonia, pneumocystis carinii pneumonia (PCP), other pneumonia, primary lung cancer, metastatic lung disease Definition: Pneumonia is a disease of the lungs and respiratory system in which the alveoli (air sacs) become inflamed, infected, or blocked and cannot exchange air (oxygen). Risk factors: People with respiratory problems tend to be more prone to pneumonia. The elderly, children, and people with complicating health problems are more affected by pneumonia. Pneumonia usually follows a cold or case of the flu. Persons with compromised immune systems such as acquired immunodeficiency syndrome (AIDS) patients, organ transplant patients, and cancer patients are at risk. Another risk factor is smoking, as this can damage the cilia (microscopic hairs) that naturally sweep impurities out of the lungs. Smoke can paralyze the cilia, allowing secretions to accumulate in the lungs. If these secretions contain bacteria, pneumonia can result. Exposure to chemicals or other pollutants on the job or in the environment can cause inflammation in the lungs, making it harder to clear the lungs of secretions. People in hospital intensive care units may be exposed to bacteria in the breathing tube of a mechanical ventilator. Sometimes a tumor will restrict or block a cancer patient’s airways, which results in the inability to clear secretions from the lungs. This can predispose the patient to pneumonia. Other risk factors for the cancer patient include radiation therapy, chemotherapy, steroids, malnutrition, surgery, neutropenia (depressed white cell count), limited mobility, antibiotics, and spleenectomy, which results in immune system problems. Etiology and the disease process: Pneumonia can be caused by bacteria, fungi, viruses, or chemical and physical damage such as inhalation of toxins and cancer. When a person breathes, the air passes through the trachea (windpipe) to the lungs, which branch into tubes called bronchi. The bronchi divide into smaller narrow tubes called brochioles that lead to small saclike alveoli (air sacs). The function of the alveoli is to exchange gases (oxygen and carbon dioxide) with the blood capillaries. In pneumonia,
Pneumonia these alveoli become inflamed or blocked so that the exchange of oxygen and carbon dioxide is diminished. How severely this exchange is restricted depends on the underlying cause of the pneumonia and the overall health of the patient. Incidence: An estimated 4 million Americans develop pneumonia each year. Pneumonia and influenza (together) are the seventh leading cause of death in the United States. In 2003, pneumonia claimed 63,241 lives; every year more than 60,000 American with pneumonia die. About 50 percent of all pneumonia is caused by respiratory viruses. Streptococcus pneumoniae (pneumococcus) is the most common pneumonia-causing bacterium. Symptoms: When people have bacterial pneumonia, they experience difficulty breathing, have shallow rapid breathing, and may have a productive cough. Their cough may produce greenish or yellow sputum (phlegm) or sometimes blood-tinged sputum. Patients with bacterial infections usually experience shaking, chills with fever, and sharp pain in the chest that gets worse when coughing or breathing deeply. Patients with viral pneumonia exhibit more flulike symptoms such as a dry cough, headache, muscle pain, fever, and fatigue. The cough may produce a small amount of clear or white sputum. Viral pneumonia can become bacterial pneumonia (a secondary infection) under the right conditions. Other symptoms include headache, loss of appetite, severe fatigue, sweating and clammy skin, and sometimes mental confusion in older adults. Screening and diagnosis: Diagnosis is made by physical examination and by listening to the sound of the breath (such as crackles) through a stethoscope. The health care provider usually orders a chest X ray and reviews the scan for consolidations (white or opaque areas) that represent infected or blocked areas. Sometimes the pneumonia is not easy to visualize with an X ray, so computed tomography (CT) may be used. The health care provider may request a culture of the sputum (Gram-staining procedure) to isolate the causal bacteria and confirm that the bacteria are sensitive to the prescribed antibiotic. A complete blood count test will allow the provider to monitor elevated white cell counts that can indicate bacterial disease. Blood tests for specific organisms may be needed to further define the cause of the pneumonia. In severe cases, arterial blood gases may be used to assess oxygenation of the blood. The diagnostic health care provider may also use a bronchoscope (flexible tube) to examine the lungs for swelling, inflammation, obstruction, or a tumor if the pneumonia is severe and not responding to treatment. 979
Pneumonia Treatment and therapy: Pneumonia is treated based on the cause of the disease. Antibiotics are used to treat bacterial pneumonia but are useless for viral pneumonia. Strains of bacteria that are resistant to antibiotics are making the treatment of pneumonia a challenge. Most people can be treated at home unless they have underlying chronic diseases such as cancer or are elderly or very young. In these cases, hospitalization is necessary to stabilize the person with intravenous antibiotics and fluids, and possibly oxygen therapy. Occasionally steroid drugs must be used to decrease inflammation or wheezing. If a patient is allowed to recuperate at home, the health care provider will encourage increased fluid intake to loosen the lung secretions and allow the patient to expectorate (spit out) phlegm. Key to recovery is rest and symptom control, such as managing fever with acetaminophen or aspirin (no aspirin in children). Sometimes postural drainage will be ordered for patients who need help removing phlegm. With assistance, the patient will lean over the side of the bed with head down and allow gravity to drain the lungs. Those assisting can gently but firmly pound the patient’s upper back to mechanically dislodge mucus. This can be done for about five to fifteen minutes, three times a day, or as tolerated by patients. Treatment for cancer patients with pneumonia must be aggressive and prompt. Bed rest and taking medications to expel phlegm to clear the airways may be prescribed. The health care provider must choose treatment approaches that complement the therapy that patients are receiving for their cancer so as not to decrease the immune response. Alternative or complementary treatments offer no cure for pneumonia but may provide some symptom relief. Acupuncture can be used to relieve congestion and may improve generalized fatigue. Some people benefit from a warm bath or room vaporizer using either plain, distilled water or distilled water with essential oils like eucalyptus added. People with asthma should avoid heat inhalations as these can irritate sensitive lung tissue. Other complementary treatments include massaging the upper back, taking homemade cough syrup of honey and other natural ingredients, and drinking echinacea herbal tea. Supplements such as zinc or vitamins A, C, and E may may support the immune sytem. Prognosis, prevention, and outcomes: Pneumonia can range in severity from mild to severe to fatal, depending on the cause and the age and health of patients. With adequate treatment of the cause, most pneumonia patients will show improvement within about two weeks. If patients have other compromising diseases, such as cancer, recovery 980
Salem Health: Cancer may be slower. If patients fail to respond to treatment, they may die of respiratory failure. Prevention is especially important for patients with cancer or infected with the human immunodeficiency virus (HIV). Measures to prevent infection include frequent washing of hands after blowing the nose or coughing, going to the bathroom, diapering a baby, and before and after food preparation. Immune-compromised people should avoid contact with anyone who has a cold or flu or has been exposed to these illnesses. They should also use a protective mask when cleaning to decrease exposure to dust and molds. The influenza and pneumonia vaccines may also be options and should be checked out with a health care provider. Robert W. Koch, D.N.S., R.N. u
For Further Information Baez-Escudero, José L., John N. Greene, Ramon L. Sandin, and Albert L. Vincent. “Pneumocystis Carinii Pneumonia in Cancer Patients.” Abstracts in Hematology and Oncology 7, no. 1 (2005). Cunha, Burke A., ed. Pneumonia Essentials. Royal Oak, Mich.: Physicians’ Press, 2007. Fein, Alan, et al. Diagnosis and Management of Pneumonia and Other Respiratory Infections. Caddo, Okla.: Professional Communications, 1999.
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Other Resources
American Lung Association http://www.lungusa.org MayoClinic.com Pneumonia http://www.mayoclinic.com/health/pneumonia/ DS00135 National Lung Cancer Partnership http://www.nationallungcancerpartnership.org See also Antiviral therapies; Bacteria as causes of cancer; Bronchial adenomas; Bronchoalveolar lung cancer; Bronchography; Candidiasis; Carcinoid tumors and carcinoid syndrome; Chromium hexavalent compounds; Coughing; Craniotomy; Esophagectomy; Hemoptysis; Infection and sepsis; Insurance; Laryngectomy; Lobectomy; Lung cancers; Mayo Clinic Cancer Center; Mycosis fungoides; Neutropenia; Pleural effusion; Pneumonectomy; Thoracentesis; X-ray tests.
Salem Health: Cancer
u Polycyclic aromatic
hydrocarbons Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1981 Also known as: Polynuclear aromatic hydrocarbons, polyaromatic hydrocarbons, PAHs Related cancers: Lung, colon, skin, and bladder cancer Definition: Polycyclic aromatic hydrocarbons (PAHs) refer to a group of chemicals formed from burning wood, coal, oil, gas, and other carbon-containing substances. Exposure routes: Inhalation, ingestion, skin contact Where found: In air (from motor vehicle exhaust, burning wood and refuse, tobacco smoke, industrial emissions, smoke from fires), contaminated water and food, meat cooked by certain high-temperature methods (such as grilling), and coal tar products used to treat skin conditions At risk: Industrial workers in coking plants; coal tar, aluminum, iron, steel, and asphalt production plants; and petroleum refineries; as well as road construction workers, smokers, and those exposed to tobacco smoke Etiology and symptoms of associated cancers: Polycyclic aromatic hydrocarbons are procarcinogens in that they are converted by the detoxification system in the human body to substances that can cause cancer. Such substances bind to deoxyribonucleic acid (DNA), the molecules that carry a person’s genetic blueprint. Studies suggest that this binding causes changes in DNA that lead to cancer. Some symptoms of associated cancers include shortness of breath, coughing, weight loss (lung cancer); blood in urine (bladder cancer); weight loss, blood in stools, change in bowel habits (colon cancer); change in a wart or mole, or a skin growth that may exhibit redness (skin cancer). History: Polycyclic aromatic hydrocarbons are naturally present in the environment (such as in coal, peat, and crude oil) and are also formed artificially by various burning processes. The involvement of substances containing polycyclic aromatic hydrocarbons in causing cancer was shown in 1775 when Percival Pott, a British surgeon, described scrotal cancer in chimney sweeps who had been exposed to coal soot. Coal tar was subsequently (1915) found to induce tumors when repeatedly applied to rabbits’ ears. In 1933 a specific polycyclic aromatic hydrocarbon isolated from coal tar , benzo(a)pyrene, was shown to cause skin
Polycythemia vera cancer in mice. Animal studies have since shown that repeated administration of this and other polycyclic aromatic hydrocarbons to animals through skin, the air, or diet causes various types of cancer, including breast, skin, stomach, lung, and bladder cancer. Human studies have shown an association between lung, bladder, colon, and skin cancer in industry workers exposed to high levels of polycyclic aromatic hydrocarbons. Polycyclic aromatic hydrocarbon emissions are regulated by several agencies. The Occupational Safety and Health Administration (OSHA) regulates the exposure of industrial workers to polycyclic aromatic hydrocarbons. The Environmental Protection Agency regulates the amount of polycyclic aromatic hydrocarbons released into surface waters (Clean Water Act) and the air (Clean Air Act) and present in drinking water (Safe Drinking Water Act). The Food and Drug Administration regulates the amount of polycyclic aromatic hydrocarbons in bottled drinking water. Jason J. Schwartz, Ph.D., J.D. See also Air pollution; Bronchial adenomas; Carcinogens, known; Carcinogens, reasonably anticipated; Chewing tobacco; Coal tars and coal tar pitches; Coughing; Lung cancers; Mineral oils; Occupational exposures and cancer; Skin cancers; Soots; Tobacco-related cancers.
u Polycythemia vera Category: Diseases, symptoms, and conditions Also known as: PV Related conditions: Essential thrombocythemia, idiopathic myelofibrosis Definition: Polycythemia vera is a rare myeloproliferative disorder that causes chronic overproduction of red blood cells and possibly of white cells and platelets. Although these cells function normally, their overabundance causes increased blood viscosity and decreased blood flow, with possible clot formation and resultant heart attack or stroke, and possible systemic decreases in oxygen supply, resulting in compromised muscle function, lung function, and visual acuity, or in angina, congestive heart failure, or gout. Risk factors: Polycythemia vera occurs more frequently in men aged sixty and older and in Jews of eastern European descent. Although family history is not a risk factor, polycythemia vera occasionally occurs in more than one family member. 981
Polypectomy Etiology and the disease process: The cause of polycythemia vera is unknown. Disease progression is slow, as is symptom onset. Polycythemia vera occurs because of a deoxyribonucleic acid (DNA) mutation—in most cases, in the JAK2 gene—in hemopoietic stem cells (blood-forming cells in bone marrow) that triggers blood cell overproduction. In rare instances, myelofibrosis—abnormal, fibrous bone marrow tissue—may develop and may lead to acute myelogenous leukemia (AML), an aggressive disease characterized by overabundance in blood and bone marrow of immature white blood cells. Incidence: The reported incidence ranges from 0.5 to 2.5 per 100,000 people worldwide. Symptoms: Overabundance of red blood cells and platelets causes the symptoms associated with polycythemia vera. Symptoms may include dizziness, enlarged spleen, fatigue, headache, itchy or flushed skin, kidney stones, profuse sweating, shortness of breath, stomach ulcers, tinnitus, and vision problems. Screening and diagnosis: Due to its slow progression and delayed expression of nonspecific symptoms, polycythemia vera may be diagnosed via routine blood testing if results indicate a 33 percent or greater increase in hematocrit level, hemoglobin concentration, and red cell count. Other indicators may be elevated platelet count or white cell count, presence of the JAK2 mutation in blood cells, or low erythopoietin (EPO) level (determined by assay). Treatment and therapy: Initial options are phlebotomy to reduce blood volume and drug therapy to decrease cell count. The platelet count-lowering drug anagrelide or the myelosuppressive drugs hydroxyurea, interferon alpha, and radioactive phosphorus (32P) may be used. However, side effects are associated with all treatments, including phlebotomy, which can result in anemia. Prognosis, prevention, and outcomes: There is no cure for polycythemia vera. If untreated, it can lead to death. If treated, life expectancy and quality of life may be unaffected. Response to therapy may be monitored via hematocrit levels and hemoglobin concentrations. Cynthia L. De Vine, B.A. See also Bone marrow aspiration and biopsy; Chlorambucil; Chronic myeloid leukemia (CML); Hematologic oncology; Hypercoagulation disorders; Myeloproliferative disorders; Radiopharmaceuticals. 982
Salem Health: Cancer
u Polypectomy Category: Procedures Also known as: Endoscopic polypectomy Definition: Polypectomy is the removal of a protruding growth (polyp), leaving the underlying tissue. Cancers diagnosed or treated: Cancers of the colon, rectum, small bowel, stomach, uterus, and nose Why performed: Most polypectomies are performed to remove polyps that are or are likely to become cancerous, thereby controlling or preventing the disease. Such polyps arise most frequently in the colon and rectum; less frequently in the stomach, small intestine, and uterus; and rarely in the nose. Most polypectomies are performed during a diagnostic endoscopic procedure (such as colonoscopy, gastroscopy, hysteroscopy, or sigmoidoscopy). Polyps that cannot be removed with an endoscope, such as polyps that are too large or too numerous, require local excision or major surgery to remove the polyp and underlying tissue completely with a margin of healthy tissue. Patient preparation: A few days before the procedure, the patient may need to stop certain medications. For gastrointestinal procedures, the patient may need to cleanse the bowel and may not eat or drink after midnight. Steps of the procedure: Endoscopic procedures are scheduled in an outpatient setting. For the procedure, sensors are placed to monitor the patient’s condition. An intravenous (IV) line is started for fluids and medications. The patient lies on the side, and sedation is given. If the patient has an electronic implant, then special precautions are taken. The appropriate endoscope is inserted through the anus (to examine colonic and rectal polyps), mouth (gastric and small intestinal polyps), or vagina (uterine polyps). The physician slowly withdraws the endoscope, carefully viewing the entire lining. When a polyp is found, its location, size, and appearance are documented. The physician may sample (biopsy), destroy (ablate), or remove (excise and retrieve) the polyp. If the polyp was not totally removed, then its location is marked with a small tattoo. All biopsy samples and excised tissues are taken to the laboratory for histopathologic evaluation. After the procedure: The patient’s condition is monitored until he or she awakens and then the patient may leave, transported by a companion. The next day, the patient resumes normal activities. Risks: Polypectomy is relatively safe, with a small risk of perforation, bleeding, infection, postpolypectomy coagulation syndrome, or reaction to the sedative.
Salem Health: Cancer
Polyps
Results: The completeness of removal varies with the polyp’s size and shape (such as broad or stalked) and the removal technique (such as type of excision, with or without ablation). Histopathologic evaluation determines whether each polyp is or is not likely to become cancerous and, if so, whether all diseased tissue was removed. Additional treatment, follow-up examinations, or both may be recommended. Patricia Boone, Ph.D. See also Biopsy; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; DPC4 gene testing; Hysteroscopy; Infection and sepsis; Juvenile polyposis syndrome; Polyps; Rectal cancer; Sigmoidoscopy; Small intestine cancer; Stomach cancers; Uterine cancer.
u Polyps Category: Diseases, symptoms, and conditions Also known as: Intestinal polyps, colorectal polyps, gastric polyps, nasal polyps, uterine polyps Related conditions: Polyps may be related to certain genetic disorders that promote their growth in the colon, stomach, and rectum. Although not cancers themselves, these disorders make the person who inherits the defective gene more susceptible to cancer.
polyps; radiation treatments to the stomach or pelvis; eating a diet high in fat and low in calcium and fiber; smoking; excessive alcohol intake; lack of exercise; and obesity. Etiology and the disease process: Like most cancers, polyps are the result of abnormal cell growth. However, not all polyps are cancerous. Mutations in genes that control cell growth cause polyps to develop. Sometimes they continue to grow and turn cancerous. In general, the larger the polyp, the more likely it is to become cancerous. Doctors consider all polyps, even benign ones, precancerous and remove them whatever their size. Incidence: Colorectal cancer is the third most common cancer and the second leading cause of death from cancer in the United States. (Lung cancer is the first.) More than 50,000 people die from colorectal cancer each year. Anyone can get polyps and colorectal cancer, but some people are more susceptible than others. Whites and African Americans are more likely to get polyps and die from colorectal cancer than are Hispanics, Asian Americans, and Native Americans. Women and men under the age of fifty get polyps and die from colorectal cancer at about equal rates. Over the age of fifty, men are more vulnerable than women. Researchers estimate that 30 percent of adults the age of fifty and older have one or more colon or rectal polyps.
Definition: A polyp is an abnormal mass of tissue that attaches to mucous membranes, tissue linings that protect and keep moist the hollow organs of the body such as the colon, stomach, nose, sinuses, and uterus. Polyps can form on mucous membranes anywhere in the body but most commonly develop in the colon or rectum, both parts of the large intestine. They usually cause no problem, but some turn into colon or rectal cancer, generally called colorectal cancer because the two cancers have so much in common. Risk factors: Risk factors for colorectal polyps include being past the age of fifty; inheriting a gene that causes polyp growth; previous colorectal, breast, ovarian, or uterine cancer; a personal or family history of
Gross pathology of a colon polyp (center). (Centers for Disease Control/Dr. Edwin P. Ewing, Jr.)
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Positron emission tomography (PET)
Salem Health: Cancer
Symptoms: Most polyps generate no symptoms. They are usually found during routine screenings for colon cancer. Very large polyps, however, can cause bleeding from the rectum, bloody stool, and changes in bowel movement patterns.
erous vegetables such as broccoli and cauliflower, not smoking, avoiding alcohol, exercising and maintaining a healthful weight, and (when prescribed by a doctor) taking aspirin. Wendell Anderson, B.A.
Screening and diagnosis: The most common screenings for colorectal cancer are as follow: • Fecal occult blood test: This test checks for blood in the stool. • Flexible sigmoidoscopy: This test examines the bottom third of the large intestine (the rectum and descending colon). The doctor inserts into the rectum a thin, flexible tube with a small camera on the end that is connected to a video monitor. This enables the doctor to look for polyps in real time. • Colonoscopy: The procedure for this test is the same as for the sigmoidoscopy, but in this test, the doctor searches the entire large intestine.
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For Further Information Adrouny, R. Understanding Colon Cancer. Jackson: University of Mississippi Press, 2002. American Cancer Society. Quick Facts Colon Cancer: What You Need to Know—Now. Atlanta: Author, 2007. Levin, B. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006. Lipkin, M: “Strategies for Colon Cancer Prevention.” Annals New York Academy of Sciences 768 (September 30, 1995): 170-179.
Treatment and therapy: When a polyp is discovered during screening, the doctor removes it and tests it for cancer. If the polyp is found to be cancerous, any of four main treatments for colorectal cancer begins. • Surgery is the main treatment. Surgeons cut out the cancerous tumor and part of the area surrounding it to prevent its spreading. • Radiation therapy uses high-energy rays to kill or shrink cancer cells. In some cases, radiation is used to shrink the tumor before surgery. Radiation is also used to ease symptoms such as pain and bleeding in late stages of cancer. • Chemotherapy (cancer-fighting drugs) may be beneficial in the early stages of cancer. The drugs also help relieve symptoms in late stages. Because chemotherapy affects cells other than cancer cells, it sometimes causes serious side effects. • Targeted therapies use manufactured proteins called monoclonal antibodies that attack only the part of the cancer cells that makes them different from normal cells. This treatment causes fewer side effects than other chemotherapies.
American College of Gastroenterology http://www.acg.gi.org
Prognosis, prevention, and outcomes: Outcomes for patients with colorectal cancer are good when the cancer is caught early. Some 90 percent of patients whose cancer is diagnosed and treated before it has spread live at least five years after diagnosis. Because doctors do not know the exact causes of polyps, prevention measures are inexact. Generally, however, doctors believe that polyps may be prevented by maintaining a diet low in fat and high in fiber and certain crucif984
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Other Resources
American Society of Colon and Rectal Surgeons http://www.fascrs.org National Cancer Institute http://www.cancer.gov National Digestive Disease Information Clearinghouse What I Need to Know About Colon Polyps http://digestive.niddk.nih.gov/ddiseases/pubs/ colonpolyps_ez/ See also Adenomatous polyps; Benign tumors; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Gastric polyps; Gastrointestinal cancers; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Juvenile polyposis syndrome; Sigmoidoscopy.
u Positron emission tomography
(PET) Category: Procedures Also known as: PET scan, 18F-FDG PET, 18F-FET PET Definition: Positron emission tomography (PET) scanning is a procedure in which a small amount of radioactive glucose or amino acid is injected into a vein and a scanner is used to make detailed, computerized pictures of areas
Salem Health: Cancer
Positron emission tomography (PET)
A PET scan shows Hodgkin disease, Stage IV B, with metastases of the bone, lymph nodes, and viscera. (©BSIP/Phototake—All rights reserved)
inside the body. Since cancer cells often utilize more glucose and amino acids than normal cells, the pictures can be used to find cancer cells in the body by looking for areas with higher uptake of these nutrients. Cancers diagnosed: A wide range of cancers Why performed: PET scans are used to screen for tumors in cancer diagnosis and to aid in tumor staging, locating metastases, and assessing treatment response, such as tumor recurrence. In addition to cancers, PET scans are effective for determining the presence of infections, heart disease, brain disorders, abnormal blood flow, and bone disorders. Patient preparation: Patients should restrict the amount of sugar and caffeine consumed on the day before the scan. On the day of the scan, patients should not ingest anything except water for a minimum of six hours before the scan. Prior to the PET scan, blood glucose levels should be less than 120 milligrams per deciliter in nondiabetics and should fall between 150 and 200 milligrams per deciliter in diabetics. Patients are asked to drink 500 milliliters of water after injection of a radioactive compound approximately 1 hour before the PET scan. For renal or pelvic imaging, 20 to 40 milligrams of furosemide may be given ten to fifteen minutes after the injection of radioactive glucose
or amino acid. Patients should also refrain from strenuous exercise for twenty-four hours before PET to minimize uptake of the radioactive compound by the muscles during the test. Just before the scan, patients are asked to remove any dentures, jewelry, or metal objects that may interfere with imaging. Steps of the procedure: Patients are injected with glucose (FDG) or tyrosine (FET) labeled with radioactive fluorine (18F). The compounds are given about an hour to distribute throughout the body. The patient then empties the bladder and lies still on the scanner bed. The PET scan takes approximately forty-five to sixty minutes, depending on the type of scan taken and the model of scanner used. Commonly, an initial whole-body scan is conducted about an hour after injection of the radioactive compound. This scan typically samples from the angle of the jaw to the level of the mid-thigh. A later scan, known as a delayed scan, is then taken approximately two hours after the injection, focusing on the organ or tissue of interest. A major complication in interpreting PET data is the presence of multiple primary and metastatic lesions throughout the body. The uptake of radioactive glucose or amino acids into these tumors and into the surrounding normal tissues is a dynamic process that peaks at different times, depending on the specific tissues examined, patient 985
Positron emission tomography (PET) preparation, and other factors. Thus if a patient undergoes serial PET scanning, then the time between injection of the radioactive compound and PET imaging should be the same in the baseline study and in subsequent studies. The National Cancer Institute consensus recommendations for FDG-PET scanning in clinical trials states that serial PET scans should be conducted at the same institution, using the same type of camera, the same dose of radioactive compound, the same imaging times, and the same acquisition and reconstruction parameters. After the procedure: The patient is asked to drink plenty of fluids for a day after the scan in order to flush the radioactive compound from the body. The PET scans are interpreted by a trained radiologist, who sends the results to the referring physician. Risks: The procedure is completely painless, with no side effects. The amount of radiation exposure is very small and similar to that from a standard X ray. Like any other procedure involving radiation, however, PET is accompanied by a small risk of tissue damage. Some patients may also experience soreness in the arm where the intravenous (IV) line was placed. Pregnant patients should inform the doctor of their condition, as PET scans may be harmful to the fetus. Results: PET scans can identify regions in the body with abnormal metabolism of nutrients, which may indicate the presence of cancer cells. These areas can then be examined more closely by computed tomography (CT) or magnetic resonance imaging (MRI) to confirm that tumors are present and, if so, where they are located. PET scans may be useful in determining the extent of spread of certain cancers, assessing how the cancer responds to treatment, and determining if the cancer has recurred. Cancers may use more energy than surrounding tissues and therefore appear brighter on the PET scan. PET scanning can be used in combination with CT scanning to produce anatomical pictures of organs and tissues that show regions of abnormal metabolism. PET/CT scanning machines are now available at many medical centers. This combination method can be more powerful than either technique used alone. R. A. Kuker and colleagues showed that a combination of delayed-phase FDGPET and CT could identify liver tumors and metastases that could not be detected by CT alone. Several important factors must be considered when analyzing PET scans. A crucial factor in analyzing PET data is the time of measurement. For example, whole-body images are composites of static images that are obtained at various predetermined times after the injection of the ra986
Salem Health: Cancer dioactive compound. These scans must be corrected for signal attenuation over time. Other factors that have an impact on data analysis are the volume of distribution, body weight, lean body mass, body surface area, and normal serum glucose or amino acid concentrations. After correcting for these factors, the standardized uptake value (SUV) is the most common assessment used. When suspected lesions are identified on a PET scan, both maximum and mean SUV are determined for regions in the tumor and in normal tissue in the same organ. The tumor-to-normaltissue SUV (T/N) ratio can be calculated. A value for the maximum SUV T/N ratio, for example, can be set as a threshold above which a suspected lesion is considered positive. When using PET to determine tumor response to treatment, experts recommend conducting PET studies six to eight weeks after radiation therapy and two weeks after chemotherapy. The SUVs of the target tumors are determined before and after treatment. The SUVs of normal tissue in the organs in which the tumors occur are also obtained as a reference, and T/N ratios are obtained. This ensures that the SUV changes are attributable to either tumor progression or treatment response, and not to normal changes in the cells over time. The shape and size of tumors frequently change during the course of treatment. These changes should be recorded along with the changes in tumor uptake values. The interpretation of PET data is key to obtaining accurate and reliable results. Many types of cancer do not appear on PET scans and may be detected only by imaging techniques with a higher resolution, such as PET/CT or MRI. Some noncancerous tissues can also appear similar to tumors on a PET scan, resulting in false positives. Ing-Wei Khor, Ph.D. u
For Further Information Christian, Paul E., and Kristen M. Waterstram-Rich, eds. Nuclear Medicine and PET: Technology and Techniques. 6th ed. St. Louis: Mosby/Elsevier, 2007. Kubota, K. “From Tumor Biology to Clinical PET: A Review of Positron Emission Tomography (PET) in Oncology.” Annals of Nuclear Medicine 15 (2001): 471486. Kuker, R. A., G. Mesoloras, and S. A. Gulec. “Optimization of FDG-PET/CT Imaging Protocol for Evaluation of Patients with Primary and Metastatic Liver Disease.” International Seminars in Surgical Oncology 4 (2007): 17-21. Also available online at http://www .issoonline.com. Shankar, L. K., J. M. Hoffman, S. Bacharach, et al. “Consensus Recommendations for the Use of 18F-FDG PET
Salem Health: Cancer as an Indicator of Therapeutic Response in Patients in National Cancer Institute Trials.” Journal of Nuclear Medicine 47 (2006): 1059-1066. u
Other Resources
Cedars-Sinai Health System http://www.csmc.edu Mayo Clinic Positron Emission Tomography (PET) Scan: Detecting Conditions Early http://www.mayoclinic.com/health/pet-scan/ CA00052 National Cancer Institute http://www.cancer.gov PETNET solutions Patient Preparation http://www.petscaninfo.com/zportal/portals/pat/ my_pet_scan/for_patients See also Angiography; Barium enema; Barium swallow; Bone scan; Bronchography; Computed tomography (CT)guided biopsy; Computed tomography (CT) scan; Cystography; Ductogram; Endoscopic retrograde cholangiopancreatography (ERCP); Gallium scan; Hysterography; Imaging tests; Lymphangiography; Magnetic resonance imaging (MRI); Mammography; Nuclear medicine scan; Radionuclide scan; Thermal imaging; X-ray tests.
u Poverty and cancer Category: Social and personal issues Definition: Cancer has higher rates of incidence and mortality among people of lower socioeconomic status. Impoverished people, whether in developed or underdeveloped countries, tend to be poorly educated about cancers and cancer prevention, have little access to screening, and have cancers discovered in later stages. Moreover, they are often unable to access and afford medical treatment. Description of the population: People living in absolute poverty are defined by the World Bank as earning one or two dollars per day in developing countries such as India and Sierra Leone and about twenty-six dollars per day in the United States. In addition to economic indicators, poverty may be defined as lacking basic human services— such as employment opportunities, safe drinking water, and basic sanitation services—and access to food, health, education, and shelter.
Poverty and cancer Incidence, death, and survival statistics: According to the World Health Organization, globally the six leading types of cancer in terms of incidence are lung cancer, breast cancer, colorectal cancer, stomach cancer, liver cancer, and cervical cancer. In the United States, the top six types of cancer, according to the American Cancer Society, are prostate cancer, lung and bronchus cancer, breast cancer, colon cancer, urinary bladder cancer, and nonHodgkin lymphoma. In 2006, approximately three million of the six million deaths from cancer occurred in developing countries. The deaths were mainly attributed to late diagnosis of the disease (in either Stage III or IV), when death is often no longer preventable. Approximately 23 percent of all malignancies in developing countries are caused by infectious agents such as hepatitis B and hepatitis C viruses (HBV and HCV, which cause liver cancer), human papillomaviruses (HPV, which causes cervical cancer), and Helicobacter pylori (H. pylori, the bacterial agent that causes stomach cancer) and are preventable with safe health and behavioral practices. In developed countries, only 8 percent of all malignancies are attributable to these infectious agents. The variance in malignancy rates in developing and developed countries suggests that poverty and poor health practices are at least partially responsible. Breast and cervical cancer rates are steady or decreasing in some developed countries such as the United States, possibly because of early detection, proper and timely treatment, and vaccination; however, the trend is different in many developing countries. For example, Pakistan is continuing to see an increase in cancer prevalence among women. It has the highest prevalence of breast cancer of any Asian country, accounting for about 25 percent of all malignant tumors among Pakistani women. Malaysia also experiences high rates of breast cancer, and 50 to 60 percent of breast cancers were diagnosed late, in Stages III and IV, contributing to low survival rates for breast cancer among Malaysian women. Cervical cancer, which is preventable through vaccination and safe sex practices, is highly endemic in Central America, Southeast Africa, and India. Approximately 80 percent of all cervical cancer deaths occur in developing countries, where prevention, detection, and treatment strategies are minimal or absent. Risk statistics: Socioeconomic status, tobacco use, poor nutrition or diet, physical inactivity, and prohibitively expensive health care are major risk factors for cancer globally. Environmental factors also are risk factors. This is particularly true in China, where, according to the Minis987
Poverty and cancer
Salem Health: Cancer
try of Health, pollution is the main reason that cancer is the country’s leading cause of death. The main difference between cancer in developing and developed countries is that developing countries are experiencing cancers largely associated with behavior and environment (cervical, liver, and stomach); these cancers are more often detected in early stages and successfully treated in developed countries. In developed countries, cancers that are preventable through diet and nutrition, physical activity, and avoiding tobacco use are endemic. For example, obesity is a leading cause of death in high- to middle-income countries, and obesity is associated with breast and colon cancer. However, developing countries often encounter food shortages, and as a result obesity and its related cancers are less prevelant. Developing countries often lack a stable health care system to address and treat cancer. If treatment is available, it is often geographically distant or not affordable except by the affluent members of the society. For example, Pakistan has numerous medical facilities that diagnose and treat cancer. However, a majority of Pakistani cancer patients are unable to afford treatment even if the facilities are in their area. Diagnostics are not typically available to socioeconomically disadvantaged groups, while higher-income groups benefit greatly from screening and physical examinations. Poor health education is a contributing risk factor for cancer. Mexico has high rates of cervical cancer, and the cancer is endemic in groups with low literacy rates and lack of access to proper health care. In 2000, 44 percent of Mexican women who died of cervical cancer lacked formal education. Areas positively correlated with cervical cancer (India, southeastern Africa, and Central America) also have high rates of infection with the human immunodeficiency virus (HIV), suggesting risky sexual practices and poor health education.
Perspective and prospects: Poverty is the greatest barrier to early diagnosis and proper treatment for cancer globally. The poor suffer greater mortality from cancer, particularly in developing countries. Financial and cultural barriers prevent socioeconomically disadvantaged people from seeking early diagnosis and treatment for the disease. Areas to be addressed in solving this problem include improvement of health education, integration of the socioeconomically disadvantaged into health care systems, and the removal of cultural barriers to prevention and timely diagnosis. Primarily, health education needs to be emphasized. Safe sex practices may help eliminate cervical and liver cancers by lowering the spread of HPV and hepatitis B and C. Better sanitation may reduce the incidence of H. pylori and reduce stomach cancers resulting from this bacterial agent. Additionally, the effects of tobacco use need to be emphasized to reduce global lung cancer rates. Proper health education may also help reduce the social stigmas and cultural barriers attached to cancer and enable more timely diagnosis. Even if people become educated regarding their health, the medical system needs to be in place and capable of adequately treating cancer. In the United States, Canada, and Western Europe, the health systems are well-equipped to diagnose and treat cancer; however, this is not true of most developing countries. However, because developing countries are often dealing with a high prevalence of infectious diseases, they often give a lower priority to the prevention of chronic diseases. The vaccination of people in developing countries against HPV and hepatitis B could help control the increase in the rates of cervical cancer and liver cancer, respectively. Samreen F. Khan, M.A.
Cultural barriers: Financial barriers are not the only reason that people in developing countries do not get cancer screening and treatment. Culture also plays a major role in preventing the early detection and proper treatment of cancer. One large cultural barrier that is often noted among impoverished populations is the role of traditional medicine. Often physicians in developing countries who were trained in and practice Western medicine incorporate traditional beliefs into their practices. In India, Pakistan, and Malaysia, traditional beliefs have been noted to interfere with the timely diagnosis of cancer. Social stigmas—such as the fear that cancer is contagious and that patients will be abandoned by their spouses and communities—also inhibit timely diagnosis and treatment for cancer in developing countries.
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For Further Information Ali, Abrar Ashraf, et al. “Carcinoma Breast: A Dilemma for Our Society.” Ann King Edward Medical College 9, no. 2 (June, 2003): 87-89. Aziz, Z., et al. “Socioeconomic Status and Breast Cancer Survival in Pakistani Women.” Journal of the Pakistan Medical Association 54, no. 9 (September, 2004): 448453. Bosanquet, Nick, and Karol Sikora. The Economics of Cancer Care. Cambridge: Cambridge University Press, 2006. Hisham, Abdullah, and Cheng-Har Yip. “Overview of Breast Cancer in Malaysian Women: A Problem with Late Diagnosis.” Asian Journal of Surgery 27, no. 2 (April, 2004): 130-133.
Salem Health: Cancer Holtz, Carol, ed. Global Health Care: Issues and Policies. Sudbury, Mass.: Jones and Bartlett, 2008. Jemal, Ahmedin, et al. “Cancer Statistics, 2007.” CA: A Cancer Journal for Clinicians 57, no. 43 (2007): 43-66. Pal, S. K., and B. Mittal. “Fight Against Cancer in Countries with Limited Resources: The Post-genomic Era Scenario.” Asian Pacific Journal of Cancer Prevention 5, no. 3 (July, 2004): 328-333. Ward, E., et al. “Cancer Disparities by Race/Ethnicity and Socio-economic Status.” CA: A Cancer Journal for Clinicians 54, no. 2 (2004): 78-93. u
Other Resources
American Cancer Society http://www.cancer.org Prevent Cancer Foundation http://www.preventcancer.org/ World Health Organization Cancer http://www.who.int/cancer/en/ See also African Americans and cancer; Carcinomatosis; Developing nations and cancer; Epidemiology of cancer; Ethnicity and cancer; Latinos/Hispanics and cancer; Native North Americans and cancer; Obesity-associated cancers; Singlehood and cancer; Statistics of cancer.
u Prayer and cancer support Category: Social and personal issues Definition: Prayer, the act of communicating with a deity or other “higher force” in which a person has faith, has helped some cancer patients cope with their disease. History and origin: The idea of healing through faith is not new. Within most formal religions—Hinduism, Buddhism, Judaism, Christianity, and Islam—some form of prayer has evolved as a means of communicating with a deity or spiritual being who the faithful believe has the power to heal and provide physical and mental solace during challenging times. Spirituality, or a strong belief in a higher power, can also exist outside the boundaries of formal religion, and in this case, prayer is often a communication with a higher force or energy that has powers beyond those of humans. An illness such as cancer is a powerful life event that often makes people face mortality and question the purpose and meaning of life. In many instances, this questioning leads them to prayer, spiritual growth, and
Prayer and cancer support a positive outlook, which helps them cope. This increased ability to cope as a result of prayer can be very helpful for patients dealing with cancer and its debilitating effects, even though it cannot cure the disease. Scientific evidence for the mind-body connection: A growing body of research indicates that the mind exerts a powerful influence on the way a body responds to trauma and stress. Cancer creates a substantial amount of stress in the body, which in turn can be detrimental to the recovery process. Analysis of data from an online support group of breast cancer patients revealed that those who prayed or meditated had a more positive mental outlook and seemed to be more in control of their situation. Doctors have found that patients with advanced cancer who believe in and practice prayer and meditation cope well with the trauma from the disease and are often able to find meaning in their experience. Scientific evidence for the use of prayer alone in cancer therapy is not conclusive; however, many positive outcomes have been observed when it is used as an adjunct to conventional medical treatment. New studies on the positive correlation between prayer and recovery of patients with a strong faith in prayer suggest that it helps speed up the recovery process. Therefore, for patients with a strong faith, the integration of spiritual practices into their medical care is overall very beneficial to them. Integrating prayer in medical care: For many years the medical community believed that there was no correlation whatsoever between spirituality and medicine. However, some physicians are beginning to acknowledge the existence of the mind-body connection in recovery, and a number of medical schools in the United States include a spirituality and prayer component in their medical curriculum as part of a complementary, adjunct strategy. Some hospitals include a spiritual representative as part of the patient’s care team. Prayer and spirituality are an integral part of the lives of many cancer patients, and they also play an important role in dealing with issues of dying and death. Many medical institutions and physicians respect their patients’ religious beliefs and help them incorporate them into their treatment regimen. Mechanics of integrating prayer: Prayer can be practiced in many different ways, either alone or in a group, silently or with the accompaniment of music, with or without affiliation with any religion. Many cancer support groups use standard forms of prayer composed by religious leaders to pray for cancer patients. In addition, many hospitals have prayer rooms and contracts with clergy from various religious organizations to cater and minister to their patients’ spiritual needs. 989
Preferred provider organizations (PPOs) If faith plays a very important role in the life of a cancer patient and is not acknowledged by the care team while making decisions for treatment, conflicts can arise and channels of communication can be closed, resulting in a stressful situation that could be detrimental to the patient’s health. When physicians inquire about and acknowledge a patient’s spiritual beliefs in a nonjudgmental, sensitive manner, they set the stage for open communication and better decision making. However, prayer should never be forced on patients, and spiritual practices should be incorporated into the treatment regimen only with their consent. On occasions when patients want to use prayer alone for their recovery and refuse or want to delay conventional medical treatment, it is the responsibility of the medical staff to explain the risks and serious health consequences involved in delaying or refusing treatment while simultaneously acknowledging the patient’s religious beliefs respectfully. Lalitha Krishnan, Ph.D. u For Further Information Dwyer, J. W., L. L. Clarke, and M. K. Miller. “The Effect of Religious Concentration and Affiliation on County Cancer Mortality Rates.” Journal of Health and Social Behavior 31 (1990): 185-202. Mytko, J. J., and S. J. Knight. “Body, Mind, and Spirit: Towards the Integration of Religiosity and Spirituality in Cancer Quality of Life Research.” Psycho-oncology 8 (1999): 439-450. Ott, Mary Jane. “Mind-Body Therapies for the Pediatric Oncology Patient: Matching the Right Therapy with the Right Patient.” Journal of Pediatric Oncology Nursing 23, no. 5 (2006): 254-257. u
Other Resources
American Cancer Society Spirituality and Prayer http://www.cancer.org/docroot/ETO/content/ ETO_5_3X_Spirituality_and_Prayer.asp MedNet 2006 Effects of Prayer and Religious Expression Within Computer Support Groups on Women with Breast Cancer http://www.mednetcongress.org/ocs/ viewabstract.php?id=306 See also Cancer care team; Integrative oncology; Medical oncology; Pediatric oncology and hematology; Psychooncology; Psychosocial aspects of cancer; Stress management; Support groups. 990
Salem Health: Cancer
u Preferred provider
organizations (PPOs) Category: Social and personal issues Definition: Preferred provider organizations (PPOs) are health care delivery systems in which a third-party payer contracts with physicians, hospitals, and other providers to deliver health services to subscribers at a negotiated rate. History: PPOs developed in the 1980’s to address the escalating costs of health care services. Burdened with the increasing expense of health insurance for employees, businesses passed costs to the consumer in greater product or service prices. American businesses, finding it hard to compete in the growing international market, pushed insurance companies to decrease their premium rates. Several models for health care delivery emerged to benefit the insurance companies, businesses, and health care providers. The PPO encouraged insurance companies and health care providers to negotiate lower product and service prices in return for a guaranteed group of subscribers. The result was reduced insurance premiums for the businesses, guaranteed customers for the health care providers, and a captive pool of subscribers for the insurance companies. Though somewhat changed beginning in the 1990’s, the PPO model still functions on the same basic principles. How PPOs work: PPOs are a blend of the traditional feefor-service system and the health maintenance organization (HMO) model. PPOs have more relaxed rules and choices than the HMO model but can be more expensive to the subscriber. A list of physicians, hospitals, and other health care service and product providers is available to the subscriber as preferred providers or network providers. When the subscriber chooses a provider on the network list, most of the medical bill is covered. The subscriber may pay a minimum copayment (copay) and sometimes must reach a deductible out-of-pocket payment for certain services before costs are covered. PPOs may require subscribers to choose primary care physicians to oversee their care. PPOs usually pay for preventive care, including screening tests such as mammograms. If the subscriber uses doctors or services not in the preferred network, PPOs usually cover some of the cost but at reduced rates, leaving the subscriber to cover the difference. This encourages the subscriber to use network providers. How PPOs differ from HMOs: PPOs are attractive to cancer patients because they provide a wider range of ser-
Salem Health: Cancer
Preferred provider organizations (PPOs)
vices with more individual choices than Questions Cancer Patients Should Ask About PPOs HMOs. However, PPO subscribers pay Being informed can help cancer patients get the best care for a reasonable for these advantages with higher premiprice. Cancer patients may have specific needs that require answers before ums, copayments, and deductibles than joining a PPO. Seeking solutions to these questions can clarify any limitations those for HMO subscribers, who have before switching to a PPO: low premiums, no or low copayments, and usually no deductibles. PPOs allow • Can I choose from a list of doctors? Which ones are in the network plan and do they accept new patients? out-of-network care with higher sub• How do I get a referral to a specialist? scriber copayments while HMOs do not • What hospitals are on the covered network plan? cover out-of-network care unless pre• What happens if I am out of town and need health care services? approved or emergency related. PPO • How do I receive emergency services through the PPO? subscribers select their doctors with ad• Are preventive services covered? Which ones? ditional costs for out-of-network physi• Are there limits on services like cancer treatments, medical tests, mental cians; HMO subscribers choose their health services, or prescription medications? Ask about any specific treatphysicians from a restricted list of netments, tests, or medications that apply to your cancer treatment such as chework providers and may find it difficult motherapy, radiation therapy, stem cell transplants, and clinical trials. to receive a specialist referral. Individ• What will my monthly premium be? ual choice of health care provider can • Is there a deductible? How much is it? increase the likelihood of continuity of • Do I have to pay at the time of my doctor visits or will I receive a bill for care? care for the cancer patient. • What is the difference in costs if I go outside the network for services? Because cancer care can be expen• Is there a maximum limit for my out-of-pocket expenses each year? Lifesive, cancer patients should research time maximum limit for out-of-pocket expenses? the difference in costs before going out Are my dependents covered? • of the PPO network for services. Cancer patients may need services that require preauthorization (preapproval) to be covered. If the patient (or doctor) u Other Resources does not obtain preapproval for the service or product, the PPO will not cover payment. Cancer patients might have American Cancer Society to pay sizable costs for their health care services or prodMedical Insurance and Financial Assistance for the ucts from their own financial means. Cancer Patient Cancer patients should consider what medications are http://www.cancer.org/docroot/MLT/content/ covered by the PPO and at what price. HMOs may have a MLT_1x_Medical_Insurance_and_Financial_ set drug formulary while PPOs use an open formulary, Assistance_for_the_Cancer_Patient with access to more medications but with higher copay.asp?sitearea=&level=1 ments for nonpreferred drugs. The PPO may offer more choices to cancer patients but at a higher price. National Cancer Institute Marylane Wade Koch, M.S.N., R.N. Clinical Trials and Insurance Coverage: A Resource u For Further Information Guide http://www.cancer.gov/clinicaltrials/learning/ Calder, Kimberly J., and Karen Pollitz. What Cancer Surinsurance-coverage vivors Need to Know About Health Insurance. Silver Springs, Md.: National Coalition for Cancer Survivorship, 2006. See also Chemotherapy; Clinical trials; End-of-life care; Marcinko, David E. Dictionary of Health Insurance and Financial issues; Health maintenance organizations Managed Care. New York: Springer, 2006. (HMOs); Home health services; Insurance; MammograOrin, Rhonda. Making Them Pay: How to Get the Most phy; Managed care; Medicare and cancer; Prevention; from Health Insurance and Managed Care. New York: Primary care physician; Screening for cancer; Second St. Martin’s Press, 2001. opinions; Survivorship issues. Palmateer, Paige. “Interest Rises in Cancer Insurance.” Central New York Business Journal, October 20, 2006. 991
Pregnancy and cancer
u Pregnancy and cancer Category: Social and personal issues Definition: While pregnancy is not a risk factor for cancer, cancer can develop during pregnancy or the postpartum period in association with the hormonal changes in a woman’s body. A woman with a diagnosis of cancer or who is a survivor of cancer, remitted or cured, should consult with her doctor regarding any potential impact of the disease or its treatment on the prospect of becoming pregnant, the expected course of a pregnancy, and the prospective outcome of a pregnancy. Incidence, death, and survival statistics: Maternal malignancy occurs in approximately 1 in 1,000 to 1,500 pregnancies. Rarer is a malignancy present in the placenta or fetus originating from the maternal cancer. Among cancers occurring in pregnant and postpartum, lactating women, breast and cervical cancers are most common: Approximately half of cancer cases occurring during pregnancy are breast or cervical cancer, and leukemia and lymphoma account for approximately one-quarter of all malignancies during pregnancy. The incidence of breast cancer is 1 in 3,000 pregnancies, and the incidence of cervical cancer is 1 in 200 pregnancies. The incidence of these cancers during pregnancy may increase because of the trend of women bearing children when older. The average estimated incidence of ovarian tumors in pregnancy is 1 in 1,000 deliveries, with the majority being benign. The use of ultrasound in early fetal evaluation may contribute to the earlier detection and therefore increased incidence of ovarian cancer. While rare, there may also be an increase in incidence of lung cancer during pregnancy due to smoking or delayed age of childbearing. Malignant melanomas, a serious type of invasive skin cancer, represent 8 percent of cancers diagnosed during pregnancy, and increased incidence is associated with a decrease in the age at which it is diagnosed (0.14 to 2.8 per 1,000 births). Hodgkin disease, a type of blood cancer, may occur in 1 per 1,000 to 1 per 6,000 of deliveries; the incidence of the disease is highest during a woman’s childbearing years, ages twenty to forty. Non-Hodgkin lymphoma (NHL) is the fourth most common cancer in pregnant women. NHL has an age-dependent increase in incidence, however (with more cases occurring in midlife), and thus there are relatively few reports of its incidence during pregnancy. Risk statistics: Various risk factors have been reported to increase the chance of a woman’s developing cancer dur992
Salem Health: Cancer ing pregnancy, including age, history of prior pregnancies, and factors associated with pregnancy. Breast cancer risks. Women who have never been pregnant or who became pregnant after the age of thirty are at a slightly higher risk of developing breast cancer than women who became pregnant when younger than thirty. It is estimated that a woman who had her first child after the age of thirty-five has twice the risk of developing breast cancer as that of her counterpart under twenty years old. Some studies have shown that both pregnancy and breastfeeding may slightly reduce the risk for breast cancer because—particularly for those women who breast-feed between 1.5 and 2 years—these conditions reduce the number of menstrual cycles in a woman’s life span. It has been reported that a pregnant woman has a 2.5-fold higher risk of being diagnosed with metastatic breast cancer and a decreased chance of being diagnosed with Stage 1 breast cancer (the early stage of invasive breast cancer), probably in part because of pregnancy-induced engorgement of the breast masking the detection of small lumps. After giving birth, a woman is at increased risk of developing breast cancer for several years. A woman who took diethylstilbestrol (DES, a synthetic form of estrogen given during pregnancy between the early 1940’s and 1971 to reduce the risk of repeated miscarriage or premature delivery) is at an increased risk of developing breast cancer. However, exposure to DES before birth in DES daughters does not appear to increase risk of breast cancer in these daughters. It should be noted that there remain other risks for breast cancer that may place a woman at risk during her pregnancy, such as a family history of breast cancer in a first-degree relative, certain breast conditions, and the onset of menses before age twelve. Cervical cancer risks. Pregnant woman infected with the human papillomavirus (HPV) may be at risk for cancer during pregnancy, although that is unlikely. HPV actually comprises a group of sexually transmitted viruses; the high-risk strains are thought to be the leading cause of cervical cancer and often may not present symptoms for some time following exposure to the virus. Some strains produce genital warts, which are very contagious. HPVinfected pregnant women with genital warts may experience growth in the warts during pregnancy because of the moist cervical environment in which the warts thrive, the hormonal changes attending pregnancy, and changes in the woman’s immune system. Regular screenings for cervical cancer, physician-conducted breast examinations, and instruction in breast self-examinations are therefore important components of prenatal visits. Although the presence of genital warts or abnormal cer-
Salem Health: Cancer vical changes warrants medical follow-up, presence of HPV is unlikely to affect the pregnancy or the newborn’s health. Also, while the genital warts may disappear on their own, or a pregnant woman may wait until after delivery for their removal, the warts can be removed safely during the pregnancy using conventional procedures such as cryotherapy or the loop electrical excisional procedure (LEEP). Diagnosing and treating cancers during pregnancy: As a woman’s breasts change and grow during pregnancy with the development of milk ducts, breasts feel lumpier and bumpier, rendering early detection of breast cancer during pregnancy difficult. However, 70 to 80 percent of painless lumps detected during or soon after pregnancy are noncancerous. Regular breast examinations should be conducted by the woman’s doctor during prenatal visits, and pregnant women should conduct breast self-examinations regularly. Nevertheless, a pregnant woman who detects a lump should visit the doctor promptly and request a diagnostic evaluation of any suspicious mass, rather than giving in to the temptation to delay until after childbirth. Mammography has not been found to harm the fetus for screening those who have signs or symptoms of a breast problem, and a mammogram can be taken as long as a lead shield is placed over the abdomen to block the effects of radiation. Because the accuracy of mammogram results during pregnancy is not as reliable as it is for nonpregnant women, ultrasound can be conducted before the mammogram to detect palpable lumps. A woman should also discuss with her doctor the use of magnetic resonance imaging (MRI). In the final analysis, however, a tissue biopsy—either needle or excisional—is the most accurate tool for diagnosing breast cancer, and it allows the physician to remove tissue from a suspicious mass at the same time. Although the resulting sample may be difficult to interpret during pregnancy, it offers the most conclusive results. Treatment of breast cancer during pregnancy should follow the standard for all women with modifications during pregnancy, such as avoiding chemotherapy during the first trimester. Pregnant women with early-stage cervical cancer are often asymptomatic or may have symptoms similar to those of their nonpregnant counterparts, such as vaginal bleeding, pain, and discharge. Pregnant women with any suspicious lesions should see their doctor or prenatal provider for a Pap test with endocervical sampling and a biopsy of the lesion. Although pregnancy offers an opportunity for screening of cervical cancer during prenatal care, colposcopy (viewing the inside of the cervix with a microscope-like device) is technically more difficult; the com-
Pregnancy and cancer plication rate following biopsy (if necessary) is higher, and vaginal bleeding due to cancer may be misdiagnosed as pregnancy related. Although noninvasive cervical cancer is rare during pregnancy, if it is detected, treatment should be delayed until after childbirth. Studies have shown no adverse outcomes for the fetus or mother when treatment is delayed, and in fact it appears that a woman with a pregnancyassociated cervical cancer has an overall better prognosis than that of a nonpregnant woman (probably because of the likelihood of detecting any abnormalities in cervical cells during the course of regular prenatal visits). Despite the postponement of treatment, however, a pregnant woman with this diagnosis should see her doctor to be reevaluated because of the limitations in accurately diagnosing disease during pregnancy. Cervical cancer during pregnancy does not appear to adversely affect the newborn. For a melanoma detected during pregnancy, standard treatment for early disease in pregnant women is surgery,
In 1 of every 1,500 to 2,000 pregnancies, the mother is diagnosed with cancer. (PhotoDisc)
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Premalignancies as it would for nonpregnant women. Most studies of the effects of melanoma on the survival rate in pregnant women—when subjects were matched for age, anatomic site, and stage—show no difference in survival rates for pregnant as opposed to nonpregnant women. Although Hodgkin disease is relatively rare in pregnant women, there are no standard guidelines for diagnosing and treating it during pregnancy. Typically, chemotherapy is delayed until after the first trimester and radiotherapy until after delivery. Breast-feeding is not recommended during active treatment for Hodgkin disease. There does not appear to be an effect of pregnancy on survival rates of women diagnosed with Hodgkin disease during pregnancy. In general, factors to consider if a woman and her doctor are deciding whether to treat a cancer occurring during pregnancy include the gestational age of the fetus (the trimester of pregnancy), the location and type of cancer, how aggressively the cancer is growing, the stage of the cancer, and the overall health of the mother. Although some chemotherapies can be used after the first trimester, during critical fetal development, women are advised to consult with their doctors before starting treatment during the pregnancy. Chemotherapeutic medication can affect the fetus when it crosses the placenta and can increase the risk of miscarriage, low birth weight, or premature birth. Survival perspective and prospects: Pregnancy does not lower the risk of survival or increase the risk of recurrence of breast cancer in women with a history of breast cancer. Studies have shown that women diagnosed with breast cancer during pregnancy did as well in the long term as did women with the same type and stage of cancer who were not pregnant when diagnosed. Although rarely occurring during pregnancy, cervical cancer during pregnancy also results in survival rates similar to those for nonpregnant women who were diagnosed at least five years following delivery. However, the survival rate of women diagnosed during the first six months postpartum is significantly worse than those diagnosed during pregnancy or nonpregnant counterparts diagnosed years later. Women diagnosed with cervical cancer during pregnancy may want to consult with their medical provider regarding options for delivery, such as by cesarean section rather than vaginally. Women who have cancer or a history of the disease are advised to talk with their doctors if they are considering becoming pregnant. Certain cancer treatments can affect fertility, and women may wish to preserve their fertility. Considerations include estrogen receptors of cancer cells, difficulty in becoming pregnant, chemotherapy’s effect on a woman’s ovaries, and delaying childbearing until five 994
Salem Health: Cancer years following treatment. Also, fertility treatment options for the woman with cancer or a history of cancer who wishes to become pregnant may be restricted due to the need to stimulate hormones during the course of most fertility treatments. Susan H. Peterman, M.P.H. u
For Further Information Adler, L., and P. Sykes. “How Little Is Known About Cervical Cancer in Pregnancy?” Annals of Oncology (European Society for Medical Oncology) 16, no. 3 (2005): 341-343. Barnea, Eytan R., Eric Jauniaux, and Peter E. Schwartz, eds. Cancer and Pregnancy. London: Springer, 2001. Koren, G., M. Lishner, and D. Farine, eds. Cancer in Pregnancy: Maternal and Fetal Risks. New York: Cambridge University Press, 1996. Schover, Leslie R. Sexuality and Fertility After Cancer. New York: John Wiley & Sons, 1997. u
Other Resources
American Society of Clinical Oncology http://www.asco.org Leukaemia Research Foundation http://www.lrf.org.uk Mother Risk http://www.motherrisk.org Susan G. Komen for the Cure http://www.cms.komen.org See also Breast cancer in pregnant women; Cervical cancer; Childbirth and cancer; Diethylstilbestrol (DES); Fallopian tube cancer; Family history and risk assessment; Fertility drugs and cancer; Fertility issues; Fibroadenomas; Genetic testing; Gynecologic cancers; Gynecologic oncology; Hodgkin disease; Imaging tests; Magnetic resonance imaging (MRI); Mammography; Sexuality and cancer; Smoking cessation; Transvaginal ultrasound; Ultrasound tests.
u Premalignancies Category: Diseases, symptoms, and conditions Also known as: Premalignant lesions, dysplasia, neoplasia, neoplasms, dysplastic syndromes, neoplastic syndromes Related conditions: Myelodysplastic syndromes in blood and bone marrow
Salem Health: Cancer Definition: Premalignancies are caused by the abnormal maturation of cells in a particular tissue. Premalignant cells are often immature and undifferentiated. An area with abnormal cells of this kind is called a premalignant lesion or a neoplasm. When the abnormal cells are limited to the tissue of origin, the condition is called dysplasia. Myelodysplastic syndromes arise when abnormal immature stem cells, called blasts, are present in the bone marrow or blood. In these syndromes, the abnormal blast cells crowd out the normal mature cells and platelets, resulting in anemia and a loss of immune function. Risk factors: General risk factors for premalignancies include exposure to environmental pollutants and tobacco smoke, older age, and a family history of certain cancers (essentially, the same risk factors as for cancer development). Premalignancies for certain types of cancers have specific risk factors. Epidermal premalignant lesions in the form of actinic keratosis are usually caused by sun damage, and basal cell lesions probably arise because of deoxyribonucleic acid (DNA) damage from ultraviolet radiation. For colorectal cancer, people with a family history of premalignant lesions or polyps are at greater risk of having polyps and colorectal cancer. Individuals who have had inflammatory bowel disease (ulcerative colitis and Crohn disease) for more than eight years are also at greater risk of developing premalignant polyps and colorectal cancer. Risk factors for gastrointestinal premalignant lesions include gastritis caused by infection with the bacterium Helicobacter pylori and gastroesophageal reflux disease (GERD), which can progress to a condition called Barrett esophagus, the only known premalignant condition for esophageal adenocarcinoma. Risk factors for Barrett esophagus are being a man, white, over fifty years old, a cigarette smoker, and obese, and having a history of reflux symptoms lasting more than five years. Risk factors for myelodysplastic syndromes include being a man and over age sixty, having had prior treatment with chemotherapy or radiation therapy, and being exposed to tobacco smoke, pesticides, mercury, and lead. Etiology and the disease process: Genetic abnormalities in the cell disrupt its normal maturation process, causing it to become premalignant. The traditional theory is that cancer progresses through a series of steps, from premalignant lesions to carcinoma in situ (localized cancer) and then to invasive carcinoma. Some researchers challenge this theory, arguing that most, if not all, of the molecular changes that occur in the cancer transformation process are present in premalignant lesions. For example, genetic analysis of premalignant lesions in mice has shown that gene
Premalignancies abnormalities and changes in protein expression in the premalignant cells can be linked to the particular phenotype of the cancer cell (that is, the physical and biochemical characteristics of the cell). One study in mice showed that the molecular profiles (genes and proteins) of lesions in different stages of breast cancer had many similarities, suggesting that there may be a limited number of molecular changes associated with tumor progression. Different cell types give rise to premalignant lesions in varied ways. In skin cancer, basal cell lesions are the most common type of premalignancy. These premalignant lesions occur in the basal epithelium of the skin, usually on the lower trunk and thighs. The premalignancies look like basal epithelium cells surrounded by a fibrous stroma and are thus called fibroepithelial premalignant tumors of Pinkus. Researchers have shown that the premalignant cells have abnormal cell cycle regulation, which most likely initiates their transformation from normal cells. In cancer progression, these abnormal basal cells grow aggressively until they predominate in the lesion, and the premalignant lesion becomes invasive basal cell epithelioma. Other premalignant tumors occur in the epidermis. Epidermal premalignant lesions can take the form of Bowen disease, where abnormal cells are present throughout the epidermis and have the potential to develop into invasive squamous cell carcinoma. Bowen disease predominantly occurs in the lower limbs and resembles dermatitis or psoriasis, with scaly patches. Epidermal premalignant lesions can also be in the form of acitinic keratosis, where abnormal cells do not penetrate the entire epidermis and have a small probability (2 to 5 percent) of developing into cancer. Actinic keratosis is usually caused by sun damage. Gastrointestinal premalignant lesions can arise from gastritis caused by infection with the bacterium H. pylori. Another condition that can result in a premalignancy is gastroesophageal reflux disease, which involves backflow of stomach acids up the esophagus, causing damage to the squamous epithelial cells lining the esophagus. This tissue damage can progress to a condition called Barrett esophagus, where normal esophageal squamous epithelial cells are replaced with specialized columnar epithelium containing goblet cells. This condition is often accompanied by dysplasia or metaplasia, and people with Barrett esophagus have a 0.5 percent risk of developing esophageal cancer (esophageal adenocarcinoma). The etiology of colorectal cancer is still unclear, but it appears to involve a genetic component, with approximately 25 percent of colorectal cancer patients having a family member with the disease. Other factors such as diet, the composition of bile acids, and exposure to carcinogens 995
Premalignancies are being studied. Individuals who have the rare familial adenomatous polyposis (FAP) syndrome, which is a hereditary genetic defect in which people develop hundreds to thousands of colorectal polyps at a young age, are at higher risk for developing colorectal cancer, and these individuals account for 1 percent of colorectal cancer cases annually. Incidence: Incidence varies depending on the type of cell from which the premalignancy arises. Symptoms: Symptoms vary depending on the organ in which the premalignant lesions occur. For example, Bowen disease predominantly occurs in the lower limbs and resembles dermatitis or psoriasis, with scaly patches. Actinic keratosis is characterized by epidermal premalignant lesions and can manifest as single or multiple scaly papules. In the colon, premalignant lesions called polyps are often discovered during a routine colonoscopy. Other signs of polyps include blood in the stool. Removal of these premalignant polyps considerably decreases the probability of developing cancer. Symptoms of myelodysplastic syndromes include shortness of breath (also known as dyspnea), fatigue, pale skin, bruising or bleeding readily, petechiae (pinpoint spots under the skin due to bleeding), fever, and frequent infections. Screening and diagnosis: Routine skin examinations can detect premalignant skin lesions, which can then be excised before they can progress to skin cancer. The ABCD and seven-point checklists provide guidelines for classifying lesions according to their risk of developing into malignant melanoma. The ABCD checklist has four criteria: “A” for asymmetry (if the lesion is bisected, asymmetry of the two halves predisposes for malignancy), “B” for border irregularity (an uneven border is a risk factor), “C” for color variation (more than one color is a risk factor), and “D” for diameter (diameter greater than 6 millimeters, or mm, is a warning sign). The seven-point checklist for malignant melanoma includes three major signs (change in size, shape, or color) and four minor signs (inflammation, crusting or bleeding, sensory change, and a diameter of 7 mm or more). In addition to the criteria in these checklists, the shape of the lesion can be used as an indicator of malignancy. A more geometrically angular shape may be associated with a higher risk of malignant melanoma. A range of screening and diagnostic tests help detect gastrointestinal lesions. Premalignancies associated with Barrett esophagus can be detected by means of endoscopic screening. Patients who are found to have Barrett esophagus and dysplasia can undergo treatment to prevent pro996
Salem Health: Cancer gression to esophageal cancer. For colorectal cancer screening, premalignant lesions (called polyps) are often discovered during a colonoscopy. They can also be found via sigmoidoscopy, in which a flexible tube with a camera is inserted into the rectum and lower colon. A small tissue sample can be taken at the same time. Another method of discovering polyps is the fecal occult blood test, which looks for blood in the stool. If blood is found, a colonoscopy is performed. Other methods include computed tomographic colonography (CTC; also known as “virtual” colonography), which involves scanning the colon by CT to produce a three-dimensional image that can be analyzed for polyps, and a double-contrast barium enema, in which barium is ingested by the patient and X rays are taken to look at the colon and rectum. Double-contrast barium enema testing is not as sensitive as a colonoscopy and is usually not used for screening. Treatment and therapy: Skin lesions that are diagnosed as premalignant can be excised from the skin if they are basal cell derived, or they can be subjected to cryotherapy, excision, curettage, or topical 5-fluorouracil application if they are of the squamous cell carcinoma type. Premalignant and malignant oral lesions can be treated with carbon dioxide laser surgery, a noninvasive method that is associated with less pain, bleeding, edema, and lower recurrence rates and risk of infection. Patients who are found to have Barrett esophagus and dysplasia can undergo ablative therapy, which includes acid-reducing drugs (including aspirin), proton pump inhibitors, antireflux surgery, or esophagectomy for more severe conditions. For colorectal premalignancies, surgery is used to remove infected parts of the colon. For patients with familial adenomatous polyposis (FAP), sometimes the entire colon is removed (colectomy) to reduce the risk of cancer progression. Drugs such as the COX-2 inhibitors, including celecoxib (Celebrex) and sulindac (Clinoril), have the potential to reduce colorectal cancer risk and could be appropriate for some people. Prognosis, prevention, and outcomes: Detecting premalignancies and treating them creates a much better prognosis than not detecting these tumors until they have become malignant or have metastasized. The timely treatment of premalignant lesions can allow patients to live disease-free for long period of time. To help prevent premalignant skin lesions, people should avoid excessive ultraviolet light exposure by using sunscreen and protective clothing, staying out of the sun during peak ultraviolet-B radiation hours, and avoiding suntanning. A diet high in fiber and low in fat may aid in the preven-
Salem Health: Cancer tion of colorectal cancer. Individuals at risk for this type of cancer because of their family history or long-standing inflammatory bowel disease should regularly undergo colonoscopy to check for polyps, which helps prevent malignancies from developing. Other types of gastrointestinal premalignancies can be prevented by early treatment of infection with H. pylori and taking steps to prevent or alleviate gastroesophageal reflux. Ing-Wei Khor, Ph.D. u For Further Information Cheah, P. Y. “Hypothesis for the Etiology of Colorectal Cancer: An Overview.” Nutrition and Cancer 14 (1990): 5-13. Chin, K., et al. “In Situ Analyses of Genome Instability in Breast Cancer.” Nature Genetics 36 (2004): 984-988. Dias Pereira, A., A. Suspiro, and P. Chaves. “Cancer Risk in Barrett’s Oesophagus.” European Journal of Gastroenterology and Hepatology 19 (2007): 915-918. Ma, X. J., et al. “Gene Expression Profiles of Human Breast Cancer Progression.” Proceedings of the National Academy of Sciences of the United States of America 100 (2003): 5974-5979. Rustgi, A. K. “Hereditary Gastrointestinal Polyposis and Nonpolyposis Syndromes.” New England Journal of Medicine 331 (1994): 1694. Schuchert, M. G., and J. D. Luketich. “Management of Barrett’s Esophagus.” Oncology (Williston Park) 21 (2007): 1382-1389. u
Other Resources
GeneticHealth Colon Cancer in People with FAP http://www.genetichealth.com/CRC_FAP_FAP_and_ Colon_Cancer.shtml The Medical Group of Ohio Do You Know Your ABCD’s of Skin Cancer Detection? http://www.themgo.com/DesktopDefault.aspx?tabid= 153&itemid=1984& Memorial Sloan-Kettering Cancer Center Colorectal Cancer Screening Guidelines http://www.mskcc.org/mskcc/html/ 65282.cfm#282976 Skin Cancer Foundation http://www.skincancer.org See also ABCD; Achlorhydria; Anemia; Barium enema; Barrett esophagus; Benign tumors; Biopsy; Bowen disease; Breast cancers; Cancer biology; Carcinomas; Cobalt
Prevent Cancer Foundation 60 radiation; Colectomy; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Crohn disease; Dysplastic nevus syndrome; Edema; Esophageal cancer; Esophagectomy; Helicobacter pylori; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; Keratosis; Melanomas; Moles; Myelodysplastic syndromes; Oncology; Pancolitis; Polyps; Rectal cancer; Sigmoidoscopy; Skin cancers; Squamous cell carcinomas.
u Prevent Cancer Foundation Category: Organizations Also known as: Cancer Research and Prevention Foundation, Cancer Research Foundation of America (CRFA) Definition: The Prevent Cancer Foundation is a nonprofit fund-raising organization that supports educational programs, cancer screenings, and research targeted at preventing cancers. History: Carolyn Richardson Aldigé, a former endocrinology researcher, initiated the Cancer Research Foundation of America (CRFA) in 1985 after her father’s death due to cancer. She felt that increased knowledge and use of prevention methods might effectively lessen the number of cancers and enhance survival. Aldigé, who became the foundation’s president, designed CRFA to encourage and support cancer prevention research, educational resources, and screenings. The CRFA’s board of directors, medical advisory board, and scientific review panel oversee its work. In 2002, the CRFA became the Cancer Research and Prevention Foundation. Five years later, the organization’s name changed again, becoming the Prevent Cancer Foundation. From 1985 to 2007, the organization secured approximately $95 million for its projects. Education: The Prevent Cancer Foundation emphasizes public awareness of basic strategies—improving nutrition, changing habits regarding smoking and sun exposure, and engaging in exercise—to prevent cancer or control it after diagnosis. The foundation provides educational material on its Web site and pamphlets in English and Spanish. Its Cancer Prevention Works, an electronic newsletter, contains research updates, news, and advice. The Prevent Cancer Foundation’s educational exhibits include Check Your Insides Out—From Top to Bottom, which contains a twenty-foot-long, eight-foot-high Super Colon that people can enter to see examples of cancerous 997
Prevent Cancer Foundation polyps. The foundation’s Save Your Skin display emphasizes the dangers of ultraviolet (UV) rays. A computer program reveals the aging effects of UV rays on facial skin. Information provided by the foundation explains how to examine skin for malignancies and avoid UV damage. During the 1990’s, the Prevent Cancer Foundation introduced software for children called Dr. Health’nstein’s Body Fun. Players virtually thrived or declined according to their decisions regarding what they ate, how much they exercised, and whether they used tobacco and other substances. The Prevent Cancer Foundation and Alabama public educators evaluated using Dr. Health’nstein’s Body Fun technology for health education. Some California, Georgia, Massachusetts, and Arizona public schools have incorporated that software into their curricula. The Prevent Cancer Foundation holds yearly national meetings for medical professionals. Its workshops demonstrate how new technologies might improve cancer prevention. It also cohosts the yearly Summit on Cancer Clinical Trials, which raises public awareness of trials and promotes participation. Outreach: Foundation grants enhance screening availability by sponsoring displays at state fairs and such mobile health services as George Washington University Cancer Center’s Mammovan, which screens uninsured women for breast cancer. Since 1994, the Prevent Cancer Foundation has funded ¡Celebremos la Vida! (let’s celebrate life) to screen Hispanic women for cervical and breast cancers. The foundation provides money for the Cancer Preventorium, started by Elmer Huerta, a board member and physician, to screen both male and female Hispanics for cancer. The Prevent Cancer Foundation sponsors Project Early Awareness, which provides breast education for minority teenage girls so that they can learn breast cancer screening methods and teach them to other young women. The foundation promotes Make the Connection, Make the Commitment, emphasizing the human papillomavirus (HPV) link to cervical cancer. In March, 2000, the Prevent Cancer Foundation initiated National Colorectal Cancer Awareness Month. The foundation distributes buddy bracelets to encourage people to schedule colonoscopies. The Prevent Cancer Foundation funds cancer education services for children and pediatric cancer research through Hope Street Kids and Tracy’s Kids. The foundation supports the Congressional Families Action for Cancer Awareness Program, which stresses prevention. Research: By 2007, the Prevent Cancer Foundation had funded an estimated 250 researchers affiliated with 150 998
Salem Health: Cancer academic institutions and medical and research centers. Twice yearly, the Prevent Cancer Foundation Scientific Review Panel, including representatives from the National Cancer Institute and major cancer centers, evaluates proposals. Any researcher who has received money from the tobacco industry cannot apply. The Prevent Cancer Foundation provides funds for various grants financed with allied groups, including the American Society for Preventive Oncology. Starting in 2002, the American Association for Cancer Research (AARC)-Cancer Research and Prevention Foundation (CRPF) Award for Excellence in Cancer Prevention Research annually honored investigators. Advocacy: The Prevent Cancer Foundation issues policy statements concerning cancer prevention issues. It has supported legislation regarding colorectal cancer and stem cell research and has urged medical professionals and pharmaceutical manufacturers to increase the availability of the human papillomavirus vaccine to uninsured and low-income young women. Elizabeth D. Schafer, Ph.D. u
For Further Information Geiger, Brian F., et al. “Using Technology to Teach Health: A Collaborative Pilot Project in Alabama.” Journal of School Health 72, no. 10 (December, 2002): 401-407. Lippman, Scott M., et al. “Cancer Prevention and the American Society of Clinical Oncology.” Journal of Clinical Oncology 22, no. 19 (October 1, 2004): 38483851. Sawyer, Kathy. “Breast Cancer Drug Testing Will Continue: Potential of Tamoxifen Is Said to Outweigh Risks.” Washington Post, May 12, 1994, p. A3. Trafford, Abigail. “On the Streets of Philadelphia, Prescriptions for Progress.” Washington Post, August 8, 2000, p. Z5.
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Other Resources
Hope Street Kids http://www.hopestreetkids.org Prevent Cancer Foundation http://www.preventcancer.org Tracy’s Kids http://www.tracyskids.org See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Dana-Farber Cancer
Salem Health: Cancer Institute; Duke Comprehensive Cancer Center; Fox Chase Cancer Center; Fred Hutchinson Cancer Research Center; Jonsson Comprehensive Cancer Center (JCCC); M. D. Anderson Cancer Center; Mayo Clinic Cancer Center; Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI); National Science Foundation (NSF); Robert H. Lurie Cancer Center.
u Prevention Category: Lifestyle and prevention Definition: Prevention of cancer can be defined as reducing cancer mortality by reducing the incidence of cancer. Cancer in the United States: The National Cancer Institute issued a report in 2005 describing various statistical aspects of cancer in the United States. Overall death rates for the most common cancers, such as breast, lung, colorectal, and prostate, had declined. Survival rates for cancer patients were rising. The incidence of cancer had been stable since the 1990’s. However, the prevalence of cancers such as melanoma of the skin and childhood cancers was increasing. Cancer remained the second leading cause of death in the United States. In 2003 more than half a million Americans had lost their lives to cancer. Lowering the number of cases of cancer is a multifaceted process of avoiding exposures to known carcinogens, modifying lifestyle habits, and taking active steps to enhance the body’s immune system. Although behaviors that help people avoid developing cancer, such as not smoking and lessening consumption of fat and alcohol, are on the rise in the United States, more needs to be done. Prevention generally falls into the categories of lifestyle, chemoprevention (use of vitamins and medicines), preventive surgery, screening, and environment. Prevention of cancer is an active process in which all Americans need to involve themselves to reduce their lifetime chance of cancer. Research suggests that as much as two-thirds of all cancer can be prevented with lifestyle changes in daily living. Every day, each person makes choices that could increase or reduce that person’s likelihood of developing cancer. No knowledge or program can prevent cancer on its own: People must make responsible choices and integrate them into their lifestyle. Nutrition: Nutrition is a key part of cancer prevention. Much has been researched and written about the importance of nutrition. Although the relationship between diet and cancer is complex, numerous studies show that nutri-
Prevention tion can make a difference in preventing cancer. The American Cancer Society promotes eating five to seven or more servings of fruits and vegetables each day as the single most important step people can take to prevent cancer. People can achieve this goal by eating vegetables and fruits at each meal and for snacks. Strawberries, raspberries, blueberries, and blackberries have cancer-fighting chemicals, as do citrus fruits such as oranges and grapefruit. Certain phytonutrients in vegetables, such as the indoles found in broccoli and cabbage, can help protect against cancer, especially hormone-related cancers. Generally the more color the vegetable has, the healthier and more protective it is. The likelihood of developing colon cancer and other gastrointestinal cancers may be decreased by eating dark green and yellow vegetables. Fruits and vegetables in their whole or natural form (fresh, frozen, dried, or canned) are more protective than supplements with dried extracts. The nutritional aspect of prevention includes other foods besides fruits and vegetables. The use of wholegrain breads and cereals adds fiber to the diet. High-fiber diets increase motility of food through the colon and are thought to protect against colon cancer. Eating less meat may be accomplished by choosing beans as a protein source; meat consumption has been associated with colon and prostate cancer. Other foods, such as garlic, onions, soybeans, and ginger, are thought to protect against cancer by some experts. Herbal teas such as red clover or green tea have demonstrated promise in studies on cancer prevention. How food is cooked can affect the nutrients or introduce carcinogens into the body. For example, meat protein cooked at high temperatures produces toxic substances. Studies have linked colorectal adenomas to red meat cooked at high temperatures. Processed meats and bacon contain carcinogens. Boiling vegetables can release nutrients into the water, so steaming is preferred to preserve the vitamins. Studies have looked at the possibility of food preservatives and additives being carcinogenic, but the studies have not been conclusive. Foods are treated with chemicals to improve taste, increase shelf life, and allow them to be transported long distances in trucks. More than three thousand preservatives and additives are used in the U.S. food supply system. Some experts say that formaldehyde, a suspected carcinogen, is either contained in or released by some food preservatives and constitutes a hazard to humans; however, this has not been proven. Some people have chosen to minimize their exposure to additives and preservatives by eating more food in the raw state and purchasing organic foods and milk. 999
Prevention Exercise: Physical activity and exercise can help protect against developing certain cancers of the breast, colon, and prostate. The most recent guidelines by the Centers for Disease Control and Prevention (CDC) recommend that adults exercise moderately (for example, walking at a brisk pace) for a minimum of thirty minutes per day, five days per week, or exercise vigorously (for example, racewalking, jogging, or running) for a minimum of twenty minutes per day, three days per week. This recommendation complements the need to decrease the epidemic of obesity in the United States, as obesity is associated with increased risk of developing cancers of the colon and rectum, breast, prostate, kidney, and uterus (endometrium). Alcohol: Alcohol use is associated with increased risk of mouth, esophagus (throat), larynx (voice box), and liver cancer. The amount of alcohol consumed affects the risk of cancer. Men are advised to have no more than two drinks per day and women no more than one drink per day. (One drink is 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof liquor.) Women who drink are at increased risk for breast cancer. When smoking is combined with excessive alcohol consumption, the risk is compounded. Excessive alcohol consumption can result in liver damage that affects the body’s ability to excrete toxins and can effect cancer treatment. Wine is associated with an increased risk of upper digestive tract cancers in heavy users; however, some studies have shown that moderate consumption of red wine, which contains phytochemicals, may convey some cancer-fighting benefits. Tobacco: Smoking and use of tobacco products is a choice made by many Americans. Smoking produces known carcinogens that can result in lung cancer as well as cancer of the upper respiratory tract (throat, mouth, and windpipe). Secondhand smoke (smoke in the environment that is inhaled by nonsmokers) can affect people’s health, so many states and cities have banned smoking in restaurants or require them to have nonsmoking sections. Many states and cities also ban smoking in workplaces, bars, public buildings, and public gathering places. Though smoking overall is declining and death rates from lung cancer in men are declining, death rates from lung cancer in women have continued to rise. Other methods of cancer prevention: Chemoprevention is a term that describes the use of natural or synthetic substances to avert cancer. Methods include the use of cancerfighting nutrients (such as phytoestrogens) in food, herbs, and supplements that are believed to help prevent cancer. Medications such as tamoxifen or raloxifene to reduce the incidence of breast cancer, and vaccines such as the hu1000
Salem Health: Cancer man papillomavirus (HPV) vaccine can prevent cervical cancer. Preventive (prophylactic) surgery is useful in some cases for patients at high risk for cancer. Preventive procedures include removal of the breast (mastectomy), ovaries, and Fallopian tubes. Cancer screening, a key part of cancer prevention, is covered by many insurance companies, including Medicare. Coverage may include mammograms for breast cancer, colorectal cancer diagnostic tests such as a colonoscopy, prostate-specific antigen (PSA) tests for prostate cancer, and Pap smears for cervical cancer. Early detection and treatment is one reason that cancer survival rates are rising. Protective clothing and gear can help reduce the cancer risk from environmental hazards. Examples of cancercausing substances that can be introduced into the workplace include silica from cement, wood dust, lacquers, wood finishes, paints, glues, solvents, asphalt, and pesticides. Wearing an appropriate mask and using proper ventilation can help decrease exposure to these toxins. Using the provided safeguards when taking (or giving) X rays in a hospital or at a dental office can decrease exposure to harmful radiation that can cause cancer. Those working outdoors and exposed to the sun’s ultraviolet (UV) rays can minimize their risk of skin cancer by staying out of the sun in midday, using sunscreen, and wearing protective clothing and hats. Cancer prevention requires vigilance on the part of each individual as well as businesses and the government. However, prevention is the best way to “treat” cancer and can save many lives. Marylane Wade Koch, M.S.N., R.N. u
For Further Information American Institute for Cancer Research. Stopping Cancer Before It Starts: The American Institute for Cancer Research’s Program for Cancer Prevention. New York: St. Martin’s Griffin, 2000. Conley, Edward J. The Breast Cancer Prevention Plan. New York: McGraw-Hill, 2006. National Cancer Institute. Cancer Trends Progress Report 2005. Bethesda, Md.: Author, 2005. Verona, Verne. Nature’s Cancer Fighting Foods. New York: Prentice Hall, 2001.
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Other Resources
American Institute for Cancer Research http://www.aicr.org Breast Cancer Prevention.com http://www.breastcancerprevention.org
Salem Health: Cancer Cancer Index Cancer Screening and Prevention http://www.cancerindex.org/clinks4p.htm Ohio State University: Extension Fact Sheet Chemoprevention the Answer to Cancer? http://ohioline.osu.edu/hyg-fact/5000/5051.html Prevent Cancer Foundation http://www.preventcancer.org Smokefree.gov http://www.smokefree.gov World Health Organization Cancer Prevention http://www.who.int/cancer/prevention/en See also Cancer care team; Carcinogens, known; Carcinogens, reasonably anticipated; Chemoprevention; Childhood cancers; Exercise and cancer; Fiber; Fruits; Garlic and allicin; Green tea; Infusion therapies; Nutrition and cancer prevention; Obesity-associated cancers; Pesticides and the food chain; Relationships; Smoking cessation; Sunscreens; Tobacco-related cancers; Wine and cancer.
u Primary care physician Category: Medical specialties Also known as: PCP, general practitioner, family practice specialist Definition: A primary care physician is a doctor who diagnoses and treats common illnesses and medical conditions. A primary care physician is often the doctor who provides the initial, or first-contact, care when an individual feels ill. By considering the individual’s health, well-being, and lifestyle, the primary care physician focuses on prevention rather than short-term acute care. There are four types of primary care in which a primary care physician may be certified: family practice medicine, pediatrics, obstetrics and gynecology, and internal medicine. A primary care physician is a generalist who does not specialize in diagnosing and treating a specific organ system, as does a cardiologist, neurologist, endocrinologist, and so on. Primary care physicians are also trained to counsel and educate patients about their disease, instruct in self-care, conduct preventive screenings, and administer immunizations. Subspecialties: Internal medicine, family medicine, pediatrics, and obstetrics and gynecology Cancers treated: All, especially skin, breast, and prostate cancers
Primary care physician Training and certification: A postgraduate primary care residency specialty program is three years in length and trains the internist in both ambulatory and hospital care. In addition to undergoing training in internal medicine practice, focusing on developing skills in diagnosing and treating a broad range of medical conditions, primary care physicians are trained in interviewing skills, recognizing and treating common psychiatric illnesses (primary or secondary to a primary medical condition), and counseling to promote behavior change. Primary care physicians are certified by their state licensing boards in their primary care specialties. The American Board of Medical Specialties (ABMS) oversees the ongoing evaluation and certification of specialists, thus setting standards for what is considered competency in practicing the medical specialty. The Accreditation Council for Continuing Medical Education (AACME) provides guidelines for continuing medical education required for primary care physicians to renew their licenses by ensuring that they maintain their competence and assimilate new knowledge to improve the care they provide patients. Services and procedures performed: The primary care physician is trained in (but not limited to) the following: interviewing the patient and family for a medical history and current symptom history; conducting a comprehensive physical examination; mental health counseling relative to the medical condition; nutrition counseling; referring patients to labs for testing blood and other specimens, as well as interpreting the results from these tests; administering and reading X rays and results of other diagnostic tests; administering electrocardiograms and screening mammograms; instructing in self-exams; and consulting with specialists and other medical care providers. Primary care physicians may be involved in early detection and treatment of all types of cancer, depending on the scope of the physician’s practice, experience, and skills, as well as the needs of the patient and the patient’s family. Primary care physicians act as gatekeepers who regulate access to medical specialists as needed. Since early detection and screening are critical to treatment and prognosis of cancers, the primary care physician is responsible for performing a thorough physical examination of the patient, taking a patient’s medical history, and interviewing the patient to define the symptoms that have prompted the patient to seek care. Primary care physicians play a critical role in educating patients about risk factors (such as smoking, diet, occupational hazards, and other lifestyle factors) thought to contribute to developing cancers, and they teach patients to conduct self-examinations as appropriate. 1001
Primary care physician Primary care physicians play a particularly important role in screening for those cancers for which preventive measures have proven effective, including but not limited to breast cancer (self-exam and mammography), cervical cancer (Pap testing), colorectal cancer (fecal occult blood test and sigmoidoscopy or colonoscopy for persons older than fifty), melanomas (skin cancer), and prostate cancer (prostate-specific antigen, or PSA, blood test and rectal exam). It has been reported that as many as 80 percent of individuals with common forms of cancer initially complain of symptoms to their primary care physicians. Studies have reported that women with breast cancer are more likely to be diagnosed earlier if they reside in areas with a rich supply of primary care physicians. Primary care physicians also can play a vital role in following cancer survivors, such as educating patients in behaviors that can reduce risk of recurring cancers and following up with maintenance visits. The primary care physician will often refer a patient with a suspected cancer to a cancer specialist. Following referral, the primary care physician can continue to be involved in the care of the patient by communicating the diagnosis; forwarding all medical records containing family and symptom history, evaluations, procedures, and lab tests used for diagnosis; helping to set a treatment plan; coordinating specialty care; referring the patient and, as needed, the patient’s family, for psychological support; treating illnesses secondary to the diagnosis and treatment of the cancer; scheduling follow-up visits for preventive care; and managing the side effects of the cancer and its treatment. Testimony to the importance of the primary care physician’s role in diagnosing cancer are reports that a typical primary care physician will have three or four patients per year who have received a new diagnosis of cancer. The benefits of having a primary care physician involved in ongoing cancer care are many. It has been reported that patients who are followed by a primary care physician as well as an oncologist or cancer specialist are more likely to receive preventive care and care for a noncancer chronic illness during the course of cancer treatment than are those who are followed only by an oncologist or cancer specialist. In addition, continuous primary care of patients who are being treated for a cancer primarily by a specialist can reduce visits to acute care or emergency room facilities and contribute to palliative care, which may enable the terminally ill cancer patient to die at home. Although chemotherapy and radiation are usually directed by a subspecialist, the subspecialist may contact the primary care physician to manage potential adverse ef1002
Salem Health: Cancer fects of treatment, such as vomiting and nausea, fever and neutropenia (a hematologic or blood disorder characterized by an unusually low number of neutrophils, a type of white blood cell that fights infection), fatigue, ongoing care following chemotherapy and radiation, sleep disturbances, exercise, depression, anxiety, pain, and ensuring that the patient maintains a healthy diet. Related specialties and subspecialties: Primary care physicians may specialize in family medicine, geriatrics, pediatrics, obstetrics and gynecology, or preventive medicine. A variety of other medical care providers—such as nurse practitioners, registered nurses, physician assistants, and osteopaths—may provide primary care in their settings of practice or work in the setting. Susan H. Peterman, M.P.H. u
For Further Information Gore, Martin E., and Douglas Russell. Primary Care and Cancer. Edited by Paul F. Engstrom. New York: Informa Healthcare, 2003. Hass, Jennifer, Celia Kaplan, et al. “Do Physicians Tailor Their Recommendations for Breast Cancer Risk Reduction Based on Patient’s Risk?” Journal of General Internal Medicine 19, no. 4 (2004): 302-309. Smith, George F., and Timothy R. Toonen. “Primary Care of the Patient with Cancer.” American Family Physician 75, no. 8 (April 15, 2007): 1207-1214. Summerton, Nicholas. Diagnosing Cancer in Primary Care. Abington, England: Radcliffe Medical, 1999.
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Organizations and Professional Societies
American Academy of Family Physicians http://www.aafp.org 11400 Tomahawk Creek Parkway Leawood, KS 66211-2672 American Association of Family Practice Physician Assistants http://www.afppa.org 1905 Woodstock Road, Suite 2150 Roswell, GA 30075 American College of Physicians http://www.acponline.org 190 N. Independence Mall West Philadelphia, PA 19106-1572 Susan G. Komen for the Cure http://cms.komen.org/komen/index.htm 5005 LBJ Freeway, Suite 250 Dallas, TX 75244
Salem Health: Cancer u
Other Resources
National Cancer Institute http://www.cancer.gov American Cancer Society http://www.cancer.org See also Gastrointestinal oncology; Gynecologic oncology; Health maintenance organizations (HMOs); Hematologic oncology; Managed care; Medical oncology; Neurologic oncology; Nutrition and cancer prevention; Nutrition and cancer treatment; Occupational exposures and cancer; Ophthalmic oncology; Pap test; Preferred provider organizations (PPOs).
u Primary central nervous
system lymphomas
Progesterone receptor assay tact immune systems. The most common type to affect the brain is diffuse histiocytic lymphoma, also known as reticulum cell sarcoma. Because of the AIDS epidemic, primary central nervous system lymphoma is projected to become the most common primary malignancy of the brain. Symptoms: Although primary central nervous system lymphoma can occur in all age groups, the average age at which it is diagnosed in normal adults is age sixty, but in immunocompromised patients it is found at the much younger average age of thirty-three. Its symptoms include headaches, seizures, focal neurologic impairment, and stupor. Screening and diagnosis: Brain magnetic resonance imaging (MRI) findings often include periventricular and deep gray matter lesions with masses usually less than 2 centimeters (cm) in AIDS and greater than 2 cm in nonAIDS patients.
Category: Diseases, symptoms, and conditions Also known as: Primary cerebral lymphomas, nonHodgkin lymphoma, reticulum cell sarcomas
Treatment and therapy: Because this tumor is highly radiosensitive, radiotherapy is the treatment of choice, with regression of the tumor in most cases. Unfortunately, recurrence and progression typically occur after one year.
Related conditions: Immunodeficient states including acquired immunodeficiency syndrome (AIDS), organ transplantation, prolonged immunosuppressive therapy, Wiskott-Aldrich syndrome, and Sjögren syndrome
Prognosis, prevention, and outcomes: The prognosis is poor, with a median survival of thirteen and a half months after diagnosis. Debra B. Kessler, M.D., Ph.D.
Definition: Primary central nervous system lymphoma is a non-Hodgkin lymphoma, primarily B-cell type; it is a type of brain tumor that occurs in both normal and immunocompromised patients.
See also Brain and central nervous system cancers; Brain scan; Carcinomatous meningitis; Ependymomas; Gliomas; Hodgkin disease; Imaging tests; Lymphomas; Magnetic resonance imaging (MRI); Meningeal carcinomatosis; Non-Hodgkin lymphoma; Organ transplantation and cancer; Radiation therapies; Recurrence; Sjögren syndrome; Spinal cord compression.
Risk factors: The main risk factor for primary central nervous system lymphoma is having AIDS. Etiology and the disease process: Primary central nervous system lymphoma, if associated with AIDS, can manifest as poorly differentiated brain masses associated with hemorrhage and necrosis, composed of B cells (B lymphocytes), although T-cell lymphomas can also occur. It is thought that the dysfunction of suppressor T cells in AIDS patients leads to this B-cell lymphocytic cancer. In patients with normal immune systems, the brain tumor is usually more focal and well-circumscribed and is usually not associated with hemorrhage and necrosis. Incidence: Primary central nervous system lymphoma makes up 1 to 2 percent of all intracranial neoplasms and 1 percent of all primary non-Hodgkin lymphomas. It occurs in 6 percent of patients with AIDS and is on the rise in both normal and immunocompromised patients, with a threefold increase since the late 1990’s in patients with in-
u Progesterone receptor assay Category: Procedures Also known as: PgR assay, hormone-response assay Definition: A progesterone receptor assay is an immunoassay performed on sections from breast tumors removed during surgery or on small samples obtained with core needle biopsy. Cancers diagnosed: Hormone-responsive breast cancer, ductal carcinoma in situ Why performed: A progesterone receptor assay is used to determine whether a cancer is likely to respond to hormonal therapy. 1003
Prostate cancer Patient preparation: The assay is performed on sections of breast tumors removed during surgery or by needle biopsy. For needle biopsy, patients are usually asked not to use powder, deodorant, or perfume the day of the biopsy. Steps of the procedure: Tumors that were removed during surgery are fixed and stained and then examined by a pathologist to determine whether the cells of the tumor express receptors for progesterone. For core needle biopsy, the patient is either upright or lying on her stomach. Alocal anesthetic is used to numb the breast, and a needle, which may be guided by X-ray imaging, is inserted into the breast mass. Samples of the mass are aspirated into the needle and then sent to a pathologist, who will stain the samples for the assay. After the procedure: After surgery, the patient will be given specific instructions by the physician about activities. Patients can usually resume normal activity immediately after a needle biopsy. Risks: For needle biopsy, the biopsied breast may occasionally show mild bruising. Results: The progesterone receptor is a member of the steroid receptor superfamily of nuclear receptors. The steroid hormone progesterone binds to the receptor in the cell and regulates the expression of genes involved in growth and cell division. Expression of progesterone (PgR) or estrogen (ER) receptors in cancer cells indicates that they will respond to signals that inhibit their growth and division, including drugs that block signaling by estrogen and progesterone. The results are presented as positive or negative based on the number of hormone-responsive cells. A positive result, particularly in early-stage cancers that are both ER- and PgR-positive, suggests that a cancer will likely respond to hormonal (endocrine) therapies and generally signals a favorable prognosis. Such therapies may include removing the ovaries in premenopausal women, treating with an antiestrogen drug such as tamoxifen, or treating with an aromatase inhibitor to block the synthesis of estrogen by the body. A negative result on the progesterone receptor assay indicates that other types of treatments should be pursued. Michele Arduengo, Ph.D., ELS See also Adjuvant therapy; Breast cancers; Hormone receptor tests; Immunocytochemistry and immunohistochemistry; Leiomyomas; Meningiomas; Receptor analysis; Tumor markers. 1004
Salem Health: Cancer
u Prostate cancer Category: Diseases, symptoms, and conditions Also known as: Adenocarcinoma of the prostate Related conditions: Benign prostatic hyperplasia (BPH), prostatitis Definition: Prostate cancer is the growth of cancer cells in the prostate. A majority of prostate cancers start in the prostate gland. This type of cancer is referred to as an adenocarcinoma. There are other types of cancer cells that start in the prostate, but adenocarcinoma is the most common. The prostate is a male reproductive gland, located in front of the rectum and below the bladder, that produces semen, the fluid that nourishes and transports sperm. The gland surrounds the urethra, the tube that carries urine outside the body. It is normally about the size and shape of a walnut. Risk factors: The older a man gets, the higher his risk of getting prostate cancer. More than 70 percent of all diagnosed prostate cancer is found in men age sixty-five or older. Men with a family history of prostate cancer in an immediate relative, such as a father, brother, or son, are two to three times more likely to develop the disease. The disease is also more common among African American men, with more men in this racial group dying from the disease than in any other ethnic group. It is less common in men who are Hispanic, Asian, Native American, or from the Pacific Islands. Etiology and the disease process: Prostate cancer is typically a slow-growing, silent disease that strikes older men. In fact, there are more men with prostate cancer who are never diagnosed and who never have symptoms than there
Incidence Rates of Prostate Cancer by Race, 2001-2005 Race
Incidence per 100,000 Men
All Black White Hispanic Asian American Indian/Native Alaskan
163.0 248.5 156.7 138.0 93.8 73.3
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008
Salem Health: Cancer
Prostate cancer
are men diagnosed with the disease. However, some men develop an aggressive illness that can be life-threatening. There is not a clear understanding as to why some men develop an aggressive form of the disease while others may never know they have it.
The Prostate Gland
Incidence: Prostate cancer is the second most common form of cancer among men in the United States—the most common is skin cancer—and the second leading cause of death, behind lung cancer. It is estimated that more than 235,000 men in the United States were diagnosed with this disease in 2006 and more than 27,000 men died from it. Symptoms: Often, there are no symptoms until the disease has spread beyond the prostate, a condition called metastasis. Common symptoms may include frequent urination, a sudden urge to urinate, a weak urine stream, dribbling after urinating, straining to urinate, the inability to prevent urine leakage, or the sensation that the bladder is not empty even after urinating. Blood in the urine or semen, painful ejaculation, and pain in the lower back, hips, or thighs are also common complaints. The symptoms for prostate cancer are similar to those for the noncancerous conditions benign prostatic hyperplasia (BPH), prostatitis, or a urinary tract infection. If these symptoms occur, it is important to be checked by a doctor to determine the cause. Screening and diagnosis: There are two tests commonly used to screen for prostate cancer: the prostate-specific antigen (PSA) blood test and the digital rectal exam (DRE). PSA is a protein produced by both normal and cancerous prostate cells that is released into the blood. This test measures the levels of PSA in the blood. High levels of PSA may be indicative of prostate cancer or noncancerous conditions. For a digital rectal exam (DRE), the physician inserts a gloved, lubricated finger into the rectum to check the prostate for any unusual characteristics, such as an increase in size, nodules, or lumps. The benefit of the DRE as a screening tool for prostate cancer is that it can reach a part of the prostate gland where most cancers generally begin. Men who are at high risk for the disease should begin testing with both a DRE and a PSA test at age forty-five. The recommended guidelines suggest testing for all other men beginning at age fifty. If the PSA is high or there are suspicious findings during the DRE, additional testing is recommended. These tests may include a transrectal ultrasound or a biopsy. With a transrectal ultrasound, a small probe is inserted into the rectum to take ultrasound images of the prostate. If a suspicious area is found during the exam, a biopsy is taken.
Prostate gland
Penis Testis Anus
Scrotum
A biopsy is usually done with local anesthesia in a doctor’s office. A small needle is inserted into the prostate to remove tissue samples. These samples are then examined under a microscope by a pathologist, a doctor who specializes in identifying diseases by examining tissues and cells, to determine if cancer cells are present and, if they are, how aggressive the disease may be. When prostate cancer is diagnosed, it is given a Gleason score. The Gleason grade is a number between two and ten that reflects how closely the cancer cells resemble normal prostate tissue. In general, a low Gleason score suggests less aggressive tumors, and a higher Gleason score suggests more aggressive tumors. The stage of the cancer refers to the extent of disease based on tumor location, size, number of tumors, and whether the cancer has spread outside the prostate gland to surrounding organs. Stages I and II refer to early-stage disease that is confined to the prostate. Stage III refers to locally advanced disease that has spread outside the prostate gland. Stage IV refers to cancer that has metastasized and possibly spread to the lymph nodes and other organs in the body. Treatment and therapy: There are several treatment options, depending on age, overall health of the patient, and stage and grade of cancer. For men with local or locally advanced prostate cancer, treatment options generally include a radical prostatectomy, radiation therapy, hormone 1005
Prostate-specific antigen (PSA) test therapy, cryotherapy, and watchful waiting. Radical prostatectomy is surgical removal of the prostate gland and surrounding tissues. Radiation therapy is the administration of radiation energy to the prostate to destroy the cancer cells. Hormone therapy involves treatment to lower testosterone levels in the body, thereby reducing prostate cancer cell growth. Cryotherapy involves inserting a probe into the prostate to destroy cells by freezing the prostate gland. Watchful waiting, sometimes referred to as active surveillance, is monitoring the progression of the disease with regular examinations and testing. This option is usually recommended for men with other medical conditions or for those who would not tolerate surgery well. For men with metastatic prostate cancer or men with returning cancer after surgery or radiation treatment, hormone therapy and chemotherapy are treatment options. Hormone therapy reduces prostate cancer cell growth, and chemotherapy destroys the cancer cells circulating throughout the body. Another option may be enrollment in ongoing clinical trials. Patients should discuss these options with their doctors and families to decide the best option to pursue. Prognosis, prevention, and outcomes: Approximately 90 percent of prostate cancer is discovered in the early stages of the disease. When discovered at this stage, the five-year survival rate is almost 100 percent. When the cancer has spread to surrounding tissues or organs, the survival and cure rates vary, depending on the type and extent of disease. As with other types of cancer, there is no definitive way to prevent prostate cancer. It is believed that good overall health; a diet low in fat and high in fruits, vegetables, and whole fibers; and plenty of exercise can strengthen the immune system and potentially slow the onset of cancer. Vonne Sieve, M.A. u
For Further Information Abdel-Wahab, May, and Orlando E. Silva, eds. Prostate Cancer: A Practical Guide. New York: Elsevier/ Saunders, 2008. American Cancer Society. Quick Facts on Prostate Cancer: What You Need to Know—Now. Atlanta: Author, 2007. Bostwick, D. G., et al. “Human Prostate Cancer Risk Factors.” Cancer 101, no. 10 (2004): 2371-2490. Ellsworth, Pamela, John Heaney, and Cliff Gill. One Hundred Questions and Answers About Prostate Cancer. Sudbury, Mass.: Jones and Bartlett, 2003. Metz, James M., and Margaret K. Hampshire. Prostate Cancer. New York: W. B. Saunders, 2008. 1006
Salem Health: Cancer Tenke, P., J. Horti, P. Balint, and B. Kovacs. “Prostate Cancer Screening.” Recent Results in Cancer Research 175 (2007): 65-81. u
Other Resources
American Prostate Cancer Initiative http://www.americanprostate.org/involved.cfm Cancer Research Institute http://www.cancerresearch.org National Cancer Institute Prostate Cancer http://www.nci.nih.gov/cancertopics/types/prostate Prostate Cancer Foundation http://www.prostatecancerfoundation.org See also Benign prostatic hyperplasia (BPH); Carcinomas; Clinical trials; Digital rectal exam (DRE); Endorectal ultrasound; Gleason grading system; Metastasis; Prostatespecific antigen (PSA) test; Prostatectomy; Prostatitis; Proteomics and cancer research; Survival rates; Transrectal ultrasound; Watchful waiting.
u Prostate-specific antigen
(PSA) test Category: Procedures Also known as: PSA blood test Definition: The protein-specific antigen (PSA) test is a simple blood test used to screen for prostate cancer. PSA is a protein produced by both normal and cancerous prostate cells that is released into the blood. High levels of PSA may be indicative of prostate cancer, as well as other noncancerous conditions such as benign prostatic hyperplasia (BPH) or an infection or inflammation in the prostate. The first PSA test determines the baseline level. The PSA levels are compared each year and monitored for any changes. Cancers diagnosed: Prostate cancer Why performed: The benefit of this test is that it can detect signs of early-stage prostate cancer when there are no symptoms. When this cancer is treated in the early stages of the disease, there is a high probability of cure. Prostate cancer is the second most common form of cancer among men in the United States—the most common is skin cancer—and the second leading cause of death behind lung cancer. It is estimated that nearly 235,000 men
Salem Health: Cancer
Prostate-specific antigen (PSA) test
in the United States were diagnosed with this disease in 2006, and more than 27,000 men died from it. Certain groups of men are at a greater risk of developing prostate cancer. Age is a risk factor; the older a man gets, the higher the risk of getting prostate cancer. More than 70 percent of all diagnosed prostate cancer is found in men sixty-five years of age or older. Men with a family history of prostate cancer in an immediate relative, such as a father, brother, or son, are two to three times more likely to develop the disease. It is also more common among African American men, with more men in this racial group dying from the disease than in any other ethnic group. It is less common in men who are Hispanic, Asian, Native American, or from the Pacific Islands. Men who are at high risk for the disease should begin testing with both a digital rectal examination (DRE) and a PSA test at age forty-five. The recommended guidelines suggest testing for all other men beginning at age fifty. The test should be repeated yearly unless a medical provider suggests otherwise. Patient preparation: No special preparation is needed for this blood test. There are indications that a recent urinary tract infection, a recent urinary catheter, prostate stones, a prostate massage, or a DRE right before the blood test may cause the PSA levels to rise. Therefore, it is recommended to avoid those situations before the blood test in order to avoid a false rise in PSA. Steps of the procedure: Since this procedure is a blood test, it takes only a few minutes to perform. The blood is then sent to a laboratory for analysis. It may take a few days up to two weeks before the test results are available. After the procedure: The patient can return to normal activity. It is important to follow up on the results of the blood test to ensure that the PSA levels are within normal limits. Risks: No risks are associated with this procedure. Results: There are several ways to interpret PSA results. A more traditional approach considers less than 4 nanograms per milliliter (ng/mL) to be normal, 4 to 10 ng/mL slightly elevated, 10 to 20 ng/mL moderately elevated, and over 20 ng/mL significantly elevated. Other physicians evaluate the PSA level based on age and suggest that the normal ranges vary by age group. For physicians who take that approach, less than 2.5 ng/mL is normal for men forty to forty-nine years old, less than 3.5 ng/ml is normal for men fifty to fifty-nine years old, less than 4.5 ng/mL is normal for men sixty to sixty-nine years of age, and less than 6.5 ng/mL is normal for men seventy or older.
A prostate with a tumor on its posterior wall. (©MedicalRF.com/ Corbis)
If the initial PSA level is found to be within normal limits, then one of the most important factors in determining whether prostate cancer is present is the change in PSA level from year to year. A dramatic rise in PSA levels from one screening to the next may be indicative of the presence of prostate cancer or other problems with the prostate. When the PSA level is elevated, it is important to have additional testing to determine the cause. Additional tests may include a transrectal ultrasound, in which a small probe is inserted into the rectum to take video images of the prostate, or a biopsy of the prostate, which involves inserting a needle into the prostate to take tissue samples. These samples are then checked for evidence of cancer. Vonne Sieve, M.A. u
For Further Information American Cancer Society. Cancer Facts and Figures. Atlanta: American Cancer Society, 2005. 1007
Prostatectomy Bostwick, D. G., et al. “Human Prostate Cancer Risk Factors.” Cancer 101, suppl. 10 (2004): 2371-2490. Ellsworth, Pamela, John Heaney, and Cliff Gill. One Hundred Questions and Answers About Prostate Cancer. Sudbury, Mass.: Jones & Bartlett, 2003. U.S. Department of Health and Human Services. United States Cancer Statistics: 1999-2002 Incidence and Mortality Web-Based Report. Atlanta: Centers for Disease Control and Prevention and National Cancer Institute, 2005. Also available online at http://www.cdc.gov. u
Other Resources
Centers for Disease Control and Prevention Cancer Prevention and Control http://www.cdc.gov/cancer Prostate Cancer Foundation http://www.prostatecancerfoundation.org See also Benign prostatic hyperplasia (BPH); Carcinomas; Digital rectal exam (DRE); Immunocytochemistry and immunohistochemistry; Pathology; Prevention; Prostate cancer; Prostatectomy; Prostitis; Proteomics and cancer research; Screening for cancer; Transrectal ultra sound; Tumor markers; Watchful waiting; Wine and cancer.
u Prostatectomy Category: Procedures Also known as: Radical prostatectomy, transurethral resection of the prostate (TURP) Definition: Prostatectomy is the surgical removal of part or all of the prostate gland. A radical prostatectomy refers to removal of the prostate gland and surrounding tissue. A transurethral resection (TURP) refers to removal of part of the prostate. Cancers treated: Prostate cancer Why performed: A radical prostatectomy is performed to remove cancer that is confined to the prostate gland and surrounding area. This procedure is not usually done when cancer has spread beyond the prostate gland to distant tissues or organs. A TURP is commonly done to relieve symptoms associated with benign prostatic hyperplasia (BPH). With BPH, the prostate gland is enlarged and squeezes the urethra, creating problems with urination. Removal of part of the prostate gland can usually alleviate those symptoms. Patient preparation: Generally, no food or drink is consumed after midnight on the day before undergoing gen1008
Salem Health: Cancer eral anesthesia. The evening before a radical prostatectomy, a bowel preparation is usually taken to cleanse the colon. Steps of the procedure: For a radical prostatectomy, the procedure varies depending on which method the surgeon uses: open, laparoscopic, or laparoscopically assisted prostatectomy. Typically, general anesthesia is used with all these procedures. Open surgery involves an incision in the lower abdomen if the retropubic approach is done or in the groin between the anus and the penis for the perineal approach. The retropubic approach is most common and allows the surgeon to remove the prostate gland and the lymph nodes, if necessary, to be checked for cancer spread beyond the prostate. This approach allows the surgeon to attempt preservation of the nerves that help control bladder and sexual function. Lymph node removal can be done with the perineal approach, but a separate incision must be made, and preservation of sexual function is not possible. The open procedure can take from one and a half to four hours to complete. With the laparoscopic and laparoscopically assisted approach, several small incisions are made in the lower abdomen. The laparoscope allows the surgeon to see inside the abdominal cavity and remove the prostate and surrounding tissue. With the robot-assisted procedure, the surgeon performs the procedure remotely with the use of a robot. Occasionally, a laparoscopic procedure may need to be converted to an open procedure if difficulty is encountered. This procedure may take four hours or more to perform. No abdominal incision is needed for a TURP. A cutting instrument or a heated wire loop is inserted through the penis to the prostate gland to remove or destroy prostate tissue. The bladder is then flushed with sterile solution to remove the destroyed tissue from the body. With all these procedures, a small flexible tube called a urinary catheter is inserted into the bladder and left in place to drain urine during the healing process. After the procedure: An open prostatectomy is considered major abdominal surgery. Patients typically remain in the hospital from two to four days. Recovery time can be as long as twelve weeks. A laparoscopic procedure is less invasive. The hospital stay is usually two days, and recovery time averages two to four weeks. The urinary catheter is typically removed one to three weeks after the procedure. With a TURP, the hospital stay is generally two to four days. The urinary catheter is generally left in place for one to three days after the procedure.
Salem Health: Cancer Risks: General complications from undergoing a major surgical procedure may include bleeding, blood clots, heart problems, infection, allergic reaction to anesthesia, and, in rare cases, death. Short-term complications from a radical prostatectomy may include urinary incontinence, which is the inability to control the bladder. This condition generally improves, and full bladder control is regained over time. Long-term complications may include erectile dysfunction and urinary incontinence. The risks from a TURP may include excessive bleeding, a urinary tract infection, or pain with urination. Some men temporarily develop problems as a result of the large amounts of irrigating fluid used to flush out the bladder. A more permanent condition that can develop is a stricture, a permanent narrowing of the urethra that can occur if the urethra is damaged during the procedure. Results: When prostate cancer is confined to the prostate gland, the cure rate is very high. Five-year survival approaches 100 percent. Overall, prostatectomy success rates are about 76 to 98 percent for men with low-risk disease, 60 to 76 percent for men with moderate-risk disease, and 30 to 76 percent for men with high-risk disease. These rates vary depending on the surgeon’s technique and experience with the procedure. Erectile dysfunction is a common side effect. The nerves that control erections are located on both sides of the prostate gland and are easily damaged, or may be removed, during the procedure. Age and erectile function before surgery can affect the likelihood of problems after the procedure. Urinary incontinence is another common problem with this procedure and includes occasional urine leakage to complete inability to control urine flow. In some cases, additional surgery may be necessary to correct the problem. With a TURP, urination problems generally stop after the swelling has subsided. After the surgical procedure, it is important for the patient to discuss monitoring his condition with additional testing to ensure that the problems have not returned. Vonne Sieve, M.A. u
For Further Information Ellsworth, Pamela, John Heaney, and Cliff Gill. One Hundred Questions and Answers About Prostate Cancer. Sudbury, Mass.: Jones & Bartlett, 2003. Marks, Sheldon. Prostate Cancer: A Family Guide to Diagnosis, Treatment, and Survival. Cambridge, Mass.: Fisher Books, 2000. Wainrib, Barbara, et al. Men, Women, and Prostate Cancer: A Medical and Psychological Guide for Women
Prostatitis and the Men They Love. Oakland, Calif.: New Harbinger, 2000. See also Benign prostatic hyperplasia (BPH); Carcinomas; Exenteration; Infection and sepsis; Obesity-associated cancers; Prostate cancer; Psychosocial aspects of cancer; Sexuality and cancer; Urinary system cancers; Urologic oncology.
u Prostatitis Category: Diseases, symptoms, and conditions Also known as: Prostatodynia, chronic pelvic pain syndrome Related conditions: Urinary tract infection, benign prostatic hyperplasia, prostate cancer Definition: Prostatitis is inflammation of the prostate gland. The prostate is a reproductive gland in men that produces semen, the fluid that nourishes and transports sperm. It is about the size and shape of a walnut and is located below the bladder. The gland surrounds the urethra, the tube that carries urine outside the body. Risk factors: Prostatitis is more common in men under age forty or men who have recently experienced a bladder infection or obstruction (such as a tumor or stone), a urethral catheterization, an enlarged prostate, or a suppressed immune system. Some sexually transmitted diseases increase the risk of developing prostatitis. Etiology and the disease process: Inflammation of the prostate can be caused by an acute or chronic bacterial infection or a nonbacterial infection. It may also be caused by abnormal nerve or muscle development in the pelvic region, a condition called prostatodynia. If an acute infection is left untreated, it may develop into a chronic condition. Incidence: Prostatitis is a common problem in adult men, encompassing about 40 percent of visits to a urologist. Symptoms: The symptoms for acute and chronic bacterial infections may include fever; frequent, painful, and difficult urination; pain in the pelvic region and lower back; and painful ejaculation. The symptoms for other forms of prostatitis can be nonspecific and mimic other conditions but are generally associated with pain in the pelvic region and lower back. Screening and diagnosis: Acute bacterial prostatitis is diagnosed with the appearance of white blood cells and bacteria in the urine. Chronic bacterial prostatitis, a rare condition, is diagnosed after a prostate massage is performed; 1009
Proteasome inhibitors fluid samples are taken and examined for the presence of prostatic bacteria. Nonbacterial prostatitis is not well understood and may be caused by infectious agents such as viruses, physical abnormalities, physical activity, or muscle spasms. It can be difficult to diagnose because the symptoms are often similar to those associated with other conditions. Treatment and therapy: Treatment for bacterial prostatitis includes administration of an antibiotic, which generally resolves the problem. Lifestyle changes, pain relievers, muscle relaxants, and physical therapy are sometimes used to treat other forms of prostatitis. Prognosis, prevention, and outcomes: Proper hygiene and avoiding sexual activity with a partner with a bacterial infection may help prevent bacterial prostatitis. The most effective way to prevent a chronic condition is to seek treatment when the symptoms first appear. Vonne Sieve, M.A. See also Bacteria as causes of cancer; Benign prostatic hyperplasia (BPH); Fever; Infection and sepsis; Prostate cancer; Prostate-specific antigen (PSA) test; Risks for cancer; Transrectal ultrasound; Urethral cancer; Urologic oncology.
u Proteasome inhibitors Category: Chemotherapy and other drugs ATC code: 101XX Definition: Proteasome inhibitors are small-molecule drugs that target the proteasome, a large protein complex responsible for the degradation of unwanted proteins in the cell. Certain proteins are marked for proteasomal degradation by ubiquitination, the process of adding multiple ubiquitin molecules to the protein. Ubiquitinated proteins are recognized by the proteasome, allowing for the degradation of specifically targeted proteins. Cells rely on the proteasome to maintain a proper balance of particular proteins, as well as to remove damaged protein. Because the proteasome is an essential component for many cellular processes, including cell division and survival, it is an attractive target for actively growing cancer cells. Cancers treated: Multiple myeloma, mantle cell lymphoma Subclasses of this group: Synthetic inhibitors, natural inhibitors Delivery routes: Intravenous (IV) injection 1010
Salem Health: Cancer How these drugs work: Proteasome inhibitors are targeted therapies with specificity for the proteasome protein complex. These agents act by binding to the proteasome, impairing its ability to degrade proteins in the cell. Because degradation of excess and damaged proteins is a necessary function for normal cellular processes such as cell proliferation, these inhibitors can induce death in actively dividing malignant cells. The only proteasome inhibitor currently approved to treat patients with cancer is bortezomib (Velcade). Bortezomib is administered by IV injection, at a recommended dosage of twice weekly for two weeks, followed by a rest period. Several cycles of this therapy may be given. Other compounds have been discovered to have proteasome inhibitory activity, but these agents are not currently indicated for the treatment of cancers. Ritonavir is an antiretroviral drug used in human immunodeficiency virus (HIV) therapy. Preclinical studies have shown that ritonavir may have activity against brain tumor cells. Lactacystin is a natural proteasome inhibitor primarily used in laboratory settings. Side effects: Bortezomib, the only proteasome inhibitor currently improved as an antineoplastic agent, is generally safe and well tolerated. The predominant side effects noted with bortezomib therapy are weakness, diarrhea and constipation, nausea and vomiting, and peripheral neuropathy, a tingling in the hands and feet. Additionally, myelosuppression such thrombocytopenia and neutropenia has been noted. Lisa M. Cockrell, B.S. See also Antineoplastics in chemotherapy; Chemotherapy; Diarrhea; Gastrointestinal complications of cancer treatment; HIV/AIDS-related cancers; Lymphomas; Mantle cell lymphoma (MCL); Moles; Multiple myeloma; Myeloma; Nausea and vomiting; Neutropenia; Thrombocytopenia.
u Protein electrophoresis Category: Procedures Also known as: Serum protein electrophoresis (SPEP) Definition: Protein electrophoresis is a laboratory test used to measure the amounts of major proteins in a patient’s blood serum, urine, or cerebrospinal fluid. Cancers diagnosed: Most metastatic cancers, especially multiple myeloma
Salem Health: Cancer Why performed: Serum protein electrophoresis is used to screen for cancer or evaluate the extent of an existing cancer, particularly multiple myeloma. It can also be used to identify other diseases, including kidney, liver, intestinal, and immune disorders, as well as malnutrition. These disorders are associated with abnormal levels of different blood proteins, which can be detected by electrophoresis. Patient preparation: There is no special preparation for this procedure. Patients undergo a normal blood test and should tell their physicians which prescription medications they are taking. Steps of the procedure: A physician or nurse will draw blood from a vein in the patient’s arm in an outpatient setting. The blood sample is transferred to the laboratory, where it is centrifuged to separate serum, the plasma without clotting factors, from the blood cells. Blood proteins are retained in the serum. A small amount of serum is then transferred to an electrophoretic paper or gel such as cellular acetate or agarose, respectively. Since proteins are charged molecules and vary in size, they will migrate differentially when a current is applied to the electrophoretic field. A fluorescent agent that binds to proteins is added to the serum for illumination. The result is a gradient of separated bands, or fractions, of proteins. A laboratory specialist studies an image of the gel to determine the relative concentrations of different proteins in the blood serum. After the procedure: A bandage is applied to the patient’s arm at the puncture site, and the patient can go home. Risks: No risks are associated with protein electrophoresis. A blood draw, however, may cause minor bleeding or bruising at the puncture site. The patient may also feel light-headed, and there is a possibility of fainting after the blood draw. Results: The major blood proteins consist of albumin and globulins. There are four types of globulin proteins: alpha-1 globulins, alpha-2 globulins, beta globulins, and gamma globulins. Normally, albumin makes up more than half of the proteins in the blood serum and is important for normal tissue growth. High levels of albumin proteins are a result of dehydration, while low levels suggest inflammatory disease, liver disease, malnutrition, or a kidney disorder. High levels of alpha-1 globulins (alpha-1 antitrypsin, thyroid-binding globulin, and transcortin) may indicate acute inflammatory disease and malignancies, while a low level can indicate liver disease. The levels of certain alpha-2 globulins (ceruloplasmin, alpha-2 macroglobulin, and haptoglobulin) can aid in cancer diagnosis. For exam-
Protein electrophoresis ple, a low level of haptoglobin may indicate tumor metastasis or liver disease. Variations in other alpha-2 globulin levels may indicate inflammation, nephrotic syndrome, or hemolysis, which is the loss of hemoglobin from red blood cells. High levels of beta globulin (transferrin and beta lipoprotein) can indicate biliary cirrhosis, hyperthyroidism, diabetes mellitus, and carcinoma in some cases, while decreased levels indicate malnutrition. High levels of gamma globulins (various antibodies) are the most indicative of cancers such as multiple myeloma, lymphocytic leukemia, or malignant lymphoma. In addition, high levels can indicate Hodgkin disease, connective tissue disorders, and chronic or acute infections. A patient whose serum protein electrophoresis yields abnormal results will be referred to a hematologist-oncologist. Bharat Burman, B.A. u
For Further Information Aziz, Khalid, and George Y. Wu. Cancer Screening: A Practical Guide for Physicians. Totowa, N.J.: Humana Press, 2002. Hoffman, Ronald, et al. Hematology: Basic Principles and Practice. 4th ed. Philadelphia: Churchill Livingstone, 2005. Keren, David F. High-Resolution Electrophoresis and Immunofixation: Techniques and Interpretation. 2d ed. Boston: Butterworth-Heinemann, 1994. O’Connell, T. X., et al. “Understanding and Interpreting Serum Protein Electrophoresis.” American Family Physician 71, no. 1 (January 1, 2005): 105-112. Wallach, Jacques. Interpretation of Diagnostic Tests. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2007.
u
Other Resources
American Cancer Society How Is Multiple Myeloma Diagnosed? http://www.cancer.org/docroot/CRI/content/ CRI_2_4_3X_How_is_multiple_myeloma_ diagnosed_30.asp?sitearea= National Cancer Institute Screening and Testing to Detect Cancer http://www.cancer.gov/cancertopics/screening See also Immunoelectrophoresis (IEP); Lactate dehydrogenase (LDH) test; Multiple myeloma; Myeloma.
1011
Proteomics and cancer research
u Proteomics and cancer
research Category: Cancer biology Definition: The term “proteome” was coined in 1994 to describe the study of all the protein forms expressed within an organism, tissue, or group of cells as a function of time, age, state, and external factors. Many technological advances have led to the emergence of the discipline termed proteomics, which is now widely employed in the cancer field. Background: Many scientists are using the rapidly emerging technologies of proteomics in an effort to identify new cancer biomarkers, specific protein species in the body that are helpful for disease prediction or treatment, and to understand the underlying mechanisms associated with cancer onset and progression. These technologies are also being applied to drug development and the identification of patients who might benefit from targeted therapies. Proteomics integrates some key fundamental technologies such as high-throughput protein separation and profiling, mass spectrometry, large databases, and bioinformatics tools to analyze and extract information from these databases. Scientific rationale: After the human genome was sequenced, it consisted of fewer genes than scientists had expected—approximately 30,000, about twice as many genes as a worm or fly. This raised the question of how human complexity can be explained by a genome with such a relatively small number of genes. Scientists realized that such complexity is achieved in part by the economical use of genes. The effective number of distinct protein species present in a cell is greatly increased through a wide variety of ways in which proteins can be modified after being synthesized, collectively called posttranslational modifications. These modifications range from the addition of biochemical functional groups such as phosphate groups (resulting in phosphorylation) and carbohydrate groups (resulting in glycosylation), the addition of other proteins or peptides, chemical changes to the amino acids of the protein, and structural changes to the protein such as formation of disulfide bridges or proteolytic cleavage of the protein. Besides their ability to undergo modifications, another characteristic of proteins is their dynamic state. They have the ability to constantly move around and bind to other proteins or cellular components. Proteins are able to respond quickly to a changing cellular environment, and they play an important role in the elaborate communica1012
Salem Health: Cancer tion pathways within and between cells. A cell’s complement of proteins in their specific posttranslationally modified forms is increasingly being recognized as playing an important role in many cellular processes and states, including cancer. Scientists believe that cancer develops through a multistep process involving the accumulation of genetic alterations that lead to altered gene expression patterns, protein structures, and functions. Because the transformation of a normal cell to a cancerous one involves changes in the proteins present in the cell, the aim of proteomics in cancer research is to monitor these changes and use the information to provide valuable information that may aid diagnosis, prognosis, and monitoring response to therapy. One goal of proteomics in cancer research is to define the expression patterns of proteins that are expressed at different levels in cells in different physiological states, such as cancer cells compared with noncancerous cells, or late-stage cancer cells compared with early-stage cancer cells. Another goal is the identification of tumor markers, proteins that are associated with particular types of cancer. Ideally, such markers would be sensitive, selective, and measurable by a noninvasive procedure (such as by analysis of blood or urine). In addition, the emergence of proteomics offers the promise of helping to elucidate the complex molecular events involved in cancer, as well as those that control clinically important tumor behaviors such as metastases, invasion, and resistance to therapy. Biomarkers may also be used to help devise optimal therapeutic treatment plans for different patient subsets and to monitor the effect of treatment. Technologies: Proteomics consists of sample preparation, protein separation, and protein identification. Since the late 1990’s, mass spectrometry has increasingly become the method of choice for analyses of complex protein samples. Mass spectrometry is a technique that generates electrically charged fragments from the proteins present in the mixture and measures particular properties of those fragments. The end product is a spectrum or chart with a series of peaks. The size of the peaks and the distance between them provide a “fingerprint” of the sample. Mass spectrometry offers the ability to measure, rapidly and inexpensively, thousands of proteins in a few drops of blood. The entire process, from collection of a few drops of blood to analyzing the “fingerprint,” can take less than one minute. Hundreds of samples can be analyzed sequentially and very small amounts of protein can be detected. The spectrum obtained from mass spectrometry experiments is difficult to analyze manually, but computers are being used to analyze such patterns and distinguish small
Salem Health: Cancer differences in patterns between patients. Bioinformatics tools are the computer-based algorithms that are used to convert raw proteomics data into a useful form that can be analyzed, compared, interpreted, and stored in large databases. Of particular interest in the field of proteomics research are high-throughput technologies that are capable of simultaneous and rapid analysis of multiple samples. One example is microarray technology, an automated technique for the simultaneous analysis of thousands of different samples affixed to a thumbnail-sized “chip” of glass or silicon. Examples of tumor markers: The tumor marker prostatespecific antigen (PSA) is indispensable in the management of prostate cancer. Patients at high risk for primary liver cancer are screened by the tumor marker alphafetoprotein, in combination with ultrasonography, a regimen that has been shown to result in earlier detection and therefore more effective treatment and longer survival for patients with this type of cancer. Available screening tests for ovarian cancer include the biomarker cancer antigen 125 (CA 125), which has also proved to be a useful marker for monitoring response to chemotherapy. A rapid fall in the CA 125 level during chemotherapy predicts a favorable prognosis. In another example for ovarian cancer, a blood test for the levels of four proteins (leptin, prolactic, osteopontin, and insulin-like growth factor II) has been shown to discriminate with high accuracy between patients with early ovarian cancer and those who were disease free. Challenges: The identification of large numbers of proteins from complex biological samples is a continuing challenge in this field. Techniques to address this challenge are evolving quickly. The biological variability among patient samples and the large concentration range over which proteins can be present also present challenges to deducing diagnostic patterns that are unique to specific types of cancer. The fast pace of technological innovation in this area should result in the identification of new biomarkers for different cancers and their use to improve diagnosis and treatment. Standardization of proteomics techniques is needed to allow for the reproducibility required for medical applications. Alarge knowledge base is needed to allow for the accurate interpretation of proteomics data. Large databases, such as the publicly available Protein Atlas, are being assembled. Frozen tissue banks will be useful to preserve tissue samples for future analysis and comparison of samples taken at different times. The main bottlenecks for proteomics research are the
Proteomics and cancer research rapid accumulation of data and the lack of suitable computational tools for analysis. Data are being collected at a faster pace than researchers can validate, interpret, and integrate with other known data. Software tools are needed in all areas of data analysis, including data collection, searching, evaluation, archiving, and retrieval. Prospects: With the ongoing rapid technological developments in this field, the prospects for identification of new highly sensitive and specific biomarkers for different cancers and their use for making significant contributions to the understanding, diagnosis, and treatment of cancer patients seems very hopeful. Jill Ferguson, Ph.D. u
For Further Information Brusic, V., O. Marina, C. J. Wu, and E. L. Reinherz. “Proteome Informatics for Cancer Research: From Molecules to Clinic.” Proteomics 7 (2007): 976-991. Cho, W. C. S. “Contribution of Oncoproteomics to Cancer Biomarker Discovery.” Molecular Cancer 6 (2007): 25-37. Liang, S.-L., and D. W. Chan. “Enzymes and Related Proteins as Cancer Biomarkers: A Proteomic Approach.” Clinica Chimica Acta 381 (2007): 93-97. Pastwa, E., S. B. Somiari, M. Czyz, and R. I. Somiari. “Proteomics in Human Cancer Research.” Proteomics—Clinical Application 1 (2007): 4-17. Reid, J. D., C. E. Parker, and C. H. Borchers. “Protein Arrays for Biomarker Discovery.” Current Opinion in Molecular Therapeutics 9 (2006): 216-221. Wu, W., W. Hu, and J. J. Kavanagh. “Proteomics in Cancer Research.” International Journal of Gynecological Cancer 12 (2002): 409-423.
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Other Resources
The Human Genome/Wellcome Trust Proteomics and Cancer http://genome.wellcome.ac.uk/doc_WTD020926.html National Cancer Institute Clinical Proteomic Technologies for Cancer http://proteomics.cancer.gov See also Alpha-fetoprotein (AFP) levels; American Association for Cancer Research (AACR); CA 125 test; Cancer biology; Chemotherapy; Pathology; Prostate-specific antigen (PSA) test; Screening for cancer; Tumor markers. 1013
Proton beam therapy
Salem Health: Cancer
u Proton beam therapy Category: Procedures
occurring in the prostate, lung, head, neck, and brain, although it is being tested in clinical trials for use on cancers occurring in many other areas as well.
Cancers treated: Primarily cancers of the prostate, lung, head, neck, and brain
Patient preparation: The patient should discuss with the cancer care team any necessary preparation for the specific procedure that he or she is undergoing. Necessary preparation may vary depending on the type of cancer being treated and the patient’s previous response to any radiation therapy.
Why performed: Proton beam therapy, like traditional radiation therapy, is performed to kill cancer cells. It may be performed as a primary treatment for a tumor, to kill any cancer cells that remain after surgical cancer treatment, or in addition to other cancer treatment options. Proton beam therapy is only offered at a few locations in the United States, and for many cancers it is still considered an experimental treatment. Proton beam therapy is a site-specific therapy, so it is designed to treat cancers that have not spread to large areas or throughout the body. It is mainly used to treat cancers
Steps of the procedure: Proton beam therapy uses highspeed protons to kill cancer cells, instead of the electrons used by most radiation therapy techniques. Atoms are made up of a nucleus of protons and neutrons surrounded by orbiting electrons. Protons have a positive charge, neutrons have no charge, and electrons have a negative charge. When free protons come very close to an atom, the electrons orbiting the nucleus are attracted to the positive charge of the protons. The electrons are then pulled out of their orbits. This is called ionization of the atom. Atoms that have been ionized are not as stable as normal atoms.
Definition: Proton beam therapy is a procedure for delivering targeted radiation therapy using protons instead of the electrons used by traditional radiation therapies.
A lung cancer patient receives proton beam therapy. (AP/Wide World Photos)
1014
Salem Health: Cancer This change to the atom means that changes also occur to the molecule of which the atom is part, and eventually to the cell of which the molecule is part. If the cell cannot repair the damage caused, then it eventually dies. Proton beam therapy begins with protons traveling around a synchrotron, a machine that makes the protons go very fast and energizes them. The protons are then sent through vacuum tubes to the machine that actually aims them at the area of the patient that will receive the radiation. The patient is positioned and held still so that the proton beam can be aimed as accurately as possible. Complex computer technology helps the doctors and technicians aim the proton beam very accurately so that it hits as little healthy tissue as possible. The protons are released in a directed stream toward the cancer cells. The protons are traveling very quickly at first, but they slow down as they get closer to the cancer. When they are traveling fast, they do not have a very strong effect on the atoms they are passing. When they are slower, however, they have an extremely strong effect. This is one reason that proton beam therapy causes less damage to healthy cells than does traditional radiation therapy. Traditional radiation therapy uses X rays, which strongly affect all the cells with which they come into contact, which makes it hard to deliver enough radiation to the cancer cells without also killing healthy cells. With proton beam therapy, doctors aided by computers can determine the right way to release the protons so that they have the maximum impact just as they come into contact with the cancer cells. Proton beam therapy may need to be repeated one or more times depending on the size and type of the cancer and other factors. After the procedure: After proton beam therapy, many individuals experience no negative side effects. Some individuals, however, may experience pain, fatigue, nausea, or diarrhea. Risks: The risks associated with proton beam therapy are believed to be somewhat lower than those associated with traditional radiation therapy for most people. This is the case because proton beam therapy causes less damage to surrounding healthy cells, so healthy tissue is less likely to be significantly damaged. Some of the risks of proton beam therapy include nausea, diarrhea, and fatigue. Damage to healthy tissue is still a possible risk of proton beam therapy. Results: The goal of proton beam therapy is generally to destroy a tumor, to reduce the size of a tumor, to reduce related symptoms, or to kill any residual cancer cells left after a tumor has been surgically removed. Success rates for
Proto-oncogenes and carcinogenesis proton beam therapy can vary drastically depending on the type of cancer, its size, and how far it has spread. It is generally found to be successful at reducing the side effects usually associated with traditional radiation therapy. If the procedure is done to completely destroy a tumor or residual cancer, then the procedure is generally considered to have been successful if the cancer does not return for five years or more. If the procedure was done to reduce tumor size, then it is considered successful if quality of life is improved. Helen Davidson, B.A. u
For Further Information Barton-Burkey, Margaret, and Gail M. Wilkes. Cancer Therapies. Sudbury, Mass.: Jones and Bartlett, 2006. Chan, Helen S. L. Understanding Cancer Therapies. Jackson: University of Mississippi Press, 2007. DeLaney, Thomas F., and Hanne M. Kooy, eds. Proton and Charged Particle Radiotherapy. Philadelphia: Lippincott Williams & Wilkins, 2008. Haas, Marilyn L., et al. Radiation Therapy: A Guide to Patient Care. St. Louis: Mosby/Elsevier, 2007.
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Other Resources
The National Association for Proton Therapy http://www.proton-therapy.org See also Afterloading radiation therapy; Brain scan; Cancer care team; External beam radiation therapy (EBRT); Gastrointestinal complications of cancer treatment; Meningiomas; Nausea and vomiting; Neurologic oncology; Radiation oncology; Radiation therapies; Virus-related cancers.
u Proto-oncogenes and
carcinogenesis Category: Cancer biology Also known as: Precursors of oncogenes Definition: Proto-oncogenes are cellular genes that may be transformed into oncogenes (cancer-causing genes). Proto-oncogenes provide signals that promote the division and specialization of normal cells or regulate programmed cell death (apoptosis). Changes in their genetic sequence or their expression level due to chromosomal translocation, point mutation, or amplification can trigger a sequence of events leading to the neoplastic transformation (abnormal growth) of a cell and subsequently to tumor formation. 1015
Psycho-oncology
Salem Health: Cancer
Particularly at risk are persons carrying chromosomal translocations or molecular rearrangements in their genome and persons infected with distinct viruses: EpsteinBarr virus (EBV) in Burkitt lymphoma, sinonasal lymphoma, and lymphomas in immunocompromized patients; human T-cell lymphotropic virus type 1 (HTLV-1) in adult T-cell lymphoma/leukemia; and human herpesvirus 8 (HHV-8) in body-cavity-based lymphomas in patients infected with the human immunodeficiency virus (HIV).
nomas; Endocrine cancers; Epstein-Barr virus; Free radicals; Gene therapy; Genetics of cancer; Giant cell tumors (GCTs); HIV/AIDS-related cancers; HRAS gene testing; Leukemias; Lymphomas; Mesothelioma; Mitochondrial DNA mutations; Molecular oncology; MYC oncogene; Nephroblastomas; Oncogenes; Oncogenic viruses; Viral oncology; Virus-related cancers; Wilms’ tumor.
Etiology and symptoms of associated cancers: B-cell lymphomas are caused by malignant B-cell lymphocytes. Through a chromosomal translocation, the BCL2 protooncogene may become rearranged, resulting in overexpression of its protein product. The protein product blocks apoptosis, thereby enabling continued growth of the malignant B cells. T-cell lymphomas show a high frequency of a characteristic chromosomal translocation, resulting in the combination of the NPM1/ALK genes and a fused oncogenic protein product. Nephroblastoma (Wilms’ tumor) is the most common malignant tumor of the kidney in children. Mutations of the WT1 proto-oncogene are found in approximately 20 percent of Wilms’ tumors, half of which additionally carry mutations in CTNNB1, a proto-oncogene encoding betacatenin. Plasmacytomas frequently show chromosomal translocations resulting in dysregulation of oncogenes followed by proliferation of a plasma cell clone. Genomic instability leads to further mutations and translocations. The oncogene CCND1 product cyclin D1 is overexpressed in 45 to 50 percent of primary ductal mammary carcinomas, in part because of amplification of the region of the genome where the proto-oncogene is located. Other oncogenes that play roles in mammary carcinomas are HER2/neu (ERBB2), MYC (c-myc), and WNT1.
u Psycho-oncology
History: Oncogenes were first discovered in certain retroviruses and were later identified as cancer-causing agents in many animals. In 1976 it was demonstrated by J. Michael Bishop and Harold Varmus that cancer-causing genes (oncogenes) carried by certain viruses are derived from normal genes (proto-oncogenes) present in the cells of their host. Further research showed that such genes can cause cancer even without viral involvement. By 2008 scientists had identified more than one hundred oncogenes in animals. Nicola E. Wittekindt, Dr.Sc. (ETH Zürich) See also Burkitt lymphoma; Cancer biology; Carcinogens, known; Carcinogens, reasonably anticipated; Carci1016
Category: Medical specialties Definition: Originally, psycho-oncology was a subspecialty of oncology that investigated, assessed, and treated the social and psychological aspects of having cancer. Psycho-oncology evolved to include the study and amelioration of pain stemming from cancer and its treatments, subjective emotional responses to receiving and carrying the diagnosis (anxiety, depression, degree of hope/hopelessness, delirium), application of patients’ effective coping, functional status and quality of patients’ lives, role of spiritual and philosophical beliefs, management of stress on caregivers and professional staffs, and the interactions between psychological and emotional factors on immune systems. Subspecialties: Behavioral medicine, health psychology, medical-liaison psychiatry/psychology, pain management, psycho-immunology, psychoneuroimmunology, psychosomatic medicine, psychosocial medicine, psychospirituality Cancers treated: All Training and certification: Because psycho-oncology is a clinical and research application of professional training, there is not a universally accepted academic credential although training programs exist at most major cancer treatment centers. Professional organizations promoting the work of psycho-oncology include the American Psychosocial Oncology Society, the British Psychosocial Oncology Society, and the International Psycho-oncology Society. Their membership consists of oncologists, psychiatrists, and allied health professionals. Those practicing or researching psycho-oncology come from several professional disciplines that apply their training to the psychological and psychosocial treatment of cancer patients and their families: residency-trained physician oncologists, residency-trained physician psychiatrists, clinical health psychologists, nurse practitioners, medical social workers, and pastoral counselors. (Pastoral
Salem Health: Cancer counselors are not routinely required to possess a state license.) Professionals follow the individual requirements of their disciplines regarding obtaining licenses to practice their specialty independently, privileges to treat patients from the institutions where they practice, and specialty board certification (where applicable) and maintaining (renewing) board certification. Specific training in psycho-oncology usually occurs as an elective track or certificate program at the major cancer treatment centers for professionals in training there. Psycho-oncology is not typically a requirement of curricula in oncology, psychiatry, health psychology, or social work. Therefore, people who engage in its practice are generally those who have actively sought out training, reflecting a high degree of interest and commitment. The National Comprehensive Cancer Network (NCCN) is an organization representing nearly all the major comprehensive cancer care centers in North America. It has produced standards for psychosocial cancer care and clinical practice guidelines for those involved in providing psycho-oncology services, including nonlicensed professionals such as pastoral counselors. Institutional regulatory and oversight bodies such as the Joint Commission of Accreditation of Heathcare Organizations (JCAHO), the American Osteopathic Association (AOA), and governmental departments of health have not yet fully incorporated these guidelines or psycho-oncological care itself as standard criteria for providing treatment to cancer patients. Reimbursement for and revenue generation by psychooncology interventions is meager relative to other cancer treatment modalities such as surgery, radiation oncology, and chemotherapy. When institutions reassess fiscal priorities, psycho-oncology services and programs are often among the first to be discontinued. Services and procedures performed: Historically, receiving a cancer diagnosis was equivalent to receiving a terminal diagnosis. In a humanely motivated effort to protect patients from completely losing hope and entering a state of despair, a cancer diagnosis routinely was not revealed to patients, though families were generally told. In the mid-1970’s people began to believe that it was generally more harmful to patients to keep their diagnosis a secret, an idea that was supported by studies on patients’ psychological reactions to having and being treated for cancer conducted at Memorial Sloan-Kettering Cancer Center in New York and the Massachusetts General Hospital in Boston. Early services in psycho-oncology promoted telling the truth to patients, encouraging patients with similar diagnoses to meet for emotional support, disseminating
Psycho-oncology treatment information, and educating professionals about quality-of-life considerations and the values in comfort care over curative intervention among grave prognostic cases. These growing changes in the environment of cancer treatment were concurrent with improvements in actual cancer treatments and growing survival rates. In the twenty-first century, psycho-oncology professionals provide multiple services under the umbrella of engaging the psychological and psychosocial aspects of having cancer. Psycho-oncology researchers have developed many instruments that assess a wide range of patients’ reactions to cancer, including pain, anxiety, depression, and delirium. These instruments assist with evaluating the efficacy of interventions and provide quantitative parameters through which ongoing research in psycho-oncological methods can be tracked and understood. Preexisting psychological “tests” or instruments were not normed on populations that were this medically ill and routinely overreported patients’ experiences. Researchers have developed scales derived from patient responses to sets of questions that are cancer specific. Psycho-oncology’s contribution to outcomes research (whether a new treatment, drug, or procedure is effective, worth the costs and risks, and so on) has moved it beyond whether the intervention increases survival to include consideration of whether the survival is worth having—it asks the question whether sustaining this life allows the patient to enjoy a high enough quality of life. In the twenty-first century, oncological treatments must not only reduce tumor growth but also promote sufficient functional status for them to be considered efficacious and beneficial. “Quality-adjusted life years” is a widely cited statistic combining survivability (how much time the treatment adds to patients’ lives) with measures of patients’ quality of life. Mortality rate statistics are inadequate by themselves. Psycho-oncology practitioners who perform consultation-liaison services commonly treat adjustment disorders that arise in cancer patients. In effect, they treat not the disease but the disturbed emotions that understandably arise in the face of coping with cancer. They treat not cancer, but patients’ reactions to having cancer. Health psychologists’ study of how patients cope with illness and comply with treatment plans has become a standard component of what psycho-oncologists work to facilitate in their patients: adaptive patterns of feeling, thinking, and behaving in facing cancer and its treatments and informed compliance with treatment plan options. Psycho-oncology practitioners unite understanding patients’ subjective experiences without judgment or reprimand, respect for patients’ rights to react in the way they 1017
Psychosocial aspects of cancer do, and compassionate positive regard for their emotional suffering with the focused treatment of the cancer itself. Practitioners of psycho-oncology also focus on preventive and behavioral health measures, helping patients effect lifestyle changes to reduce the risk of developing or exacerbating cancer. Reducing sun exposure and high-fat, high-calorie food intake; eliminating tobacco use; and achieving and maintaining healthy levels of exercise can reduce cancer risk. Psycho-oncology’s contribution to cancer treatment includes the provision of comfort and palliative care so that patients who are terminally ill do not suffer needlessly as a result of aggressive or invasive treatments that prolong life at the cost of reducing functional ability. Helping patients and their loved ones deal with life-threatening disease means that psycho-oncologically oriented treatments encourage inclusion of patients’ spiritual beliefs, religious practices, and search to find meaning when death is inevitable. Finally the high emotional demands of dealing with life and death, the uncertainty of treatments, and cancercaused physical and emotional pain profoundly affect not only patients but also health care professionals and caregivers. Psycho-oncology interventions include protocols and strategies to avoid provider burnout and depression. Paul Moglia, Ph.D. u For Further Information Barraclough, Jennifer. Cancer and Emotion: A Practical Guide to Psycho-Oncology. New York: Wiley, 1999. Bearison, David J., and Raymond K. Mulhern, eds. Pediatric Psychooncology: Psychological Perspectives on Children with Cancer. New York: Oxford University Press, 1999. Holland, Jimmie C., et al., eds. Psycho-Oncology. New York: Oxford University Press, 1998. Lewis, Clare E., Jennifer Barraclough, and Rosalind O’Brien. The Psychoimmunology of Cancer. New York: Oxford University Press, 2002. u
Organizations and Professional Societies
American Psychosocial Oncology Society http://www.apos-society.org 2365 Hunters Way Charlottesville, VA 22911 American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 1018
Salem Health: Cancer National Comprehensive Cancer Network http://www.nccn.org 500 Old York Road, Suite 250 Jenkintown, PA 19046 u
Other Resources
British Psychosocial Oncology Society http://www.bpos.org International Psycho-oncology Society http://www.ipos-society.org National Breast Cancer Coalition http://www.natlbcc.org See also Anxiety; Cancer care team; Depression; Exercise and cancer; Immune response to cancer; Medical oncology; Oncology social worker; Pain management medications; Prayer and cancer support; Psychosocial aspects of cancer; Stress management; Support groups.
u Psychosocial aspects of cancer Category: Social and personal issues Definition: Psychosocial aspects of cancer involve the full array of behavioral, cognitive, emotional, and social factors associated with the disease. Included are the coping mechanisms patients employ in dealing with the physical and emotional stressors caused by the illness and its treatment. Reactions to cancer diagnosis: Despite significant advances in treatment and steadily increasing rates of survival, cancer is perceived by most to be a frightening and painful disease. Receiving the diagnosis of cancer evokes the possibilities of disabling illness, suffering, changes in appearance and physical abilities, altered social and professional goals, loss of personal control and independence, and even death. Shock, emotional “numbing,” and denial are common responses to the diagnosis. Treatment of the disease may be associated with unpleasant and often severe side effects such as pain, disfigurement, fatigue, and nausea. Not surprisingly, cancer diagnosis typically engenders distress, and patients commonly experience at least periodic feelings of hopelessness, fear, and dysphoria during the course of their illness. Although a minority of cancer patients develop psychiatric illnesses, many experience unpleasant psychological or social problems that hinder coping skills and quality of life. The manner in which patients adapt to cancer is determined by individual
Salem Health: Cancer and family characteristics, illness-related factors, and cultural and societal influences. Individual and family characteristics: The developmental stage of the patient at the time that cancer is diagnosed and treated influences how the illness is perceived and which developmental tasks may be disrupted. For example, cancer treatment in childhood or adolescence involving changes in appearance, pain, or weakness can hinder self-confidence and make social development more difficult. In early adulthood, illness-related disruptions can affect job performance and modify career goals and perceptions of self-worth. In later adulthood, cancer can markedly alter financial status and long-awaited expectations for retirement years. Other factors influencing the extent that cancer affects psychosocial functioning include personality, emotional maturity, coping style, and prior experience with illness. General coping tasks of all cancer patients involve regulating stress and anxiety caused by the diagnosis and treatment requirements; adapting to changes in social, familial, and occupational roles; coping with new role demands associated with being a patient, including participating in treatment efforts, maintaining a sense of self-worth, continuing relations with family and friends (such as spouses and employers); and developing acceptance and satisfaction with post-illness circumstances. Personality variables such as optimism, flexibility and openness to change, emotional expressiveness, and acceptance of emotional support appear to help with coping. For some, prior exposure to a serious illness—whether their own illness or that of someone close to them—makes adaptation to cancer more difficult. A history of psychiatric illness before cancer diagnosis also appears to be a risk factor for poor coping. Some cancer patients, including those without prior psychiatric histories, develop psychiatric illness in response to stressors associated with cancer. The most common of these are depression and anxiety. Left untreated, these conditions can markedly reduce patients’ quality of life, adherence to treatment regimens, and overall adaptation to cancer. Fortunately, effective medicines and psychological therapies exist to treat psychiatric illness in cancer patients. In most cases, cancer affects all members of a patient’s family, and the response of the family in turn affects the patient’s adaptation to the illness. Family members’ reactions to a diagnosis of cancer can be extreme and sometimes mirror the struggles and adaptive demands experienced by the patient. Parents of children with cancer are faced with unusually difficult challenges; however, most are able to effectively deal with the worry, family disrup-
Psychosocial aspects of cancer tion, and myriad behavioral and emotional demands that accompany the diagnosis. A family’s makeup, relationships, cohesiveness, communication patterns, and especially level of support have been identified as factors contributing to cancer patients’ psychosocial response to their illness. The impact of serious illness frequently alters family members’ roles and responsibilities, necessitating adaptation to these changes. Families are the primary providers of support to most patients, and a family environment characterized by high levels of communication and emotional expressiveness, along with low levels of conflict, predicts better adjustment in cancer patients. Having a family that is critical, emotionally distant, or unresponsive to patient distress appears related to poorer patient adaptation to the challenges of cancer. Patients who lack support from family or friends may benefit from participating in support groups in terms of improved mood, coping skills, pain tolerance, and general mental health. Illness-related factors: Disease-related factors contributing to psychosocial adaptation to cancer include the type, stage, and location of the disease; its symptoms; treatment demands and side effects; and the prognosis for rehabilitation, cure, or survival. Certain types of cancer appear to be particularly potent in producing emotional distress in patients. For example, the diagnosis of breast cancer and awareness of associated treatments and potential side effects (such as surgical intervention and disfigurement, chemotherapy and hair loss, radiation and infertility) can be profoundly disturbing to many women, especially those of childbearing age. Other types of cancer associated with behavioral or lifestyle factors (such as smoking and lung cancer) may produce debilitating guilt and self-reproach in the patient. For most, initial emotional turmoil gives way to a return to more normal coping strategies and gradual adaptation to the demands of their health status. Pain, diminished strength and physical abilities, and attendant loss of independence are some of the symptoms associated with cancer that require psychosocial adaptation in patients. For those patients who have a realistic hope of cure, unpleasant or painful treatment side effects, such as nausea, weakness, vomiting, or hair loss, are endured with the hope of long-term benefits. Counseling, meditation, support groups, and medication may be employed to assist the patient in controlling psychological symptoms stemming from treatment. Because patients are increasingly surviving cancer, there is greater awareness of how individuals adapt to life after their illness. Many survivors find positive aspects to their experience with ill1019
Psychosocial aspects of cancer ness, including examining life goals and searching for more meaningful pursuits and spiritual growth. Many survivors struggle with anxiety associated with fears of recurrence of the disease or how they will cope as they resume roles and activities disrupted by their illness. Although successful coping is seen in most individuals, some experience esteem issues, grief, difficulties with intimacy, and a heightened sense of vulnerability even after several years of survival. In terminal cases, the transition from active treatment to palliative or comfort care, and the attendant confrontation with the inevitability of death, can be very difficult for patients and their friends and family. Reactions to this change often involve shock and denial of physical realities. Similar to what is seen at initial diagnosis, after a period of distress, most patients draw on their usual means of coping and adapt to new therapeutic goals such as pain control, comfort care, and maximizing quality of life. Increasingly, terminal care is provided at the homes of patients, with benefits to the patient and family resulting from greater comfort and closeness during the patient’s final days. Progress in the control of symptoms of advanced illness (such as pain) has significantly improved the quality of life for many patients and thereby facilitated psychosocial adjustment to end-of-life issues. Cultural and societal influences: Cultural and societal factors that influence adaptation to cancer change as knowledge, perceptions, and beliefs about the illness evolve. Historically, when effective treatment options were limited and a culture of paternalism held sway in medicine, the diagnosis of cancer was kept from individuals, because the disease typically led to death and patient awareness was viewed as merely adding to the suffering. Treatment advances, coinciding with overall efforts in medicine to increase patient participation in medical care, have curtailed this practice. Improved patient-physician communication and a greater sense of autonomy and control in the patient are some of the benefits of this change. Increased public access to medical information (such as via the Internet) has led to heightened awareness of cancer and has reduced the prevalence of some associated myths (for example, that cancer is a contagion), which previously contributed to stigmatizing those with the disease. Greater exposure to accurate information regarding treatment alternatives for many forms of cancer has led to a generally less grim view of the disease by the general public. Consequently, reflexive catastrophic emotional responses to the diagnosis may be reduced. However, overall increases in optimism regarding cancer may be tempered in some cases by access to starkly realistic prognostic and treat1020
Salem Health: Cancer ment information associated with the more virulent types of the disease. Also, access to inaccurate sources of information, such as those erroneously attributing the cause of cancer to inadequate personality traits or “toxic” relationships, may unnecessarily add to the psychological burden of the patient. Greater awareness and cultural acceptance of mental health problems and the availability of effective treatment has increased the likelihood of cancer patients receiving care for depression and anxiety. Treatment of these conditions has been found to improve the quality of life of cancer patients. Paul F. Bell, Ph.D. u
For Further Information Gatchel, Robert, and Mark Ooordt. Clinical Health Psychology and Primary Care. Washington, D.C.: American Psychological Association, 2003. Goldman, Larry, Thomas Wise, and David Brody. Psychiatry for Primary Care Physicians. Chicago: American Medical Association, 1998. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006.
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Other Resources
American Cancer Society Counseling, Psychological, and Social Services http://www.cancer.org/docroot/PED/content/ PED_13_3x_Counseling_Psychol_and_Social_ Services.asp?sitearea=PED Cancer Coping Center http://www.cancercopingcenter.com National Cancer Institute Coping with Cancer http://www.cancer.gov/cancertopics/coping National Institutes of Health Cancer: Coping with Cancer http://health.nih.gov/result.asp/105 See also Aging and cancer; Anxiety; Cancer care team; Cancer education; Case management; Childhood cancers; Cognitive effects of cancer and chemotherapy; Complementary and alternative therapies; Counseling for cancer patients and survivors; Depression; Elderly and cancer; End-of-life care; Fatigue; Fertility issues; Financial issues; Grief and bereavement; Palliative treatment; Personality and cancer; Prayer and cancer support; Primary care physician; Psycho-oncology; Rehabilitation; Relationships; Self-image and body image; Sexuality and cancer; Singlehood and cancer; Smoking cessation; Stress management; Support groups; Transitional care.
Salem Health: Cancer
u Radiation oncology Category: Medical specialties Also known as: Radiotherapy oncology Definition: Radiation oncology is the treatment of cancers using radiation, including therapeutic high-dose, highenergy forms of ionizing radiation, to shrink tumors and kill cancer cells. As one of the four major approaches to the treatment of cancer (along with surgery, chemotherapy, and biological therapy), radiation oncology is at the forefront of cancer treatment and research. Subspecialties: Clinical radiation therapy, radiation and cancer biology, radiation physics Cancers treated: Many cancers, but particularly cancers of the brain, head and neck, lung, breast, prostate, skin, rectum, cervix, and uterus, as well as lymphomas and sarcomas Training and certification: The structure of accredited radiation oncology programs and residencies varies. In North America, most radiation oncologists have completed a radiation oncology residency in a program approved by the American Council of Graduate Medical Education (ACGME), the American Board of Radiology (ABR), or the Royal College of Physicians and Surgeons of Canada. Radiation oncologists must possess a broad and deep command of both cancer biology and imaging technology. They study the etiology of cancer; its evaluation, diagnosis, and treatment in a clinical setting; the ways radiation interacts with various cancers at all levels, from molecular to multicellular; the physics of radiotherapeutic technologies and associated machines such as linear accelerators and hyperthermia devices; techniques such as interstitial brachytherapy, intraoperative radiotherapy, and stereotactic radiosurgery; and a host of other disciplines associated with radiation therapy, such as nuclear medicine, oncology, diagnostic radiology, and surgical pathology. During postdoctoral training, students may elect to focus on research, as in radiation biology; on the integration of advanced technologies and radiation physics with clinical research; or on clinical practice. Most residencies in clinical radiation oncology require at least three, more often four, years to complete, usually following a first postgraduate year (PGY-1) of surgical, medical, or flexible internship. After receiving their primary certification, radiation oncologists usually must renew certification every several years, depending on their subspecialties. The American Board of Radiology, for example, requires its diplomates
Radiation oncology to satisfy its “maintenance of certification” (MOC) program to maintain their primary certification. Services and procedures performed: All radiation oncologists participate in the evaluation, staging, treatment, and therapy of their patients. They are the overseers of the cancer patient’s radiation oncology team, ensuring the precision and accuracy of radiation treatment, and they work with physicians treating the patient’s cancer in other ways. Throughout the course of radiation therapy, radiation oncologists are responsible for monitoring the patient’s progress, side effects, and treatment to meet two goals: that the cancer is effectively halted or reduced in size, and that the patient’s comfort is at the same time adequately addressed. The balance of these objectives is essential to achieving the best outcome. Radiation oncologists head a team of medical professionals who together design and deliver the patient’s radiation treatments. In concert with the patient’s primary oncologist, the radiation oncologist learns about the specifics of the patient’s cancer to determine the role radiation therapy will play in its treatment, then meets with the patient to evaluate his or her probable response to radiation therapy. Along with a radiation physicist and a dosimetrist, the radiation oncologist will then design the treatment plan, which involves simulations, immobilization devices, calculating radiation dosages, and conducting periodic checks to confirm accurate delivery of treatment. The types of procedures radiation oncologists design and perform with the radiology team fall into two major categories. In the various forms of external beam radiation, the most common type of radiotherapy, the radiation oncologist uses a machine similar to an X-ray machine to direct high-energy X and gamma rays to the specific area of the body where the tumor resides. Treatments are given on a daily basis, usually for one to eight weeks and sometimes more than once a day, depending on the tumor and its aggressiveness. Brachytherapy—also known as internal, implant, interstitial, or intracavitary radiation therapy—is the other main form of radiotherapy. The radiation oncologist implants, in the form of capsules called needles or seeds, a small amount of a radioactive substance in the body near the tumor while the patient is under general anesthesia. Among the radioactive materials used are cesium, iridium, iodine, phosphorus, and palladium. Other procedures include electron therapy, including total skin treatment; radioimmunotherapy, in which monoclonal antibodies are enlisted to deliver the radiation by binding to the tumor cells; proton beam therapy, which uses protons to deliver higher doses of radiation to tumors 1021
Radiation oncology
Salem Health: Cancer
Linear accelerators, including this one at St. Catherine Hospital in Garden City, Kansas, are used in radiation therapy. (AP/Wide World Photos)
than can be accomplished using conventional X and gamma radiation; neutron therapy, which can work in oxygen-free environments, such as the depths of a large tumor, to deliver radiation to cancers that cannot be treated by other forms of radiation; and stereotactic radiosurgery, such as the Gamma Knife, used to treat head and neck cancers by delivering a very high dose of radiation targeted directly at a tumor and sparing surrounding, healthy tissue. Finally, radiation oncologists offer palliative treatment for those whose outcome is not expected to be survival but whose pain can be ameliorated by halting the growth of a tumor or shrinking its size. Related specialties and subspecialties: Many radiotherapy subspecialists work with the radiation oncologist. While radiation oncologists oversee care and integrate it with that of surgeons, chemotherapy oncologists, and other physicians, the day-to-day application of radiotherapy to the patient’s tumor is often carried out by others on the radiology team. 1022
First, radiation physicists, certified by the American Board of Radiology or the American Board of Medical Physics, work directly with the radiation oncologist, oversee dosimetrists, develop quality-control programs for procedures, and perform safety tests on equipment. Their education usually consists of four years of college, two to four years of graduate school, and one or two years of clinical physics training. Radiation therapists, under the supervision of radiation oncologists, administer the daily treatments, keep records, and check the performance of machines. They typically have two to four years of college education and have been certified by the American Registry of Radiologic Technologists. Many states also require licensing for radiation therapists. Dosimetrists calculate dosages and durations of radiation with the goal of doing the greatest damage to the tumor while limiting damage to normal tissue. Because of the complexity of determining treatment dosages, dosimetrists often start as radiation therapists and, with additional
Salem Health: Cancer training, advance to dosimetry. There are also intensive dosimetry programs lasting one to two years. Dosimetrists are certified by the Medical Dosimetrist Certification Board. Radiation oncology nurses are charged with caring for radiation patients from before the beginning of treatment through its completion. They are also the patient’s first line of communication regarding what to expect during the procedure and how to identify and evaluate side effects. All radiation oncology nurses are registered nurses, and most are also accredited in the specialty of oncology nursing, which requires the completion of a master’s degree program. Christina J. Moose, M.A. u For Further Information Cukier, Daniel. Coping with Chemotherapy and Radiation Therapy. 4th ed. New York: McGraw-Hill, 2004. Delfino, Michelangelo, and Mary E. Day. We Live and Die by Radiation. Mountain View, Calif.: MoBeta, 2006. Leibel, Steven A. Textbook of Radiation Oncology. 2d ed. Philadelphia: Saunders, 2004. Parker, Robert G. Radiation Oncology for Cure and Palliation. New York: Springer, 2003. Schlegel, W., et al., eds. New Technologies in Radiation Oncology. New York: Springer, 2006. u
Organizations and Professional Societies
American Board of Radiology http://www.theabr.org/index.htm 5441 East Williams Boulevard, Suite 200 Tucson, AZ 85711 American College of Radiology http://www.acr.org 1891 Preston White Drive Reston, VA 20191 American Society for Therapeutic Radiology and Oncology http://www.astro.org P.O. Box 631567 Baltimore, MD 21263 International Radiosurgery Support Association http://www.irsa.org 30905 Hoffman Street Harrisburg, PA 17110 National Association for Proton Therapy http://www.proton-therapy.org 7910 Woodmont Avenue, Suite 1303 Bethesda, MD 20814
Radiation therapies u
Other Resources
Radiation Oncology Online Journal http://www.rooj.com/default.htm RT Answers http://www.rtanswers.org See also Afterloading radiation therapy; Boron neutron capture therapy (BNCT); Brachytherapy; Cobalt 60 radiation; External beam radiation therapy (EBRT); Ionizing radiation; Iridium seeds; Linear accelerator; Nuclear medicine scan; Proton beam therapy; Radiation therapies; Radiopharmaceuticals; Stereotactic needle biopsy; Stereotactic radiosurgery (SRS); X-ray tests.
u Radiation therapies Category: Procedures Also known as: Radiotherapy, external beam radiation therapy (EBRT), internal beam radiation therapy (IBRT), systemic radiation therapy, stereotactic radiosurgery, afterloading radiation, implants, brachytherapy, tomotherapy, proton therapy, intensity-modulated radiation therapy (IMRT), image-guided radiation therapy (IGRT), Mammosite therapy, radioimmunotherapy Definition: Radiation therapy uses high doses of radiation to kill cancer cells and prevent metastasis (the spread of disease). Most cancers may be treated with one or more of the three types of radiation therapy. About 50 to 60 percent of all cancers may be treated by radiation therapy during the initial treatment phases, and an additional 12.5 percent of patients may need a second course of treatment later in their disease to manage symptoms caused by the growth of their tumor. The radiation oncologist, with other physicians involved in the care of the patient, will determine if the patient’s cancer is appropriately treated with radiation. Cancers treated: Most, such as breast, prostate, thyroid, and gynecological cancers Why performed: Radiation therapies are performed to kill, stop, or slow the growth of cancer cells in the body. Cancer is usually treated with surgery, chemotherapy, and radiation, which is called multimodal therapy. Radiation, as a component of this combined approach to care, may be used before, during, or after surgery; in combination with chemotherapy; or alone. Some patients who are not able to tolerate aggressive surgeries or chemotherapies may benefit, to some degree, from radiation therapy. Many patients develop side effects from their cancers that may be treated 1023
Radiation therapies with radiation. Spinal cord compression or bony metastases may be treated to reduce paralysis or pain. There are three ways to administer radiation to a patient. When a machine outside the body delivers radiation to a tumor inside the body, the process is called external beam radiation therapy (EBRT). Internal beam radiation therapy (IBRT) uses sources, applicators, or a high-dose remote afterloader to place radioactive material in the body near the cancer site. Systemic radiation therapy uses a radioactive substance that is injected or swallowed and then travels to cancer cells in tissues of the body. EBRT uses X-ray beams that may be given by a linear accelerator, a machine that generates high-energy radiation beams; by a machine with a radioactive source, cobalt 60; by a tomotherapy unit, which is a linear accelerator coupled with a computed tomography (CT) scanner that delivers radiation in spirals around the body; or by a robotically controlled accelerator that delivers radiation while tracking and controlling for patient movement or organ movement during the treatment. Proton beam therapy,
Salem Health: Cancer one of the newer of the external beam radiation therapies, uses a machine that generates protons to damage the deoxyribonucleic acid (DNA) of cancer cells. With proton therapy, the radiation beam of protons enters the body with a low dose of radiation, deposits its highest dose at the site being treated, and then stops without traveling through the body. Advances in external beam therapy, based on the ability to better plan therapies, continue to develop rapidly. Conformal radiation therapy (3D-CRT) develops a threedimensional model of the tumor and then uses shaped beams to treat the cancer from several directions. Intensity-modulated radiation therapy (IMRT) uses sophisticated treatment planning to vary the strength of the radiation beam in an attempt to lessen damage to the normal tissues surrounding the tumor. Tomotherapy is considered a type of IMRT and image-guided radiation therapy (IGRT), as the beams spiral around the body, allowing for precise and focused radiation beams based on data from a CT scan. IGRT is used to visualize the tumor location prior
A radiologist, seated, checks his work on an MRI screen as he uses radio waves to burn a cancerous tumor. (AP/Wide World Photos)
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Salem Health: Cancer to treatment, as tumor movement occurs daily, and to control for tumor movement with respiration (respiratory gating). In addition to a CT scan, ultrasound may be used. Stereotactic radiosurgery is a type of radiation therapy that delivers a large, precise dose to a defined tumor site. It is most commonly used for brain tumors, but applications in the abdomen and other sites are being explored. A cobalt 60 source machine is used with a head frame for brain tumors, and a robotically control linear accelerator may be used for both brain tumors and tumors outside the head (extracranial tumors). It is called radiosurgery because of its accuracy. The radiation beam is considered as accurate as a knife (or scalpel) and may treat tumors that surgeons cannot reach using traditional surgical techniques. Intraoperative radiation therapy is used at the time of surgery to deliver external beam radiation directly to the tumor during the surgical procedure. The surgeon locates the cancer and moves normal tissues and organs out of the way, and then an accelerator delivers radiation directly to the tumor. The patient is asleep (under anesthesia) during the procedure, which is done in a special lead-lined operating room. IBRT is delivered by several methods and is often referred to as brachytherapy. IBRT using a remote-controlled machine called a high-dose remote afterloader (HDR) unit sends high-dose radioactive material through catheters or needles placed in the patient for a period of minutes, and then the sources are withdrawn, so that the patient is not radioactive. When patients are exposed to radiation sources for a period of hours or days, the process is called lowdose-rate brachytherapy. Applicators or cases that house radioactive sources are placed in the patient and left for a prescribed period of time. The area around the patient is considered radioactive until the source is removed. Therefore, staff must limit their exposure to the patient, and visitors are not allowed. Permanent brachytherapy is a type of low-dose therapy in which radioactive seeds are placed in the patient and remain while giving off low doses of radiation for weeks or months. The patient gives off some radioactivity in very small doses. The primary safety consideration is to keep children away from the area of the implant. For example, a man undergoing permanent brachytherapy for prostate cancer must not allow children to sit on his lap. Systemic radiation therapy is given as a capsule or liquid swallowed by the patient, or it may be given in a vein (injected intravenously). The radioactive liquid then moves throughout the body. The patient may stay in a special room in the hospital, and body fluids are handled carefully, as the radiation materials are eliminated from the body through urine, saliva, and sweat. When the radioactivity has dipped to safe levels, the patient may be discharged
Radiation therapies from the hospital. In some cases, the patient may be able to go home after treatment with special instructions about handling wastes. Breast cancer is one of the most commonly treated cancers using external beam radiation therapy. Use of an HDR unit decreases the treatment time of several weeks to just five days. This procedure is often referred to as Mammosite therapy, named for the company that initially developed the procedure for commercial use. Prostate cancer may also use external beam radiation, an HDR unit, or implantable seeds (low-dose brachytherapy) to kill cancer cells. Thyroid cancer is often treated with radioactive iodine, a systemic radiation therapy in a liquid form that is swallowed by the patient. Gynecological cancers may be treated with an HDR unit or low-dose brachytherapy with an applicator that is left in for a period of time. Patient preparation: The radiation oncologist, a physician with specialized training in radiation therapy care, will see the patient in a consult visit to determine if radiation therapy is appropriate for his or her cancer. Patients are generally referred to the radiation oncologist by the patient’s surgeon or medical oncologist. The physicians treating the patient will discuss whether external, internal, or systemic radiation is most appropriate. Prior to receiving treatment, patients have a simulation using a CT scanner or fluoroscopic simulator to allow the physician to visualize the area to be treated. A simulation may take up to two hours. To assist in positioning the patient for treatment, small marks may be placed on the skin. Later in the treatment room, the marks will be used with wall-mounted positioning lasers to place the patient in the correct position to receive the treatment. The simulation data are used to plan the radiation dose amounts to be given by the linear accelerator, the HDR unit, or any other source of radiation, such as implantable seeds. The simulation information is given to the physicist and dosimetrist, who load the data into a sophisticated treatment-planning computer. The physician then verifies the treatment site, the treatment plan, and the radiation dose to be given. Steps of the procedure: The steps of the radiation treatment will depend on the type of radiation therapy that the patient receives. Regardless of whether external, internal, or systemic therapy is used, treatment planning is still the key to accurate radiation placement and dosing. For external beam therapy, the treatment plan will outline the patient position on the treatment table, determine the shape of the beam, define the number of treatments to be given, and prescribe the daily and cumulative doses the patient is to receive. The patient has four to six weeks of treatment depending on the treatment plan, five days a week, with 1025
Radiation therapies two days a week off for normal cells to rest and recover. If an HDR unit is to be used, then catheters may be implanted at the time of surgery, or hollow needles may be placed just before the treatment. HDR treatments usually take place once or twice a day for approximately five days. For patients receiving internal radiation, a simulation and treatment plan are still necessary. For low-dose brachytherapy, such as prostate seed implants, additional imaging studies may be needed. Seeds are implanted during a surgical procedure with the patient under general anesthesia. Low-dose brachytherapy, such as used in gynecological cancers, may use applicators that are placed in a treatment room and then loaded with the radioactive source. Patients receiving systemic radiation also need treatment planning to determine the amount of radioactive liquid needed to treat the cancer. After the procedure: Most external beam treatments are done on an outpatient basis, and the patient may leave immediately after the daily treatment. Patients are not radioactive during treatments. A few external beam treatments, such as intraoperative radiation therapy and select stereotactic radiosurgery, may require hospitalization. Internal beam radiation treatments may be done on either an inpatient or an outpatient basis, depending on the method used to deliver the radiation therapy. If an HDR unit is used to deliver high-dose radiation, then the patient may be able to go home between treatments. If the internal beam radiation therapy requires that the radioactive source stay in the patient for a period of hours or days, then the patient is usually hospitalized, as the bodily fluids are emitting radioactive waste. Systemic radiotherapy may be either inpatient or outpatient in nature. Risks: The risks from radiation depend on the site being treated and the type of radiation therapy being used. EBRT is a local treatment, so risks involve the area around the site being treated. For example, if abdominal radiation is used, then bowel and bladder problems may develop. Skin reactions, similar to sunburn, may occur. Hair loss, called alopecia, may occur if radiation is given to the head or other body areas with hair follicles. Xerostomia, or dry mouth, may occur with radiation of the head and neck areas, and dental problems may also occur with this radiation site. Fatigue is often associated with any radiation procedure. Side effects usually go away within two to three months after therapy is completed. Late side effects, those developing six or more months after therapy is completed, may include infertility, lymphedema, joint pain, or other problems, as well as a risk of a second cancer due to the radiation. There is always a risk that not all cancer cells will be killed by the radiation. 1026
Salem Health: Cancer Results: Cancer cell kill is expected after any method of radiation treatment. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Penson, D. F., M. S. Litwin, J. L. Gore, et al. “Quality of Life After Surgery, External Beam Irradiation, or Brachytherapy for Early Stage Prostate Cancer.” Urologic Oncology 25, no. 5 (September/October, 2007): 442-443. Tao, Y., D. Lefkopoulos, D. Ibrahima, et al. “Comparison of Dose Contribution to Normal Pelvic Tissues Among Conventional, Conformal, and Intensity-Modulated Radiotherapy Techniques in Prostate Cancer.” Acta Oncologica, September 28, 2007, 1-9.
u
Other Resources
American Cancer Society http://www.acs.org American Society for Therapeutic Radiology Oncology http://www.astro.org Medline Plus Radiation Therapy http://www.nlm.nih.gov/medlineplus/ radiationtherapy.html National Cancer Institute Radiation Therapy and You http://www.cancer.gov See also Accelerated partial breast irradiation (APBI); Afterloading radiation therapy; Angiography; Barium enema; Barium swallow; Bone scan; Boron neutron capture therapy (BNCT); Brachytherapy; Brain scan; Bronchography; Cobalt 60 radiation; Computed tomography (CT)-guided biopsy; Computed tomography (CT) scan; Cystography; Ductogram; Endoscopic retrograde cholangiopancreatography (ERCP); External beam radiation therapy (EBRT); Gallium scan; Gamma Knife; Hysterography; Imaging tests; Intensity-modulated radiation therapy (IMRT); Iridium seeds; Linear accelerator; Lymphangiography; Magnetic resonance imaging (MRI); Mammography; Microwave hyperthermia therapy; Nuclear medicine scan; Positron emission tomography (PET); Proton beam therapy; Radiation therapies; Radiofrequency ablation; Radionuclide scan; Radiopharmaceuticals; Stereotactic needle biopsy; Stereotactic radiosurgery (SRS); Thermal imaging; Thyroid nuclear medicine scan; Wire localization; X-ray tests.
Salem Health: Cancer
u Radical neck dissection Category: Procedures Also known as: Classical radical neck dissection Definition: A radical neck dissection is a surgical procedure that involves the excision of a primary malignant cancer and several adjacent head and neck structures (salivary glands, sternocleidomastoid muscle, cervical lymph nodes, fatty tissue, jugular vein, and spinal accessory nerve). Cancers treated: Squamous and basal cell carcinomas of the head and neck, lymphoma, thyroid carcinoma, metastatic cancer Why performed: On gross examination of the neck, masses that preserve the outer tissue can suggest a benign tumor but cannot eliminate the possibility of cancer. Microscopically, benign tumor cells have an increased, orderly growth while malignant cells have an increased, disorderly growth and large nuclei relative to the surrounding cytoplasm. Cervical lymph node samples possessing cancerous cells strongly suggest microscopic spread outside the neck. Extensive infiltration of the neck by a tumor can affect breathing, speech, and movement as well as blood circulation to the head. Surgery may be necessary to restore the function of the affected structures. The procedure is performed when malignant cancer has spread to adjacent facial and neck structures. Introduced in 1906 by George W. Crile, it remains the standard surgical treatment for metastasis. Patient preparation: Surgical risk assessment, tissue biopsy, and computed tomography (CT) and/or magnetic resonance imaging (MRI) are done. Steps of the procedure: A hockey-stick-shaped incision is made over the anterolateral neck. The superficial neck muscle (platysma) is cut and retracted. The submandibular gland and duct, lymph nodes, a segment of the facial artery, and the tail of the parotid gland are removed or ligated. The sternocleidomastoid muscle is cut above the clavicle and retracted. The posterior omohyoid, anterior trapezius, spinal accessory nerve, jugular vein, surrounding lymph nodes, and the upper border of the sternocleidomastoid are ligated, cut, and removed. After the procedure: The patient is monitored until stable. A breathing tube may be put in place to protect the airway until the wound heals. Food intake may be withheld for at least twenty-four hours after the operation. The patient may be discharged if stable after a few days.
Radiofrequency ablation Risks: Bleeding is the most common complication because of the dense capillary network around the head and neck. Breathing problems, infections, formation of an abnormal connection between the esophagus and the trachea, shoulder muscle paralysis, and significant disfigurement can also occur. Results: Although neck dissection has veered toward preserving function, radical neck dissection remains a sound surgical option for advanced stages of cancer. Aldo C. Dumlao, M.D. u
For Further Information Brockstein, Bruce, and Gregory Masters, eds. Head and Neck Cancer. Boston: Kluwer Academic, 2003. Kelloff, Gary, Ernest T. Hawk, and Caroline C. Sigman. Cancer Chemoprevention. Totowa, N.J.: Humana Press, 2004. Thaller, Seth R., and W. Scott McDonald. Facial Trauma. Miami: Informa Health Care, 2004. See also Basal cell carcinomas; Benign tumors; Carcinomas; Computed tomography (CT) scan; Imaging tests; Infection and sepsis; Lymphomas; Magnetic resonance imaging (MRI); Metastasis; Metastatic squamous neck cancer with occult primary; Oral and maxillofacial surgery; Salivary gland cancer; Thyroid cancer.
u Radiofrequency ablation Category: Procedures Also known as: RFA, thermal ablation Definition: Radiofrequency ablation is the application of high-energy radio waves (radiofrequency thermal energy) through a catheter probe to heat and destroy abnormal tissues. As a cancer treatment, radiofrequency ablation is used to ablate (destroy) cancerous tumors by directing the radiofrequency heat directly to the tumor, causing the cancerous cells to die. According to the Society of Interventional Radiology, radiofrequency energy is safer than many cancer therapies because it is absorbed by living tissues as simple heat, and the heat generated by radiofrequency does not alter the basic chemical structure of cells. Radiofrequency ablation technology was originally developed for the treatment of cardiac arrhythmias in the early 1990’s and has since been used as a cancer treatment after clinical studies proved its efficacy. The technology is approved by the Food and Drug Administration (FDA). Radiofrequency applications vary, depending on the 1027
Radiofrequency ablation
Salem Health: Cancer In some cases, radiofrequency ablation can be used to ease certain side effects of cancer treatment, such as chronic pain caused by some cancers. Radiofrequency ablation may be used in combination with chemotherapy or other cancer treatments to improve a patient’s quality of life and survival. The recommendation for radiofrequency ablation is dependent on the type of cancer, the patient’s overall medical condition, the number of tumors, and the tumor size and location.
Patient preparation: Tests performed before the procedure include positron emission tomography (PET) testing and computed tomography (CT) scanning. Radiofrequency ablation does not interfere with most standard cancer therapies and can be performed for some patients who are actively receiving chemotherapy. A few days before the procedure, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician. Other anticoagulant medications may be prescribed if necessary before the procedure. Antiarrhythmic mediRadio frequency catheter ablation of a kidney tumor (inset); the kidney in the cations may also need to be discontinued. Pabody (background). (© Kevin A. Somerville/Phototake—All rights reserved) tients with diabetes may need to adjust their diabetes medications, insulin dosages, or meal type of catheter used and the dose of energy applied. plan, as directed by the physician. Patients must not eat or Newer RFA applications involve ablation with multiple drink for eight hours beforehand. electrodes to treat large or multiple tumors and ablation Patients should remove all makeup and nail polish. The with liposomal therapy, a method of delivering heatpatient will change into a hospital gown before the proceactivated chemotherapy drugs via synthetic capsules called dure. liposomes. The coating on the liposome capsules allows the medication to remain in the circulation for a longer Steps of the procedure: An intravenous (IV) line is inperiod of time, so the drugs selectively target cancer cells serted into a vein in the patient’s arm to deliver medicaand decrease the side effects for healthy tissue. tions. A sedative is usually given before the procedure so that the patient will be in a form of light sleep during the Cancers treated: Primary and metastatic liver cancer, procedure. General anesthesia is used in some cases. An early-stage breast cancer, lung cancer, bone cancer, prosinterventional radiologist usually performs the procedure, tate cancer, and kidney and adrenal gland cancers; RFA is although a surgeon can also do so. also being investigated as a treatment option for many If general anesthesia is not used, then a local anesthetic other cancers is injected into the procedure site to numb the area. A thin, needlelike probe is placed through a puncture or small inWhy performed: Radiofrequency ablation is a minimally cision in the skin and is guided by ultrasound or CT into the invasive, percutaneous procedure that offers an alternative core of the tumor. Once it is in place, thin, hook-shaped treatment option for some patients with tumors that cannot be surgically removed, for patients who are not surgical wires (tines) on the end of the probe extend upon deployment to an area beyond the diameter of the tumor. Localcandidates because of comorbid conditions or other risk ized radiofrequency energy is transmitted through the factors, or for those who desire a less invasive treatment. 1028
Salem Health: Cancer probe, which is attached to a radiofrequency generator. Energy is applied for ten to fifteen minutes to each targeted area, thereby heating and destroying the tissue. The temperature of the applied energy is carefully controlled; beyond 60 degrees Celsius, cells begin to die, resulting in an area of tissue death surrounding the probe. The probe may be deployed more than once for tumors larger than 3 centimeters. Multiple tumors may be treated during the ablation procedure. A small region of normal cells around the tumor (margin) is also heated and destroyed with the goal of eradicating cancer in surrounding tissues. The procedure lasts from two to four hours. After the procedure: The RFA probe is removed and pressure is applied to the insertion site to prevent bleeding. No stitches are needed unless a small incision was made. A small sterile dressing (bandage) will cover the insertion site. The patient may need to stay in bed from one to six hours after the procedure to prevent bleeding. Most patients stay in the hospital overnight for observation after the procedure, but some patients go home the same day of the procedure. The patient may experience discomfort for two to three days afterward. Pain medication may be prescribed, or the patient may take acetaminophen (Tylenol) to relieve discomfort as needed. The patient should not drive or operate machinery for eight hours after the procedure. Within twenty-four hours, the patient is usually able to return to light activity but should avoid vigorous physical activity and heavy lifting after the procedure, as directed by the physician. The average recovery time is from three to seven days, after which the patient may resume regular activities. The recovery time for radiofrequency ablation is much faster than that for surgical treatment, which can take from two to three months for full recovery. Patients usually have a follow-up CT or magnetic resonance imaging (MRI) scan one week after the procedure to evaluate the effectiveness of the treatment. Thereafter, follow-up CT scans and blood tests are performed every three months or more frequently, based on the patient’s condition. Risks: The risks of radiofrequency ablation vary in relation to the type of cancer being treated and the area that is being ablated. For example, the risks of RFA applications for lung cancer include pleural effusion and pneumothorax. The risks of RFA applications for liver cancer include portal vein thrombosis, liver abscess, or acute renal insufficiency. The physician performing the procedure will discuss the potential risks of the procedure with the
Radiofrequency ablation patient, depending on the type of cancer that is being treated. The rate of overall complications is 1 to 4 percent, according to the Society of Interventional Radiology, depending on the disease treated and the patient’s overall health. Most complications are minor and are often relieved on their own without further treatment or intervention. The risk of infection is rare, since there is no open wound associated with the procedure. Results: Radiofrequency ablation is a safe and effective treatment option. Tumors from 1 to 10 centimeters in size can be successfully treated with radiofrequency ablation. A tumor or lesion that is successfully ablated should be reduced in size, or disappear altogether, and show no blood flow on follow-up CT scans. In addition to other cancer treatments, radiofrequency ablation can reduce the size of an inoperable tumor. RFA also can ease tumor-related symptoms, such as flushing, diarrhea, or hypertension, that are associated with some hormone-secreting tumors. Long-term outcomes following radiofrequency ablation are promising. Based on literature reviews, complete tumor ablation with low recurrence rates can be achieved, particularly for smaller cancers. Research is ongoing to evaluate the long-term outcomes of the procedure. For example, RFA in combination with standard radiation therapy has shown two-year and five-year survival rates of 50 and 39 percent, respectively, for the treatment of Stage I and Stage II non-small-cell lung cancer. Research shows the local recurrence rate after RFA of colorectal cancer liver metastases averages less than 10 percent. Recurrence rates are related to the lesion size. Repeat radiofrequency ablations can be performed for patients who develop new or recurrent tumors. Radiofrequency ablation does not preclude patients from undergoing other cancer treatments if necessary. Angela M. Costello, B.S. u
For Further Information Ellis, Lee M., et al. Radiofrequency Ablation for Cancer: Current Indication, Techniques, and Outcomes. New York: Springer, 2003. Patti, Jay W., et al. “Radiofrequency Ablation for CancerAssociated Pain.” The Journal of Pain 3, no. 6 (2002): 471-473. Phillips, Carmen. Radiofrequency Ablation Making Inroads as Cancer Treatment. Bethesda, Md.: National Cancer Institute, 2005. Also available online at http:// www.cancer.gov. Wood, B. J., et al. “Percutaneous Tumor Ablation with Radiofrequency.” Cancer 94, no. 2 (2002): 443-451. 1029
Radionuclide scan u
Other Resources
American Cancer Ablation Centers http:///www.cancerablation.com American Society of Clinical Oncology http://www.asco.org Society of Interventional Radiology http://www.sirweb.org See also Adenoid cystic carcinoma (ACC); Adrenal gland cancers; Bone cancers; Bone scan; Breast cancers; Carcinoid tumors and carcinoid syndrome; Computed tomography (CT) scan; Hyperthermia therapy; Liver cancers; Lung cancers; Prostate cancer; Virus-related cancers.
u Radionuclide scan Category: Procedures Also known as: Nuclear medicine scan Definition: A radionuclide scan is the detection of electromagnetic radiation, usually gamma rays, emitted from an injected radioactive tracer that has been taken up by an organ in the body to be studied, with the goal of producing an image. The most common radioisotope used is technetium 99m, whose gamma rays are absorbed by a sodium iodide crystal detector. The radiation absorbed by this detector is used to generate an image that is interpreted by a radiologist or nuclear medicine physician. The exceptions are positron emission tomography (PET) scanning, which uses positron emission; gallium scanning, which uses gallium as the radionuclide; and some thyroid imaging, which uses iodine. Cancers diagnosed: Virtually all types of cancer, especially metastases Why performed: A radionuclide scan is used to diagnose primary and secondary cancer (bone scan, iodine scan, PET scan) and to diagnose various ailments, including but not limited to the following: hypothyroidism or hyperthyroidism (thyroid scan), bone fractures and bone infection (bone scan), kidney obstruction (renal scan), inflammatory disorders such as sarcoid and fever of unknown origin (gallium scan), cardiomyopathy multiple uptake gated acquisition (MUGA scan), coronary artery disease (cardiac single photon emission computed tomography, or SPECT) pulmonary embolus (lung scan), and Alzheimer’s disease (brain SPECT). 1030
Salem Health: Cancer Patient preparation: The preparation for a radionuclide scan is minimal to none; the scan is usually performed as an outpatient procedure. For some procedures, the patient may be asked to fast several hours prior to the scan. Steps of the procedure: The radioisotope is prepared by the technologist and injected into a peripheral vein by the radiologist or nuclear medicine physician. The patient is then placed supine on a table under a gamma camera that houses the detectors. The scan time is usually about one hour. After the procedure: The scan is generated by the computer attached to the camera and read by the radiologist the same day. The patient will need to contact his or her doctor for the radiologist’s report and any follow-up therapy. Risks: The risks of this type of scan include minor pain or bruising at the injection site. If the patient is pregnant, then the scan should be avoided if possible, since the radiation dose, although small in most cases, is not negligible. Radioactive iodine should not be administered to a pregnant patient because of risk to the fetus. Results: The scan results are dependent on the type of scan performed and the reason for the study. Debra B. Kessler, M.D., Ph.D. See also Appendix cancer; Bone scan; Electromagnetic radiation; Gallium scan; Imaging tests; Ionizing radiation; Nuclear medicine scan; Positron emission tomography (PET); Thyroid cancer.
u Radiopharmaceuticals Category: Chemotherapy and other drugs ATC code: V10 Definition: Radiopharmaceuticals are a class of therapeutic drugs that carry a radioactive isotope in trace quantities. These drugs deliver radiation to kill a targeted region of malignant cells. Cancers treated: Various cancers metastasizing to bone tissues, especially prostate cancer and thyroid cancer, Bcell non-Hodgkin lymphoma, and polycythemia vera Subclasses of this group: Radioisotopes of iodine, phosphorous, rhenium, samarium, strontium, and yttrium Delivery routes: These drugs are administered intravenously, orally in capsule or liquid form, or through a direct injection to the site of cancer, on an inpatient or outpatient basis, depending on the specific drug, the type of cancer,
Salem Health: Cancer
Radiopharmaceuticals
Common Radiopharmaceuticals Used in Cancer Therapy Drug
Brands 131
Iodine 131 ( I), sodium iodide
Delivery Mode Cancers Treated Oral
Thyroid cancer
Phosphorus 32 ( P), sodium phosphate, chromic phosphate
Oral, IV
Polycythemia vera; bone metastases; cancers causing malignant ascites, pleural effusion, pericardial effusions, and brain cysts
Rhenium 186 (186Re) HEDP
IV
Bone metastases; breast cancer
32
153
Samarium 153 ( Sm) EDTMP
Quadramet
Injection
Bone metastases
Strontium 89 ( Sr), strontium chloride
Metastron
Injection
Bone metastases
Yttrium 90 (90Y) ibritumomab tiuxetan
Zevalin
IV
B-cell non-Hodgkin lymphoma
89
and its location. When possible, these drugs are best delivered directly to the tumor site to limit damage to normal cells. How these drugs work: Initially, radiopharmaceuticals were developed to diagnose various medical problems, including tumors. Using radiographic imaging, nuclear medicine specialists detect the radiation emitted by these drugs and track their activity within an organ. Since the 1980’s, the role of radiopharmaceuticals has been expanded to palliation and therapy of metastatic cancers. In this case, a slightly larger amount of the radioactive isotope is used to destroy a group of cancerous cells by interfering with cell division. Instead of photons (used for imaging), the drugs emit beta particles and gamma rays that damage the machinery needed for mitosis. The radioactive isotope is attached to a carrier molecule that is capable of targeting a specific organ or group of cells. For example, radiopharmaceuticals for bone cancer therapy have a mineral-like carrier molecule taken up by bone tissues. Radiopharmaceuticals for specific organs may have a monoclonal antibody that recognizes the cell surface receptors of certain tissue cells. Once the drug reaches its target area, the isotope emits radiation slowly over short distances. The half-life, or time required for half of the radiation to be emitted, for these drugs is two to fifty days, depending on the isotope. In almost all cases, radiopharmaceuticals are used when chemotherapy has failed, or in conjunction with secondline chemotherapy. Radiopharmaceuticals are especially helpful in cancers that have metastasized to neighboring bones, such as prostate and thyroid cancers. Studies have shown that these drugs are valuable in palliative care for patients experiencing pain from cancerous bone tissue, resulting in better disease management and improved quality of life.
Side effects: The side effects of radiopharmaceuticals vary depending on the specific radioactive isotope, its dosage, and the individual patient’s physical condition. An excessive dose of these drugs may result in toxicity that affects normal cells as well as malignant cells, which could lead to an intensification of the cancer. The most common side effect of radiopharmaceuticals, however, is a decrease in the patient’s white blood cell and platelet counts. Other common side effects include black or bloody stools, coughs, fevers or chills, back or side pain, difficulty in urination, unusual bleeding or bruising, and nausea and vomiting. Less common side effects include bone pain and irregular heartbeat. Patients who take iodine 131 for thyroid cancer may also experience loss of taste and tenderness in the salivary glands and neck. Since children and older adults are particularly sensitive to radiation, they may experience more side effects during and after treatment with radiopharmaceuticals. Bharat Burman, B.A. u
For Further Information Ballantyne, Jane C., ed. The Massachusetts General Hospital Handbook of Pain Management. 3d ed. Philadelphia: Lippincott Williams & Wilkins, 2006. Leibel, Steven A., and Theodore L. Phillips, eds. Textbook of Radiation Oncology. 2d ed. Philadelphia: Saunders, 2004. Parker, R. G., N. A. Janjan, and M. T. Selch. Radiation Oncology for Cure and Palliation. New York: Springer, 2003.
u
Other Resources
Radiation Oncology Online Journal http://www.rooj.com/default.htm 1031
Radon Society of Radiopharmaceutical Sciences http://www.srsweb.org See also Bone cancers; Chemotherapy; Imaging tests; Non-Hodgkin lymphoma; Nuclear medicine scan; Prostate cancer; Radiation oncology; Thyroid cancer; X-ray tests.
u Radon Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1994 Also known as: Radon-222, thoron (radon-220), actinon (radon-219) Related cancers: Lung cancer Definition: Radon is an invisible, odorless, radioactive gas produced naturally from uranium in rocks and soil. Except for areas rich in uranium-ore deposits, radon is usually present at low levels in water, soil, and outdoor air. It decays spontaneously to form solid radioactive products called radon daughters that emit ionizing radiation, mostly as alpha particles and gamma radiation. Radon gas may seep into buildings from underlying soil and accumulate at dangerous levels in indoor spaces. Its levels can be measured by using radon test kits. Exposure routes: Inhalation, ingestion Where found: Uranium mines and mills, hard-rock mines, phosphate mines, granite formations, groundwater, soil, air, building materials At risk: Workers in uranium mining and milling, workers in iron-ore and fluorite mining, general population exposed to indoor radon levels of 4 picoCurie per liter (pCi/L) or higher Etiology and symptoms of associated cancers: Radon is the second leading cause of lung cancer after cigarette smoking and accounts for 15 percent of lung cancers worldwide. Most of the risk to humans is from inhaled radon daughters that can lodge in the lungs and emit energetic particles. Damage to epithelial cells in lung tissue can eventually lead to cancer. For smokers, the risk of lung cancer is even greater because of the synergistic effects of radon and smoking. The deadliest of all cancers, lung cancer has an overall five-year survival rate of less than 15 percent. Radonrelated lung cancers include squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. In its early stages, lung cancer may be asymptomatic or have nonspe1032
Salem Health: Cancer cific symptoms (weight loss, fatigue, and fever). By the time symptoms develop that are suggestive of the disease (chronic coughing, shortness of breath, hoarseness, bloody sputum, difficulty swallowing, wheezing, and chest pain), the cancer has usually spread to other organs. History: Once produced commercially for use in radiotherapy, radon is used mostly in research. Scientists established radon’s carcinogenicity primarily from occupational studies conducted between the 1950’s and 1980’s that revealed high mortality rates from lung cancer among underground uranium miners. In 1984 exposure to radon in buildings came to be recognized as a potential health hazard. In the Indoor Radon Abatement Act of 1988, the U.S. Environmental Protection Agency (EPA) recommended that indoor radon levels not exceed average levels outdoors (about 0.4 pCi/L). This standard is one tenth of the recommended safety level for homes. Anna Binda, Ph.D. See also Air pollution; Benzene; Bronchoalveolar lung cancer; Carcinogens, known; Carcinogens, reasonably anticipated; Ionizing radiation; Lung cancers; Occupational exposures and cancer; Risks for cancer.
u RB1 gene Category: Cancer biology Also known as: Retinoblastoma 1 (including osteosarcoma), OSRC Definition: The RB1 gene (a tumor-suppressor gene), which is 180 kilobase pairs with 27 exons, can become inactivated and cause retinoblastoma, a rare childhood cancer of the retina, occurring from in utero to about five years of age. Gene location and function: The retinoblastoma gene, RB1, is on chromosome 13q14.2. This ubiquitously expressed gene codes for a 110 KDa tumor suppressor (pRB), which regulates cell division. The retinoblastoma protein regulates the progression of cells through the cell cycle and the exiting of differentiating cells from the cell cycle. This protein controls cell cycle by sequestering transcription factors and by deacetylating histones, involved in gene silencing. To lose the tumor-suppressor ability, both copies of the RB1 gene must be mutated. Individuals with an inherited form of retinoblastoma have a germ-line mutation of one RB1 gene. During development, the second copy of the RB1 gene is mutated; control of the cell cycle is lost, and tumors develop. These tumors may be in both eyes. Other individuals have sporadic retinoblastoma in
Salem Health: Cancer which mutations occur in the same somatic cell to inactivate both copies of the RB1 gene. Sporadic retinoblastoma is often in only one eye. RB1 gene inactivation: Causes of RB1 gene inactivation include chromosome rearrangements of the 13q14 region; nucleotide changes, loss of heterozygosity (loss of the normal copy); and CpG hypermethylation in the RB1 promoter region (which silences the gene). Molecular screening: Methods to screen for RB1 gene mutations include multiplex polymerase chain reaction (PCR) sequencing of the gene, a protein truncation test, and methylation analysis. The usual clinical screening for retinoblasoma requires examination of the eyes under anesthesia. Molecular screening could eliminate anesthesia-related risks and reduce the financial and psychological costs of clinical screening. Individuals without germline RB1 mutations will not need the clinical screening. Fetuses that have highly penetrant germ-line mutations could be delivered early and treated sooner to save their vision. People with inherited forms of retinoblastoma (have one defective RB1 gene) have an increased risk of developing other cancers, such as those of the bladder, pineal gland, bone, and skin. Incidence: Retinoblastoma accounts for 3 percent of cancers in children under the age of fifteen. The frequency of retinoblastoma is about 1 in 20,000. About 60 percent of those with retinoblastoma have RB1 mutations only in the tumor and not in other cells. Some 40 percent of retinoblastoma cases are hereditary. Of hereditary cases, 90 percent are due to new mutations occurring near the time of conception; 10 percent are due to a mutation inherited from a parent. Susan J. Karcher, Ph.D. See also Cancer biology; Childhood cancers; Fibrosarcomas, soft-tissue; Oncogenes; Pineoblastomas; Retinoblastomas; Simian virus 40; Tumor-suppressor genes.
u Receptor analysis Category: Procedures Also known as: Receptor status test Definition: Receptor analysis refers to diagnostic testing procedures carried out on cells or tissues to determine the abundance or functional integrity of specific receptors. Cancers diagnosed: Breast cancer, colorectal cancer, prostate cancer, lung cancer, leukemia
Receptor analysis Why performed: Many factors that stimulate cell growth start the mitogenic cascade by binding to specific cellular receptors, and one of the hallmarks of cancer is cell growth in the absence of these factors. This observation points to the critical role that receptors play in tumor cell growth and provides the basis for selecting among drug regimens that target receptor-signaling pathways. Breast cancer is the most prominent tumor type in which receptor analysis plays a role, but abnormal growth factor receptors may also be a feature of other solid tumors (colorectal, prostate, lung) and some hematologic (blood) malignancies. Patient preparation: Tissue samples are required and are obtained as part of tumor resection surgery or biopsy. Procedures done under general anesthetic require an overnight fast. Receptor analysis is performed on tumor tissue that is removed, and the patient requires no special or additional postoperative care. Sample collection in leukemia and lymphoma patients is by a simple blood draw, which requires no fasting or special postvenipuncture care. Steps of the procedure: After the appropriate tumor tissue samples are collected by the surgeon or phlebotomist, receptor analysis proceeds by fixing and processing the tissue for immunohistochemistry (IHC) or deoxyribonucleic acid (DNA) sequence analysis. IHC involves placing a very thin slice of tumor on a microscope slide and incubation with antibody preparations that react with the receptors of interest. After a washing step, other reagents are added that bind to the antireceptor antibodies and lead to chemical reactions that produce a visible color in cells that have the receptors. Pathologists then examine the tissue to determine the percentage of tumor cells that express the receptor. In breast cancer, receptors for estrogen and progesterone are routinely determined by IHC, as is the orphan receptor HER2/neu (Erb B2). IHC is also used to determine androgen receptor expression in prostate cancer. In lung and colorectal cancer, DNA sequence analysis is done to characterize mutations in the epidermal growth factor receptor (EGFR). In suspected lymphoproliferative disorders, analysis of the T-cell receptor gene by polymerase chain reaction can be used to determine monoclonal expansion (a sign of malignancy). After the procedure: The operative or biopsy site is kept clean and dry to avoid infection. No special instructions regarding receptor analysis are required. Risks: The risks and side effects of the sample acquisition procedure may be significant; however, receptor analysis itself carries no additional risk to the patient. Some assays for the estrogen receptor have large interlaboratory vari1033
Reconstructive surgery ability and high false negative rates for tumors with low receptor expression. Results: In general, retention of normal receptor status by malignant cells is a favorable prognostic sign and forms the basis for a range of endocrine-based therapeutic options. In breast cancer patients, 25 to 35 percent of patients are expected to have amplified HER2/neu receptors, and a humanized monoclonal antibody to HER2 overexpressing breast cancer cells inhibits growth of the cells. The antibody trastuzumab (marketed as Herceptin) increases the clinical benefit of first-line chemotherapy in metastatic breast cancer that overexpresses HER2. Breast cancers that express estrogen and progesterone receptors may grow in response to these hormones, and patients may therefore benefit from antiestrogen drugs such as tamoxifen. In prostate cancer cells, androgen receptors (ARs) are often overexpressed, and loss of the receptors is an unfavorable sign. AR-positive prostate cancer patients can be treated with leuprolide, which acts at the pituitary to decrease the secretion of gonadotropins. Lower gonadotropin levels result in lower androgen levels, which slows the growth of AR-positive tumor cells. Tumors that are found to overexpress the EGFR may be treated with cetuximab, a monoclonal antibody that competitively inhibits the receptor, or with small molecules that inhibit the kinase activity of the receptor. Tumors can express a wide variety of other growth factor receptors, notably those for insulin-like growth factor I (IGF-I) and for vascular endothelial growth factor (VEGF). Inhibiting these receptors with specific compounds is a promising area of cancer research. John B. Welsh, M.D., Ph.D. u
For Further Information Carpenter, G., ed. The EGF Receptor Family: Biologic Mechanisms and Role in Cancer. Amsterdam: Elsevier Academic Press, 2004 Chang, J., et al. “Prediction of Clinical Outcome from Primary Tamoxifen by Expression of Biologic Markers in Breast Cancer Patients.” Clinical Cancer Research 6 (2000): 616-621. Chen, W. Y., and G. A. Colditz. “Risk Factors and Hormone-Receptor Status: Epidemiology, Risk-Prediction Models and Treatment Implications for Breast Cancer.” Nature Clinical Practice Oncology 4 (2007): 415423. Schally, A. V., and A. M. Comaru-Schally. “Hypothalamic and Other Peptide Hormones.” In Holland-Frei Cancer Medicine 7, edited by D. W. Kufe et al. Hamilton, Ont.: BC Decker, 2006. 1034
Salem Health: Cancer Sequist, L. V., et al. “Molecular Predictors of Response to Epidermal Growth Factor Receptor Antagonists in NonSmall-Cell Lung Cancer.” Journal of Clinical Oncology 25 (2007): 587. Slamon, D., et al. “Use of Chemotherapy Plus a Monoclonal Antibody Against HER2 for Metastatic Breast Cancer That Overexpresses HER2.” New England Journal of Medicine 344 (2001): 783-792. Taube, S. E., et al. “Cancer Diagnostics: Decision Criteria for Marker Utilization in the Clinic.” American Journal of Pharmacogenomics 5 (2005): 357-364. Wang, Y., et al. “Inhibition of the IGF-I Receptor for Treatment of Cancer: Kinase Inhibitors and Monoclonal Antibodies as Alternative Approaches.” Recent Results in Cancer Research 172 (2007): 59-76. See also Androgen drugs; Antiestrogens; Biopsy; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Bronchial adenomas; Colorectal cancer; Colorectal cancer screening; Epidemiology of cancer; HER2/neu protein; Hormone receptor tests; Leukemias; Lung cancers; Lymphomas; Medical oncology; Monoclonal antibodies; Oncology; Progesterone receptor assay; Prostate cancer; Rectal cancer; Risks for cancer.
u Reconstructive surgery Category: Procedures Also known as: Plastic surgery, cosmetic surgery Definition: Reconstructive surgery is surgery to rebuild areas lost as a result of cancer or cancer treatment, as well as injury. Cancers treated: Many different types of cancers, especially breast and skin cancers Why performed: Reconstructive surgery may be performed to correct problems caused by cancer or cancer treatment. It is often performed to restore better functioning to the affected area. It can also be performed for cosmetic reasons. When it is done for cosmetic reasons, it is usually performed to restore a more symmetrical appearance, to reduce the signs left by cancer and cancer treatment, and to improve self-esteem. Patient preparation: Patient preparation depends in large part on the procedure that is being done. Preparation before surgery generally includes not eating or drinking any fluids for a certain number of hours before the surgery, stopping certain medications such as blood thinners, or be-
Salem Health: Cancer ginning to take medications such as antibiotics to help prevent infection. The surgeon and the surgeon’s health care team will provide the patient with the necessary information about what to do, and what not to do, in the hours, days, and weeks before the surgery. In some cases, mental health support may be suggested for before the surgery, as well as afterward, if the surgery is going to make a great change in the individual’s appearance. Steps of the procedure: The steps of reconstructive surgery will vary depending on the type of surgery. For many types of surgery, there will be more than one option, and the surgeon will decide which one to use based on the desires of the patient, the patient’s health level, body type, and other factors. Most reconstructive surgery involves using skin, fat, muscle, or tissue from one area of the body and moving it to another location to reconstruct the desired area. Sometimes prosthetics are used in addition to the material from another area of the patient’s body. For example, one possible method of breast reconstruction involves using some tissue from the patient in addition to an implant made of saline. Five main types of procedures are used during cancer treatment and afterward. The first type is a simple closure of the wound area, in which the wound created by the removal of cancerous tissue is closed using sutures. This generally allows for healing with minimal scarring and a coloration that matches the surrounding skin. If the area removed is too large to be closed using sutures, then a skin graft might be used. In this procedure, skin is removed from another site on the patient’s body and is placed over the area that needs to be closed. A donor site will usually be selected for the best possible match of coloration to the recipient area, and minimal visibility. When more than just skin is desired, a local flap may be used. The surgeon will take skin and tissue from an area next to the site of the wound and move it over the wound. The flap remains connected to its original surroundings by veins and arteries. If a local flap is not available or appropriate for some reason, then the surgeon may decide to use a pedicle flap, a section of tissue that is removed from one area but left attached to the blood supply in that area. The flap is anchored to the recipient site with its original source of blood still intact. The other alternative is to use a free flap. A free flap is completely removed from the donor site, including the severing of all arteries and veins. The flap is then moved to the recipient site and connected. This is generally a longer and more complex surgery than a local or pedicle flap, be-
Reconstructive surgery cause the surgery team must use microsurgery to connect the flap to the adjacent area so that blood can flow in and out of the tissue, keeping it alive. After the procedure: The aftercare for reconstructive surgery will vary depending on the type of procedure and the area of the surgery. Usually there will be a hospital stay of short to moderate duration after the procedure, although some more minor procedures may be performed on an outpatient basis. Healing will take varying lengths of time depending on the type of procedure used and the location on the body of the surgery. For most reconstructive surgeries, as with most surgeries, it will take a few weeks or longer for the patient to return to their normal level of activity. Some reconstructive surgeries can be followed up at a later time, generally after the wound has mostly or completely healed, with additional cosmetic procedures. For example, after breast reconstruction, the nipple can be reconstructed at a later time, after the breast itself has healed. Additionally, tattooing of the nipple and areole can be done at a later time to try to match the existing breast as nearly as possible. Risks: There are risks associated with any kind of surgical procedure. The risks of reconstructive surgery are generally low when the procedure is performed by a certified reconstructive surgeon who is experienced in the procedure. A patient who has questions about the surgeon’s training, qualifications, or experience with the type of procedure being considered should never hesitate to ask. The risks associated with reconstructive surgery are generally the same as those associated with any other type of surgery, including excessive bleeding, infection, pooling of blood beneath the skin, bruising, and problems with wound healing. Procedures that are done under general anesthesia have the risks associated with general anesthesia, including changes in blood pressure or heart rhythm. Complications from general anesthesia are generally rare, although certain diseases and conditions can increase these risks. Reconstructive surgery is generally considered to be relatively low risk for individuals who are otherwise in reasonably good health. Certain diseases and conditions can interfere with the healing process or can cause an increased risk of complications. Individuals who have high blood pressure, diabetes, or immune system problems or who have conditions that affect the blood’s ability to clot may be at increased risk of complications. Individuals who smoke may be required to quit smoking for a few months before the surgery to decrease the likelihood of side effects or complications and to increase the body’s ability to heal effectively. This kind of requirement generally depends on 1035
Rectal cancer
Salem Health: Cancer
the specific surgeon who is doing the procedure. In general, individuals who smoke have a more difficult time healing completely after surgery and may have increased visibility of scars. In addition to the risks associated with any type of surgery, each reconstructive procedure may have its own associated risks. For example, there is a small risk of breast implant rupture associated with breast reconstruction. Individuals should talk carefully with their surgeons and any other health care providers to discuss all the possible risks associated with the specific procedure that they are considering before making a final decision.
cancer; Fibrosarcomas, soft-tissue; Gynecologic oncology; Head and neck cancers; Infection and sepsis; Lip cancers; Orthopedic surgery; Otolaryngology; Psychosocial aspects of cancer; Risks for cancer; Sexuality and cancer; Skin cancers.
Results: Reconstructive surgery is often very successful. It is important, however, for the individual to talk to his or her surgeon about what realistic expectations for the procedure should be, as the results of reconstructive surgery can vary. Nearly all procedures will result in some scarring, which will usually fade with time but never disappears completely. Reconstructive surgeries often cannot change some things with which the individual was unhappy before the cancer. In many cases, the procedure is a large improvement, but the reconstruction is not a 100 percent perfect match because of a number of factors. In cases of skin grafts, the area from which the skin is taken is usually not a perfect match in terms of pigmentation and tone for the area to which it is moved. For breast reconstruction, the reconstructed breast is often a close match, but not a perfect match, of the other breast. The more realistic the expectations of the reconstructive procedure, the more likely the individual is to be satisfied with the results. Helen Davidson, B.A.
Related conditions: Colon cancer
u For Further Information Berry, Daniel J., and Scott P. Steinmann. Adult Reconstruction. Philadelphia: Lippincott Williams & Wilkins, 2007. Kryger, Zol B., and Mark Sisco, eds. Practical Plastic Surgery. Austin: Landes Bioscience, 2007. Park, Stephen S. Facial Plastic Surgery: The Essential Guide. New York: Thieme, 2005. Sarwer, David B., and Thomas Pruzinsky, eds. Psychological Aspects of Reconstructive and Cosmetic Plastic Surgery: Clinical, Empirical, and Ethical Perspectives. Philadelphia: Lippincott Williams & Wilkins, 2006. u
Other Resources
American Society of Plastic Surgeons http://www.plasticsurgery.org See also Aids and devices for cancer patients; Basal cell carcinomas; Breast reconstruction; Exenteration; Eyelid 1036
u Rectal cancer Category: Diseases, symptoms, and conditions Also known as: Colorectal cancer
Definition: The rectum is the last 8 inches of the colon (large intestine). Almost all (98 percent) of rectal cancers are adenocarcinomas. Adenocarcinomas are cancers that begin in cells that line internal organs of the body, in this case, the lining of the rectum. Since the colon and rectum are continuous, cancer may develop in both places simultaneously. Often colon and rectal cancer are talked about together as colorectal cancer because their causes and treatments are similar. Risk factors: Rectal cancer usually develops slowly, so more than 90 percent of newly diagnosed cases occur in people over age fifty. In addition to age, diet is a major risk factor. The link between diet and rectal cancer is well established. Rectal cancer is more likely to develop in people who eat large amounts of animal fats (such as red meat) and saturated vegetable oils (such as corn oil but not olive or fish oils). It has been shown, for example, that Africans who eat mainly a plant-based diet have low levels of colorectal cancer, but when these people move to Western countries and adopt a meat-based diet, their incidence of colorectal cancer rises to the same level as that of other people living in these countries. Other lifestyle factors that increase the risk of rectal cancer include heavy alcohol use, smoking, obesity, and lack of physical exercise. A family history of colorectal cancer or a history of many polyps developing in the colon and rectum, especially at an early age, also increase the risk of rectal cancer. Although risk factors are important screening tools, about three-quarters of people who develop rectal cancer have no specific risk factors. Etiology and the disease process: The exact cause of rectal cancer is unknown, but both genetics and the environment play a role in its development. The cells lining the colon and rectum are replaced about every six days. These cells develop in interior tissue layers and work their way to lining the rectum, after which they stop dividing. Cancer
Salem Health: Cancer develops when these cells continue to divide after reaching the rectal lining. The cells then form tumors that grow into the rectal wall. Researchers have found that cells lining the wall of the rectum must develop at least four genetic defects to become cancerous. Incidence: The American Cancer Society estimates that about 41,400 new cases of rectal cancer occurred in 2007 and that rectal cancer causes about 16,000 deaths annually. The lifetime risk of developing cancer of either the colon or rectum is nearly 6 percent. Rectal cancer is more common in industrialized countries than in developing countries. It affects slightly more men than women and is highest among Jews of Eastern European descent (Ashkenazi Jews). Most people diagnosed with colorectal cancer are over age sixty, although people who are genetically predisposed to the disease may develop it in childhood or early adulthood. Symptoms: Rectal cancer often has few symptoms until the disease becomes advanced. The most common symptoms include changes in bowel activity (constipation or diarrhea), blood in the stool, abdominal pain, a continuous feeling that the rectum is full, and general fatigue. Screening and diagnosis: Abnormal cells gradually become cancerous over ten to fifteen years, so screening is an essential part of prevention and early treatment. Individuals with no specific risk factors should be screened beginning at age fifty, while those with specific risk factors (such as a family history of polyps) should discuss earlier screening with their doctor. A colonoscopy is used to detect polyps (growths) or abnormalities in the rectal lining. If abnormalities are detected, a biopsy (tissue sample) is taken and the tissue examined under the microscope for cancer. An ultrasound of the rectum may also be done to determine how far the cancer has spread. Rectal cancer is evaluated using the four-stage TNM (tumor/lymph node/metastasis) system. Tumors are graded based on their invasiveness, with T1 indicating penetration into the layer below the surface lining and T4 indicating invasion of the tumor into other organs. Lymph nodes (N) are graded for involvement, with higher numbers indicating greater spread of the disease. Metastasis is evaluated as either absent (M0) or present (M1). Combining this information results in cancer stages designated as I (least advanced) to IV (most advanced). Treatment and therapy: Treatment depends on the stage of the cancer. People who have only surgery have a 30 to
Rectal cancer
Age-Adjusted Death Rates for Colorectal Cancer by Race, 2001-2005 Deaths per 100,000 People Race
Men
Women
All races Black White American Indian/Alaska Native Hispanic Asian/Pacific Islander
22.7 31.8 22.1 20.5 16.5 14.4
15.9 22.4 15.3 14.2 10.8 10.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The overall age-adjusted death rate from colorectal cancer was 18.8 per 100,000 people.
50 percent chance of developing additional colorectal cancer. Radiation and chemotherapy used in conjunction with surgery decrease the likelihood of recurrence. Radiation may be used both before and after surgery. Chemotherapy involves administration of multiple antineoplastic drugs. Prognosis, prevention, and outcomes: Survival rates depend on the stage at which the cancer is detected. Five-year survival rates are as follows: Stage I, 72 percent; Stage II, 54 percent; Stage III, 39 percent, and Stage IV, 7 percent. With widespread screening leading to early treatment, survival rates continue to improve. Martiscia Davidson, A.M. u
For Further Information Delaini, Gian D., ed. Rectal Cancer: New Frontiers in Diagnosis, Treatment, and Rehabilitation. New York: Springer, 2005. Levin, Bernard, ed. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: American Cancer Society, 2006. Pochapin, Mark B. What Your Doctor May Not Tell You About Colorectal Cancer: New Tests, New Treatments, New Hope. New York: Warner Books, 2004.
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Other Resources
American Cancer Society All About Colon and Rectal Cancer http://www.cancer.org/docroot/CRI/CRI_2x .asp?sitearea=LRN&dt=10 Colon Cancer Alliance http://www.ccalliance.org 1037
Recurrence National Cancer Institute Colon and Rectal Cancer http://www.cancer.gov/cancertopics/types/ colon-and-rectal See also Abdominoperineal resection (APR); Adenocarcinomas; Adenomatous polyps; Anal cancer; Anoscopy; APC gene testing; Bethesda criteria; Colectomy; Coloanal anastomosis; Colon polyps; Colonoscopy and virtual colonoscopy; Colorectal cancer; Colorectal cancer screening; Colostomy; Computed tomography (CT) scan; Crohn disease; Cyclooxygenase 2 (COX-2) inhibitors; Desmoid tumors; Diarrhea; Digital rectal exam (DRE); Diverticulosis and diverticulitis; DPC4 gene testing; Duodenal carcinomas; Endorectal ultrasound; Enteritis; Enterostomal therapy; Epidermoid cancers of mucous membranes; Family history and risk assessment; Fecal occult blood test (FOBT); Gardner syndrome; Gastric polyps; Gastrointestinal cancers; Gastrointestinal complications of cancer treatment; Gastrointestinal oncology; Hemorrhoids; Hereditary cancer syndromes; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; MLH1 gene; MSH genes; Nuclear medicine scan; Peutz-Jeghers syndrome (PJS); PMS genes; Polyps; Rectal cancer; Small intestine cancer.
u Recurrence Category: Diseases, symptoms, and conditions Also known as: Return of cancer, metastases Related conditions: Metastasis Definition: When cancer returns after a period of remission, it is called a recurrence. Cancer can come back months or years after the original diagnosis. Risk factors: An oncologist will assess the patient’s risk of recurrence based on several factors. Tumor cells are graded based on how closely they resemble normal cells when viewed under a microscope. The less like normal cells, the higher the grade and the greater the likelihood the cancer will recur. If cancer is found in the lymph nodes, the risk of recurrence is greater, even if the cancerous lymph nodes are removed. Etiology and the disease process: A recurrence happens because cancer cells were left behind when the patient was first treated. These cells may have remained at the original site or may have traveled to another location in the body. 1038
Salem Health: Cancer Incidence: The incidence of recurrence varies greatly for different cancers and with the presence or absence of risk factors. Symptoms: Some general symptoms may indicate that cancer has recurred: for example, a new lump or swelling somewhere in the body, back pain, shortness of breath, weight loss, pain or weakness in the arms or legs, or a new onset of headaches. The specific symptoms of a recurrence will depend on the type of cancer. Screening and diagnosis: Based on the oncologist’s assessment of the risk of recurrence, a patient will be given a schedule for follow-up care. Such care will include regular doctor visits and tests specific to the type of cancer previously diagnosed. Treatment and therapy: Treatment will vary according to the type of cancer and how widespread the recurrence is. Surgery is an option for some types of cancer, and most patients will receive some form of chemotherapy, radiation therapy, or hormonal therapy. The drugs used to treat a recurrence are frequently different from the drugs used to treat the original cancer. Patients with advanced cancer may want to consider entering a clinical trial to evaluate an experimental therapy. Prognosis, prevention, and outcomes: Prognosis after a recurrence of cancer will depend on a number of factors, including whether the cancer returned in the same location in the body (local recurrence) or at another site (distant recurrence). Generally speaking, the prognosis is poorer for cases of distant recurrence. A recurrence cannot always be prevented; however, abiding by recommended follow-up care guidelines are the best way to ensure that any recurrence will be caught early. Melanie Hawkins, B.S.N., R.N., O.C.N. See also Chemotherapy; Clinical trials; Cobalt 60 radiation; Hormonal therapies; Lumps; Nutrition and cancer prevention; Oncology; Risks for cancer; Staging of cancer; Weight loss.
u Rehabilitation Category: Procedures Definition: Rehabilitation aims to treat the physical, emotional, and psychological limitations often experienced by cancer patients. The goal of rehabilitation is to help the individual with cancer participate as fully and independently as possible in daily life. During rehabilitation, the cancer
Salem Health: Cancer
Rehabilitation
Rehabilitation enables the patient with cancer to participate as fully and independently as possible in daily life. (Digital Stock)
patient works to regain skills and abilities that were lost through the effects of cancer or cancer treatment. Cancers treated: All types of cancers beginning before, during, or after cancer treatment Why performed: The specific goals of rehabilitation are different for each individual. In general, the goal of rehabilitation is to allow the individual to function as fully and independently as possible. The rehabilitation team will include different allied health professionals depending on the goals and needs of the individual. Often the rehabilitation team will include many health professionals, such as a physical therapist, an occupational therapist, a rehabilitation nurse, a psychologist or psychiatrist, a nutritionist or registered dietician, the individual’s physician or oncologist, pain management specialists, a case manager, and home health workers. The rehabilitation team will work together with the patient and the patient’s family and loved ones to help the patient regain as high a degree of functioning as possible. The specific activities included in the rehabilitation plan
usually comprise dressing, bathing, cooking, eating, and other activities of daily living. Some individuals may receive help recovering the ability to drive, take public transportation, or other aspects of mobility. For individuals whose job skills were affected by cancer or cancer treatment, regaining the skills necessary to return to a job is usually considered a high priority. An occupational therapist or other member of the rehabilitation team may help the individual determine what skills are required, work to improve those skills, and seek ways to modify the employment environment so that the individual may return to work sooner. The individual may have goals in addition to those necessary for return to employment or for daily living. Many recreation and leisure activities that were formerly pleasurable may become difficult or impossible because of cancer or cancer treatment. Rehabilitation therapists listen to the patient to address additional goals, such as the ability to go camping or sailing, play sports, or play music. Patient preparation: Before beginning to meet with a rehabilitation specialist, it may help the patient to consider 1039
Rehabilitation specific goals for rehabilitation. Making a list of activities or skills on which the patient would like to work can help the rehabilitation therapist look beyond the activities of daily living to other activities important in that individual’s life. Goals can be very specific, such as being able to knit or type again, or more general, such as being able to play with children or grandchildren. The patient preparation required before the individual rehabilitation sessions will vary depending on the type of therapy. The rehabilitation specialist will give the patient specific information about what steps to take before a session, which may include things such as doing gentle stretches to warm up or even mentally preparing to meet the challenges that rehabilitation therapy provides. Steps of the procedure: The steps of rehabilitation are very individualized. They depend on the type of therapy that is being done and on the specific needs and goals of the patient. Rehabilitation therapy often breaks down the goal activity or skill into smaller parts or steps and then works on one step at a time. For example, an occupational therapist who is helping a cancer patient regain the ability to feed himself may work on the action of bringing the food to the mouth as one activity, the act of using a spoon or fork to scoop food as a separate activity, and the act of cutting food as yet a separate skill. As these different aspects of the skill of feeding oneself are mastered, they can be combined into more complex sequences of actions. Another way of approaching rehabilitation can be from the standpoint of increasing the day-to-day abilities of the patient in the affected areas. In this case, the rehabilitation therapist might focus on getting food from the plate or bowl and into the mouth using the hands and then slowly add skills, such as beginning to help the patient use a spoon, then a fork, and then working on cutting food. Rehabilitation also often helps to identify assistive devices that individuals can use to help them accomplish various tasks. In some cases, these devices are only necessary for a short time; in other cases, they will be used by the individual for the rest of his or her life. For instance, a rehabilitation specialist may help an individual regain the ability to walk using a walker, or may help an individual who had a leg amputated master the use of a prosthetic leg. After the procedure: The steps after rehabilitation will vary depending on the type of therapy performed. After therapy that involves physical activity or exercise, a series of stretches and cooldown activities is usually performed. Often the rehabilitation therapist will assign the individual exercises or activities to practice each day, sometimes several times a day, before the next session. This approach can help to ensure that the progress made during the session is 1040
Salem Health: Cancer maintained until the next session. The patient’s family members or caregivers may be shown how to help the individual complete these exercises. Rehabilitation therapy may be continued for weeks, months, or even longer. When the therapy has ended, the therapist may give the patient a list or set of exercises or activities to continue to do to help keep up the skills that were gained during therapy, or to help the patient continue to make improvements. Risks: The risks associated with rehabilitation are generally mild but are different for different forms of rehabilitation therapy. There are some risks that during physical therapy individuals may strain or pull muscles, or otherwise overextend or injure themselves, especially if the proper stretching and warmup routine is not followed before the therapy. Risks of occupational therapy and other forms of rehabilitation therapy that involve the patient working to perform certain actions or movements, such as the movements of dressing or bathing, may also result in strain or injury if the individual pushes too hard to accomplish the task before his or her body is ready. An individual working on regaining the ability to walk may fall if not carefully monitored. Generally, these and other physical risks from rehabilitation are very low if the therapy is overseen by a qualified health professional. There may also be some emotional risks relating to rehabilitation. The issues discussed with a psychologist or psychiatrist can often be painful or upsetting as they help the individual with cancer work through the fear, uncertainty, and feelings of hopelessness that often accompany cancer diagnosis and treatment. Although discussions with a psychologist or therapist can often be very upsetting, they can usually help the patient deal effectively with these new emotions. Results: The results of rehabilitation are usually very positive. With consistent effort by the patient and the rehabilitation team, many skills and abilities that have been lost can be regained. Many people can return to jobs and activities in which they would not have been able to participate without rehabilitation. Psychological and emotional rehabilitation is usually effective at helping the individual regain a positive outlook and overcome the fear and unhappiness often associated with cancer and cancer treatment. A comprehensive rehabilitation plan that involves many different allied health professionals, as well as family, friends, or other caregivers, is often especially effective. It is important for the rehabilitation team to help the patient develop a realistic view of the amount of work required by rehabilitation, the length of time that it will take to reach rehabilitation goals, and what rehabilitation goals
Salem Health: Cancer are likely to be realistic overall. Having realistic expectations can help reduce frustrations and negative feelings that may occur during the rehabilitation process as hurdles are met and overcome. Helen Davidson, B.A. u For Further Information Davis, Carol M., ed. Complementary Therapies in Rehabilitation. 2d ed. Thorofare, N.J.: Slack, 2004. Galvin, Jan C., and Scherer Marcia J., eds. Evaluating, Selecting, and Using Appropriate Assistive Technology. Austin, Tex.: Pro-Ed, 2004. Macky, Hazel, and Susan Nancarrow. Enabling Independence: A Guide for Rehabilitation Workers. Malden, Mass.: Blackwell, 2006. Stidwill, Howard. Exercise Therapy and the Cancer Patient: A Guide for Health Care Professionals and Their Patients. Belgium, Wisc.: Champion Press, 2005. u
Other Resources
National Rehabilitation Information Center http://www.nairc.com See also Aids and devices for cancer patients; Amputation; Cancer care team; Case management; Cognitive effects of cancer and chemotherapy; Cordectomy; Exercise and cancer; Head and neck cancers; Home health services; Limb salvage; Nutrition and cancer treatment; Occupational therapy; Pain management medications; Self-image and body image; Transitional care.
u Relationships Category: Social and personal issues Definition: Cancer can affect a person’s relationships with others in many significant ways. The diagnosis can bring fear, anxiety, concern for the future, sadness, confusion, and many other emotions. Any time of high emotion and stress can cause tension in even the strongest relationships. During treatment there may be changing roles and responsibilities at home and at work that can lead to stress and tension. Even after successful treatment, when life may be returning to normal, changes in roles and expectations can lead to frustration and conflict. Although cancer can put an enormous strain on relationships, it can also make them stronger, as families work together, priorities and values are reassessed, and friends and families show their love and support for one another.
Relationships Spouses: A cancer diagnosis can put a lot of strain on a relationship. There may be fear, anxiety, and sadness on the spouse’s part as the person is forced to contemplate the possibility of losing the individual who has been diagnosed. Roles within the relationship may change, as the person who was once the primary caregiver may now be the one who receives the caregiving. Also, the spouse may face a huge increase in responsibilities as that person assumes the tasks of taking the partner to treatment or to various doctors’ offices, being supportive, and doing any household tasks the individual with cancer can no longer do. If the patient can no longer work, the spouse may have to work longer hours or take an additional job. Talking about fears, frustrations, and other feelings can be an extremely important part of maintaining a good relationship during cancer treatment. Although a cancer diagnosis can bring strain to a relationship, it can also cause people to reevaluate their priorities and spend more time together, or to remember how important they are to each other. Working together through cancer can be difficult, but it can also bring incredible strength to a relationship. Gay and lesbian couples may have an even more difficult time because medical personnel may not allow them access to their hospitalized partner and may not permit them to make any decisions regarding care, especially if some family members are not aware of the relationship. Finding a cancer care team that is respectful of the relationship and being honest about feelings can help to reduce the impact of some of these possible issues. Children: When a parent has cancer, it can be very difficult for the parent to decide how much to tell children about the cancer itself, treatments the parent may be undergoing, the prognosis, how life for the family may be changing, and all of the other issues that the family will be facing. Deciding what to tell a child depends on a number of factors, including the child’s age and maturity and the parent’s comfort level in talking with the child. Many parents are hesitant to tell children that a parent has been diagnosed with cancer. Often parents do not want the children to worry or be afraid. It is normal for a child to feel upset, confused, or worried when told that a parent has been diagnosed with cancer. However, often if a child is not told, the resulting anxiety and worry will be even worse. Children are aware when something is wrong in the family from a very young age. They can be aware of a parent’s stress or anxiety and may believe that things are much worse than they actually are. Telling a child the truth about the situation in a way that is age appropriate can help quell some fears that are unfounded and also help the child cope with fears and feelings that are realistic. 1041
Relationships
Salem Health: Cancer
The sense of trust that develops between a parent and child is extremely important. If a child finds out about a parent’s cancer diagnosis from another source, it can be difficult or nearly impossible for the parent to regain that sense of trust. It is hard to keep a secret from children if many other people know. Other family members or adults in the child’s life who know about the diagnosis may bring it up. The child may even overhear a parent talking about cancer. Children who find out indirectly may not even let their parents know that they are aware of the cancer but instead may feel alone and try to cope with their fears and sadness on their own. If it is a brother or sister who has been diagnosed with cancer, it may be even more important to let siblings know what is going on in a way that they can understand. This way, parents and other caregivers can help them express their fears and concerns and provide support for their ill sibling. No matter who in the family has been diagnosed with cancer, it can make relationships between children and their parents strained. Children may act out their fears and frustrations in many different ways, including clinging to a parent, withdrawing from the family, being irritable, or acting younger than their age. When parents are under extreme stress and have fears of their own, it can be difficult to maintain a close positive relationship with their children. Allowing children to provide assistance so that they feel they are helping the family and providing truthful information that they can understand can help alleviate some of these pressures. Coworkers: Relationships between coworkers can vary dramatically from person to person and workplace to workplace. Some coworkers are close friends who discuss intimate details of their lives during breaks and after work, and some coworkers discuss only business and never personal subjects of any kind. Because these differences exist before a cancer diagnosis, relationship changes in the workplace may be hard to predict. Some coworkers may have misunderstandings about cancer, such as a belief that it is contagious, which may cause them to react in unexpected ways. Other people may be fearful of talking to the person with cancer for fear of saying the wrong thing. Tension can also occur in the workplace if the person with cancer has to miss a lot of time for treatment or 1042
can no longer perform all of the assigned duties. Even if a coworker does not blame the person with cancer, having an increased workload can be frustrating. Like other relationships, those at work often can benefit from openness and truthfulness. Cancer patients should tell only those people with whom they are comfortable sharing this fact, but often at least their immediate supervisor will need to know so that patients can schedule their work around treatments and follow-up appointments. If cancer patients are comfortable talking to coworkers and letting them know that they appreciate their concern and that it is okay to talk about it, it can help everyone at the workplace improve their relationships and may clear up some misunderstandings. Extended family and friends: When a person has been diagnosed with cancer, relationships with extended family and friends may change dramatically. Some people who were not especially close friends may become invaluable sources of help during the stressful time. Unfortunately, others may draw away from the person with cancer, and might show that they are not as good friends as was once thought. Many people are not sure what to say or how to help. If the person with cancer feels comfortable, letting friends and relatives know ways that they can help, such as picking up a child from school, helping with the housework, or just coming for a visit, can make people feel needed and more comfortable. Helen Davidson, B.A.
The relationships, or bonds with other people, that a cancer patient has may undergo some changes and strains during and after treatment; often they are strengthened. (©Nicholas Sutcliffe/Dreamstime.com)
Salem Health: Cancer u For Further Information Fincannon, Joy L., and Katherine V. Bruss. Couples Confronting Cancer: Keeping Your Relationship Strong. Atlanta: American Cancer Society, 2003. Harpham, Wendy Schlessel. When a Parent Has Cancer: A Guide to Caring for Your Children. New York: Perennial Currents, 2004. Jennings, Lesajean McDonald. A Guide for Men as They Walk Through the Experience of Breast Cancer with the Women in Their Lives: Specifics to Support Emotional and Relationship Health. Auburn Hills, Mich.: Jessies Legacy, 2004. Knox, Sally M. The Breast Cancer Care Book: A Survival Guide for Patients and Loved Ones. Grand Rapids, Mich.: Zondervan, 2004. National Cancer Institute. Taking Time: Support for People with Cancer and the People Who Care About Them. Bethesda, Md.: Author, 2003. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute http://www.cancer.gov The Wellness Community http://www.thewellnesscommunity.org See also Aging and cancer; Anxiety; Breast cancer in men; Breast cancer in pregnant women; Cancer care team; Caregivers and caregiving; Long-distance caregiving; Psychosocial aspects of cancer; Sexuality and cancer; Singlehood and cancer; Stress management; Vasectomy and cancer; Young adult cancers.
u Renal pelvis tumors Category: Diseases, symptoms, and conditions Also known as: Gurnistical tumors Related conditions: Renal cell carcinomas, kidney cancer Definition: Renal pelvis tumors are masses that develop in the center of the kidney and can become malignant (cancerous). Risk factors: Risk factors for renal tumors include smoking, misusing certain pain medicines over an extended period of time, and having certain genetic conditions, such as von Hippel-Lindau disease or hereditary papillary renal cell carcinoma.
Renal pelvis tumors Etiology and the disease process: Renal pelvis tumors develop in the kidney tubule (or renal tubule), which is the portion of the kidney constituting the basic filtration unit of the kidney. Incidence: Renal pelvis tumors affect less than 1 percent of the population, with approximately 40,000 people diagnosed with cancer. It predominantly affects men over the age of fifty-five. Symptoms: Symptoms of renal pelvis tumors include blood in the urine, a noticeable lump in the abdomen, pain in the side or back, weight loss, and anemia. Screening and diagnosis: Diagnosis of renal pelvis tumors is confirmed with a physical exam, urinalysis, and urine cytology tests. The urinalysis determines if abnormalities, such as blood, protein, sugar, and solids, exist in the urine. Urine cytology is a microscopic examination of urine to detect any abnormal cells that have sloughed off the walls of the bladder or kidney and been released in the urine. If necessary, cytoscopy is performed with a very narrow tube with a light and camera inserted through the urethra to examine the inside of the bladder and ureter. Further imaging studies can help determine if the cancer has spread to other layers of the organs or beyond the urinary tract. Tumors found in the collecting duct are transitional or medullary carcinomas. If bladder or kidney cancer is suspected, a physician may order a computed tomography (CT) scan, pyelography, or biopsy. The CT scan provides a three-dimensional view of the urinary tract to determine if any masses or tumors exist. Pyelography involves injecting a special dye into the vein or urethra and examining a series of X rays to determine if abnormalities exist. The biopsy is typically performed during cytoscopy, and abnormal cells can be detected with a microscope. The staging of the disease according to the National Cancer Institute is as follows: • Stage I: The tumor is 7 centimeters (cm) or smaller and is found only in the kidney. • Stage II: The tumor is larger than 7 cm and is found only in the kidney. • Stage III: Cancer is found in the kidney and in one nearby lymph node; or in an adrenal gland or in the layer of fatty tissue around the kidney and may be found in one nearby lymph node; or in the main blood vessels of the kidney and may be found in one nearby lymph node. • Stage IV: Cancer has spread beyond the layer of fatty tissue around the kidney and may be found in one nearby lymph node; or to two or more nearby lymph nodes; or 1043
Report on Carcinogens (RoC)
Salem Health: Cancer
to other organs, such as the bowel, pancreas, or lungs, and may be found in nearby lymph nodes. Treatment and therapy: Renal pelvis tumors that are noncancerous can be closely monitored for an increase in size or for malignant development. If necessary, they can be removed with surgery. Malignant renal tumors do not respond to chemotherapy or radiation therapy, and therefore surgery is required to remove the cancerous tumor. Renal pelvis tumors are sometimes also treated with immunotherapy, which stimulates the patient’s immune system to recognize tumor cells as targets and to attack the malignant tumor cells. This is accomplished by administering therapeutic antibodies to enable the immune system to destroy tumor cells.
Incidence Rates of Kidney and Renal Pelvis Cancer by Race, 2001-2005 Incidence per 100,000 People Race
Men
Women
All races Black American Indian/Alaska Native White Hispanic Asian/Pacific Islander
18.3 21.3 19.5 18.8 17.4 9.1
9.2 10.1 12.7 9.5 9.6 4.6
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The age-adjusted incidence rate from cancer of the kidney and renal pelvis was 23.2 per 100,000 people per year.
Prognosis, prevention, and outcomes: If renal pelvis tumors are treated early, the prognosis is very good. However, because symptoms often go unnoticed, diagnosis is not usually made until the cancer is in later stages, resulting in a mortality rate of nearly 30 percent of people diagnosed with malignant renal tumors. Robert J. Amato, D.O. u For Further Information Figlin, Robert A., ed. Kidney Cancer. Boston: Kluwer Academic, 2003. Kurth, K. H., G. H. J. Mickisch, and Fritz H. Schroder, eds. Renal, Bladder, Prostate, and Testicular Cancer: An Update. New York: Parthenon, 2001. Patel, Uday, ed. Carcinoma of the Kidney. New York: Cambridge University Press, 2008. u
Other Resources
American Cancer Society Detailed Guide: Kidney Cancer http://www.cancer.org/docroot/cri/content/ cri_2_4_1x_what_is_kidney_cancer_22.asp Kidney Cancer Association http://www.kidneycancer.org/ National Cancer Institute Kidney Cancer http://www.nci.nih.gov/cancertopics/types/kidney See also Adrenal gland cancers; Angiogenesis inhibitors; Corticosteroids; Endocrine cancers; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary 1044
papillary renal cell carcinomas; Kidney cancer; Nuclear medicine scan; Smoking cessation; Urinary system cancers; Von Hippel-Lindau (VHL) disease.
u Report on Carcinogens (RoC) Category: Carcinogens and suspected carcinogens Also known as: RoC Definition: The Report on Carcinogens (RoC) is a U.S. government document, issued by the National Toxicology Program (NTP) of the U.S. Department of Health and Human Services (DHHS), which identifies and profiles substances that are known to cause cancer or that are reasonably anticipated to cause cancer in a significant number of persons residing in the United States. It is published every two years by the Department of Health and Human Services to comply with the Public Health Service Act, Section 301(b)(4). The first edition was published in 1980. Content: The RoC lists substances for which there is published scientific evidence establishing a relationship between exposure to the substance and the development of cancer. The substances are categorized as “known to be human carcinogens” or “reasonably anticipated to be human carcinogens” based on human and laboratory animal studies and epidemiological studies. The report presents information on each substance. It identifies regulations and guidelines pertaining to the substance and discusses how they decrease the risk of exposure. All substances nominated for review are included in the report with explanations of why they were included in or excluded from the list.
Salem Health: Cancer
Resveratrol
Review process: The process begins with a substance being nominated for review. Requests for RoC nominations are published in the Federal Registry. Sources include the public, other agencies, and reviews of scientific literature. A nomination is reviewed by several scientific committees within the Department of Health and Human Services. These committees consider background information, additional literature searches, and public comments when making their recommendations. The secretary of the department makes the final review and approval before submitting the report to Congress. Affiliated agencies: Agencies that are involved with the nomination and review process are the Agency for Toxic Substances and Disease Registry (ATSDR), the Consumer Product Safety Commission (CPSC), the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), the National Center for Environmental Health (NCEH), the National Institute for Occupational Safety and Health (NIOSH), the Occupational Safety and Health Administration (OSHA), the National Institutes of Health (NIH), the National Cancer Institute (NCI), and the National Institute of Environmental Health Sciences/NTP (NIEHS/NTP). Limitations: The RoC will not include a substance if exposure is limited to a small number of people. The report does not discuss the benefits of a substance versus its risk of causing cancer. It does not provide the specific conditions under which a substance will cause cancer to develop. The focus of the report is to present technical and scientific information—the supported facts—and not to discuss the many variables involved for cancer to develop. Carol Ann Suda, B.S., M.T. (ASCP), S.M.
Red grapes are a good source of resveratrol, thought to have cancer-preventing properties. (U.S. Department of Agriculture)
Resveratrol has become synonymous with cancer prevention and is thought to have protective antioxidant, antiinflammatory, and life-extending properties.
See also Air pollution; Asbestos; Carcinogens, known; Carcinogens, reasonably anticipated; Cigarettes and cigars; Dioxins; National Cancer Institute (NCI); Occupational exposures and cancer; Pesticides and the food chain.
Cancers treated or prevented: Leukemia, prostate cancer, breast cancer, stomach cancer, colon cancer, pancreatic cancer, thyroid cancer, skin cancer
u Resveratrol
Delivery routes: Oral via food and dietary supplements; significant food sources include red grapes, red wines, red and purple grape juice, berries (including raspberries, blueberries, cranberries, and bilberries), peanuts, and peanut butter
Category: Lifestyle and prevention Also known as: Trans-3,4’,5-trihydroxystilbene, polyphenolic phytoalexin Definition: Resveratrol is a compound manufactured by plants as part of their defense mechanism against disease. These compounds, which belong to the stilbene chemical classification, are also known as polyphenolic phytoalexins.
How this substance works: Resveratrol is a stilbene compound manufactured by plants as a defense mechanism against diseases. It is primarily found in red grape skins, and laboratory experiments find that it functions as an antioxidant against cell-damaging free radicals. It has also been found to prevent some cancers, slow or halt the stages 1045
Retinoblastomas
Salem Health: Cancer
of cancer progression and metastasis, decrease inflammation and heart disease, and extend life span. Its chemical structure is very similar to estrogen, and it is considered a phytoestrogen compound. While it has shown some promise in preventing estrogen-sensitive cancers, one study found that it actually stimulated the growth of breast cancer cells. While only a small number of studies have tested resveratrol in humans, initial results show that the body rapidly metabolizes it. Thus, blood levels of resveratrol may not reach the protective levels that have been observed in the lab setting and it may only provide limited health benefits to humans. Recommended doses for resveratrol have yet to be determined.
fects one eye). The bilateral type is hereditary and affects 25 percent of children with retinoblastoma. The unilateral type is not hereditary and occurs during prenatal development. The unilateral type affects 75 percent of children with retinoblastoma.
Side effects: Caution is advised for individuals with food allergies or sensitivities to resveratrol-containing foods. There have been no reported side effects or drug interactions, but women with a history of estrogen-sensitive cancers are advised to avoid resveratrol dietary supplements because of its estrogen-like chemical structure. Individuals taking anticoagulant, antiplatelet, or nonsteroidal antiinflammatory drugs (NSAIDs) should also avoid dietary supplements, as high doses of resveratrol may increase the risk of bleeding. Unsafe intake of alcohol should be avoided, as it may increase cancer risk as well as other health risks. Alice C. Richer, R.D., M.B.A., L.D.
Etiology and the disease process: During prenatal development of a child, the youngest cells (retinoblasts) divide and redivide to form the differentiated cells of the retina. Sometimes gene mutations occur, causing an abnormality in chromosome 13. This causes some retinoblasts to multiply uncontrolled, creating a tumor of undifferentiated cells: a retinoblastoma. From this point onward, the retinoblastoma is classified into bilateral and unilateral types. The uncontrolled tumor can fill the entire orbit and glaucoma can develop, which can cause pain and vision loss. If the condition remains untreated, the cancer can spread through the brain and spinal cord and then to other parts of the body (second tumor).
See also Antioxidants; Beta-carotene; Bioflavonoids; Calcium; Carotenoids; Chemoprevention; Coenzyme Q10; Complementary and alternative therapies; Cruciferous vegetables; Curcumin; Dietary supplements; Essiac; Free radicals; Fruits; Garlic and allicin; Glutamine; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Nonsteroidal anti-inflammatory drugs (NSAIDs); Nutrition and cancer prevention; Phenolics; Phytoestrogens; Wine and cancer.
Incidence: Generally 200 to 300 children per year are diagnosed with retinoblastoma in the United States; the disease occurs equally in boys and girls. The rate of incidence is higher in infants (newborn to one year) and younger children, and lower in older children (between two and twelve years). About 95 percent of children diagnosed with the disease are younger than five.
u Retinoblastomas Category: Diseases, symptoms, and conditions Also known as: Cancer of the retina Related conditions: Second extraocular tumors or cancer, trilateral retinoblastomas (pineoblastomas) Definition: Retinoblastomas are rare cancers (malignant tumors) of the retina of the eye in young children. The retina is the innermost light-sensitive layer of the eye wall and is responsible for vision. There are two types of retinoblastoma, bilateral (affects both eyes) and unilateral (af1046
Risk factors: There are no risk factors for retinoblastoma; however, this disease creates a risk of a secondary cancer as it can spread outside the eye to other parts of the body. More children with the bilateral type have died from a second tumor than from the original retinoblastoma. Retinoblastoma also places patients at risk of developing other types of cancer.
Symptoms: The most common symptom (60 percent) is leukocoria, a white pupil or white reflex. The second is strabismus (crossed eyes), which accounts for 20 percent of cases, and third, inflammation (red irritation and swelling) around the eyes, 10 percent. Screening and diagnosis: The main screening by an ophthalmologist is to check for a normal red reflex in the eye (normally blood vessels in the back of the eye reflect red). If white reflex (cat’s-eye reflex) is observed, it is due to leukocoria. The doctor will also examine the corneal light reflex to check for strabismus and look for inflammation around the eyes or vision problems, including a decrease in vision. A blood test may be performed to check for deoxyribonucleic acid (DNA) mutations. Diagnosis of retinoblastoma is confirmed by ophthalmoscopic examination, ultrasound, computed tomogra-
Salem Health: Cancer
Retinoblastomas ameter and 8 mm in thickness, radiation therapy is used. Radiation therapy can consist of an external beam of X rays or internal radiation (plaque radiotherapy). In plaque radiotherapy, radioactive material is placed near the tumor to kill cancer cells. When all other treatments fail to control the tumor, pain, and blindness, enucleation, or surgical removal of the eye, is performed to save the child’s life. Prognosis, prevention, and outcomes: The disease was nearly always fatal one hundred years ago. The prognosis improved from an 80 percent survival rate in the 1960’s to more than 95 percent in the 1990’s. Retinoblastoma is highly curable if diagnosed and treated early. The prognosis for vision and a second tumor depends on the stage of the disease and treatment efficacy. Retinoblastoma cannot be prevented, because of its genetic component; however, the defective gene can be detected through tests of amniotic fluid, which allows for the option of terminating the pregnancy. Another option is in vitro fertilization, in which an embryo without the defective gene can be implanted in the womb. Arun S. Dabholkar, Ph.D. u
Retinoblastoma. (Custom Medical Stock Photo)
phy (CT) and magnetic resonance imaging (MRI) scans, and if absolutely necessary, spinal tap and bone marrow biopsy. The following are the three stages of retinoblastoma: • Stage I: Intraocular; the tumor remains inside the eye. • Stage II: Extraocular; the tumor spreads outside the eye or to another part of the body (second tumor). • Stage III: Recurrent; cancer returns in the eye or another part of the body after being treated. The hereditary form of retinoblastoma can recur years after treatment. Treatment and therapy: Treatment depends on the size of the tumor. For tumors less than 3 millimeters (mm) in diameter and 2 mm in thickness, photocoagulation, a laser treatment, is used to kill blood vessels that nourish the tumor. If the tumor is less than 5 mm in diameter and 3 mm in thickness, cryotherapy is used to freeze the cancer cells. Chemotherapy (oral or intravenous) can also be used to kill cancer cells. When the tumor is less than 16 mm in di-
For Further Information Albert, Daniel M., and Arthur Polans, eds. Ocular Oncology. New York: Marcel Dekker, 2003. Melamud, Alex, Rakhee Palekar, and Arun Singh. “Retinoblastoma.” American Family Physician 73, no. 6 (2006): 1039-1044. Parker, James N., and Philip M. Parker, eds. The Official Parent’s Sourcebook on Retinoblastoma: Directory for the Internet Age. San Diego, Calif.: Icon Health, 2005.
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Other Resources
Genetics Home Reference Retinoblastoma http://ghr.nlm.nih.gov/condition=retinoblastoma Ocular Oncology at Bascom Palmer Eye Institute http://www.eyecancermd.org/retinoblastoma/ index.html Retinoblastoma.com http://retinoblastoma.com/retinoblastoma/ See also Cancer biology; Childhood cancers; Computed tomography (CT) scan; Eye cancers; Genetics of cancer; Oncogenes; Ophthalmic oncology; Pineoblastomas; RB1 gene; Sarcomas, soft-tissue; Tumor-suppressor genes; Virus-related cancers. 1047
Rhabdomyosarcomas
Salem Health: Cancer
u Rhabdomyosarcomas Category: Diseases, symptoms, and conditions Also known as: Embryonal rhabdomyosarcomas, alveolar rhabdomyosarcomas, botryoid rhabdomyosarcomas, soft-tissue sarcomas Related conditions: Li-Fraumeni syndrome, BeckwithWiedemann syndrome, Costello syndrome Definition: Rhabdomyosarcomas are soft-tissue, malignant tumors that develop from cells called rhabdomyoblasts, which normally develop into skeletal, cardiac, and smooth muscles. This cancer develops from embryonal cells and is more common in children than in adults. Risk factors: There are no known environmental factors that increase the risk of rhabdomyosarcoma. There is some evidence that suggests that an increased risk of rhabdomyosarcoma occurs with certain related, inherited conditions. These syndromes are rare, but children may inherit an increased risk of the tumor when these diseases are present. There is no evidence that lifestyle-related risk factors, including use of drugs or X rays during pregnancy, have an impact on rhabdomyosarcoma. Etiology and the disease process: There is no known cause for most cases of rhabdomyosarcoma, but it is assumed that there is a genetic component. With embryonal rhabdomyosarcomas, research has demonstrated that a small piece of deoxyribonucleic acid (DNA) on chromosome 11 may be missing. Incidence: The annual incidence of rhabdomyosarcoma is 4.5 cases per 1 million children under the age of fourteen. These cases represents 3.5 percent of all malignancies in
Age-Specific Annual Incidence Rates for Rhabdomyosarcoma, 1975-1995 Age (years)
Incidence per 1 Million Children
5 and under 5-9 10-14 15-19
6.4 4.4 3.1 3.6
Source: L. A. G. Ries et al., eds., Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program, 1975-1995, NIH Pub. No. 99-4649 (Bethesda, Md.: National Cancer Institute, SEER Program, 1999)
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children under the age of fourteen. The ratio of boys to girls is 1.5:1. Symptoms: The symptoms of rhabdomyosarcoma depend on the initial site of the tumor. Tumors on the trunk, groin, arms, or legs may be first noticed as swelling that causes little or no pain. Tumors that grow inside the abdomen or pelvis may cause nausea, vomiting, difficulties with bowel and bladder function such as constipation or frequent urination, and pain. These symptoms are caused by pressure on internal organs. Masses that grow in the bladder or vagina may cause bleeding. Tumors in the ear or in the sinuses have symptoms similar to ear infections or sinus infections and cause pain in the area affected. A rhabdomyosarcoma of the eye, or orbital area, may cause the eye to bulge, or the child may appear cross-eyed. If the tumor goes undetected for a period of time, the child may develop symptoms of fatigue, cough, weight loss, enlarged lymph nodes, and generalized muscle weakness. This may indicate that the rhabdomyosarcoma has already metastasized (spread) to other parts of the body. Screening, diagnosis, and staging: There is no screening test for rhabdomyosarcoma. If a family has a history of cancer, particularly childhood cancer, it is important to tell the pediatrician at the first visit. Parents should take note of any unusual lumps, swellings, or blood in the stool or urine, as many tumors are picked up by parents bathing the child or changing a diaper. Children should be taken to the doctor if they complain of persistent pain in any area or if a bump or swelling does not go away. Diagnosis begins with imaging (X-ray) studies, as tumors may be hidden or hard to see. Tests may include ordinary X rays, computed tomography (CT) scans, a magnetic resonance imaging (MRI) scan, a bone scan, and a positron emission tomography (PET) scan. These scans can detect the location of the tumor, reveal any spread to other areas, and in the case of the PET scan, determine whether the tumor may be cancer. Abiopsy, the removal of a small piece of the tumor for review under the microscope by a pathologist, usually follows imaging studies. A bone marrow biopsy is done once the diagnosis of rhabdomyosarcoma is made to determine if the tumor has spread. Staging rhabdomyosarcoma is important to determine the treatment needed to best effect cure. Generally staging begins with the pathology review and initial biopsy or surgery. Staging is done in two ways: clinical groups I-IV and TNM (tumor/lymph node/metastasis) stages I-IV. Clinical group staging is based on how much of the tumor is removed during the initial surgery and knowledge of the extent of the disease. The TNM stage is determined by size
Salem Health: Cancer
Rhabdomyosarcomas
Rhabdomyosarcoma was biopsied from the buttock of this two-month-old baby boy. (Dr. P. Marazzi/Photo Researchers, Inc.)
and type of the tumor (T), spread to lymph nodes (N) and distant organs, and metastases (M). Once the clinical group and TNM stage are determined, patients are categorized as low, intermediate, or high risk. Treatment and therapy: Surgery is the initial treatment of choice to remove as much of the rhabdomyosarcoma as possible. If surgery may be disfiguring or damaging, only partial tumor removal is possible. Chemotherapy is used to kill any cells remaining after surgery or to attack cells that may have spread elsewhere in the body. Radiation therapy may be used, especially if part of the tumor has been left behind after surgery or the tumor has metastasized. A team will make the best treatment decisions for the child based on staging, location of the tumor, and other factors. Prognosis, prevention, and outcomes: The prognosis for rhabdomyosarcoma depends on the stage at diagnosis, the site and the size of the tumor, the success of surgical removal, and whether the tumor has spread. Approximately 70 percent of children diagnosed will be disease-free at five years, and rhabdomyosarcoma is considered a curable disease. Depending on the site of surgery, there may be re-
sidual damage to the patient such as loss of an eye or other body part or organ. There is no way to prevent rhabdomyosarcoma. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Magne, N., and C. Haie-Meder. “Brachytherapy for Genital-Tract Rhabdomyosarcoma in Girls: Technical Aspects, Reports, and Perspectives.” Lancet Oncology 8, no. 8 (August, 2007): 729-739 Rodeberg, D. A., C. Erskine, and E. Celis. “In Vitro Induction of Immune Responses to Shared Tumor-Associated Antigens in Rhabdomyosarcoma.” Journal of Pediatric Surgery 42, no. 8 (August, 2007): 1396-1402
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Other Resources
American Cancer Society Detailed Guide: Rhabdomyosarcoma http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_rhabdomyosarcoma_53.asp 1049
RhoGD12 gene National Cancer Institute Childhood Rhabdomyosarcoma http://www.cancer.gov/cancertopics/types/ childrhabdomyosarcoma See also Alveolar soft-part sarcomas; Amputation; Beckwith-Wiedemann syndrome (BWS); Breast cancer in children and adolescents; Childhood cancers; Fibrosarcomas, soft-tissue; HRAS gene testing; Limb salvage; Orbit tumors; Pleuropulmonary blastomas; Sarcomas, softtissue; Testicular cancer; Tumor markers; Vaginal cancer.
u RhoGD12 gene Category: Cancer biology Also known as: Guanine nucleotide binding protein, tumor-suppressor gene Definition: RhoGD12 is an oncogene, the product of which suppresses the metastatic potential of several types of tumors, including those of the bladder, lung, prostate, ovarian, breast, and colon. The RhoGD12 gene is expressed within a variety of neoplastic cells. The method of regulation of expression of the gene is unknown. Tumors that have undergone metastasis appear to downregulate the gene, while increased expression is correlated with reduced levels of metastasis. Significance: Mortality associated with cancer can be the result of two separate but interrelated processes: growth of the primary tumor and metastasis of the growth to distal sites, potentially any organ in the body, which may result in damage to that organ. Removal of the primary tumor by surgery may eliminate one growth, but if metastasis has taken place, the tumor may recur at other sites, potentially proving fatal. Elimination of metastatic growth sites has been addressed using chemotherapy, a method of treatment that may have significant side effects. The discovery of the RhoGD12 suppressor gene potentially opens another method to limit metastasis. The gene product has been found to suppress metastasis, apparently by interfering with the function of endothelin, a member of a protein family involved in cell signaling and cell dissemination from primary tumors. Endothelin-1 was found to be overexpressed in several forms of cancers, but particularly in ovarian cancers, and appears to play an important role in the development of these forms of cancers. Measurement of endothelin-1 in abdominal fluids may potentially represent a screening mechanism for early-stage cancer. Because it appears to be an important factor in the metastasis of these neoplasms, 1050
Salem Health: Cancer use of the RhoGD12 gene product has the potential of suppressing metastasis, providing a means to treat these diseases. History: In 2002 cancer researchers attempted to correlate the likelihood of metastasis of various types of neoplasms with the expression of specific genes. Using a technique known as microarray analysis, a method to measure expression of large numbers of genes in a cell, it was discovered that the level of expression of one specific gene, now called RhoGD12, correlated with lack of metastasis. That is, the greater the level of expression, the less likely metastasis would take place. Richard Adler, Ph.D. See also Bladder cancer; Breast cancers; Cancer biology; Chemotherapy; Colorectal cancer; Lung cancers; Metastasis; Oncogenes; Oncogenic viruses; Ovarian cancers; Prostate cancer; Proto-oncogenes and carcinogenesis; Tumor-suppressor genes.
u Richter syndrome Category: Diseases, symptoms, and conditions Also known as: Diffuse large-cell lymphoma, diffuse large B-cell lymphoma, Richter transformation, Richter’s syndrome Related conditions: Chronic lymphocytic leukemia (CLL), high-grade non-Hodgkin lymphoma (NHL) Definition: Richter syndrome, named after Maurice Nathaniel Richter, an American pathologist, is a very rare type of cancer that primarily affects adults and can be found most often in women. Only 10 percent of patients diagnosed with Richter syndrome are under the age of fifty. Leukemia is a cancer of the white blood cells, and Richter syndrome is an advanced type of lymphocytic leukemia that starts in the bone marrow as chronic lymphocytic leukemia but develops or transforms into diffuse large-cell lymphoma. This transformation of the cancer type is very aggressive and has the ability to travel through the blood and access the entire body. When chronic lymphocytic leukemia transforms into diffuse large-cell lymphoma, it does so quickly and causes sudden deterioration of the patient’s health, which leads to an extreme exacerbation of symptoms and often to death of the patient. Risk factors: To develop Richter syndrome, a person first must have chronic lymphocytic leukemia, a rare cancer of the blood. Of those patients with chronic lymphocytic leukemia, those who smoke or have had exposure to pesti-
Salem Health: Cancer cides and radiation, as well as those who have family members with chronic lymphocytic leukemia, are more likely to develop Richter syndrome. Some genetic influence may also play a role in the transformation of chronic lymphocytic leukemia to diffuse large-cell lymphoma. It is important to remember, however, that these risk factors are not determinant but have been shown to be possibly related to Richter syndrome. Etiology and the disease process: There is no known cause for Richter syndrome. Onset of Richter syndrome or of the transformation of chronic lymphocytic leukemia to diffuse large-cell lymphoma is thought to be typically brought about by a variation in the patient’s lymphocytes accompanied by rapid tumor growth, swelling of lymph nodes, fever, and weight loss caused by a reduction in appetite. Incidence: Cases of Richter syndrome are extremely rare, occurring in only 2 to 3 percent of patients with the aggressive form of non-Hodgkin lymphoma, chronic lymphocytic leukemia. This translates to approximately 1 in 20 patients whose chronic lymphocytic leukemia will transform into diffuse large B-cell lymphoma. Symptoms: Symptoms of lymphoma include swelling of the lymphatic system, particularly swelling of the lymph nodes in the neck, armpit, or groin. Symptoms of Richter syndrome often include fatigue, decreased appetite, fever, night sweating, weight loss, and breathlessness. Screening and diagnosis: Screening for Richter syndrome is performed on patients with chronic lymphocytic leukemia who are judged to be at risk to develop the syndrome. Diagnosis of Richter syndrome is done through microscopic examination of cells and biopsy of the bone marrow of a select “flat” bone, including bones of the rib, hip, and shoulder. Further tests include blood tests, bone scans, and X rays to assess the cancer and its spread within the body. Treatment and therapy: Treatment for Richter syndrome is typically chemotherapy; however, because this cancer is very aggressive, chemotherapy often is not successful. Bone marrow transplantation is also a potential treatment, but this option is rare and usually occurs within clinical trials. The two medications typically used to treat diffuse large-cell lymphoma are doxorubicin and cyclophosphamide. These drugs are often used in combination with radiation. Another popular treatment option is called the RChop regimen, which consists of a monoclonal antibody and four types of chemotherapy. Monoclonal antibodies
Richter syndrome are used to improve the body’s immune response. Additionally, supportive therapies, such as steroids, are used to help alleviate the side effects of the aggressive medicinal regimen. Prognosis, prevention, and outcomes: Prognosis for Richter syndrome is survival for less than one year following diagnosis, as patients with Richter syndrome typically do not respond well to treatment because of the advanced state of their cancer, as well as their depressed immune response. As genetic factors play a role in this cancer, prevention steps are limited but include maintaining a healthy lifestyle without the use of tobacco products and without exposure to pesticides, herbicides, and radiation. Anna Perez, M.Sc. u
For Further Information Catovsky, D., J. Fooks, and S. Richards. “Prognostic Factors in Chronic Lymphocytic Leukaemia: The Importance of Age, Sex, and Response to Treatment in Survival—A Report from the MRC Chronic Lymphocytic Leukemia 1 Trial.” British Journal of Haematology 72 (1989): 141-149. Robertson, L. E., et al. “Richter’s Syndrome: A Report on Thirty-nine Patients.” Journal of Clinical Oncology 11 (1993): 1985-1989. Rodriguez, J., et al. “Allogenic Haematopoietic Transplantation for Richter’s Syndrome.” British Journal of Haematology 110 (2000): 897-899. Souhami, Robert L., et al., eds. Oxford Textbook of Oncology. 2d ed. New York: Oxford University Press, 2002. Tsimberidou A. M., and M. J. Keating. “Richter Syndrome: Biology, Incidence, and Therapeutic Strategies.” Cancer 103 (2005): 216-228.
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Other Resources
American Cancer Society Chronic Lymphocytic Leukemia http://www.cancer.org/docroot/CRI/content/CRI_ 2_4_4X_Chronic_Lymphocytic_Leukemia_62.asp Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Lymphoma Information Network http://www.lymphomainfo.net National Cancer Institute http://www.cancer.gov See also Chronic lymphocytic leukemia (CLL); Clinical trials; Leukemias; Lymphomas; Medical oncology; NonHodgkin lymphoma; Oncology. 1051
Risks for cancer
u Risks for cancer Category: Lifestyle and prevention Definition: Risk is defined as the probability that exposure to a hazard will result in a negative outcome, such as the occurrence of cancer. Although cancer is one of the most feared diseases in the modern world, the majority of cancer risks can be reduced through simple lifestyle choices. Concepts of risk: There are several concepts of risk. Absolute risk is defined as the probability that an event will occur over a defined period. Age-specific lifetime risk estimates are a type of absolute risk. For example, a woman may have a cumulative 30 percent lifetime risk of breast cancer but only have a 5 percent chance of developing the disease in the next five years. Risk is frequently described in epidemiological studies (studies of population-wide patterns of disease) using a ratio known as a relative risk (RR), which compares the incidence of disease in people who have a certain risk factor, such as family history, to those who do not have the risk factor (control group). Many studies of cancer risk factors have found higher or lower relative risks that are so slight that they could be the result of random chance. These are referred to as statistically insignificant. When assessing risk, it is also important to know the effect size, rather than just a percentage increase in risk. For example, an increase in risk from 1 to 2 percent is a much less significant finding than an increase in risk from 20 to 40 percent, yet both increases in risk could be reported in the media as a 50 percent increase in risk. Risk perception: Risk means different things to different people. Experts often see risk differently from the average person, because experts tend to evaluate risk based on statistics and technical information. The average person, however, may judge risks based on technical information and many other factors, such as how familiar the risk is, whether the risk can be controlled, the catastrophic potential of the outcome, and the voluntariness of the exposure. Men and women also tend to perceive risk very differently, which may be related to how much power individuals feel they have over their exposure to hazards. Many people are willing to tolerate a higher level of risk from activities seen as beneficial or enjoyable, such as smoking and drinking. The perceived risk goes down as the perceived benefit goes up. Because cancer is so common, represents such a burden on society, and is a highly dreaded disease, public health researchers are very interested in understanding risk factors for cancer. One of the most important messages com1052
Salem Health: Cancer ing out of this research since the early 1980’s is that the majority of risks for cancer can be mitigated through lifestyle changes. Tobacco use: Tobacco use is responsible for about onethird of all cancer deaths. The use of tobacco not only greatly increases the risk for lung cancer but also appears to influence the risk for cancer of the larynx, oral cavity, esophagus, bladder, kidney, pancreas, stomach, and cervix. Women who smoke are at a higher risk of developing lung cancer than male smokers, as are heavy smokers—for example, a person who smokes forty cigarettes a day for twenty years is at higher risk than one who smokes twenty a day for forty years. No matter how long or how much a person has used tobacco, it is never too late to quit: The risk of cancer begins to decrease as soon as tobacco use stops. Cigars and pipes are often seen as less harmful than cigarettes. However, even if cigar and pipe smokers do not inhale, they are at increased risk for cancer of the oral cavity and lungs. Pipe smokers also are at increased risk for lip cancers in areas where the pipe stem rests. Using chewing tobacco and dry snuff increases the risk of cancer in the cheek, gums, and lips. Diet and obesity and overweight: Poor diet, overweight, and obesity are responsible for about 30 percent of cancer deaths. Diets low in vegetables, fruits, whole grains, and beans and high in animal protein and fat have been convincingly linked to higher risk for many cancers, including those of the colon, rectum, stomach, and esophagus. However, the link between diet and breast cancer risk is unclear. Some researchers have found associations with fat intake and increased risk, while others have not. Similarly, while fiber intake was once thought to protect against colon cancer, the evidence now is inconclusive. High fat intake is a major risk factor for cancers. In the large, well-known Nurses’ Health Study, which followed more than 87,000 women for up to twenty-four years, researchers compared the occurrence of breast cancers in women who ate the most animal fat to women who ate the lowest amount and found a statistically significant relative risk of 1.33 (33 percent increased risk). Plant fats, such as those from avocados and walnuts, do not appear to increase the risk of cancer. Processed meats, such as bacon, hot dogs, and sausage, may be particularly risky to eat. In a study that followed nearly 200,000 men and women for seven years, people who consumed the most processed meats increased their risk of pancreatic cancer by 68 percent over those who consumed few or no meat products. Other studies have
Salem Health: Cancer shown increased risk of stomach and colorectal cancers associated with eating processed meats, pork, and red meat. Preparing meat at high temperatures (for example, grilling or using a wok) can create higher levels of cancercausing substances in the meat. These studies suggest that eating red meat, processed meats, and pork should be limited to two to three times a week at most, particularly in childhood, when eating habits are being established. A poor diet increases the risk of overweight and obesity, which are responsible for about 10 percent of cancer deaths in men and 15 percent in women. Researchers have identified three major ways that excess weight—especially in the midsection—may increase cancer risk. One is that body fat secretes substances that seem to promote inflammation throughout the body, increasing the chance of deoxyribonucleic acid (DNA) damage that allows cancer to start. The second is that being overweight can lead to higher blood levels of insulin and insulin-related growth factors, which promote the development of some cancers. Third, excess body fat also changes the levels of several reproductive hormones, such as estrogen and testosterone. Preventing weight gain is best, but losing excess body fat also seems to lower cancer risk. In the Nurses’ Health Study, postmenopausal women who lost 22 pounds or more and kept it off had a 30 percent lower breast cancer risk than postmenopausal women who did not lose weight. Another major study, the Iowa Women’s Health Study, followed more than 33,000 women for up to fifteen years. Women who lost weight after menopause had a 23 percent lower risk of breast cancer compared with women who gained weight throughout adulthood. Women who began to lose weight before menopause reduced their risk even more. Losing weight benefits men as well: Among almost 70,000 men in the Cancer Prevention Study II, those who lost at least 11 pounds over a ten-year period had a 16 to 17 percent overall lower risk of prostate cancer and 42 percent lower risk of aggressive forms of prostate cancer. Lack of exercise: Sedentary lifestyles are responsible for an estimated 5 percent of cancer deaths. Since regular physical activity helps prevent obesity, an indirect association between physical activity and cancer risk has been hypothesized for some time. The understanding that activity level itself is directly linked to cancer risk is new in the last several years. Physical activity changes the body’s levels of hormones, insulin, and other growth factors, improves the immune system, and has an anti-inflammatory effect, all of which may help prevent cancer. Studies consistently show that after controlling for weight, colon cancer risk drops 40 to 50 percent with exer-
Risks for cancer cise. Similarly, regular moderate exercise may reduce risk of breast cancer 30 to 40 percent, with greater benefits after menopause. Exercise may also independently lower the risk of prostate, lung, endometrial, ovarian, and kidney cancers, although confirming studies are needed. Environmental hazards: Environmental hazards that increase the risk of cancer include radon, asbestos, certain chemicals (such as pesticides), and aflatoxins. Environmental hazards, combined, are blamed for about 7 percent of cancer deaths. Many of these hazards are related to occupational exposure. For example, people who work with herbicides are at increased risk of lymphoma, and construction workers are at higher risk of lung cancer from asbestos. Asbestos exposure is also related to an increased laryngeal cancer incidence, and exposure to cement dust raises the risk for pharyngeal cancer. Radon, a naturally occurring radioactive material, is known to increase the risk of lung cancer among underground miners exposed to high levels. Household levels of radon exposure have not been shown to increase lung cancer risk. Aflatoxins are naturally occurring toxins produced by certain species of fungus, which are found on foods such as corn, peanuts, various other nuts, and cottonseed. Highlevel aflatoxin exposure is a risk factor for liver cancer, and infection with hepatitis B increases this risk. Foodborne aflatoxin exposure is most common in Africa, China, and Southeast Asia. The average American is very concerned about carcinogens, and believes that the current risk from potentially carcinogenic chemicals, such as pesticides or cleaning agents, is unacceptably high. Up to 70 percent of Americans say they try to avoid contact with chemicals and chemical products in everyday life. Although it is not possible to know for sure, the best guess is that about 2 to 3 percent of cancer deaths are caused by carcinogenic chemicals. Genetics: About 5 to 10 percent of cancer deaths are related to genetic factors and factors present at birth. A family history of any cancer raises a person’s risk, but the increase varies by type of cancer. Breast-ovarian cancer syndrome results from mutations in the BRCA1 or BRCA2 gene. People with this mutation have an 80 to 90 percent lifetime risk of breast cancer and a 20 to 60 percent chance of developing ovarian cancer. Men with this syndrome have an elevated risk of prostate cancer, and both sexes are at increased risk of melanoma and pancreatic cancer. Hereditary forms of colon cancer, melanoma, pancreatic cancer, and brain cancers are also known. Both low and high birth weight have both been identi1053
Robert H. Lurie Cancer Center fied as risk factors for testicular cancer. Among men, but not women, being relatively short at birth is associated with increased risk of colorectal cancer in adulthood. Because studies that follow people from birth for sixty to eighty years are expensive and logistically difficult, very little research has been done on other possible risk factors that are present at birth. Viral and bacterial infections: About 5 percent of cancer deaths are related to viral infections. Several different types of infections raise a person’s cancer risk. For example, people infected with one of the viruses that cause hepatitis are more susceptible to liver cancer and lymphoma. Chronic infection with Helicobacter pylori, a bacterium that lives on the lining of the stomach, increases risk for stomach cancer and lymphoma. Human immunodeficiency virus (HIV) and Epstein-Barr virus are linked to lymphoma as well. People with inflammatory bowel disease have above-average rates of colon cancer. Cervical and anal cancers are associated with the human papillomavirus (HPV). The risk is greater for people who have chronic, untreated infections, so screening for viruses to catch them early is important in preventing cancer. Alcohol: Alcohol use is associated with increased risk for mouth, esophageal, laryngeal, pharyngeal, breast, and liver cancers. About 3 percent of cancer deaths are related to alcohol consumption. Alcohol may increase cancer risk in several ways: It may reduce the body’s ability to absorb vitamins, raise the level of hormones in the body, or suppress the immune system. There may be some association with diet as well, since heavy drinkers tend to have poorer diets than abstainers. All types of alcohol—beer, wine, and liquor—increase risk equally. People who drink more than three drinks a day are at the highest risk. One study says that for the average woman, having just one drink a day increases the lifetime risk of breast cancer from 1 in 8 (12.5 percent) to about 1 in 7 (about 14.25 percent). Moderate alcohol intake (two drinks a day for men and one a day for women) may have cardiovascular benefits for men over age fifty and women over age sixty that outweigh the increased risk of cancer, although people who do not drink should not start in the hope of gaining cardiovascular benefits. Screening: Although screening does not, by itself, prevent cancer, it does reduce the risk of advanced or latestage cancer. The earlier a case of cancer is detected, the better the chances of survival. There are simple screening tests for many common cancers, including breast, prostate, ovarian, colorectal, and oral. Lisa M. Lines, M.P.H. 1054
Salem Health: Cancer u
For Further Information Colditz, Graham A., and Cynthia J. Stein. Handbook of Cancer Risk Assessment and Prevention. Boston: Jones and Bartlett, 2004. Pensiero, Laura, Michael Osborne, and Susan Oliviera. The Strang Cancer Prevention Center Cookbook: A Complete Nutrition and Lifestyle Plan to Dramatically Lower Your Cancer Risk. New York: McGraw-Hill, 2004. Ropeik, D., and G. M. Gray. Risk: A Practical Guide for Deciding What’s Really Safe and What’s Dangerous in the World Around You. Boston: Houghton Mifflin, 2002. Slovic, P. The Perception of Risk. London: Earthscan, 2000.
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Other Resources
American Cancer Society Who Is at Risk? http://www.cancer.org/docroot/WHO/WHO_0.asp American Institute for Cancer Research Recommendations for Cancer Prevention http://www.aicr.org/site/PageServer?pagename= dc_home_guides Siteman Cancer Center, Washington University School of Medicine Your Disease Risk http://www.yourdiseaserisk.wustl.edu/ See also Air pollution; Asbestos; Cancer education; Carcinogens, known; Carcinogens, reasonably anticipated; Cell phones; Chewing tobacco; Cigarettes and cigars; Developing nations and cancer; Dioxins; Family history and risk assessment; Genetics of cancer; Geography and cancer; Native North Americans and cancer; Obesityassociated cancers; Occupational exposures and cancer; Pesticides and the food chain; Plasticizers; Prevent Cancer Foundation; Radon; Report on Carcinogens (RoC); Tobacco-related cancers.
u Robert H. Lurie Cancer
Center Category: Organizations Definition: The Robert H. Lurie Cancer Center of Northwestern University is a university-based comprehensive cancer center located in Chicago. The Feinberg School of
Salem Health: Cancer Medicine on Northwestern University’s Chicago campus, basic science research labs at both the Chicago and Evanston campuses, and five affiliated teaching hospitals are integrated to provide state-of-the-art cancer care. Founding and history: The Cancer Center was established at Northwestern University in 1974. In 1991 the Cancer Center was dedicated as the Robert H. Lurie Cancer Center of Northwestern University, and in 1998 the name was changed to the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, reflecting the designation from the National Cancer Institute as a comprehensive cancer center. In 1987 Robert H. Lurie, for whom the center is named, began treatment for advanced colon cancer at the center. Lurie was forty-six years old at the time of his diagnosis, and he was at the peak of a successful career in real estate. Lurie exemplified an individual who believed in living life to the fullest and in not giving in to his illness. Before he died in 1990, Robert Lurie and his wife, Ann, determined they would endow the center to further cancer research. The decision to use Robert Lurie’s name for the center reflects that individual’s tenacious battle with cancer and is meant to symbolize the center’s dedication to the research and treatment of individuals dealing with cancer. Ann Lurie has continued her involvement in the cause of cancer research and treatment; in addition to the endowment of the Robert H. Lurie Comprehensive Cancer Center, she has made a gift to Children’s Memorial Hospital to establish a new medical center, scheduled to open in 2012 on Northwestern University’s Chicago campus, for the care of children and for pediatric research initiatives. Current facilities: An outpatient clinical cancer center in downtown Chicago, the collaboration of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the Northwestern Medical Faculty Foundation, was opened in 2003. All physicians at the cancer center are faculty of the Feinberg School of Medicine. The cancer center provides oncology diagnostic and treatment services as well as patient access to clinical trials. The Division of Hematology/Oncology (for cancers and disorders of the blood), the Division of Surgical Oncology (for cancers of skin, breast, and the gastrointestinal system), and the Division of Gynecology Oncology (for cancers of the female reproductive system) are housed in the cancer center. Clinical inpatient treatment and clinical research is conducted at the teaching hospitals affiliated with the Feinberg School of Medicine. The hospitals included are Northwestern Memorial Hospital, Rehabilitation Insti-
Robert H. Lurie Cancer Center tute of Chicago, Jesse Brown VA Medical Center, and Children’s Memorial Hospital. Research: Basic science research laboratories for the cancer center are on the Evanston, Illinois, campus of Northwestern University. The three divisions of the research center are the Basic Sciences Division, the Clinical Sciences Division, and the Cancer Prevention and Control Division. The Basic Sciences Division has research programs in viral oncogenesis; tumor invasion, metastasis and angiogenesis (TIMA); hormone action and signal transduction in cancer; cancer genes and molecular targeting; and cancer cell biology. The Clinical Sciences Division has breast cancer, prostate cancer, and hematologic malignancies research programs. The Cancer Prevention and Control Division researches the preventive themes of epidemiology, chemoprevention, biomarkers and early detection, and behavioral science and the cancer control themes of the costs and patterns of oncology treatments, measurement, analysis and interpretation of quality of life, and palliative and rehabilitation oncology. A collaboration of the Robert H. Lurie Cancer Center and Northwestern University’s International Institute for Nanotechnology, Northwestern University Center of Cancer Nanotechnology Excellence (NU-CCNE) was established in 2005. This center is funded by the National Cancer Institute. The NU-CCNE includes scientists, cancer biologists, engineers, and clinicians working together toward the research goal of designing and testing nanomaterials and nanodevices for their application in the setting of clinical care for cancer screening, diagnosis, and treatment. Clinical research is conducted in the inpatient and outpatient facilities of the cancer center with access to clinical trials. Specialization: Two Specialized Programs of Research Excellence (SPORE) at the Robert H. Lurie Comprehensive Cancer Center—the Breast Cancer SPORE and the Prostate Cancer SPORE—are supported by the National Cancer Institute. The cancer center has a program for stem cell transplantation and is known for its research in hematologic malignancies. The Genetic Testing and Counseling Services provide a full range of genetic counseling, testing, screening, and research. The pediatric oncology program includes specialists in the treatment of children with leukemia, brain and spinal cord tumors, and other solid tumors. A special program of palliative care is offered at the cancer center; the program includes consultation services, an acute inpatient palliative care unit, and a home hospice program. Vicki Miskovsky, B.S., R.D. 1055
Rothmund-Thomson syndrome u For Further Information Dollinger, M. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day, 4th ed. Kansas City, Mo.: Andre McMell, 2002. Leonard, John P., and Morton Coleman. Hodgkin’s and Non-Hodgkin’s Lymphoma. New York: Springer, 2006. Waller, Alexander, and Nancy L. Caroline. Handbook of Palliative Care in Cancer. 2d ed. Boston: ButterworthHeinemann, 2000. u
Other Resources
National Cancer Institute Cancer Centers Program http://cancercenters.cancer.gov/cancer_centers/ rhiccc.html National Comprehensive Cancer Network Robert H. Lurie Comprehensive Cancer Center http://www.nccn.org/members/profiles/ northwestern.asp Robert H. Lurie Comprehensive Cancer Center http://www.cancer.northwestern.edu/home/index.cfm See also American Association for Cancer Research (AACR); American Cancer Society (ACS); American Institute for Cancer Research (AICR); Clinical trials; Genetic counseling; National Cancer Institute (NCI); Prevent Cancer Foundation.
u Rothmund-Thomson
syndrome Category: Diseases, symptoms, and conditions Also known as: RTS, Rothmund dystrophy, Thomson’s disorder, poikiloderma congenitale Related conditions: RAPADILINO syndrome, BallerGerold syndrome Definition: In 1868, August von Rothmund, a German ophthalmologist, published an account of a syndrome that included cataracts, a depressed nasal bridge, and skin degeneration, with familial links. Then, in both 1923 and 1936, Matthew S. Thomson, a British dermatologist, reported a disorder with the same defining characteristics. After some controversy over whether the reports described the same disorder, the disease became known as Rothmund-Thomson syndrome. As suggested by the time elapsed between Rothmund’s and Thomson’s accounts, Rothmund-Thomson syndrome is extremely rare. It is an 1056
Salem Health: Cancer inherited disorder that affects many body systems and is usually diagnosed during early infancy, typically between the ages of three and six months. Risk factors: Family history is the only known risk factor for Rothmund-Thomson syndrome. The disorder is inherited as an autosomal recessive trait, which means that both parents of an affected child have one copy of the defective gene that is responsible for the disorder but do not have the disorder themselves. If both parents have one copy of the defective gene, each of their children has a 25 percent chance of having both defective genes and the disorder, a 25 percent chance of not having the gene, and a 50 percent chance of having one defective gene, like the parents. Etiology and the disease process: The defective gene responsible for Rothmund-Thomson syndrome is called adenosine triphosphate (ATP)-dependent deoxyribonucleic acid (DNA) helicase Q4, or RECQ14. To date, it is the only gene that has been associated with Rothmund-Thomson syndrome, although it is commonly believed that there are others. Mutations in RECQ14 have been detected in about 66 percent of affected individuals. At birth, an affected child’s skin appears normal. Usually, by the age of six months, a characteristic rash has developed on the child’s face and later spreads to the buttocks and extremities. The rash eventually changes into a chronic pattern of several skin abnormalities, collectively known as poikiloderma. At birth, and as the child ages, many other abnormalities may be diagnosed, including skeletal defects, growth delays, vision disturbances, and possibly bone and skin cancers. The clinical features, disease progression, and severity can vary from case to case. Incidence: Only about 300 cases of Rothmund-Thomson syndrome have been reported in scientific literature. It does not seem to affect one group more than another, as it has been found in all races and many nationalities. More than 90 percent of patients develop the characteristic skin symptoms by their first birthday. Symptoms: The initial rash that is characteristic of most cases of Rothmund-Thomson syndrome begins as abnormally red, swollen patches, usually on the face, that are accompanied by blistering and abnormal accumulations of fluid between the layers of tissue under the skin. Additional areas of the body become involved as the disorder progresses, including the arms, legs, hands, feet, and buttocks. Eventually, a collective group of findings, known as poikiloderma, begins. The swollen skin begins to shrink, groups of small blood vessels widen abnormally, and patchy areas of abnormally decreased or increased coloration appear. Skin that is exposed to the sun usually shows
Salem Health: Cancer greater abnormalities, and the individual can develop thickened skin or cancerous skin changes later in life. Skeletal abnormalities may be present from birth or develop as the child grows. They include unusually small, short hands and feet and underdeveloped or absent thumbs and forearm bones. The development of osteosarcoma, a bone cancer, can occur later in life. Affected individuals may also have characteristic abnormalities of the head and face, including a prominent forehead, sunken nasal bridge, and a protruding lower jaw. Growth delays can lead to shortened height. Some other common characteristics of Rothmund-Thomson syndrome that may begin in childhood include gray, sparse hair; absent eyebrows and eyelashes; cataracts; excessive cavities and unusually small or missing teeth; and abnormally developed nails. Irregular menstruation in women and delayed sexual development and reduced fertility in both sexes can also occur because of deficient activity of the ovaries in women or testes in men. Screening and diagnosis: The only way to screen for Rothmund-Thomson syndrome is genetic testing for family members of affected individuals. The diagnosis of Rothmund-Thomson syndrome is usually based on physical examination and family history. Some skin cell and lymphocyte tests may show changes that have been seen with Rothmund-Thomson syndrome, but they are not considered diagnostic. Testing to determine the extent of the disorder and monitoring for complications includes X rays for skeletal abnormalities, routine eye examinations for the early diagnosis of cataracts, endocrine tests, and a complete blood count. Treatment and therapy: Treatment of RothmundThomson syndrome primarily involves annual physical examinations to monitor for skin and bone changes as well as complications that develop as the person ages, such as endocrine deficiencies. Cataracts should be removed if they decrease vision. For cosmetic purposes, skin conditions can be treated with a variety of medications or laser therapy. People who develop cancer should receive treatment based on the type of cancer.
Rothmund-Thomson syndrome Prognosis, prevention, and outcomes: RothmundThomson syndrome usually is not a life-threatening disease unless the individual develops bone cancer or allows skin cancer to go untreated. Use of sunscreen and avoiding repeated or excessive sun exposure are recommended. There is no prevention or cure for the disorder. Dorothy P. Terry, R.N. u
For Further Information Broom, M. A., et al. “Successful Umbilical Cord Blood Stem Cell Transplantation in a Patient with RothmundThomson Syndrome and Combined Immunodeficiency.” Clinical Genetics 69, no. 4 (April, 2006): 337343. Kumar, P., et al. “Late-Onset Rothmund-Thomson Syndrome.” International Journal of Dermatology 46, no. 5 (May, 2007): 492-493. Wang, L. L., et al. “Association Between Osteosarcoma and Deleterious Mutations in the RECQ14 Gene in Rothmund-Thomson Syndrome.” Journal of the National Cancer Institute 95, no. 9 (May 7, 2003): 669674. u
Other Resources
Genetics Home Reference Rothmund-Thomson Syndrome http://ghr.nlm.nih.gov/condition=rothmund thomsonsyndrome National Organization for Rare Disorders Rothmund Thomson Syndrome http://www.rarediseases.org/search/rdbdetail_abstract .html?disname=Rothmund%20Thomson% 20Syndrome See also Bone cancers; Bone scan; Childhood cancers; Complete blood count (CBC); Computed tomography (CT) scan; Dermatology oncology; Ewing sarcoma; Eye cancers; Eyelid cancer; Family history and risk assessment; Genetic testing; Genetics of cancer; Ophthalmic oncology; Skin cancers; Stem cell transplantation; Sunscreens.
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Salivary gland cancer
u Salivary gland cancer Category: Diseases, symptoms, and conditions Also known as: Parotid gland cancer Related conditions: Throat, neck, and mouth cancers Definition: Salivary gland cancer is cancer that develops in the glands found in the mouth, nose, sinuses, and larynx (voice box) that secrete saliva. Risk factors: The main risk factor for developing salivary gland cancer is exposure to radiation in the head and neck. This exposure often occurs for other medical conditions. Workplace exposure to certain metal dusts and silica dust also increase the likelihood of developing salivary gland cancer. Tobacco use increases the risk of developing squamous cell salivary gland cancer as well as squamous cell cancers of the throat and mouth. A few studies suggest that a diet high in animal fat and low in vegetables or a family history of salivary gland cancer are risk factors, but these studies have not been conclusive, and these risk factors appear minor compared with radiation exposure. Etiology and the disease process: The salivary glands produce saliva that contains enzymes to help digest food. There are three pairs of major salivary glands. The largest are the parotid glands located in front of and below each ear. The paired sublingual salivary glands are found under the tongue, and the pair of submandibular salivary glands are located below the jawbone. There are also between six hundred and one thousand microscopic glands, called minor salivary glands, located in the lining of the mouth, the nose, sinuses, and larynx. About 80 percent of all salivary tumors develop in the parotid glands and another 10 to 15 percent develop in the submandibular glands. Most of the tumors that develop in these salivary glands are benign (not cancerous). Tumors that begin in the minor salivary glands are usually malignant (cancerous). Malignant tumors are classified as low grade if they grow slowly and high grade if they grow aggressively and rapidly. Salivary glands contain a mix of several different types of cells. Each type of cell gives rise to a different type of tumor. About a dozen specific types of cancer can develop in these glands. There are four major types of salivary gland cancer. Mucoepidermoid carcinomas usually develop in the parotid glands. They may form low-grade or high-grade tumors. Acinic cell carcinomas also start in the parotid gland. They usually grow slowly but also tend to invade surrounding tissues. 1058
Salem Health: Cancer Adenoid cystic carcinomas are low-grade but persistent tumors that often cause the cancer to recur after surgery. Polymorphous low-grade adenocarcinomas usually begin in the minor salivary glands and grow slowly. There are another half a dozen or so rare or very rare malignant carcinomas that can develop in the salivary glands. Of these, sebaceous adenocarcinoma, oncocytic carcinoma, and salivary duct carcinoma tend to have the worst outcomes. Basal cell adenocarcinomas, clear cell carcinomas, cystadenocarcinomas, and mucinous adenocarcinomas tend to be curable or have good outcomes. Other rare salivary gland cancers include squamous cell carcinoma, undifferentiated carcinomas, and mixed malignant carcinomas, all of which tend to be high-grade, aggressive cancers. Incidence: Salivary cancer is rare, as most tumors that form in the salivary glands are benign. The American Cancer Society estimates that between 2 and 3 people per 100,000 population develop salivary gland cancer each year. Of these cancers, 85 percent are in the parotid gland. Most people are first diagnosed with salivary gland cancer
A man with a parotid gland tumor. (Scott Camazine/Photo Researchers, Inc.)
Salem Health: Cancer
Salivary gland cancer
Distribution and Five-Year Survival Rates for Salivary Gland Cancer by Histology, 1988-2001 Histology Squamous cell carcinoma Adenocarcinoma Adenoid cystic carcinoma Mucoepidermoid carcinoma, poorly differentiated Acinic cell carcinoma Mucoepidermoid carcinoma, other Malignant mixed tumor Mucoepidermoid carcinoma, well differentiated Other
Total Cases (%)
Survival Rate (%)
17.1 15.2 13.5 13.2 12.4 6.7 5.2 3.3 13.3
45.6 59.9 84.1 90.4 95.8 66.1 82.2 98.6 N/A
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
between the ages of fifty and seventy, although this cancer occasionally can develop in children and young adults. Symptoms: Salivary gland cancer often shows no symptoms in its early stages. The most common symptom is a lump on the face or neck or in the mouth. Other symptoms include pain in these areas and numbness or weakness on one side of the face. These symptoms also can be caused by a variety of other conditions unrelated to salivary gland cancer. Screening and diagnosis: Although there is no specific screening for salivary gland cancer, many cases are first detected during routine dental examinations. Diagnosis begins with a complete physical examination and patient history. This is followed by a series of imaging scans. These may include magnetic resonance imaging (MRI) and a computed tomography (CT) or computed axial tomography (CAT) scan. These scans help provide a threedimensional view of soft tissue within the body. An ultrasound helps to pinpoint tissue of different densities and helps locate the tumor. A positron emission tomography (PET) scan uses a small amount of radioactive glucose (sugar) to locate tumors. Malignant cells divide faster than healthy cells and use more glucose, making them show up as bright spots on the scan. Diagnosis is confirmed by a fine needle aspiration biopsy, in which a sample of tissue is removed and examined for malignant cells under a microscope. Salivary gland cancer is staged using the TNM system where T stands for the size of the tumor, N stands for the degree to which the cancer has spread to the nearby lymph nodes, and M stands for whether the cancer has spread
(metastasized) to distant sites. The stages for salivary gland cancer are as follows: • Stage 1: The tumor is less than 2 centimeters (cm) in diameter and has not spread to nearby tissue, lymph nodes, or distant sites. • Stage II: The tumor is larger than 2 cm but less than 4 cm and has not spread to nearby tissue, lymph nodes, or distant sites. • Stage III: The tumor is larger than 4 cm or has grown into nearby tissue, but has not spread to the lymph nodes. Alternately a tumor of any size that has spread to lymph nodes on the same side of the neck as the tumor is considered as Stage III. • Stage IV: The tumor is of any size but has invaded nearby structures (bones, skin, and so on) and lymph nodes, or has spread to distant sites. Treatment and therapy: Treatment depends on the stage of the cancer and the health of the patient. Surgery is generally recommended for Stage I, II, and III salivary gland cancer. For Stage I, the cancer and the salivary gland are usually removed. For Stage II, the surgeon removes more facial tissue and may remove some lymph nodes in the neck on the same side as the tumor. For Stage III cancer, the tumor, some tissue, and lymph nodes on both sides of the neck are removed. Surgery may damage nerves in the face and neck. This may cause difficulty eating and speaking and can be quite disfiguring. Radiation therapy is usually done after surgery, especially if the cancer cannot be completely removed. Chemotherapy is sometimes done after Stage III surgery, although this is not yet standard procedure. Stage IV cancer can rarely be cured. Radiation therapy and drugs are used 1059
Salpingectomy and salpingo-oophorectomy to relieve pain and improve quality of life. Some experimental chemotherapy may be used. Prognosis, prevention, and outcomes: It is important to remember that most tumors arising in the salivary glands are not cancerous. Malignant tumors of the salivary gland make up less than 1 percent of all tumors found in the body. Whether a salivary gland cancer can be cured depends on the specific cell type of the cancer, whether the tumor is high grade or low grade, and the degree to which the cancer has invaded nearby tissues or spread to other parts of the body. Squamous cell cancer, for example, has a poor outcome, with a five-year survival rate of only about 25 percent. The best outcomes are associated with slow-growing, low-grade tumors that are diagnosed early. The worst outcomes are associated with late-stage aggressive high-grade tumors. According to the American Cancer Society, overall five-year survival rates for all salivary gland cancers by stage are Stage I, 86 percent; Stage II, 66 percent; Stage III, 53 percent; and Stage IV, 32 percent. Avoiding unnecessary radiation exposure to the head and neck and workplace exposure to nickel alloy dust, silica dust, and similar fine metal or mineral dusts is the best way to prevent most salivary gland cancers. Avoiding all tobacco products also helps reduce the risk of squamous cell salivary gland cancer. Martiscia Davidson, A.M. u
For Further Information Brockstein, Bruce, and Gregory Masters, eds. Head and Neck Cancer. Boston: Kluwer Academic, 2003. Carper, Elise, Kenneth Hu, and Elena Kuzin. One Hundred Questions and Answers About Head and Neck Cancer. Sudbury, Mass.: Jones and Bartlett, 2008. Icon Health. The Official Patient’s Sourcebook on Salivary Gland Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2004. Myers, Eugene N., et al., eds. Cancer of the Head and Neck. 4th ed. Philadelphia: Saunders, 2003. u
Other Resources
American Cancer Society Detailed Guide: Salivary Gland Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=54 National Cancer Institute Salivary Gland Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ salivarygland 1060
Salem Health: Cancer See also Adenoid cystic carcinoma (ACC); Cell phones; Chewing tobacco; Computed tomography (CT) scan; Dry mouth; Head and neck cancers; Mucosa-associated lymphoid tissue (MALT) lymphomas; Nasal cavity and paranasal sinus cancers; Occupational exposures and cancer; Oral and maxillofacial surgery; Oral and oropharyngeal cancers; Radical neck dissection; Radiopharmaceuticals; Sjögren syndrome; Taste alteration; Throat cancer; Tobaccorelated cancers; Young adult cancers.
u Salpingectomy and salpingo-
oophorectomy Category: Procedures Also known as: Unilateral or bilateral salpingooophorectomy Definition: Salpingectomy is the surgical excision of one or both Fallopian tubes to diagnose suspicious tubo-ovarian masses that are, or may become, cancerous; salpingooophorectomy includes surgical excision of one or both ovaries for the same reason. Cancers diagnosed or treated: Invasive cervical, uterine, and ovarian cancers; hydatidiform mole; rarely, Fallopian tube cancer Why performed: Salpingectomy is performed in order to remove and examine tubal or tubo-ovarian masses suspicious for cancer and to determine the extent of malignant disease spread. These masses may be fluid-filled (cystic), solid, or mixed and can also be hormone-secreting or hormone receptive. A salpingo-oophorectomy is often performed alongside a hysterectomy in women who are postmenopausal and are suspected of having an endometrial, tubal, and/or ovarian mass at risk for encroaching on other pelvic organs. It is also performed in women of childbearing age who have a suspected malignancy and have completed their families. Women with localized, unilateral disease who still wish to bear children may have only the diseased Fallopian tube and ovary removed, although this is not recommended in the light of the more common occurrence of disease in both tubes and ovaries. Salpingo-oophorectomy may also be done to remove masses of an infectious origin (for example, tubo-ovarian abscess caused by pelvic inflammatory disease) or endometriosis that has irreversibly damaged these organs. A bilateral salpingo-oophorectomy is performed prophylactically when patients are at high risk for developing gynecologic cancers associated with BRCA1 and BRCA2 gene mutations, particularly ovarian and breast cancers.
Salem Health: Cancer
Salpingectomy and salpingo-oophorectomy
Patient preparation: The patient undergoes preoperative evaluation for any contraindications to the procedure (such as a pregnancy test) and evaluation of coexisting diseases to determine her fitness to undergo surgery and general anesthesia. Patients are instructed to take nothing per mouth the night before the procedure. Steps of the procedure: After the patient is anesthetized, placed in the lithotomy position, and the vagina, external genitalia, pubic area, and inner thighs have been surgically prepped and draped, a transverse or vertical incision is made above the pubic bone. An incision extended up to the level of the umbilicus is preferred, as it provides a wider surgical field and provides a wider incision through which a large mass can be removed. The incision is taken down to the pelvic cavity. The uterine and ovarian vessels are identified, dissected, and separated from the ureters. The supporting broad, round, and suspensory ovarian ligaments of the Fallopian tubes and ovaries with their vessels are then dissected, isolated, cut, and ligated. In a simultaneous hysterectomy, the uterus and uterine vessels are also dissected away from other pelvic structures, cut, and ligated. When disease extending outside the reproductive tract is suspected, biopsies of suspicious lesions, sampling of lymph nodes around the pelvis and abdominal aorta, and abdominal cavity washings are done. Laparoscopic removal of the Fallopian tubes and ovaries is done in conjunction with a hysterectomy. It is done through two small abdominal incisions through which sleeved trochars accommodating a scope and any of several instruments for probing, grasping, cutting, and cauterizing are inserted. The uterus, Fallopian tubes and ovaries, vessels, and ligaments are dissected, cut, and ligated. The organs are removed vaginally, and the remaining vaginal cuff is closed off.
Other risks include deep vein thrombosis, pulmonary embolism, perforation of the bladder or bowel, and intractable bleeding. Results: Cross-sectional examination of both grossly normal and diseased Fallopian tubes should be done, documenting size, depth of penetration, and location along the length of the specimen, although primary tubal cancers account for only 0.1 to 1.8 percent of all female reproductive tract cancers. When a mass encompassing both Fallopian tube and ovary is encountered intraoperatively, it is presumed to be of ovarian origin until proven otherwise during pathological examination, where tubal tissue is recognized within the mass. A gross and microscopic examination of tubal or ovarian masses may reveal whether they are cancerous by evaluating individual cells and the tissue architecture for signs of cancerous changes. On gross examination, masses that preserve the outer tissue surrounding the ovaries can suggest no malignancy but cannot eliminate the possibility of early invasive cancer. Central necrosis and hemorrhage may be present in large tumors as they outgrow their blood supply but do not necessarily imply malignancy, as they can occur in both benign and malignant masses. Microscopic changes pointing to a nonmalignant origin of the tumor include increased but orderly growth of ovarian cells but no elements of disordered growth of abnormal cells and distortion of the tissue architecture. Microscopic examinations that reveal disordered
After the procedure: The patient is monitored in the postanesthesia care unit until she is fully awake and her vital signs are stable. Once the patient is stable in unit, she may be discharged to the gynecologic ward for postoperative monitoring. Once the patient is stable, ambulatory, urinating, and eating, she may be discharged home after a few days. Risks: The most significant risk of a salpingectomy is an ectopic pregnancy.
A salpingo-oophorectomy. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Sarcomas, soft-tissue
Salem Health: Cancer
growth and abnormal cells of tubal or ovarian origin are suggestive of Fallopian tube cancer or ovarian cancer. An invasive hydatidiform mole that has spread from the uterus can exhibit characteristic cells and tissues of placental and fetal origin. Lymph node samples and washings from the abdominal cavity possessing cancerous cells strongly suggest microscopic spread outside the reproductive tract. Aldo C. Dumlao, M.D. u For Further Information Haas, Adelaide, and Susan L. Puretz. The Woman’s Guide to Hysterectomy: Expectations and Options. Berkeley, Calif.: Celestial Arts, 2002. Memorial Sloan-Kettering Cancer Center. “CancerReducing Benefits of Preventive Surgery May Be Specific to Gene Mutation.” Science Daily, June 5, 2006. Also available at http://www.science daily.com. Rosenthal, Sara M. The Gynecological Sourcebook. 4th ed. New York: McGraw-Hill, 2003.
See also BRCA1 and BRCA2 genes; Cervical cancer; Fallopian tube cancer; Gynecologic cancers; Hydatidiform mole; Hysterectomy; Hystero-oophorectomy; Laparoscopy and laparoscopic surgery; Oophorectomy; Ovarian cancers; Pregnancy and cancer; Risks for cancer; Uterine cancer.
u Sarcomas, soft-tissue Category: Diseases, symptoms, and conditions Also known as: Rhabdomyosarcoma, leiomyosarcoma, hemangiosarcoma, Kaposi sarcoma, lymphangiosarcoma, synovial sarcoma, neurofibrosarcoma, liposarcoma, fibrosarcoma, mesothelioma Related conditions: Osteosarcoma, bone cancer Definition: Sarcomas are divided into two categories: sarcomas of bone and sarcomas of soft tissue. Soft-tissue sarcomas describe a class of malignant tumors that develop from connective tissue, which usually derives from an embryonic layer called mesoderm, is involved in structural support, and is found in linings or coverings of muscle, organs, nerves, and joints. These sarcomas can develop in any part of the body. However, more than half arise in the arms or legs, just under 20 percent in the head and neck area, and the rest in the internal organs. Risk factors: The cause of most soft-tissue sarcomas is unknown; however, for some, there may be an association with heredity, radiation therapy, immune disorders, or en1062
A scanning electron micrograph of a sarcoma cell. (Steve Gschmeissner/Photo Researchers, Inc.)
vironmental factors. For example, sarcomas may follow radiation therapy used in treating thyroid disease, breast cancer, lymphoma, or tuberculosis of the skin. Historically, sarcoma develops about ten years after such treatment. For some soft-tissue sarcomas, there is an inherited component. Heredity plays a part in about 5 percent of patients stricken with neurofibromatosis, a benign but often disfiguring condition of the nerves in which the sarcoma may develop in the surrounding connective tissue sheaths. Additionally, there is an increased sarcoma risk associated with inherited diseases such as Gardner syndrome, LiFraumeni syndrome, intestinal polyposis, tuberous sclerosis, basal cell nevus syndrome, and retinoblastoma. Genetic testing has linked soft-tissue sarcoma with a mutated tumor-suppressor gene in some cases and heritable chromosome rearrangement in others. The most prominent environmental risk factor is the association between asbestos and mesothelioma. The connection is so strong, in fact, that it is unlikely that the disease is produced in any other way. The mesothelium is a protective connective tissue lining covering most of the body’s internal organs, including lungs (pleura), the abdominal cavity (periosteum), and the heart (pericardium). Mesothelioma usually occurs in job-related settings where asbestos dust is prevalent. Some investigators have named vinyl chloride, dioxin, and herbicides containing the chemi-
Salem Health: Cancer
Sarcomas, soft-tissue
cal phenoxyacetic acid as causative agents for other softtissue sarcomas, but the association is weak. Viruses are the cause of Kaposi sarcoma in people with defective immune systems. Kaposi sarcoma usually involves the skin but may affect other areas as well. Etiology and the disease process: Whatever its origin or cause, a sarcoma begins as a solid mass that grows from a central point outward with the least mature elements on the periphery. Surrounding the mass is a pseudocapsule, which is composed of compressed tumor cells bordered by inflammatory cells and fibrous components. The degree of pseudocapsule containment may have important implications on the progress of the tumor and the prognosis of the disease. Sarcomas generally are contained within anatomical borders such as muscle sheaths, but as the disease progresses, these borders are challenged and the tumor grows into new compartments until these are also breached. Compartmental breakdown poses special challenges for the surgeon and radiologist. Incidence: Soft-tissue sarcoma is a relatively uncommon malignancy representing about 1 percent of all cancers. It has an annual incidence in the United States of just under 9,300 cases, with women affected slightly less than men. Approximately 3,500 people die of soft-tissue sarcoma annually. The average occurrences of the most prevalent forms are fibrosarcoma, 23 percent; liposarcoma, 19 percent; rhabdomyosarcoma, 13 percent; synovial sarcoma, 8 percent; and neurofibrosarcoma, 5 percent of total softtissue sarcomas. Symptoms: Symptoms will vary with the location, size, and type of the softtissue sarcoma. For example, a sarcoma may appear as a seemingly harmless lump under the skin or as an abdominal growth that exhibits symptoms only after it becomes quite large. As the sarcoma grows and presses on nearby organs, nerves, muscles, or blood vessels, symptoms will correspond to the degree of interference with those tissues. For example, pressure on the nerves may result in pain or paralysis, while interference with the blood supply may cause an accumulation of fluid in the surrounding tissue spaces (edema). Similarly, restriction in mobility follows joint involvement, and internal growths may cause obstructions of the bowel, urinary
tract, or chest cavity. As the tumor progresses, signs such as weight loss, fever, and fatigue may become apparent. Additionally, specific endocrine gland involvement may cause goiter, hypoglycemia, or pituitary dysfunction. Screening and diagnosis: Early detection brings the most favorable result. However, the tumor is usually painless and often will grow unobserved. Once a tumor is suspected, imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI), radioisotope studies, and tissue biopsy will help define its aggressiveness and characteristics. Additionally, arteriograms are useful in defining the extent of tumor growth and in outlining the irregularity of the vascular network. Chest films using CT scans are essential in evaluating metastatic spread to the lungs. The pathologist examining the biopsy tissue pays close attention to how fast the cells are dividing and compares the tissue’s structure to the surrounding normal tissue. The information from the biopsy report allows for formal grading and staging of the sarcoma. All the information from the biopsy, imaging, staging, and past experience sets the best course of treatment and gives an estimate of the patient’s prognosis. The pathologist grades the sarcoma according to the degree of new blood vessels supplying the tumor, how far it has reached into surrounding tissues, how fast the cells are dividing (mitosis), and their degree of structural abnormality. The grading systems vary somewhat according to the parameters set by the Musculoskeletal Tumor Society (MTS) or the American Joint Committee (AJC), but both are a measure of the tumor’s aggressiveness.
Common Sarcomas Sarcoma
Tissue
Typical Location
Fibrosarcoma Hemangiosarcoma Kaposi sarcoma Leiomyosarcoma
fibrous tissue blood vessels blood vessel walls smooth muscle
Liposarcoma Lympangiosarcoma
fatty tissue lymph vessels
Mesothelioma Neurofibrosarcoma Rhabdomyosarcoma Synovial sarcoma
mesothelium peripheral nerves skeletal muscle synovial tissue
arms, legs, trunk arms, legs, head, trunk general locations uterus, gastrointestinal tract, blood vessel linings arms, legs, trunk arms, or area exposed to radiation lungs, heart, intestine arms, legs, trunk arms, legs joints
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Sarcomas, soft-tissue Staging further defines the tumor by characterizing its aggressiveness and anatomic profile. The designation T1 indicates a tumor less than 5 centimeters (cm), T2 more than 5 cm, and T3 signifies the invasion of major blood vessels, nerves, or bones. The letter N describes the presence or absence of metastasis to the local lymph nodes and respectively receives an N1 or N0 description. Similarly, M1 or M0 represents the presence or absence, respectively, of metastasis to distant areas. The sarcoma is staged from IA through IVB depending on severity. For example, at the lower end of the system the tumor might receive the most favorable grade (G) of 1A and its GTNM parameters might look like this: G1, T1, N0, M0. At the opposite extreme, the GTNM description would have this designation: G3, T3, N1, M1. Treatment and therapy: The staging system combined with tumor location sets the course of treatment. The treatment decisions incorporate surgery, radiation therapy, and possibly chemotherapy in a multidisciplinary approach. Typically, surgery alone is reserved for grade 1 tumors, where the surgeon is able to incise the tissue using wide margins. Generally, however, surgery alone invites recurrence. Combining surgery with radiation allows for less radical surgery and may eliminate the need for such debilitating outcomes as amputation. Soft-tissue sarcomas are not always what they seem. They may appear well encapsulated, but there is no true capsule, and the surgeon must resect the tumor beyond its apparent margins. This requires using wide or even radical incisions when extracting the tumor and may include limb amputation. In the past, less aggressive surgical removal resulted in recurrence in almost a third of the cases, effectively doubling the likelihood of metastasis. Conversely, aggressive surgery combined with radiation therapy and possibly chemotherapy results in recurrence rates as low as 5 percent. Like surgery, radiation therapy usually targets a larger area than seems affected. Past experience with sarcomas dictates the total destruction of the primary tumor, as any recurrence is associated with metastasis and a poor prognosis. Because of this, maintaining function or anatomical form is an important but secondary consideration. Softtissue sarcomas tend to grow along fascial planes, which are the connective tissue surrounding muscles, bones, organs, nerves, blood vessels, and other structures, and accordingly, this is factored in during treatment. Radiation therapy may be used before or after surgery, and there are advantages and disadvantages to each, but the effectiveness is the same. Beyond traditional radiation therapy, techniques using 1064
Salem Health: Cancer intraoperative irradiation and interstitial implantation are coming into use. Intraoperative radiation therapy ( IORT) sends a concentrated beam of radiation directly into the exposed sarcoma during surgery. This technique allows doctors to administer high doses of radiation to tumors without exposing nearby healthy organs to radiation. Interstitial implantation is a radiotherapeutic technique in which the physician implants radioactive isotopes directly into tissue. Chemotherapy, although gaining status with newer drug combinations, still has limited use and has resulted in mixed outcomes when applied to soft-tissue sarcomas. The four-drug program CYVADIC—cyclophosphamide, vincristine, doxorubicin (Adriamycin), dacarbazine (DTICDome)—has yielded some encouraging results, as has the combination of methotrexate and cisplatin, especially in more advanced sarcomas. Although chemotherapy results in mixed outcomes, it has found a place when used for limb salvage together with surgery and irradiation. Newer forms of therapy being investigated include angiogenesis inhibitors that block the formation of blood vessels feeding the tumors and biological therapies that enlist the body’s own immune system in the fight against the disease. Prognosis, prevention, and outcomes: Prognosis depends on the health of the patient; the size, location, type, grade, and stage of the tumor; and whether the tumor has recurred. For example, sarcomas of the arms or legs respond better than those of other locations, and older patients generally have a poorer result. When the tumor is still small and localized, the five-year survival rate is about 90 percent. As the tumor becomes more aggressive, survival becomes increasingly difficult. Recurrence rates rise considerably when the tumor exceeds 10 cm in diameter, and beyond 20 cm, there is little hope of containment. Location of the tumor is critical. When tumors arise in the extremities, they are usually noticed earlier, are easier to remove surgically, and are more amenable to radiation therapy. Conversely, tumors in the pelvis, chest, paraspinal region, neck, and abdomen pose greater barriers to complete resection and effective radiation therapy. In general, lymph node metastasis is uncommon, with an overall incidence of 5 to 15 percent. According to the National Cancer Institute (NCI), the five-year survival rate for sarcomas as a group is 68 percent. Included in the overall picture is a five-year survival rate of 84.1 percent for localized sarcomas; 61.5 percent for regional stage sarcomas; 16.3 percent for sarcomas with distant spread; and 54.3 percent for unstaged sarcomas. Over 90 percent of those living beyond five years
Salem Health: Cancer
Saw palmetto
reach the ten-year mark. Considering this, the NCI states that survival beyond five years is tantamount to being cured. Specifically, the metastasis-free survival rates are 75 percent for all grade 1 tumors, 71 percent for grade 2 tumors, and 41 percent for grade 3 tumors. Richard S. Spira, D.V.M.
u Saw palmetto
u For Further Information Albritton, K. H. “Sarcomas in Adolescents and Young Adults.” Hematology/Oncology Clinics of North America 19 (2005): 527-546. Geisinger, K. R., et al. “Soft-Tissue Sarcoma.” New England Journal of Medicine 353 (2005): 2303-2304. Ghert, M. A., et al. “The Surgical and Functional Outcome of Limb-Salvage Surgery with Vascular Reconstruction for Soft-Tissue Sarcoma of the Extremity.” Annals of Surgical Oncology 12 (2005): 1102-1110. Liu, J., et al. “Wild-Type p53 Inhibits Nuclear Factor-κBInduced Matrix Metalloproteinase-9 Promoter Activation: Implications for Soft-Tissue Sarcoma Growth and Metastasis.” Molecular Cancer Research 4 (2006): 803-810. Meyer, W. H., and S. L. Spunt. “Soft-Tissue Sarcomas of Childhood.” Cancer Treatment Reviews 30 (2004): 269-280. Zhang, L., et al. “Vascular Endothelial Growth Factor Overexpression by Soft-Tissue Sarcoma Cells: Implications for Tumor Growth, Metastasis, and Chemoresistance.” Cancer Research 66 (2006): 8770-8778.
Definition: Saw palmetto, or Serenoa repens, is a small fan palm native to the Atlantic and Gulf coastal plains that can be found as far inland as southern Arkansas. The olivesized fruit of this plant is enriched with fatty acids and phytosterols, and its extracts have been the subject of research for the treatment of certain cancers, especially prostate cancer.
u
Other Resources
MayoClinic.com Soft-Tissue Sarcoma http://www.mayoclinic.com/health/ soft-tissue-sarcoma/DS00601 National Cancer Institute Soft-Tissue Sarcoma http://www.cancer.gov/cancertopics/types/ soft-tissue-sarcoma See also Alveolar soft-part sarcomas; Bone cancers; Childhood cancers; Computed tomography (CT) scan; Endotheliomas; Ewing sarcoma; Fibrosarcomas, soft-tissue; Gallium scan; Gastrointestinal stromal tumors (GISTs); Hemangiopericytomas; Hemangiosarcomas; Hyperthermic perfusion; Li-Fraumeni syndrome (LFS); Limb salvage; Liposarcomas; Malignant fibrous histiocytoma (MFH); Mesenchymomas, malignant; Rhabdomyosarcomas; Spinal axis tumors; Synovial sarcomas; Tumor lysis syndrome; Young adult cancers.
Category: Lifestyle and prevention; complementary and alternative therapies Also known as: Serenoa repens, Sabal serrulatum, Permixon
Cancer treated or prevented: Prostate cancer Delivery route: Oral by capsule How this substance works: Used as an herbal supplement, saw palmetto is considered to be safe, effective, and relatively inexpensive. It enjoys widespread use in the United States but is also popular in Germany and France for the treatment of prostate disorders. Saw palmetto inhibits 5-alpha-reductase, an enzyme that converts testosterone into its most potent form, dihydrotestosterone (DHT). Its effects have been compared to Proscar (finasteride), which is a prescription drug that results in the shrinkage of an enlarged prostate, a condition called benign prostatic hyperplasia (BPH). While studies of the efficacy of saw palmetto are somewhat inconsistent, it largely lacks the adverse side effects of Proscar, such as decreased libido and gastrointestinal irritation. The most studied form is Permixon, which is made by using hexane as a solvent in the extraction process of the sterols and fatty acids found in the dried fruits of the saw palmetto berry. Other mixtures include ethanol, methanol, or less commonly nettle root or pumpkin seed oils. Although the extract is much studied, it is not fully understood which are its active components, but phytosterols and fatty acids seem to be the most proficient at treating symptoms. Similarly, the mechanism by which saw palmetto actually works is yet unclear. Some suggest that it acts as an anti-inflammatory, blocks the chemical conversion of testosterone to DHT, or promotes prostate epithelial involution. Whichever is correct, studies have shown that saw palmetto relieves symptoms caused by prostate disorders, including decreased urine stream and flow, post-voidance dribbling, overflow incontinence, and excessive retention of urine in the bladder. Relief of prostate swelling aids a return to sexual function, which also contributes to the popular use of saw palmetto among older men. 1065
Schwannoma tumors Not all studies agree on the therapeutic efficacy of saw palmetto; a double-blind, randomized study by Dr. Stephen Bent of the University of California, San Francisco, and his coworkers that was funded by the National Institutes of Health (NIH) and the National Center for Complementary and Alternative Medicine (NCCAM) found that saw palmetto was no more effective in reducing symptoms associated with BPH than a placebo. This raises the question of whether it is a medically useful substance. Overall, the Moores Cancer Center of the Medical Center of the University of California, San Diego, states that “this treatment modality is thought to manage symptoms of cancer, side effects from conventional therapies and/or control pain.” Researchers warn, however, that saw palmetto should be used as a supplement to cancer treatment, not in place of standard therapy. Side effects: Almost all patients reported that adverse side effects were mild and infrequent, differing little from those reported after placebo use. Some reports indicate that saw palmetto can cause gastrointestinal distress, but this can largely be alleviated by taking saw palmetto with food. Dwight G. Smith, Ph.D. See also Complementary and alternative therapies; Fruits; Herbs as antioxidants; Nonsteroidal anti-inflammatory drugs (NSAIDs); PC-SPES; Prostate cancer.
u Schwannoma tumors Category: Diseases, symptoms, and conditions Also known as: Schwann cell tumors Related conditions: Malignant peripheral nerve sheath tumors (MPNSTs), neurofibromatosis, schwannomatosis Definition: Schwannoma is a benign (noncancerous) encapsulated solitary tumor formed by Schwann cells of the peripheral nerves: cranial nerves, spinal nerves, and autonomic nerves. Schwannomas generally occur in the head, neck, and upper and lower limbs. A common cranial nerve schwannoma is the vestibular schwannoma (unilateral and nonhereditary), which affects the eighth cranial nerve, which governs hearing and balance. Other schwannommas include trigeminal, facial, and hypoglossal. Less than 1 percent of schwannomas become cancerous. When schwannomas are found in children, they are usually associated with neurofibromatosis. Schwannomatosis is newly identified neurofibromatosis of multiple schwannomas. Risk factors: There are no known risk factors for schwannomas. 1066
Salem Health: Cancer Etiology and the disease process: The etiology of schwannomas is unknown. The nerve fiber, or axon, of peripheral nerves is sheathed in glial cells called Schwann cells. Sometimes Schwann cells abnormally proliferate to form a tumor, or schwannoma. The cells of schwannomas are spindle-shaped neoplastic Schwann cells. Incidence: Schwannoma is generally a disease of adults and can commonly occur between the ages of forty and sixty. The incidence rate for vestibular schwannoma is 1 per 100,000 people per year. Symptoms: Schwannomas are generally slow-growing, small, painless tumors, although sometimes they can be painful and be as large as 10 centimeters. Subcutaneous tumors (under the skin) can be palpated during physical examination. In vestibular schwannoma, additional symptoms are hearing loss, dizziness, and ringing in the ears. Other cranial nerve schwannomas can have symptoms related to the function of that nerve. Screening and diagnosis: A medical history and physical examination of the patient plus X rays, ultrasound, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and biopsy are used to diagnose schwannoma. Vestibular schwannoma also requires a hearing test (audiogram). According to the World Health Organization (WHO), schwannoma is a grade I tumor, and malignant peripheral nerve sheath tumors are grades III and IV. Treatment and therapy: Chemotherapy is usually not effective. Radiotherapy and surgery are the main treatments. Rarely occurring malignant tumors may also require chemotherapy. Prognosis, prevention, and outcomes: Schwannomas cannot be prevented. Prognosis is good with early diagnosis and surgery but worsens if the tumor is detected at a later state. For example, an untreated vestibular schwannoma can cause pressure on the neighboring facial nerve, causing paralysis of the face on the affected side, and can further press on the brain stem, even resulting in death. The recurrence rate of malignant peripheral nerve sheath tumors after surgery is high. Arun S. Dabholkar, Ph.D. See also Acoustic neuromas; Brain and central nervous system cancers; Computed tomography (CT) scan; Fibrosarcomas, soft-tissue; Gliomas; Magnetic resonance imaging (MRI); Mediastinal tumors; Neurofibromatosis type 1 (NF1); Orbit tumors; Spinal axis tumors.
Salem Health: Cancer
u SCLC1 gene Category: Cancer biology Also known as: Small-cell carcinoma of lung, smallcell lung cancer (SCLC) Definition: The SCLC1 gene is located on a region on the short arm of chromosome 3 that is frequently deleted in neoplastic lung cells associated with small-cell carcinomas, cells of epithelial origin. Significance: Approximately 110,000 cases of small-cell carcinomas of the lung are diagnosed annually, accounting for some 60 percent of all forms of lung cancer diagnosed yearly. Small-cell carcinomas of the lung are most commonly associated with people exposed to airborne carcinogens, particularly those associated with cigarette smoke. This form of lung cancer is particularly aggressive and has undergone metastasis at the time of diagnosis. SCLC cells frequently express a number of unusual neuroendocrine markers, including dopa-decarboxylase (DDC), and evidence suggests that these cells originate from a form of neuroendocrine cells that differentiate into epithelial cells in the lung. Cancer cells in general arise from mutations that disrupt normal regulation of cell divisions, frequently at the level of internal cell signaling. Expression of neuroendocrine markers in SCLC neoplasms appears to affect the RHOA (ras homolog) family of genes in particular, the products of which are part of the signaling mechanism to stimulate cell division. Other oncogenes also appear to be altered in cell lines originating from SCLC neoplasms. Regulation of oncogenes in a cell in part involves the production of tumor suppressors, proteins that either regulate oncogene expression or serve as stop signals to prevent the cell from undergoing replication. The region of the short arm on chromosome 3 that is deleted, 3p14-23, and specifically the SCLC1 gene, appears to encode one or more tumor suppressors. Deletions of this region of chromosome 3, the region which encodes the SCLC1 gene, appears to take place during the early stages of formation of the neoplasm. Whether the deletion is required for development of this form of cancer is unknown, but this specific mutation seems to occur in nearly all cases of SCLC that have been analyzed. The mechanism of the deletion is also unknown. History: The presence of this particular deletion in smallcell carcinomas of the lung was first noted in 1982. Scientists had established a number of lung-cancer cell lines in the laboratory, the purpose of which was to study characteristics unique to each group; twelve lines originated as
Screening for cancer SCLC cases. All were observed to have the same deletion on chromosome 3, while cells from other lines did not. Richard Adler, Ph.D. See also Bronchial adenomas; Bronchoalveolar lung cancer; Cancer biology; Cigarettes and cigars; Lambert-Eaton syndrome (LEMS); Lung cancers.
u Screening for cancer Category: Procedures; lifestyle and prevention Also known as: Testing, cancer detection Definition: Screening tests are tests or procedures that can detect the presence of a specific cancer in persons who are not experiencing any symptoms. Cancers diagnosed: The most common cancer screenings detect breast, cervical, colorectal, and prostate cancer. Some require a blood test, while others require more extensive screening procedures. Why performed: The purpose of screening tests is to allow early identification of cancer and prevent the progression of any existing cancer. Screening and early detection can save human lives, minimize the trauma of cancer illness, and conserve limited health care resources spent on costly cancer therapies. People participate in screenings for various reasons. Sometimes they see screening as a preventive measure, and sometimes they undergo screening because they are at high risk for a cancer. Often health-conscious people participate in routine cancer screenings, and their health insurance pays the bill. Medicare (health insurance for older adults and the disabled) Part B covers certain key preventive cancer screening tests such as colorectal screening, mammograms, Pap smears and pelvic examinations, and prostate cancer screenings within certain parameters. Screening for cancer offers many advantages for the public. Screening can save the life of someone who may have died without early intervention. When cancer is discovered, treatment can be started immediately and decrease the possibility of radical surgery or therapy. Early intervention also results in lower health care costs. A primary advantage is that the person who receives negative (benign) results has peace of mind that, at that point in time, cancer is not present. This is reassuring for anyone but especially for someone with a family history of cancer or who has other high risks for cancer. However, the disadvantage of screening is that some false negatives may occur so the person does not believe there is a problem even when symptoms surface. Con1067
Screening for cancer
Two Grading Systems for Sarcomas American Joint Committee (AJC) G1 Low-grade G2 Moderately differentiated G3 Poorly differentiated Musculoskeletal Tumor Society (MTS) G1 Well-differentiated G2 High-grade
versely, “false positives” can cause undue anxiety until further tests confirm there is no cancer. Sometimes the screening finds a cancer that is not treatable or is so advanced that the screening does not alter the negative outcome for the person. Another disadvantage is that borderline reports from cancer screenings can result in excessive testing and associated costs. Breast self-exam (BSE): Breast cancer can be detected through several screening tests. One is palpation of the breast tissue through a monthly breast self-examination (BSE). Palpation is a noninvasive way to examine and screen for abnormalities in the breast such as cysts, lumps, or thickening. The patient can be taught to do an examination of her breasts each month and note visual or palpable changes in the breasts. Patient preparation. The patient should stand unclothed from the waist up and view her breasts in a mirror. The best time to complete an examination is a few days after the completion of the menses, when swelling and tenderness are lessened. Steps of the procedure. A breast self-examination is a five-step process: • The woman observes her breasts in the mirror, with her hands on her hips, for any visual changes in color, shape, and size. She looks for dimpling, swelling, or puckering of the skin as well as changes in the nipples or redness or rash on the breast. • She raises her arms over her head and observes the same as above. • She gently squeezes the nipples and observes for any liquid or discharge. (None should be present unless the woman is breast-feeding.) • She lies down and examines each breast with the opposite hand in a circular pattern, starting at the nipple and working outward. She palpates all breast tissue from the collarbone to the abdomen and from the armpit to the cleavage area. • She palpates the breast again in a sitting or standing position in the same pattern. Some women find that the ex1068
Salem Health: Cancer amination is best completed when the skin is wet and slippery, such as in the shower. After the procedure. The woman should record any observation and the date of each examination in a journal to be sure that it is completed monthly, preferably after the menses. This simple screening can detect early changes in the woman’s breasts. Risks. None. Results. The woman makes an appointment with her health care provider if abnormalities are noted. She should schedule her annual examination with the health care provider, which includes a clinical breast exam (CBE). Mammograms: A screening mammogram uses X rays to detect breast cancer. Mammography offers a noninvasive way to screen the breasts for cancer. A screening mammogram is useful when a woman has no history of problems with her breasts. Two X-ray views are taken of each breast. Scheduling the mammogram a week after the menses can decrease the patient’s discomfort, as hormonal soreness or tenderness is less at that time. An annual screening mammogram is recommended primarily for women over the age of forty. A screening mammogram can detect suspicious areas that may be breast cancer long before a mass can be palpated. Patient preparation. The patient should avoid use of powders, deodorant, or lotion before the mammogram, since particles from these products can be viewed as abnormalities on the X ray. The patient completes paperwork such as her history, last menses, risk factors, childbearing, surgeries, implants, birth control, hormone therapy, or any problems. The patient undresses from the waist up and wears an examination gown into the X-ray room. The patient can expect the X rays to take about a half hour. Steps of the procedure. The patient stands in front of the X-ray machine. A radiology technician exposes one breast at a time and places it on a film holder; the breast is compressed for a few seconds between the holder and a plastic paddle to take the X ray. Good compression is necessary for accurate X rays. Next the patient moves her side toward the machine, and the breast is compressed from the side. The X ray is repeated. After the procedure. A radiologist reads the X ray either immediately or at a later time, depending on the facility’s availability to the radiologist. Risks. The risk of radiation exposure through a screening mammogram is considered minimal. Most authorities agree that the benefit of screening for breast cancer outweighs the risk of low-dose radiation. Results. Screening mammograms do not detect breast cancer 100 percent accurately. A normal result means that
Salem Health: Cancer the mammogram detects no abnormalities, though a cancer can be hidden in dense breast tissue. Screening mammograms may be read as borderline, which may suggest that further testing (such as a diagnostic mammogram, ultrasound, or biopsy) is indicated to confirm the diagnosis of breast cancer. Pap smear: The Pap smear is a screening test to detect changes in the cervix that may lead to cervical cancer in women. Early detection can increase the chance of successful treatment. All women need this screening examination, including sexually active women over the age of eighteen and those at risk for cervical cancer, such as women who had a previous abnormal pap smear. This test is usually performed during the woman’s annual gynecological exam. Patient preparation. The woman should avoid douching or using any vaginal medications within forty-eight hours of the test. For accurate results, she should avoid intercourse within twenty-four hours of the screening. Optimal time for a Pap smear is at midcycle of the menses; a Pap smear cannot be performed during the menses. The woman should empty her bladder before the test to decrease discomfort. Steps of the procedure. The Pap smear does not take long to perform. The patient lies on her back with her knees bent and her feet slightly apart. The health care provider will lubricate a speculum (an instrument that holds the walls of the vagina apart) and place it into the vagina. The patient will feel pressure as the provider swabs the cervix for a sample to examine. The sample is swabbed on a glass slide and sprayed with preservative. The slide is sent to the lab for microscopic examination for abnormal cells. After the procedure. There are usually no side effects of this test. The lab results will be sent to the patient. Risks. One risk is a false positive, which would lead to further testing, or a false negative, which might cause the person to ignore other warning signs of cervical cancer. Results. Results are categorized as negative if no abnormal cells are seen. The patient usually receives a written notification of the results. Patients need to seek further testing from their health care provider for abnormalities. Fecal occult blood, sigmoidoscopy, colonscopy: Colon cancer is the third leading cause of cancer death in the United States today. The first screening test for colon cancer is the fecal occult blood sample. This test detects blood in the stool. The next screening is a sigmoidoscopy or colonoscopy. Regular rectal and colon screening is advised in persons over fifty years of age and in those at high
Screening for cancer risk. This includes a fecal test annually, a sigmoidoscopy every five years, and a colonoscopy every ten years after age fifty-five. Patient preparation. Certain medications (aspirin and aspirin products, ibuprofen products, iron tablets, and vitamin supplements) should be avoided for a week before screening. Prescribed medications can usually be taken, but the physician should be consulted. Asigmoidoscopy or colonoscopy requires preparation of the bowel. The exact preparation used may vary by provider preference, but these preparations usually include a diet of clear liquids for twenty-four hours prior to the test as well as a liquid laxative about two to four hours before the examination. Steps of the procedure. Both a sigmoidoscopy and colonoscopy require the insertion of a rigid or flexible tube that contains a lens and a light into the colon. The provider can visualize the rectum, lower colon (or sigmoid colon), or upper colon. After the procedure. Patients may need someone to drive them home after this test, especially if they have sedation. The patient can experience some soreness and mild cramping due to the air that was injected into the colon for the test, but this condition improves as the air is passed. No other aftercare is required. Risks. A slight risk of bleeding is possible, especially when the patient has decreased clotting capacity. A perforated (torn) colon is a serious but rare complication following a sigmoidoscopy or colonoscopy. Results. A normal result is one where the colon walls are smooth and without polyps, inflammation, or tumors. An abnormal result would be present when the colon shows precancerous polyps or tumors. A biopsy and surgical removal of the polyps or tumors would be scheduled. Digital rectal exam (DRE) and prostate-specific antigen (PSA) blood test: Prostate cancer is the second leading cause of death in men sixty-five years of age or older. By the age of fifty, men should have screening tests for prostate cancer; in high-risk men, screening should start at the age of forty-five. The main screening tests for prostate cancer are digital rectal exam (DRE) and the prostatespecific antigen (PSA) blood test. The prostate is the male reproductive organ located under the bladder and in front of the rectum. Patient preparation. No special preparation is required. Steps of the procedure. For the digital rectal exam, the patient is dressed in an examination gown and placed in a relaxed position (such as lying on his side or resting over an exam table) with the rectum accessible. The doctor inserts a well-lubricated, gloved finger into the rectum and feels the size of the prostate. 1069
Second opinions After the procedure. No residual patient discomfort occurs. Risks. None. Results. If abnormal results are reported from either the digital rectal exam or prostate-specific antigen test, the patient will need further testing to confirm a cancer diagnosis. Marylane Wade Koch, M.S.N., R.N. u For Further Information Finkel, Madelon L. Understanding the Mammography Controversy: Science, Politics, and Breast Cancer Screening. Westport, Conn.: Praeger, 2005. Miller, Anthony B., ed. Advances in Cancer Screening. Boston: Kluwer Academic, 1996. Querna, Elizabeth. “Breast Cancer Screening: What Is the Best Way to Find Out If You Have the Disease?” U.S. News & World Report, September 9, 2004. u
Other Resources
Centers for Disease Control National Breast and Cervical Cancer Early Detection Program http://www.cdc.gov/cancer/nbccedp/about.htm MayoClinic.com Prostate Cancer Screening: Should You Get a PSA test? http://www.mayoclinic.com/health/prostate-cancer/ HQ01273 National Cancer Institute Screening and Testing to Detect Cancer http://www.cancer.gov/cancertopics/screening See also Biopsy; Bone scan; Brain scan; Breast selfexamination (BSE); Breast ultrasound; Clinical breast exam (CBE); Colorectal cancer screening; Complete blood count (CBC); Core needle biopsy; Genetic testing; Imaging tests; Magnetic resonance imaging (MRI); Mammography; Nuclear medicine scan; Pap test; Positron emission tomography (PET); Radionuclide scan; Testicular self-examination (TSE); Ultrasound tests; Urinalysis; X-ray tests.
u Second opinions Category: Social and personal issues Definition: A second opinion is a medical diagnosis from a health care professional who was not the patient’s initial source of information. There are two types of second opinions. In one, the patient gives the second doctor all previous medical test results, sharing information and concerns 1070
Salem Health: Cancer from the first doctor. In the other, the patient sees the second doctor and starts over with all new testing, so that the new opinion is not influenced by that of the first doctor. This is difficult to do if the two doctors are in the same health maintenance organization (HMO), as the medical records within an organization are shared information. Other sources of advice: Before, or in addition to, asking another doctor for an opinion, patients can review their test results and ask their health provider questions about them. Patients may want to determine how likely false positives and false negatives are for the tests that they took. Cancer patients can use readily available resources to help evaluate their medical condition: Internet (WebMD, Mayo Clinic, American Cancer Society, National Cancer Institute), books (local bookstore, public library, medical or hospital library), and pamphlets from cancer organizations, cancer hospitals, or government sources (American Cancer Society, Centers for Disease Control and Prevention). Friends and relatives who have had cancer may be able to provide advice, although specificity may be lacking. Alternative medicines and treatments may offer another perspective on cancer, although many may lack scientific evidence as to their efficacy. Media can serve as a source of information about current medical advances and new treatments for cancer. Information on clinical trials is available through the registry of federally and privately supported clinical trial conducted in the United States and worldwide provided by the U.S. National Institutes of Health. Financial and insurance issues: Second opinions are usually not covered by insurance. Patients should call their insurance company to determine if second opinions are covered and what the cost would be for retesting and reevaluation. Some insurance plans require preauthorization for some tests, which may take several weeks. Preauthorization may also be needed if patients wish to see a specialist in their particular cancer. Patients are advised to keep a list of names, phone numbers, and conversations to avoid insurance confusion. Time factor: The severity or extent of the cancer can make it necessary that the patient start treatment as soon as possible, leaving little time for a second opinion. Patients are advised to take the earliest appointments possible, so that a second opinion does not delay treatment too much. The final decision: Cancer patients must feel at ease with their final decisions and be willing to live with the consequences, whether the outcome is positive or negative. Second opinions, particularly where cancer is concerned, can
Salem Health: Cancer facilitate confidence in these decisions, allowing patients to trust their chosen medical team, as they will be working together for an extended period of time. Suzette Buhr, R.T.R., C.D.A. See also Cancer care team; Clinical trials; Elderly and cancer; Financial issues; Health maintenance organizations (HMOs); Insurance; National Cancer Institute (NCI); Preferred provider organizations (PPOs).
u Self-image and body image Category: Social and personal issues Definition: Self-image refers to a person’s perception of his or her personality and physical, mental, spiritual, and social characteristics. Body image contributes to selfimage and refers to how people view their physical appearance and functioning. Cultural influences: In contemporary culture, physical appearance influences how individuals perceive themselves and how others judge them. Messages from popular media celebrate physical beauty and encourage people to aspire to idealized standards of appearance. Body image has a strong influence on most people’s overall self-image, and physical changes can powerfully affect how they view themselves. People with cancer commonly experience changes in their bodies resulting from the disease and its treatments. Changes may involve physical appearance, how a person feels, or how well they function. The extent to which these changes influence cancer patients’ images of themselves and their bodies is influenced by factors such as the severity and permanence of these changes, the stage of life in which they occur, and the personality traits of the individual.
Self-image and body image can significantly affect how cancer patients feel about themselves and their bodies. Activities previously accomplished with ease may be markedly more difficult or even impossible to perform because of pain or reduced strength. These experiences can sap cancer patients’ confidence and lessen views of themselves as competent, effective, and independent individuals. Cancer patients may feel “betrayed” by their bodies and perceive themselves as deficient, even after surviving their illness. Changes in functioning: Changes in body functioning caused by cancer can also affect people’s self-perceptions. Some types of cancer may result in the loss of limbs or other body parts and markedly alter independence and functionality. Cancer treatment may change how patients eliminate body waste and necessitate the use of colostomy bags (for bowel movements) or urostomy bags (for passing urine). Other treatments can cause sterility or alter sexual functioning. These circumstances can shake the foundation of patients’ self-perceptions and require considerable ongoing coping and adaptation.
Changes in appearance: Visible changes in appearance, stemming from the cancer itself or from its treatment, can profoundly affect body image. Overt changes may cause cancer patients to be highly focused on appearance and hypersensitive to attention from others (such as questions about health). Insecurity over appearance often leads to distress and diminished body image. Hidden or less visible changes in appearance (such as breast or testicle removal and surgical scarring) can still cause significant anxiety, alter self-perceptions, and lead to a person’s avoiding interactions and intimacy with friends and family at a time when social and family support is a vital component to successfully coping with cancer. Changes in how the body feels: Illness-related factors (such as pain) and treatment side effects (such as fatigue)
A chemotherapy patient is fitted for a wig. (© Owen Franken/ Corbis)
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Self-image and body image Permanence of changes: Whether physical changes caused by cancer are temporary or permanent affects the extent to which these changes alter body image. For most patients with cancer, altered self-perceptions resulting from temporary physical changes, such as hair loss or weight loss, are limited to the duration of treatment. Most regain former perceptions of their body and self when these changes disappear. Some individuals continue to struggle with altered body image and view themselves as “damaged” even after treatment has ended. Permanent physical changes resulting from cancer typically have a bigger impact on body image. A period of bereavement, involving initial shock, “numbing,” anger, and denial, may be seen in some patients. Most patients employ coping mechanisms developed before their illness to adapt to their altered physical state. Other patients have significant long-term struggles in dealing with their changed appearance or functioning and may develop psychiatric illnesses such as anxiety and depression. Developmental considerations: The age and developmental level at which cancer occurs influence patients’ self-perceptions. Cancer-related factors causing children and adolescents to feel nauseated or weak or to look sick or what the young person perceives as different from others can make it hard for them to develop healthy self-images and body images. Young adults with cancer may feel unattractive and “damaged” and fear that they will never find a mate. Older adults with cancer may fear abandonment from loved ones or loss of social or occupational standing resulting from looking unhealthy. Cancer and associated functional loss in geriatric patients may bolster established fears of losing control and independence. Personality factors: Personality, coping style, and selfperceptions before the illness influence how cancer affects people’s self-image. People who are optimistic, flexible, emotionally expressive, and willing to accept emotional support appear to adapt best to stressors caused by cancer, including those related to body image. Also, those with a robust self-esteem before their illness appear to cope well. People whose feelings of self-worth were closely tied to their appearance before they developed cancer, who have difficulty accepting emotional support, and who have histories of psychiatric illness appear to have the most difficulty adapting to physical changes associated with their illness. Management approaches: A number of approaches have been identified to assist individuals with cancer to maintain or enhance their self-image and body image. Participation in support groups in which cancer patients and sur1072
Salem Health: Cancer vivors discuss their experience with illness and share methods of coping has been found to promote healthy adaptation. Using wigs, hats, scarves, or makeup may boost confidence in appearance and increase social interaction and acceptance of support. Participating in treatment and rehabilitation efforts and developing alternate interests and skills to take the place of those that are no longer possible as a result of cancer can increase physical confidence. Keeping a healthy diet, engaging in exercise, and maintaining good sleep habits help those with cancer reestablish a sense of control over their bodies. Finally, cancer patients and survivors struggling with self-image and body image concerns or psychiatric illness are advised to seek or be referred for mental health care, as a number of effective psychological and medical treatments exist. Paul F. Bell, Ph.D. u
For Further Information Gatchel, Robert, and Mark Ooordt. Clinical Health Psychology and Primary Care. Washington, D.C.: American Psychological Association, 2003. Goldman, Larry, Thomas Wise, and David Brody. Psychiatry for Primary Care Physicians. Chicago: American Medical Association, 1998. Sadock, Benjamin James, and Virginia Alcott Sadock. Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences—Clinical Psychiatry. 10th ed. Philadelphia: Wolter Kluwer/Lippincott Williams & Wilkins, 2007.
u
Other Resources
American Cancer Society Look Good . . . Feel Better http://www.cancer.org/docroot/ESN/content/ ESN_3_1X_Look_Good_Feel_Better .asp?sitearea=EMP Cancer.Net Self-Image and Cancer http://www.ascocancerfoundation.org/patient/ Coping/Emotional+and+Physical+Matters/ Self-Image+and+Cancer See also Aging and cancer; Aids and devices for cancer patients; Amputation; Breast reconstruction; Counseling for cancer patients and survivors; Exercise and cancer; Fatigue; Hereditary polyposis syndromes; Ileostomy; Limb salvage; Nausea and vomiting; Personality and cancer; Psychosocial aspects of cancer; Rehabilitation; Sexuality and cancer; Sterility; Stress management; Support groups; Young adult cancers.
Salem Health: Cancer
u Sentinel lymph node (SLN)
biopsy and mapping Category: Procedures Definition: A sentinel lymph node (SLN) biopsy is a procedure in which the first lymph nodes to which cancer is likely to spread from the primary tumor are removed and examined to determine whether cancer cells are present. The process of identification of the SLNs is called SLN mapping. Cancers diagnosed or treated: Mainly breast cancer and malignant melanoma; SLN is being studied for use with other cancer types Why performed: Cancer cells spread first to one or several lymph nodes, called the sentinel lymph nodes (SLNs), before spreading to more distal lymph nodes and other sites in the body. Determining whether a SLN contains cancer cells provides the doctor with valuable information about whether the cancer has spread from its primary location. Patient preparation: A small dose of a radioactive tracer compound and a blue dye are injected near the patient’s tumor several hours before surgery to allow these chemicals time to travel from the tumor region to any SLNs. Steps of the procedure: Once the radioactive tracer compound and dye have reached the lymph nodes, the surgeon scans the area with a small Geiger counter and removes the radioactive lymph nodes through a small incision, using the presence of the blue dye for additional visual confirmation. A pathologist performs a preliminary examination of the nodes under a microscope, and if cancerous cells are seen while the patient is still in surgery, additional lymph nodes may be removed at that time. After the procedure: Pain or bruising at the biopsy site and temporary discoloration of urine or skin may occur. Some patients report postoperative nerve damage or swelling caused by lymph fluid accumulation in the area of the surgery. Rarely, a patient may be allergic to the blue dye used for sentinel node identification. Patients undergoing the procedure typically spend one day or less in the hospital.
Sertoli cell tumors cancer has not spread to the lymph nodes, and a positive result indicates that cancer is present in the SLN and therefore may be present in other lymph nodes. In this case, removal of other lymph nodes in the area may be performed. Jill Ferguson, Ph.D. See also Axillary dissection; Biopsy; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Lymphadenectomy; Lymphangiography; Lymphedema; Mastectomy; Melanomas; Merkel cell carcinomas (MCC); Penile cancer.
u Sertoli cell tumors Category: Diseases, symptoms, and conditions Also known as: Androblastomas, large-cell calcifying Sertoli cell tumors, sclerosing Sertoli cell tumors Related conditions: Leydig cell tumors, Sertoli-Leydig cell tumors of the ovaries Definition: Sertoli cell tumors are rare, typically benign tumors that form in the Sertoli cells of the testes, which nourish the sperm-producing germ cells. Risk factors: Sertoli cell tumors are believed to arise from genetic abnormalities. Having a family history of testicular cancer may increase the risk. Sertoli cell tumors are often associated with Peutz-Jeghers syndrome (PJS), a rare inherited condition that causes many noncancerous growths to form in the stomach and intestines. Etiology and the disease process: Sertoli cell tumors are thought to arise from chromosomal abnormalities. Benign tumors do not typically progress, but malignant tumors can spread to the lymph nodes, bone, liver, or lungs. Incidence: Sertoli cell tumors account for only 1 to 3 percent of testicular tumors. These tumors are almost always benign in children but are cancerous in approximately 20 percent of the adults who have them.
Risks: A low percentage of SNL biopsies for breast cancer can turn out to be negative when other lymph nodes in the area do contain cancer.
Symptoms: Sertoli cell tumors are often painless and produce no symptoms, aside from a lump in the testicles. In rare cases, these types of tumors can release male or female hormones. Release of the female hormone, estrogen, can cause the patient to develop symptoms such as breast tenderness and enlargement, or loss of sexual desire. Release of the male hormone testosterone can cause boys to go into puberty prematurely.
Results: Doctors use SLN biopsy results to help determine the stage of cancer. A negative result implies that the
Screening and diagnosis: The doctor will feel the testicles and abdomen to identify any lumps or masses. An ul1073
Sexuality and cancer trasound can be used to visualize the tumor. If the tumor is cancerous, the patient may have a computed tomography (CT) scan of the abdomen and pelvis, and a chest X ray to determine disease progression. Treatment and therapy: Surgery to remove the testicles (orchiectomy) is the standard treatment for Sertoli cell tumors. In younger patients, the surgeon will attempt to spare the testes from significant damage. Cancerous tumors can be treated with chemotherapy, radiation, and surgery to remove the involved lymph nodes. Prognosis, prevention, and outcomes: There is no way to prevent Sertoli cell tumors. The prognosis is good for children with nonmalignant tumors who have surgery to remove the tumor. Following surgery, patients may need to be monitored for several years to check for a recurrence. Stephanie Watson, B.S. See also Benign tumors; Cobalt 60 radiation; Computed tomography (CT) scan; Family history and risk assessment; Leydig cell tumors; Orchiectomy; Peutz-Jeghers syndrome (PJS); Testicular cancer; Ultrasound tests.
u Sexuality and cancer Category: Social and personal issues Definition: A substantial number of men and women with cancer report some negative effect of the disease or its treatment on their sexual lives. Some studies report that a majority of cancer patients experience long-term problems with sexual function. Sexual response: Sexual response is often categorized into several components or dimensions, all of which can be affected by cancer and cancer treatment. Sexual desire refers to the experience of sexual thoughts, fantasies, daydreams, or desire for sexual activity. Sexual arousal comprises physiological and psychological events in preparation to engage in or continue sexual activity, including erection of the penis, lubrication of the vagina, and subjective feelings of excitement or anticipation. Orgasm is a peak of physiological and psychological arousal usually accompanied by rhythmic pelvic muscular contractions and intense pleasure, often (but not always) followed by resolution of sexual arousal and feelings of relaxation and well-being. In men, orgasm is usually accompanied by emission and ejaculation of semen. Sexuality is not merely the sum of sexual responses but also comprises a person’s self-concept as a sexual person, preferences for sexual partners and sexual activities, inter1074
Salem Health: Cancer actions with current and potential future partners, and experience within a sexual culture. Sexual values, ideals, and scripts are often rooted early in life and develop over a period of many years. In the face of serious illness, deeply held sexual beliefs can help or hinder recovery toward a satisfying sexual life. Effects of cancer on sexuality: Generally, the effects of cancer on sexuality are both physical and psychological. The emotional distress of living with cancer can take an even larger toll when combined with the physical impact of the disease. Tumors of certain size and location can directly affect physical aspects of sexual function, particularly when they interfere with nerve and blood vessel pathways important to sexual function. More commonly, however, sexual function is affected by treatment-related side effects such as fatigue, nausea, changes to physical appearance, and pain. In advanced cancers, the discomfort and fatigue associated with disease are also likely to limit sexual expression. Effects of treatment on sexuality: Although the effects of any cancer and its treatment can threaten to disrupt sexual function, certain types of cancers are especially high risk. Cancers of the reproductive organs (such as the cervix, ovary, uterus, vagina, prostate, testicle, penis) are associated with a high rate of sexual problems that often persist after treatment because of the potential for damage to nerves, blood vessels, and other tissues involved in sexual responses. Other cancers of the pelvic region and lower abdomen, such as bladder, colorectal, and anal cancers, may also affect sexual function due to the organs’ proximity to and shared neurovascular environment with the reproductive system. In women, breast cancer may affect sexual function through negative effects on body image, particularly when the breasts are strongly connected with sexual attractiveness and femininity, and through posttreatment alteration of pleasurable breast sensations. Chemotherapy: In addition to fatigue and other general physical symptoms, systemic chemotherapy can cause changes to testicular and ovarian function that decrease the production of sex hormones (testosterone and estrogen). These changes may result in decreased sexual desire and problems with sexual arousal, such as erectile dysfunction and poor vaginal lubrication. Although in men the hormonal effects of chemotherapy often reverse after treatment, women are susceptible to permanent loss of ovarian function. Other effects of chemotherapy include irritation of mucous membranes, including the lining of the vagina and the mouth, which can interfere with kissing, oral sex, and vaginal penetration.
Salem Health: Cancer Surgery: Surgical treatment of pelvic and lower abdominal cancers can damage nerves and occasionally blood vessels that are important to sexual arousal responses. Despite advances in surgical techniques to reduce pelvic nerve damage, erectile and ejaculatory dysfunctions remain common in men after procedures such as radical prostatectomy, radical cystectomy, and abdominoperineal resection. In women, sexual arousal problems, orgasm problems, and painful intercourse are common for a year or more after radical hysterectomy, though the effects of other abdominal surgeries on sexual function may be less severe than in men. Surgical menopause after removal of the ovaries may also affect short-term and long-term sexual function. Partial or complete removal of external genital tissue (such as vulvectomy or penectomy) perhaps poses the greatest threat to sexual function, though penile and vulvar cancers are rare. Radiation: Radiation to the pelvic region can cause sexual difficulties by damaging nerves and blood vessels that control genital function and by affecting testicular and ovarian function, causing difficulties similar to those caused by other treatments. Furthermore, in women pelvic radiation can cause vaginal inflammation, sores, and scarring. This damage may lead to permanent shortening or collapse of the vaginal canal, limiting vaginal penetration because of pain and physical limitations. The severity of radiation side effects depends on the dose of radiation received and the extent of the irradiated region. Unlike surgery, the effects of radiation progress over a period of time. Hormonal therapy: Adjuvant hormonal treatments, such as tamoxifen, for certain cancers have become more common. Effects are similar to those of other causes of decline in sex hormone levels and include changes in sexual interest and arousal. Prognosis and treatment for sexual problems: Sexual problems often resolve over time or with treatment. The quality of sexual function before diagnosis and treatment is an important predictor of sexual recovery, as are age, general health status, and the partner’s receptiveness to further sexual activity. When aggressive treatment causes significant physical damage, adjustment to long-term changes in sexual function is necessary. It is important not to underestimate the effects of psychological and relationship factors on sexual function. Although physical changes resulting from disease or treatment can be devastating, psychological adaptation to these changes may be the ultimate limiting factor in recovery.
Sexuality and cancer Ongoing problems with depression or anxiety can inhibit sexual desire and hinder efforts to resume sexual activity. Changes in appearance, health, fertility, or physical functioning may cause a sense of decreased self-worth, anxiety about recurrence, feelings of unattractiveness, and concern about a partner’s rejection or abandonment. Sexual problems may also have origins in intimacy problems and conflict between sexual partners. Finally, rigid or unrealistic expectations of sexual activity or a lack of knowledge about sexuality can create barriers when recovery necessitates changes to the sexual repertoire. Individual, couple, or group therapy is helpful in addressing these issues. In many cases the resumption of a fulfilling sex life hinges on building confidence and intimacy between partners, reevaluating beliefs about sexuality and sexual personhood, and orienting the patient and partner toward experiencing pleasure and satisfaction rather than achieving a specific goal (such as maintaining a full erection or always having an orgasm with sexual activity). The use of sexual aids such as lubricants and vibrators can enhance sexual enjoyment in patients who have altered sexual function after cancer. Medical interventions for sexual problems are available, although it is inadvisable to pursue these options in lieu of counseling or psychotherapy. Medical treatment options are diverse and include local or systemic hormonal supplementation (although with some cancers hormonal treatment is contraindicated), the use of prescription medications for erectile dysfunction (such as Viagra, or sildenafil; Cialis, or tadalafil; Levitra, or vardenafil), penile injection therapy, and penile and clitoral vacuum devices. Invasive surgical options are less common. Reconstructive surgery, when possible, may improve body image. Penile prosthesis surgery can partially restore erectile function when other treatments have failed or are unacceptable. Although reparative surgery may address neurological or vascular causes of sexual dysfunction, current evidence to support this approach is limited. Sexuality is increasingly viewed as an important element of quality of life, but more often than not, health care providers are hesitant to discuss sexual issues with their patients. Referral to a provider with special expertise in sexual problems can be helpful. Although there is no recognized medical specialty in sexual medicine, physicians with expertise in sexual problems are represented in several fields, including urology, gynecology, psychiatry, and endocrinology. The American Association of Sex Educators, Counselors, and Therapists (AASECT) also provides referrals and certification for mental health professionals with special expertise in human sexuality. Andrea Bradford, M.A. 1075
Sézary syndrome
Salem Health: Cancer
u For Further Information Katz, Anne. Breaking the Silence on Cancer and Sexuality: A Handbook for Healthcare Providers. Pittsburgh: Oncology Nursing Society, 2007. Leiblum, Sandra R., ed. Principles and Practice of Sex Therapy. 4th ed. New York: Guilford Press, 2007. Owens, Annette F., and Mitchell S. Tepper, eds. Sexual Health. Westport, Conn.: Praeger, 2007. Schover, Leslie R. Sexuality and Fertility After Cancer. New York: Wiley, 1997. u
Other Resources
American Association of Sex Counselors, Educators, and Therapists http://www.aasect.org American Cancer Society Sexuality for Men and Their Partners http://www.cancer.org/docroot/MIT/ MIT_7_1x_SexualityforMenandTheirPartners.asp American Cancer Society Sexuality for Women and Their Partners http://www.cancer.org/docroot/MIT/ MIT_7_1x_SexualityforWomenandTheirPartners.asp National Cancer Institute Sexuality and Reproductive Issues http://www.cancer.gov/cancertopics/pdq/ supportivecare/sexuality Sexual Health Network http://www.sexualhealth.com See also Anxiety; Depression; Elderly and cancer; Fatigue; Fertility issues; Living with cancer; Nausea and vomiting; Pregnancy and cancer; Psychosocial aspects of cancer; Relationships; Self-image and body image; Sterility; Stress management; Young adult cancers.
u Sézary syndrome Category: Diseases, symptoms, and conditions Also known as: Baccaredda-Sézary syndrome, cutaneous T-cell lymphoma, T-cell erythroderma, Sézary-Baccaredda syndrome, Sézary-Bouvrain syndrome, Sézary’s disease, Sézary erythroderma Related conditions: Mycosis fungoides; some experts consider Sézary syndrome to be an advanced form of mycosis fungoides, while others consider it a separate disease. 1076
The back of a man with Sézary syndrome. (©ISM/Phototake— All rights reserved)
Definition: Sézary syndrome is a variant of cutaneous Tcell lymphoma. In this disease, T lymphocytes (the cells that help the immune system by killing bacteria in the body) become cancerous, affecting the skin and blood. After these cancerous cells enter the bloodstream, the disease may spread to other organs. It is named for Albert Sézary, A. Baccaredda, and Yves Bouvrain, who first described it in 1938. Risk factors: There are no known risk factors for Sézary syndrome. Exposure to certain chemicals or viruses has been thought to increase risk, but these ideas have not been proven. Etiology and the disease process: Sézary syndrome develops slowly, usually over years. In early stages, the skin itches and forms dry, dark patches. Then tumors, called mycosis fungoides, form on the skin, and the skin may become infected. When many tumor cells appear in the blood and travel throughout the body, this disease has progressed into Sézary syndrome. The disease may then spread to the
Salem Health: Cancer
Sézary syndrome
lymph nodes or other organs such as the lungs, liver, or spleen. Incidence: Sézary syndrome affects only about 1 out of 1 million people. Most cases appear in people who are over the age of fifty. Men get this disease more often than women, and African Americans develop it more often than members of other ethnicities. Symptoms: Symptoms include itching; a dry, red skin rash; skin tumors; and enlarged lymph nodes. Screening and diagnosis: A physical exam is the general screening tool for this disease. If Sézary syndrome is suspected, blood tests or skin biopsies may be used to confirm the diagnosis. Other tests, such as X rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), or lymph node biopsies, may be used to see if the disease has spread to other parts of the body. Sézary syndrome involves these stages: • Stage I: Only parts of the skin are affected with a red, scaly rash. There are no tumors, and lymph nodes are normal. • Stage II: Either lymph nodes are normal or enlarged but have no cancerous cells and the skin has a red, scaly rash but no tumors or the lymph nodes are normal or enlarged but do not contain cancerous cells although the skin has tumors. • Stage III: Most of the skin is affected by a red, scaly rash, but the lymph nodes, either normal or enlarged, do not contain cancerous cells. • Stage IV: In addition to the skin rash, either cancer cells are in the lymph nodes or cancer cells have spread to other organs. • Recurrent: The cancer has been previously treated but has returned, either where it began or in another area of the body.
Relative Survival Rates for Sézary Syndrome, 1988-2001 Years
Survival Rate (%)
1 2 3 5 8 10
97.1 95.1 92.4 88.4 84.5 82.6
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Treatment and therapy: The three treatments generally used for Sézary syndrome are radiation therapy, chemotherapy, and phototherapy. In radiation therapy for this disease, a special type of radiation that only penetrates the outer layers of the skin (total skin electron beam radiation) may be directed to the entire body to kill cancer cells in the skin. Another method is to direct radiation only to small areas of skin that are highly affected. Chemotherapy for this disease may involve traditional systemic chemotherapy (putting chemicals that kill cancer cells into the bloodstream by mouth or intravenously) or a topical cream that contains chemicals that kill cancer cells. With one type of phototherapy for this cancer (PUVA therapy, psoralen plus ultraviolet light A), patients are given certain drugs that make cancer cells sensitive to light; then a laser light is shone on the skin to kill the cancer cells. In another type of phototherapy (extracorporeal photochemotherapy), patients are given certain drugs; then some of the blood cells are taken out of the body, exposed to a special light, then reinserted into the body. Sometimes patients who are treated with phototherapy need to avoid sunlight. Other treatments, such as steroid creams, may be used to ease the itching and swelling of the skin with this disease. Clinical trials testing biological therapy (using the body’s own immune system) and bone marrow transplants to fight this type of cancer are ongoing. Prognosis, prevention, and outcomes: Sézary syndrome is difficult to cure and no way of preventing it is known, but treatments can relieve symptoms. Patients who are diagnosed with Sézary syndrome at Stage I of the disease have a survival rate of twenty or more years and generally do not die of causes related to this disease. However, 50 percent of those whose disease progresses into Stage IV eventually die of causes related to this disease within five years. Marianne M. Madsen, M.S. u
For Further Information Foss, F. “Mycosis Fungoides and the Sézary Syndrome.” Current Opinion in Oncology 16, no. 5 (September, 2004): 421-428. Siegel, Richard S., et al. “Primary Cutaneous T-Cell Lymphoma: Review and Current Concepts.” Journal of Clinical Oncology 18, no. 15 (August, 2000): 29082925. Zackheim, Herschel S., ed. Cutaneous T-Cell Lymphoma: Mycosis Fungoides and Sézary Syndrome. New York: Informa Healthcare, 2004. 1077
Side effects u
Other Resources
Cutaneous Lymphoma Foundation http://www.clfoundation.org National Cancer Institute Mycosis Fungoides and the Sézary Syndrome http://www.cancer.gov/cancertopics/pdq/treatment/ mycosisfungoides/Patient See also Cutaneous T-cell lymphoma (CTCL); Itching; Lymphomas; Mycosis fungoides.
u Side effects Category: Diseases, symptoms, and conditions Also known as: Concomitant events, adverse events (AEs), adverse effects, adverse drug reactions (ADRs), complications Definition: Side effects include any unintended action, reaction, effect, or change in a person’s condition that occurs as a result of medical treatment in addition to the intended action, effect, or change in condition. It can be caused by medication, drug interactions, an unintentional overdosage, a drug allergy, a vaccination, or any other procedure, therapy, or treatment. Side effects may also be associated with diseases and conditions, nutritional or herbal supplements, comorbid conditions (those existing simultaneously with another condition), lifestyle behaviors, and medications unrelated to the condition being treated. General side effects from drugs: All drugs, whether prescription or over-the-counter (OTC), can cause side effects ranging in duration from acute (transient) to chronic (long-term) and in intensity from mild to life-threatening. Whether or not a person experiences drug-related side effects depends on a number of factors, including individual differences in physiologic makeup. All prescription and OTC drugs have known, documented (labeled) side effects. Those of prescription drugs are listed on each medication’s package insert (PI). The PI for each marketed drug must be approved by the U.S. Food and Drug Administration (FDA) and must include comprehensive efficacy data, pharmacokinetic and pharmacodynamic data (information on the way the body absorbs, distributes, and metabolizes the drug), dosage and administration data, and safety data including contraindications (a listing of known conditions that may preclude safe usage), warnings (a listing of serious side effects), precautions (a listing of poten1078
Salem Health: Cancer tial concerns involving drug interactions, laboratory test interactions, carcinogenesis, mutagenesis, impairment of fertility, pregnancy, teratogenicity, use by nursing mothers, pediatric use, geriatric use, adverse reactions, and an assessment of potential for drug abuse and dependence), signs and symptoms indicative of overdose, and treatment recommendations in the event of overdose. In general, the most commonly experienced drug-related side effects involve the gastrointestinal system (including anorexia, constipation, diarrhea, nausea, and vomiting). Other commonly experienced side effects involve the nervous system (including fatigue, headache, and insomnia). The Physicians’ Desk Reference (PDR), a commercially published, annually updated reference book, is a compendium of PIs. It is available to the public in original format, in layterm format, and in CD-ROM format. An online version is also available to medical professionals. Drug interactions: Drug-related side effects may occur due to any of the following types of interaction: one medication with another medication (a “drug-drug interaction”), one therapy with another therapy (a “concurrent therapy interaction”), and a medication with a certain food type (a “drug-food interaction”). Drug-drug interactions. Concomitant use of certain medications can result in either a reduction of or an increase in the effects of either or both drugs, thereby increasing the incidence or severity of side effects. For example, antidiarrheal drugs taken with tranquilizers can increase the sedative effect; anticoagulants with antacids can decrease absorption of the anticoagulant and increase bleeding; diuretics with decongestants can increase hypertension; and antihistamines with antitussives (cough medications) can increase drowsiness. Concurrent therapy interactions. Concurrent therapy interactions can occur when two or more different types of treatments are used simultaneously for the same indication (to treat the same symptom). For example, combined treatment with chemotherapy and radiation therapy, as is administered for many types of cancer, can result in a decrease in neutrophils (white blood cells) as well as other types of blood cells. When administered to those with diabetes, the resultant decrease in cell count could increase the risk of infection. In addition to adverse drug interactions, however, the possibility exists that a drug-drug interaction may have a positive synergistic effect. In such cases, either the efficacy of the concomitant drugs is greater than that of each drug individually or the side effects associated with the concomitant drugs are fewer or less severe than those associated with either drug individually.
Salem Health: Cancer Drug-food interactions. The presence in the gut of certain types of foods may affect the bioavailability and safety profiles of an orally administered drug by interfering with its ADMET profile. ADMET stands for the following properties: • absorption into the circulatory system • distribution to organs and tissues • metabolism of the parent compound into metabolites • excretion of the parent compound and metabolites, usually via urine and feces • toxicity (harmfulness) of the parent compound and metabolites For example, an enzyme present in grapefruit may inhibit drug metabolism, resulting in the presence of more parent compound in the circulatory system than would otherwise be there. This could increase in the incidence or severity of side effects caused by drugs in the following drug classes: analgesics, antiarrhythmics, antibiotics, anticoagulants, anticonvulsants, antidepressants, antihypertensives, antitussives, and chemotherapy agents. Certain foods may also block drug absorption if taken within a certain interval before or after a drug dose. For example, ingestion of a dairy product shortly before or after taking the antibiotic tetracycline can result in the drug’s reduced efficacy. Obversely, the systemic presence of certain types of drugs may affect nutrient absorption, nutrient metabolism, or appetite. The magnitude of a drug-food effect, however, is dependent upon such variables as drug dosage and route of administration; duration of the interval between medication ingestion and food ingestion; and the age, weight, gender, and health status of the person taking the medication. Unintentional overdosage. Toxicity can occur as the result of an unintentional overdose either from taking more than the correct dose at any one time or from taking the correct dose more often than prescribed or recommended. Side effects of acute toxicity include blurred vision, dizziness, headache, loss of muscle coordination, nausea, and vomiting. For certain antihypertensive drugs, dosages only slightly higher than the recommended therapeutic dose can cause bradycardia (slow heartbeat), hypotension, or vomiting. Since the route of excretion for most drugs is renal (through kidney metabolism), hepatic (through liver metabolism), or both, overdosage can result in renal or hepatic toxicity. An overdosage of analgesics (painkillers) is the most prevalent cause of acute hepatoxicity (liver failure) in the United States. Toxicity can result not only from drug exposure but also from radiation exposure. Such toxicity can be minimized by limiting the volume of tissue irradiated.
Side effects Drug allergies: Certain drugs can cause allergic reactions, whereby the immune system launches a histamine response to rid the body of the drug. The resultant adverse events can range in intensity from life-threatening to mild and include anaphylactic symptoms (apnea, bronchoconstriction, cyanosis, and loss of consciousness), anxiety, confusion, diarrhea, dizziness, hives and itching, lung congestion, mouth and throat edema, nausea, rash, and tachycardia (rapid heartbeat). The most common trigger for allergic reactions is antibiotics in the penicillin family. Others include anticonvulsants, barbiturates, insulin, iodine (present in radiographic contrast dyes), and sulfa drugs. Photoallergies and phototoxicities: Photoallergy and phototoxicity are two types of photosensitivity that can be caused by prescription or over-the-counter drugs. Occurrences can be either acute and isolated, or chronic. Photoallergies can occur following the topical administration of certain medications that undergo structural change when exposed to the ultraviolet wavelengths of sunlight, resulting in the production of antibodies that cause the photosensitivity. Symptoms include incidence of an eczema-type rash a few days after treatment. Phototoxicity can occur following topical, oral, or injected administration of certain medications. These medications absorb ultraviolet wavelengths of sunlight and then distribute them transdermally (through absorption by the skin), resulting in cell death. Symptoms occur a few days after treatment and can last up to twenty years after the treatment’s cessation. Drugs that cause photosensitivity can exacerbate existing skin conditions and may precipitate or exacerbate certain autoimmune disorders, such as lupus. Drugs that most commonly cause photosensitivity are in the following drug classes: antianxiety medications, antibiotics, anticholesterol medications, antidepressants, antiepileptic medications, antifungals, antihistamines, antihypertensives, diuretics, neuroleptic medications, nonsteroidal antiinflammatories (NSAIDs), and vaccinations. Side effects of chemotherapy: Chemotherapy drugs are often among the most toxic, given that their function is to destroy or otherwise mitigate tumor tissue. Hence, these agents often have strong side effects that are managed by other drugs. Among the side effects of chemotherapy are alopecia (hair loss), anemia, anorexia, anxiety disorders, bradycardia, congestive heart failure, constipation, decreased fertility, depression, diarrhea, dyspnea (shortness of breath), fatigue, febrile neutropenia, heart arrhythmias, hypertension, incontinence, insomnia, lymphedema, muco1079
Side effects sitis (mouth sores), nausea, peripheral neuropathy (nerve damage), pulmonary infections due to a compromised immune system, renal (kidney) damage (sometimes requiring dialysis), skin and nail changes, and vomiting. Other procedures, therapies, and treatments: Diagnostic procedures, and non-drug-related therapies or treatments, such as surgery and radiation therapy, can also cause side effects. Diagnostic procedures. Imaging procedures are among the most common diagnostic procedures. For example, a patient undergoing computed tomography (CT) scan with ingestion or injection of contrast medium may undergo a reaction to the contrast dye. Magnetic resonance imaging (MRI) may induce headache or nausea resulting from the noise of the machine or, in cases where contrast is used, injection site pain. Nuclear scans, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) scans, may cause fever or (rarely) tissue damage. Nonpharmaceutic therapies or treatments. Side effects may also result from non-drug-related therapies or treatments, including acupuncture, blood product transfusions, hyperbaric oxygen therapy, metabolic therapy, plasmapheresis (for prevention of potential side effects), radiation therapy, surgery (including bone marrow, organ, or peripheral blood stem cell transplantation), and wholebody heat therapy. For cancer patients, toxic side effects may occur from radiation exposure, but risk is minimized by limiting the volume of tissue irradiated. Nutritional supplements. All vitamins and other nutritional supplements can cause side effects. Hypervitaminosis, or toxicity due to the cellular storage of an overabundance of fat-soluble vitamins (A, D, E, K), is the primary cause of nutritionally related side effects. For example, acute vitamin A toxicity can cause alopecia, blurry vision, bone calcification or inflammation. Symptoms of chronic vitamin A toxicity include alopecia, fatigue, dizziness, drowsiness, nausea, kidney damage, liver damage, elevated cholesterol, and prostate cancer. Toxic doses of mineral supplements can occur with excessive amounts of iron and zinc. Herbal supplements can cause side effects as well; dimethyl sulfoxide (DMSO), valerian, and yohimbe are only a few examples of herbals that can have toxic and sometimes life-threatening side effects. Herbal supplements can also negatively interact with prescription preparations like anesthesia, anticoagulants, and beta- blockers. One reason that nutritional supplements can be particularly dangerous concerns the way they are regulated: Manufacturers of supplements are not required to test those supplements for either safety or efficacy prior to market1080
Salem Health: Cancer ing them. Unless a manufacturer makes specific claims that a supplement can treat, cure, or prevent a specific disease, that manufacturer does not need to prove to the FDA that those claims are true, provide quality assurance that the supplement actually contains what the label states that it contains, or provide quality control to ensure that the supplement is contaminant-free. Diseases and conditions: Having a specific disease or condition may predispose an individual to experience side effects. Moreover, disease-related physiologic changes may cause pharmacodynamic anomalies and resultant reduction in drug efficacy or increase in incidence of drugrelated adverse events. Cancer’s side effects include bone metastasis, resulting in pain, fracture, and resultant hypercalcemia due to calcium from damaged bone being released into the bloodstream. Chronic lymphocytic leukemia causes alterations in the immune system, resulting lysis (dissolution) of red blood cells. Retinoblastoma results in glaucoma, eye pain, and vision loss. A comorbid condition—a concurrent condition that is unrelated to the primary disease—may also predispose an individual to experience side effects and precipitate disease-related physiologic changes that may cause pharmacodynamic anomalies and resultant reduction in drug efficacy or increase in incidence of drug-related adverse events. In the case of cancer, a variety of comorbidities have side effects that mitigate treatment. Some comorbid conditions may predate the primary disease, while others develop after onset of the primary disease. For example, cancer treatment may be compromised by comorbidities such as compromised cardiac or lung function (which makes the patient a poor surgical risk and a poor risk for concomitant chemotherapy and radiation therapy); Alzheimer’s disease (which makes the patient a poor risk for brain irradiation to counteract brain metastasis); and diabetes, hypertension, renal problems, or congestive heart failure (all of which interfere with the healing process). Cancers that affect comorbid conditions, on the other hand, include small-cell lung cancer (SCLC), which may cause Lambert-Eaton syndrome (LEMS) and resultant muscle weakness. Special populations: Drug therapy used by those in certain subpopulations—geriatric, pediatric, and adult females—requires increased vigilance given the possibility of increased incidence of drug side effects at dosages that would otherwise be considered therapeutic. Geriatric populations. Clinically significant ageassociated differences in a drug’s efficacy profile or safety
Salem Health: Cancer profile can occur in the elderly, who tend to take more medications, which increases the potential for drug reactions and drug-drug interactions. The elderly also have a decreased metabolic rate, which increases both a drug’s mean residence time in the body and the resultant potential for toxicity. Often, these drug-related side effects—which can include fatigue, weight loss, and loss of balance—are attributed to natural aging changes, signs or symptoms of underlying diseases, and an existing or newly acquired medical condition rather than to the drugs themselves. Therefore, dosing both by body weight and by metabolic rate is an important consideration in the elderly population. Pediatric populations. Drug-related side effects are of great concern regarding those in the pediatric population, in which drugs can have a significant impact on growth, development, and maturation at many levels: behavioral, cognitive, immunological, physiological (organ systems), physical, sexual, and skeletomuscular. Additional concerns include the possibility of teratogenicity (genetic mutations) or of reductions in body weight gain. Also of concern is the possibility that, because of differences in developing systems as opposed to mature, adult systems, drug-related adverse events or drug interactions may not be immediately identifiable but rather may be manifested at a later state of growth, development, or maturation. Women. The risk of drug-related side effects is sometimes gender-dependent. Hormonal differences, including cyclic hormonal variations as well as physiologic differences, may cause women to be at greater risk for side effects than men. The tendency for women both to weigh less and to have a higher percentage of body fat also predisposes them to the possibility of additional side effects related to toxicity. With respect to body fat, a certain amount of drug is often stored in adipose tissue for later release, thereby resulting in an amount of drug present systemically that exceeds the intended therapeutic dose, given the cumulative effect of the administered dose combined with release of previously stored drug. Another concern for women is the possibility of impairment of fertility and the possibility of maternal or fetal risk during pregnancy. Therefore, dosing by body weight is an important consideration in managing a drug’s safety margin for women. Lifestyle: Lifestyle choices can either increase or decrease the likelihood of the incidence of adverse events. Certain lifestyle choices, moreover, are associated with both negative and positive side effects. An example of the latter is caffeine consumption (via chocolate, certain soda
Side effects drinks, coffee, tea): Positive effects include bronchodilation (an effective asthma treatment), decreased fatigue, and increased alertness; negative effects can include dizziness, impairment of fine motor control, increased excretion of calcium (contributing to osteoporosis), increased respiratory rate, insomnia, and tachycardia. Negative lifestyle choices include smoking and alcohol or narcotic consumption. The negative side effects associated with smoking include cardiopulmonary adverse events, increased incidence of certain forms of cancer, and increased incidence of complications following breast reconstruction surgery. The negative side effects associated with alcohol or narcotic consumption include hypertension and hepatic adverse events, including an increased risk of acute liver failure resulting from acetaminophen hepatotoxicity. Positive lifestyle choices include healthy eating habits, optimal weight maintenance, and regular exercise. The positive side effects of these choices may include an overall improvement in general health, a decrease in blood pressure, a decrease in cholesterol levels (LDL and triglycerides), a reduction in heart attack risk, and a reduction in stroke risk. Beneficial side effects: Although the term “side effects” has an inherently negative connotation, not all side effects are undesirable, unwanted, or deleterious to one’s health. In certain instances, a side effect can actually be desirable. In addition to beneficial side effects from positive lifestyle choices, unintended beneficial side effects have been associated with certain drugs. This often results in their off-label (unindicated) use for their efficacy in treating conditions for which they were not originally developed. Examples include aspirin, which in addition to being used as an analgesic has a beneficial side effect as an anticoagulant in helping to prevent heart attacks. Similarly, DMSO (approved for treatment of interstitial cystitis) can improve the efficacy of certain chemotherapy drugs, and tamoxifen (used to treat breast cancer) may be useful in preventing breast cancer and also decreases blood cholesterol levels. It should be noted, however, that these drugs can be associated with negative side effects as well. Cynthia L. De Vine, B.A. u
For Further Information Cukier, Daniel, et al. Coping with Chemotherapy and Radiation Therapy. 4th ed. New York: McGraw-Hill, 2004. Galloway, D. “Treating Patients with Cancer Requires Looking Beyond the Tumor.” OncoLog 49, nos. 7/8 (July/August, 2004). 1081
Sigmoidoscopy
Salem Health: Cancer
Kelvin, Joanne, and Leslie Tyson. One Hundred Questions and Answers About Cancer Symptoms and Cancer Treatment Side Effects. Sudbury, Mass.: Jones and Bartlett, 2004. Physician’s Desk Reference, 2008. 62d ed. Montvale, N.J.: Thomson Healthcare, 2007. u
Other Resources
American Cancer Center of the University of Pennsylvania OncoLink http://www.oncolink.com/coping/ American Cancer Society http://www.cancer.org See also Anemia; Anxiety; Appetite loss; Chemotherapy; Chronic lymphocytic leukemia (CLL); Cobalt 60 radiation; Depression; Diarrhea; Fatigue; Fever; Infection and sepsis; Nausea and vomiting; Nutrition and cancer prevention; Nutrition and cancer treatment; Weight loss.
u Sigmoidoscopy Category: Procedures Also known as: Proctosigmoidoscopy Definition: Sigmoidoscopy is the insertion of a slender, lighted tube (sigmoidoscope) through the anus to examine the lining of the rectum and lower colon. Sigmoidoscopes vary in insertion tube design (such as size, flexibility, and viewing angle), viewing technology (lens, fiber-optic, or electronic), and procedural capabilities (sample, destroy, remove, or treat abnormalities). Cancers diagnosed: Sigmoid colon cancer, rectal cancer Why performed: For cancer, sigmoidoscopy may be performed as a screening procedure to detect abnormalities in the rectum and lower colon; as a diagnostic procedure to determine the cause of symptoms, confirm other findings, or plan treatment; or as a follow-up procedure to verify that tissues healed properly after surgery. Patient preparation: A few days before the procedure, the patient may need to stop certain medications (such as
Sigmoidoscope The lower colon is inspected with a sigmoidoscope. (©Visuals Unlimited/Corbis)
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Salem Health: Cancer aspirin products and blood thinners). The day of the procedure, the patient cleans his or her rectum and lower colon (such as with an enema). Steps of the procedure: Sigmoidoscopy is scheduled in a physician’s office or other outpatient setting. The patient wears a gown and lies on the side, awake; if needed, sedation or local anesthetic may be given. First, the physician performs a digital rectal exam. The sigmoidoscope (.25 to .5 inch wide, 10 to 26 inches long) is lubricated and carefully inserted through the anus. Puffs of air gently expand the rectum and lower colon as the physician advances the sigmoidoscope, steering around bends until the sigmoidoscope is fully inserted. The physician slowly withdraws the sigmoidoscope, carefully viewing the lining for abnormalities. When an abnormality is found, its location and characteristics are recorded. Depending on the abnormality, it may be sampled (biopsied), destroyed (ablated), removed (excised and retrieved), or otherwise treated. All biopsy samples and excised tissues are taken to the laboratory for histopathologic evaluation. After the procedure: The patient leaves and resumes normal activities, unless sedation or anesthetic was needed. The patient may feel bloated and have cramps until the extra air passes. Risks: Sigmoidoscopy is relatively safe, with a small risk for these side effects: perforation, bleeding, infection, irritation, and discharge. Results: A normal bowel has smooth folds lining the muscular wall, with an even distribution of blood vessels. Abnormalities include inflammation, stricture, vascular changes, anatomic distortions, and abnormal growths, such as mucosal growths, polypoid lesions (polyps), and cancer. Histopathologic evaluation determines whether an abnormal growth is or is not likely to become cancerous and, if the abnormal growth was removed, whether the diseased tissue was completely removed. Additional treatment, follow-up examinations, or both may be recommended. Patricia Boone, Ph.D. See also Adenomatous polyps; Anal cancer; Colon polyps; Colorectal cancer; Colorectal cancer screening; Diarrhea; Digital rectal exam (DRE); Endoscopy; Enterostomal therapy; Fecal occult blood test (FOBT); Gastrointestinal complications of cancer treatment; Hemorrhoids; Hereditary polyposis syndromes; Medicare and cancer; PeutzJeghers syndrome (PJS); Polypectomy; Polyps; Premalignancies; Primary care physician; Rectal cancer; Screening for cancer.
Silica, crystalline
u Silica, crystalline Category: Carcinogens and suspected carcinogens RoC status: Reasonably anticipated human carcinogen since 1991; known human carcinogen since 2000 Also known as: Quartz, cristobalite, tridymite, sand Related cancers: Lung cancer is related to exposure to respirable quartz and cristobalite but not to amorphous silica. Definition: Respirable crystalline silica, primarily quartz dusts occurring in industrial and occupational settings, is known to be a human carcinogen, based on studies in humans indicating a causal relationship between exposure to respirable crystalline silica and increased lung cancer rates in workers. Respirable crystalline silica was first listed in the Sixth Report on Carcinogens (RoC), published in 1991 by the National Toxicology Program of the U.S. Department of Health and Human Services, as “reasonably anticipated to be a human carcinogen” based on evidence of carcinogenicity in experimental animals; however, the listing was revised to “known to be a human carcinogen” in the Ninth Report on Carcinogens in 2000. Exposure route: Inhalation Where found: Silica sand has been used in the manufacture of glass and ceramics and in foundry castings and has been used as an abrasive in sandpaper and grinding and polishing agents. It is also found in sandblasting materials, in oil and natural gas recovery, in quarries, in water filtration for sewage treatment plants, and in the production of silicon. Cristobalite is a major component of refractory silica bricks. Extremely fine grades of silica sand known as flours may be used in toothpaste, scouring powders, metal polishes, paints, rubber, paper, plastics, wood fillers, cements, road-surfacing materials, and foundry applications. Crystalline silica is also found in tobacco products. At risk: Quarry and granite workers as well as workers involved in the ceramic, pottery, refractory brick, and diatomaceous earth industries are most at risk. Etiology and symptoms of associated cancers: Marked and persistent inflammation, specifically inflammatory cell-derived oxidants, may provide a mechanism by which respirable crystalline silica exposure can result in lung cancer. History: Crystalline silica is composed of silicon and oxygen. The mineral is ubiquitous in both nature and people’s daily lives. Scientists have known for decades that prolonged excessive exposure to crystalline silica dust in min1083
Simian virus 40 ing environments can cause silicosis, a lung disease. During the 1980’s, studies were conducted that suggested that crystalline silica also was a carcinogen. As a result of these findings, crystalline silica has been regulated under the Occupational Safety and Health Administration’s Hazard Communication Standard (HCS). Debra B. Kessler, M.D., Ph.D. See also Asbestos; Bronchial adenomas; Carcinogens, known; Carcinogens, reasonably anticipated; Chewing tobacco; Lung cancers; Mesothelioma; Occupational exposures and cancer; Prevention; Tobacco-related cancers.
u Simian virus 40 Category: Carcinogens and suspected carcinogens Also known as: Simian vacuolating virus 40, SV40 Related cancers: Malignant mesothelioma, osteosarcoma, choroid plexus tumors, ependymomas, non-Hodgkin lymphoma Definition: Simian virus 40 is a polyomavirus of the family Papovaviridae and is found in several species of monkeys. Exposure routes: The actual route of exposure of simian virus 40 in humans is under investigation. There is speculation that millions of Americans were exposed to the virus between 1955 and 1963 during the mass immunizations with the original Salk (injectable) and Sabin (oral) polio vaccines. However, some people too young to have received the original polio vaccines have tested positive for exposure to the virus. Therefore, other routes of exposure, such as person to person, may be possible. Where found: As a latent infection in several species of macaque monkeys; also in biomedical research labs to transform human cells or be inoculated into laboratory animals for oncology studies At risk: People who were vaccinated with the Sabin and Salk polio vaccines between 1955 and 1963; about one hundred army camp men who were inoculated with adenovirus vaccines contaminated with simian virus 40 in the 1950’s and 1960’s; lab researchers working with the virus Etiology and symptoms of associated cancers: Carcinogenesis may be induced by inactivation of cellular tumor-suppressor proteins (TP53 and RB1). History: The virus was discovered in 1960 in the rhesus macaque kidney cells used to amplify the polio virus for 1084
Salem Health: Cancer the original Salk and Sabin polio vaccines. In 1961, after learning that inoculated simian virus 40 caused cancer in laboratory animals, the U.S. federal government required that new stocks of polio vaccine be free of the virus. Since then, the Salk and Sabin vaccine stocks have been produced using human or African green monkey cell lines extensively screened for viral contaminants. The National Cancer Institute has reported that forty years of epidemiological studies in the United States and Europe have not shown increased cancer risk in people who may have been exposed to simian virus 40. However, polymerase chain reaction (PCR) testing has revealed traces of simian virus 40 in many malignant mesothelioma tumors and (in one study) 42 percent of non-Hodgkin lymphomas, among others. However, association does not mean causation, and PCR testing techniques for simian virus 40 have not been standardized. Lab contamination could also be a problem. The linkage between simian virus 40 exposure and cancer in humans is still being actively investigated. Lisa J. Shientag, V.M.D. See also Adenoviruses; Carcinogens, known; Carcinogens, reasonably anticipated; Ependymomas; Hodgkin disease; Human T-cell leukemia virus (HTLV); Lymphomas; Medical oncology; Mesothelioma; Non-Hodgkin lymphoma; Oncogenes; RB1 gene; TP53 protein; Tumor-suppressor genes.
u Singlehood and cancer Category: Social and personal issues Definition: The development and outcome of all kinds of cancer are influenced by a variety of risk factors, such as ethnicity, genetic disposition, preventive health behavior, and socioeconomic or sociodemographic factors. The impact of singlehood as a sociodemographic factor on cancer is rather complex but seems to show a trend toward a statistically unsalutary outcome of this chronic disease. Description of the population: Singlehood defines the marital status of individuals who never married or are separated, divorced, or widowed. Incidence, death, and survival statistics: The impact of singlehood on the incidence, death, or survival of cancer patients is very complex, because the studies and surveys conducted on this topic are often differently designed, investigating only one specific kind and stage of cancer in a specific population group. Therefore, the survival or death
Salem Health: Cancer
Singlehood and cancer
percentages in the individual studies cannot be generalized for all cancers and population groups. However, studies suggest that there may be a trend toward a generally less beneficial impact of singlehood on cancer survival or mortality, as well as on the quality of life of cancer patients. Studies also suggest that the evolution of cancer and therefore cancer incidence may not be affected by marital status per se; however, several surveys indicate that single individuals may be less willing to participate in specific screening programs, such as breast, prostate, or colorectal screenings, to help diagnose and subsequently remove the cancer at an earlier stage or before it becomes inoperable. Some studies suggest a link between a person’s marital status, and cancer mortality and quality of life after diagnosis. (PhotoDisc) The most attractive model of the generally more salutary effect of marriage on cancer survival and quality of life relies studies about the relationship between major life events, on social support, such as access to appropriate health depression, personality factors, and the risk of cancer. The care, and mood. Some investigators have found an interacoutcome failed to support the hypothesis that psychologition between mood and the body’s immune function, cal factors are risk factors of cancer. These results are in which may affect cancer survival. agreement with numerous other studies that failed to find an association between depression and cancer deaths. Risk statistics: Only a few analytical studies have been conOther studies and surveys have investigated the reladucted to assess the direct relationship between singlehood tionship between several sociodemographic factors, such (or marital status in general) and the etiology of cancer. as marital status, and preventive health behaviors, for exThere is one analysis from an Italian databank containing ample, participating in screening programs to detect candata (collected between 1983 and 2001) from almost cer at early stages. In 2004, the U.S. Centers of Disease 18,000 incident cancer cases, assessing the relationship Control and Prevention (CDC) published data from the between marital status and the development of cancer at 1999 Behavioral Risk Factor Surveillance System. These different sites such as oral cavity and pharynx, esophagus, data showed that not having a mammogram within the past stomach, colon, rectum, liver, gallbladder, pancreas, lartwo years to detect breast cancer in women over the age of ynx, breast, endometrium, ovary, prostate, bladder, kidforty was associated with, among other factors, not being ney, and thyroid, as well as Hodgkin disease, multiple currently married. Other studies support this finding that myelomas, and sarcomas. The analysis, published in 2004, being single may be associated with fewer positive intenindicated that never-married individuals, but not divorced tions and lower attendance rates at screening programs. or widowed individuals, were at a significantly increased risk of oral cavity and pharyngeal cancers but at a reduced Perspective and prospects: Studies and surveys have risk of cancer of the colon, liver, bladder, kidney, and thyshown that marital status, such as singlehood, may play a roid. Overall, the study suggested that marital status is not role in cancer mortality, the quality of life after cancer dimaterially associated with cancer risk. agnosis, and the overall adjustment to the disease, alHowever, because there is the not uncommon belief though it does not directly affect the evolution of human that cancer may be associated with psychological distress cancer. Therefore, health care professionals should take that may, for example, arise from major life events such as sociodemographic characteristics into consideration in adbecoming a widow or widower, many studies have focused dition to ordinary clinical health care when treating cancer on the relationship between psychological factors and cancer risk. In 2002, the Danish Cancer Society published the patients, such as providing social and psychological support, as needed, to improve quality of life or adjustment to results of a review of several prospective and retrospective 1085
Sjögren syndrome the disease. They should also be more aware of properly identifying those having trouble coping with cancer. Future studies should particularly pay attention to determining whether an increased risk from cancer may be introduced by the very medications used to treat depression or other psychological distress that may arise from specific sociodemographic factors, such as being single through death or divorce. Silke Haidekker, Ph.D. u For Further Information Coughlin, S. S., et al. “Nonadherence to Breast and Cervical Cancer Screening: What Are the Linkages to Chronic Disease Risk?” Preventing Chronic Disease 1, no. 1 (January, 2004): A04. Kravdal, O. “The Impact of Marital Status on Cancer Survival.” Social Science and Medicine 52, no. 3 (February, 2001): 357-368. Randi, Giorgia, et al. “Marital Status and Cancer Risk in Italy.” Preventive Medicine 38, no. 5 (May, 2004): 523528. u
Other Resources
American Cancer Society The Single Woman and Cancer http://www.cancer.org/docroot/MIT/content/ MIT_7_2X_The_Single_Woman_and_Cancer .asp?sitearea=MIT Breastcancer.org Single Women: Finding Your Way http://www.breastcancer.org/tips/intimacy/single.jsp See also Aging and cancer; Depression; Ethnicity and cancer; Personality and cancer; Psychosocial aspects of cancer; Relationships; Statistics of cancer; Stress management.
u Sjögren syndrome Category: Diseases, symptoms, and conditions Also known as: Sicca syndrome, Sjögren disease, Sjögren’s syndrome, SS Related conditions: Lymphoma, rheumatoid arthritis, scleroderma, systemic lupus erythematosus (SLE) Definition: Named after Swedish ophthalmologist Henrik Sjögren, Sjögren syndrome is a chronic disorder in which the body’s immune system attacks and destroys the glands that make lubricating fluids, such as tears and saliva. It is commonly associated with inflammatory disorders, such 1086
Salem Health: Cancer as rheumatoid arthritis and systemic lupus erythematosus. Patients with this syndrome have been found to have a higher incidence of lymphoma than the general population. Risk factors: Risk factors for Sjögren syndrome include a history of rheumatic disease, gender, age, and a family history of the disease. Etiology and the disease process: The etiology of Sjögren syndrome is unknown. Given the prevalence of this disorder among women, hormones are suspected to play a role. Genetic, viral, and neuroendocrine causes have also been investigated. In primary Sjögren syndrome (50 percent of cases), the disorder occurs alone. In the secondary form of the syndrome, it is accompanied by an underlying autoimmune connective tissue disorder, such as rheumatoid arthritis, polymyositis, scleroderma, or systemic lupus erythematosus. Incidence: Although Sjögren syndrome occurs in both sexes and all age groups, 90 percent of patients are women, and the average age of onset is the late forties. As many as 4 million people in the United States are affected. Sjögren syndrome is one of the most prevalent autoimmune disorders but is commonly misdiagnosed or underdiagnosed because of its generalized symptoms. The syndrome is rare in children. Symptoms: The hallmark symptoms of Sjögren syndrome are dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca, or KCS). Other oral symptoms include a sore, cracked tongue and lips; difficulty chewing, speaking, or swallowing; salivary gland enlargement; and tooth decay. Other eye-related symptoms include a gritty sensation in the eyes (especially in the morning); itching, burning, or redness of the eyes; intolerance to light (photosensitivity); and an inability to tear. Other symptoms include fever; fatigue; muscle and joint pain; dry, itchy skin; digestive problems; and vaginal dryness. These symptoms may be associated with involvement of other organs (such as the lungs, kidneys, intestines, stomach, and blood vessels) or with lymphoma. In women, symptom onset commonly coincides with the onset of menopause. Screening and diagnosis: Because many symptoms of Sjögren syndrome are generalized and symptoms may be treated individually, Sjögren commonly goes undiagnosed or misdiagnosed. The average time from onset of symptoms to diagnosis is more than six years. Diagnosis is commonly made when the complex syndrome of symptoms has been noted.
Salem Health: Cancer No single test confirms the diagnosis. Diagnostic testing includes blood tests for the presence of certain antibodies, such as rheumatoid factor, antinuclear antibodies (ANAs), and the extractable nuclear antigen antibodies SSA and SSB. Differing antinuclear antibody profiles help to distinguish between the primary and secondary forms of Sjögren syndrome. Nonspecific laboratory abnormalities commonly noted in Sjögren syndrome include increased erythrocyte sedimentation rate, mild anemia, elevated immunoglobulin levels, and a low albumin level. Ophthalmologic tests include a Schirmer test to measure the production of tears and a Rose-Bengal staining test to detect corneal inflammation and dryness on the surface of the eye. Dental tests include salivary flow rates to determine the presence of decreased saliva production, biopsy of the lip or salivary gland, and salivary scintigraphy. Treatment and therapy: Sjögren syndrome has no known cure. Treatment is lifelong and generally focuses on controlling and relieving symptoms (by increasing lubrication and moisturization of affected tissues), limiting organ involvement, and helping improve quality of life. Moisture replacement therapies, such as artificial tears, are used to ease dry eye symptoms. Chronic dry eye may be treated with prescription cyclosporin (Restasis) or punctal occlusion, in which the tear-draining ducts of the eyes are plugged to help maintain moisture. Prescription drugs (cevimeline, pilocarpine) are also used to stimulate salivary flow. For many patients, fluid intake is necessary with and between meals because of dry mouth. Patients should avoid medications that are known to dry secretions, including antihistamines and decongestants. Other treatments vary depending on the involved organ, severity of symptoms, and presence of any coexisting autoimmune disorders. Medications such as nonsteroidal anti-inflammatory drugs and corticosteroids (such as prednisone) may be prescribed to reduce autoimmune effects and treat musculoskeletal symptoms. Hydroxychloroquine, an antimalarial drug, may be used to treat fatigue and joint pain associated with primary Sjögren syndrome or to decrease antibody levels or sedimentation rate. Cytotoxic agents should be used cautiously because they can increase the risk of lymphoma. Prognosis, prevention, and outcomes: Prognosis varies with the type and severity of disease, although Sjögren
Sjögren syndrome syndrome generally is not fatal if diagnosed and treated early. Some people experience only very mild symptoms; others suffer from periods of severe disease. Symptoms can remain stable, go into remission, or worsen over the course of the disease. Individuals with secondary Sjögren syndrome typically have milder disease than those with primary Sjögren syndrome. Debilitating joint pain and fatigue can affect quality of life. Lymphoma develops in approximately 6 percent of people with Sjögren syndrome who have systemic disease. Although Sjögren syndrome has no known preventive measures, early diagnosis and treatment are extremely important for preventing major organ damage and other complications. Jaime Stockslager Buss, M.S.P.H., ELS u
For Further Information Fremes, R., and N. Carteron. A Body Out of Balance: Understanding and Treating Sjögren’s Syndrome. New York: Avery, 2003. Rumpf, T. P., and K. M. Hammitt. The Sjögren’s Syndrome Survival Guide. Oakland, Calif.: New Harbinger, 2003. Smedby, K., et al. “Autoimmune and Chronic Inflammatory Disorders and Risk of Non-Hodgkin Lymphoma by Subtype.” Journal of the National Cancer Institute 98 (2006): 51-60. Wallace, D. J., ed. The New Sjögren’s Syndrome Handbook. 3d ed. New York: Oxford University Press, 2004. Zintzaras, E., M. Voulgarelis, and H. M. Moutsopoulos. “The Risk of Lymphoma Development in Autoimmune Diseases: A Meta-Analysis.” Archives of Internal Medicine 165 (2005): 2337-2344.
u
Other Resources
National Institute of Neurological Disorders and Stroke Sjögren’s Syndrome Information Page http://www.ninds.nih.gov/disorders/sjogrens/ sjogrens.htm Sjögren’s Syndrome Foundation http://www.sjogrens.org See also Dry mouth; Family history and risk assessment; Lymphomas; Non-Hodgkin lymphoma; Primary central nervous system lymphomas; Salivary gland cancer.
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Skin cancers
Salem Health: Cancer
u Skin cancers Category: Diseases, symptoms, and conditions Also known as: Basal cell carcinomas, squamous cell carcinomas, melanomas Related conditions: Actinic keratosis, Bowen disease Definition: Skin cancers are the result of uncontrolled mitosis (cell division) in the epidermal cells of the skin. The three most common skin cancers are basal cell carcinomas (BCCs), squamous cell carcinomas (SCCs), and melanomas. Each is named for the cell type (basal cell, squamous cell, or melanocyte) that gives rise to the cluster of cells dividing uncontrollably. This cluster of cells is a skin cancer. Risk factors: Exposure to sunlight and other sources of ultraviolet (UV) radiation is the overwhelmingly predominant risk factor in all the common skin cancers. Ozone in the stratosphere absorbs UV radiation so that it does not reach the earth, so the destruction and thinning of the stratospheric ozone layer constitute a secondary risk factor.
Etiology and the disease process: The epidermis, the outermost layer of the skin, sits on a deeper layer, the dermis. Cells in the bottom layer of the epidermis, called the basal cell layer, divide to form keratinocytes, or squamous cells, which move to the surface of the skin to form a protective cover for the organism. As the keratinocytes move to the surface, they become packed with the protective protein keratin, take on variable amounts of the pigment melanin, flatten, attach firmly to neighboring keratinocytes, and die. These cells form a layer of dead, protective cells that are continually being sloughed off and must be replaced by new keratinocytes derived from mitosis in cells of the basal cell layer. In the basal cell carcinomas, one of the cells from the basal cell layer escapes the cellular control mechanisms and divides repeatedly to form a mass of cells no longer coordinated with the rest of the organism. In the squamous cell carcinomas it is one of the keratinocytes (squamous cells) in which control of cell division is lost. The basal cell layer also contains cells called melanocytes that produce the melanin that gives skin its color. Normally, the melanin is passed from the melanocytes to the keratinocytes as the latter move to the surface of the
A metastatic basal cell epithelioma on a person’s back. (©Lester V. Bergman/Corbis)
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Salem Health: Cancer epidermis. Control of a melanocyte’s mitosis may also be lost, resulting in a melanoma. All the skin cancers are most commonly triggered by UV radiation from the sun or some other source such as a tanning lamp. The UV light damages deoxyribonucleic acid (DNA), the material that forms the cell’s genes. As a result, the damaged gene no longer performs its function. If that function was to control mitosis, the organism may lose control over that cell’s division process. The cell divides, forming a mass of cells growing out of control, a tumor. The tumor itself is minimally harmful, though it may be unsightly. However, if the cancerous cells move into the lymphatic and circulatory systems, they may be carried to other sites in the body, where they may lodge and produce other tumors. This process of spreading the cancer throughout the body is called metastasis and, untreated, will normally end in death. The skin carcinomas do not normally metastasize, but melanomas often do.
Skin cancers
Skin Cancer Prevention Tips from the Skin Cancer Foundation
• • • • • • • • • • •
Incidence: Skin cancers are the most common cancers in the United States, with more than 1 million cases diagnosed annually. Basal cell carcinoma makes up about 75 percent of skin cancer cases, squamous cell carcinoma about 20 percent, and melanoma only 3 percent. The remaining 2 percent are produced by other, far less common, types of skin cancer. Skin cancer is more frequent in men than in women, in light-complexioned people than in darkskinned ones, in people who spend a lot of time outdoors than those who spend more time indoors, and in older people than in younger ones. Symptoms: Most skin cancer lesions are on the skin of the arms, face, and legs, the body parts most often exposed to the sun. The lesions differ depending on the cells involved. Basal cell and squamous cell carcinomas often begin as red or other colored spots on the skin. Unlike other skin lesions, the spots do not heal or, if they do go away, they reappear. These spots are often rough to the touch. Melanomas are often brown, appearing much like a mole. If the molelike spot is round and smooth edged, contrasts sharply with the surrounding skin, and does not change, it is probably a harmless mole. If it is asymmetric and roughedged, fades into the surrounding skin, and grows in size, it is probably a melanoma. Screening and diagnosis: Individuals can screen themselves by periodically checking their skin for indications of these cancers and for precursors of skin cancer. Actinic
Avoid sunburns. Do not try to get a tan, and stay out of tanning parlors. Head for shade, especially between 10 a.m. and 4 p.m. Use a sunscreen with a sun protection factor (SPF) of 15 or greater. Use a sunscreen that blocks UVA and UVB rays. Thirty minutes before going out, apply 1 ounce of sunscreen to all exposed areas. Reapply every two hours or more often if swimming or sweating. Remember to apply sunscreen to commonly overlooked areas such as ears, lips, around the eyes, neck, hands, feet, and scalp (especially if hair is thinning). Wear protective clothing, including long-sleeved shirts and long pants in darker colors. Wear UV-blocking sunglasses and a broad-brimmed hat. Keep newborns out of the sun. Use sunscreen on babies the age of six months and up.
keratosis and Bowen disease are two of the most common precursors of skin cancer. Both begin as colored or rough spots or bumps on the skin that do not respond to treatment with ointments. They should be watched carefully, as should moles. If any of these skin abnormalities change in size, shape, or color, they should be shown to a dermatologist. Regular examination by a dermatologist is one way to screen for potential skin cancers. If upon examination, skin cancer is suspected, a biopsy will probably be the next step. The dermatologist will cut out all or part of the suspect skin and send it to a laboratory for a microscopic examination of the cells in the sample. Four of the most common types of biopsy are the shave biopsy, in which a thin layer of the troublesome skin is shaved off and submitted to the laboratory; the punch biopsy, in which a small cylinder samples the lesion through its entirety; the incision biopsy, in which a part of the suspicious patch of skin is cut out; and the excision biopsy, in which the entire patch of troublesome skin is removed. Biopsies of nearby lymph nodes are carried out if the cancer is thought to have spread beyond the lesion itself. Fine needle biopsy of a lymph node consists of inserting a very slender needle into a lymph node adjacent to the lesion and drawing some cells from the lymph node into the needle for examination. A second type of lymph node biopsy removes an entire lymph node for examination. If microscopic examination of the cells submitted in the biopsy reveals that some of the cells are cancer cells, further diagnosis is often combined with treatment. 1089
Skin cancers Based on the observation of one or more dermatologists, on the results of the biopsy, and on any other information available, the cancer is staged. Staging determines and reports how far the cancer has spread. Basal cell and squamous cell carcinomas are often not staged because they spread so infrequently, although squamous cell carcinoma spreads and is staged more frequently than basal cell carcinoma. When these two types of skin cancers are staged, the system used is similar to the one for melanomas. The staging systems used for melanomas are based on the size of the melanoma (how far it has spread laterally in the skin), its depth into the skin (a measure of spread downward), and whether it has spread into the lymph or elsewhere beyond the skin. To give the general idea of such a staging system, here is a simplified version. • Stage 0: Only the top layer of the skin is involved (for all subsequent stages, deeper skin layers are involved). • Stage I: The lesion is less than 2 millimeters (mm) thick (or deep into the skin). • Stage II: The lesion is more than 2 mm thick (deep). • Stage III: The cancer has spread into the lymph, cartilage, muscle, or bone nearby. • Stage IV: The cancer has spread through the blood and lymph to distant sites in the body. Treatment and therapy: Surgery is usually the treatment of choice for skin cancer or for its precursors. Cryosurgery, freezing the skin with liquid nitrogen, is often used to remove precancers such as actinic keratoses. Excision biopsy itself is a minor surgery and may be designed to remove the entire cancerous lesion. If it fails to do so, or if the biopsy was a scrape, punch, or incision biopsy, a more extensive surgery may attempt removal of the entire lesion. The excised tissue is examined to see whether all the cancer cells were removed. Lymph nodes in the affected area are examined and removed if their invasion is suspected. If the surgery is extensive, a skin graft may be required to cover the wound. The skin is taken from another part of the patient’s body, usually some part that is normally covered by clothing. Often, the excision to remove the cancer is small enough to be covered by stretching skin in the area of the surgery and no graft is needed. This is a good argument for careful screening to catch the cancer early. A treatment system called curettage and electrodesiccation combines cutting out the cancerous skin with an instrument called a curette, a small surgical device with a handle attached to a sharpened spoon or ring. The size used is determined by the size of the skin lesion. Curettage is followed by insertion of electrical probes and applica1090
Salem Health: Cancer tion of electrical stimuli to the area to kill cancer cells left behind. This is the electrodesiccation part of the process. Mohs surgery consists of a series of scrapes from the diseased area. Each layer scraped off is tested for cancer cells. The scraping continues until no cancer cells are found in the last layer scraped, an indication that the outermost cancer cells in the lesion were removed by the previous scrape. As an alternative to surgery, chemicals may be applied to the lesion to destroy it. Often surgery is followed by a chemical application to kill any cancer cells missed by the surgery. Chemotherapy may be topical, with the chemical applied to the skin lesion, or systemic, with the chemical taken by mouth. Radiation is used to kill cancer cells and, in skin cancers that have not metastasized, can be applied directly to the cancerous spot. However, radiation is capable of causing cancer in healthy cells, as high-energy radiation (UV radiation) is the primary cause of skin cancers. Therefore, the side effects of radiation treatment may include problems, even cancers, later in life. Prognosis, prevention, and outcomes: Caught early, skin cancers are almost always curable, so good screening practices are essential defenses against the diseases. Minimizing exposure to sunlight and other sources of UV light (tanning salons) is an excellent preventive measure. With these simple measures applied consistently, skin cancers need not be a scourge. However, they are the most common cancers contracted by the people of the United States today. This may be because when skin cancer patients received the damaging sun exposure early in their lives, the preventive measures were not known or practiced. As this knowledge has become widespread, skin cancers may decline in the future. Protecting the stratospheric ozone layer, which absorbs UV radiation before it reaches the earth, would also help to minimize the occurrence of skin cancers. Such global action requires international cooperation and may not be as important as individuals’ efforts to protect themselves. Nonetheless, it would be an important contribution to the control of skin cancers. Carl W. Hoagstrom, Ph.D. u
For Further Information Colver, Graham. Skin Cancer: A Practical Guide to Management. London: Martin Dunitz, 2002. Hill, David, J. Mark Elwood, and Dallas R. English, eds. Prevention of Skin Cancer. Boston: Kluwer Academic, 2004. McClay, Edward F., Mary-Eileen T. McClay, and Jodie
Salem Health: Cancer Smith. One Hundred Questions and Answers About Melanoma and Other Skin Cancers. Sudbury, Mass.: Jones and Bartlett, 2004. Rigel, Darrell S., et al., eds. Cancer of the Skin. Philadelphia: Elsevier, 2005. u
Other Resources
American Cancer Society http://www.cancer.org MedlinePlus Skin Cancer http://www.nlm.nih.gov/medlineplus/skincancer.html Skin Cancer Foundation http://www.skincancer.org See also Basal cell carcinomas; Bowen disease; Carcinomas; Core needle biopsy; Dermatofibrosarcoma protuberans (DFSP); Dermatology oncology; Itching; Keratosis; Melanomas; Merkel cell carcinomas (MCC); Metastasis; Moles; Needle biopsies; Squamous cell carcinomas; Sunscreens.
Small intestine cancer
u Small intestine cancer Category: Diseases, symptoms, and conditions Also known as: Small bowel cancer, small bowel neoplasm, small intestine adenocarcinoma Related conditions: Familial adenomatous polyposis Definition: Small intestine cancer is a primary cancer that arises in the small intestine (small bowel), the part of the digestive system that connects the stomach and the colon. Risk factors: Small intestine cancer is between fifteen and one hundred times more likely to occur in individuals who have Crohn disease or celiac disease. Individuals who have the genetic conditions familiar adenomatous polyposis (FAP), nonpolyposis colorectal cancer, and Peutz-Jeghers syndrome also have a higher risk of developing small intestine cancer. Tobacco and alcohol use and a diet heavy in animal fats have been found to increase small intestine cancer in some, but not all, studies. Etiology and the disease process: There are five kinds of small intestine cancer: adenocarcinoma, sarcoma, car-
A secondary tumor on the small intestine; it spread from the primary site on the sigmoid colon. (CNRI/Photo Researchers, Inc.)
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Small intestine cancer
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ries of tests. These include a physical examination, blood work, liver function tests, and a fecal occult blood test to test for blood in the stool. Imaging studies Survival Rates (%) may include abdominal X rays, an upCancer Type 1-Year 2-Year 3-Year 5-Year 8-Year 10-Year per gastrointestinal endoscopy, a barAll types, ium enema and lower gastrointestinal excluding carcinoids 55.1 37.3 32.6 27.5 24.8 24.3 X rays, and a computed tomography Carcinoids 89.9 87.5 84.8 76.5 67.1 61.5 (CT) scan. Definitive diagnosis comes from a biopsy of polyps in the intestine. Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. To stage the cancer, a laparotomy SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) may be performed. In this surgical procedure, the abdomen is opened and samples are taken to determine how far the cancer has spread. Likewise, a lymph cinoid tumors, gastrointestinal stromal tumors (GIST), node biopsy may also be done to determine how far the and lymphoma. These cancers arise from different cell cancer has spread. types. Adenocarcinoma is the most common type of small Staging is done based on the degree of invasiveness of intestine cancer, making up about half of all diagnosed the tumor, how far the cancer has spread, and whether it cases. can be completely removed with surgery: The development of small intestine cancer is thought to • Stage I: The tumor is localized and has invaded the inbe similar to the development of colorectal cancer. Like testinal wall only to a limited degree. colorectal cancer, it begins as a benign (noncancerous) • Stage II: The cancer has grown through the intestinal polyp (growth) on the wall of the intestine. Adenocarwall but has not spread to the surrounding lymph nodes. cinoma, for example, develops from glandular, fluid• Stage III: The cancer has spread to the lymph nodes. secreting cells. Over time, changes occur in the cells in the • Stage IV: The tumor has spread to distant organs such polyp that cause it to become cancerous. Most small intesas the lung or liver. tine cancer develops in the duodenum, which is the part of the small intestine closest to the stomach. In time the polTreatment and therapy: The preferred treatment for all yps may grow to block the intestine. small intestine cancer is surgical removal of the diseased portion of the bowel. This is usually followed by chemoIncidence: Small intestine cancer is rare. It accounts for therapy, radiation therapy, or both. When the cancer canonly 1 to 2 percent of all cancers of the gastrointestinal sysnot be removed, palliative care includes surgery to bypass tem. The American Cancer Society estimates that in 2006 any portions of the small bowel that are blocked by polyp about 6,200 new cases were diagnosed in the United States growth. and that about 1,100 people died from the disease. This cancer is slightly more common in men than in women and Prognosis, prevention, and outcomes: Small intestine in blacks than in whites. The average age at diagnosis is cancer is difficult to treat successfully because it is rarely sixty. Internationally, small intestine cancer is more comdiagnosed at an early stage. The American Cancer Society mon in the United States and Western Europe and less estimates the five-year survival rate for people with small common in Asia. intestine cancers diagnosed in each stage as 65 percent for
Relative Survival Rates for Small Intestine Cancer, 1988-2001
Symptoms: In its early stages, small intestine cancer causes few signs. In later stages, possible signs include unexplained weight loss, abdominal cramps or pain, a lump in the abdomen, or blood in the stool. These symptoms are general and may be caused by many other diseases and conditions. Screening and diagnosis: Because of the rarity of small intestine cancer, routine screening is not done. Because symptoms are general, diagnosis requires an extensive se1092
Stage I, 48 percent for Stage II, 30 percent for Stage III, and 9 percent for Stage IV. Martiscia Davidson, A.M. u
For Further Information Icon Health. The Official Patient’s Sourcebook on Small Intestine Cancer: Directory for the Internet Age. San Diego, Calif.: Author, 2004. Keane, Maureen, and Daniella Chace. What to Eat If You Have Cancer. 2d ed. New York: McGraw-Hill, 2007.
Salem Health: Cancer
Smoking cessation including cancer, heart disease, and lung disease. Cancer was among the first diseases causally linked to smoking, and cigarette smoking is the primary cause of cancer mortality in the United States (responsible for at least 30 percent of all cancer deaths). Smoking is the leading risk factor for lung cancer. Smoking cessation is a difficult challenge that involves overcoming both physical and psychological dependence. Most smokers are addicted to nicotine, a psychoactive drug naturally found in tobacco products that produces dependence and makes quitting difficult. In addition, smoking becomes a routine or habit that can be hard to break, especially when it is as a coping mechanism for stress or anxiety. Cessation is difficult and may require multiple attempts. Users commonly relapse because of withdrawal symptoms and mental dependence. Cigarette cravings are usually the worst during the first two to three days of smoking cessation.
Zeh, H. “Cancer of the Small Intestine.” In Cancer: Principles and Practice of Oncology, edited by Vincent T. DeVita, Jr., Samuel Hellman, and Steven A. Rosenberg. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. u
Other Resources
American Cancer Society Detailed Guide: Small Intestine Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=86 National Cancer Institute Small Intestine Cancer Treatment http://www.cancer.gov/cancertopics/pdq/treatment/ smallintestine/patient See also Barium swallow; Bile duct cancer; Crohn disease; Duodenal carcinomas; Enteritis; Esophagectomy; Fiber; Gastrointestinal cancers; Hereditary polyposis syndromes; Leiomyosarcomas; Ovarian epithelial cancer; Upper gastrointestinal (GI) endoscopy; Zollinger-Ellison syndrome
Quit and relapse rates: An estimated 46.5 million American adults are former smokers, and more than half of all living adults who ever smoked have quit. In addition, approximately 70 percent of current U.S. adult smokers and 62 percent of high school age smokers report that they
u Smoking cessation
How to Quit Smoking
Category: Lifestyle and prevention Definition: Smoking cessation is the stopping of the smoking of cigarettes, cigars, or pipes. Most smokers are physically addicted to nicotine and psychologically addicted to the habit. The depth of the problem: About 21 percent of adults in the United States (45.1 million people) are smokers. In 2006, the number of cigarettes consumed totaled 371 billion. The use of tobacco products varies with gender, age, and ethnic background. According to the Centers for Disease Control, in 2006 more men smoked (23.9 percent) than women (18.0 percent). Smoking was more common among adults between the ages of eighteen and forty-four (23.7 percent) and forty-five to sixtyfour (21.8 percent) than among those age sixty-five and older (10.2 percent). Overall smoking rates are highest among American Indians and Alaska Natives (32 percent), non-Hispanic whites (21.9 percent), and those identifying as black (23 percent). Each year, an estimated 438,000 people in the United States die prematurely from smoking or exposure to secondhand smoke, and another 8.6 million suffer from serious smoking-related illnesses,
Get ready. • Set a date to quit smoking. • Get rid of all tobacco products, ashtrays, and lighters at home, in your car, and at work. • Do not let people smoke around you. Get medicine. Talk to a doctor or pharmacist. Choose nonprescription aids such as nicotine gum, patches, or lozenges. • Or choose prescription aids such as a nicotine inhaler or nasal spray, buproprion hydrochloride, or varenicline tartrate.
• •
Get help. Tell your friends and family that you are quitting and enlist their support. • Ask a health care provider, such as a doctor or nurse, for help. • Get help from your state’s quitline or other supportive group.
•
Stay quit. If you start smoking again, set a new quit date. Avoid alcohol and smokers. Eat a balanced, healthful diet, and exercise. Stay positive that you can quit.
• • • •
Sources: Agency for Healthcare Research and Quality; U.S. Department of Health and Human Services
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In the long term, the health benefits of smoking cessation can be substantial. Smoking cessation greatly reduces the risk of premature death by reducing the risk of smoking-related diseases. Even former smokers live longer than those who continue to smoke. Smoking cessation lowers the risk of developing and dying from lung cancer, other types of cancer, and other diseases (such as heart disease, stroke, and emphysema). The risk of developing cancer declines with the number of years of smoking cessation. For example, about ten years after quitting, a former smoker’s risk of dying from lung cancer is 30 to 50 percent less than the risk faced by those who continue to smoke. Additional benefits include an improved sense of taste and smell and increased lung funtion. Women who stop smoking before or during pregA nicotine patch is one way to stop smoking and lessen the risk of developing cannancy reduce their risk of having miscarcer. (Digital Stock) riages and having babies that are small or have low birth weights. would like to quit. In 2005, an estimated 42.5 percent of Although cessation is beneficial at all ages, the earlier a adult smokers and 54.6 percent of high school students had person stops smoking, the greater the health benefits. attempted to quit smoking during the preceding twelve months. Smoking cessation methods: Smoking cessation is a However, not all smokers are successful in their attwo-step process that includes overcoming the physical tempts to stop smoking, and many try several times before dependence on nicotine and breaking the smoking habit. they are able to quit. Less than 10 percent of smokers who Methods used to increase smoking cessation rates include attempt to quit on their own have long-term success. The medications, counseling, support groups, behavioral thermajority of smokers cite symptoms of withdrawal and apies, and alternative therapies such as hypnotism and cravings as the main reasons for smoking relapse. Most reacupuncture. lapses occur within three months of quitting. SmokingMedications that have proven to be effective in treating cessation aids can increase the chances of success. tobacco dependence include nicotine replacement theraAlthough research findings conflict, some studies sugpies (NRTs) and non-nicotine treatments, such as bugest that women are less successful than men in their atpropion hydrochloride (Zyban) and varenicline tartrate tempts to quit smoking. Success in quitting seems to in(Chantrix). NRTs are designed to provide users with small crease with higher levels of education. Motivation to quit amounts of nicotine that help reduce the craving for cigasmoking also increases success rates. rettes and relieve the withdrawal symptoms associated with smoking cessation, making it easier to quit. Some are available over the counter without a doctor’s prescription. Health benefits of cessation: Smoking cessation leads to Although they contain some nicotine, NRTs are not as bad almost immediate health benefits for people with and as smoking because they do not contain the toxins and carwithout smoking-related diseases. For example, almost cinogens found in tobacco products. Types of NRTs inimmediately after quitting, people experience improved clude gums, inhalers, nasal sprays, lozenges, and patches. circulation, decreased blood pressure and pulse rates, and Although these treatments have been shown to be safe and increased body temperature in the hands and feet. In adeffective when used as directed, smokers should talk with dition, cessation also leads to an almost immediate imtheir health care providers before beginning any smoking provement in such respiratory symptoms as coughing, cessation medication. wheezing, and shortness of breath. Carbon monoxide and Nicotine gum (such as Nicorette) was the first pharmanicotine levels in the body rapidly decrease. 1094
Salem Health: Cancer cologic smoking cessation aid approved by the U.S. Food and Drug Association (FDA). First approved in 1984, it is available over the counter. The recommended treatment is typically ten to fifteen pieces of gum per day for twelve weeks. Available only by prescription, the nicotine inhaler (Nicotrol) is a plastic cylinder that looks like a cigarette and has a cartridge that delivers nicotine. Each cartridge delivers up to four hundred puffs. The maximum recommended dosage is sixteen cartridges a day for up to twelve weeks. Side effects include mouth and throat irritation. Nicotine nasal sprays are dispensed from pumps similar to over-the-counter decongestant sprays. The nicotine is rapidly absorbed through the nasal membranes and quickly reaches the bloodstream. A usual dose is two sprays, one in each nostril. The maximum recommended dosage is forty total doses per day. Side effects include nose and throat irritation. Nicotine patches (such as Nicoderm) release a constant amount of nicotine into the body throughout the day. Most patches are replaced daily, and treatment periods typically range from six to ten weeks. They come in different shapes and sizes and are available over the counter or by prescription. Side effects of nicotine patches include skin irritation, dizziness, headache, and nausea and vomiting. In 2002, the first and only over-the-counter nicotine lozenge was introduced to the market. It comes in the form of a hard candy and slowly releases nicotine as it dissolves in the mouth. Treatment typically consists of up to twenty lozenges per day for twelve weeks. The most common side effects are sore teeth and gums, indigestion, and throat irritation. Available only by prescription, bupropion hydrochloride (Zyban) was approved by the FDA as a smoking cessation aid in 1997. Unlike with NRTs, treatment with bupropion begins while the user is still smoking—specifically, one week before the quit date—and continues for seven to twelve weeks. Length of treatment is individualized. Common side effects include insomnia, dry mouth, and dizziness. The prescription drug varenicline tartrate (Chantrix) was approved in 2006 for smoking cessation. Typically, this nicotine-free tablet is taken twice daily for twelve weeks. Common side effects include headache, nausea and vomiting, gas, insomnia, and change in taste perception. Symptoms of smoking withdrawal: Smokers who try to quit may face physical and psychological symptoms of withdrawal. Physically, the body reacts to the absence of nicotine. Symptoms of withdrawal include dizziness, de-
Smoking cessation pression, irritability, anxiety, sleep disturbances, headaches, difficulty concentrating, drowsiness, and increased appetite. They typically start within a few hours of the last cigarette and peak about two to three days later. Mentally, the smoker must break the habit of coping with stress by smoking. Jaime Stockslager Buss, M.S.P.H., ELS u
For Further Information Aldrich, Matthew. Stop Smoking. Chicago: Contemporary Books, 2006. Centers for Disease Control and Prevention. Targeting Tobacco Use: The Nation’s Leading Cause of Death, 2005. Bethesda, Md.: Author, 2005. DeNelsky, Garland Y. Stop Smoking Now! The Rewarding Journey to a Smoke-Free Life. Cleveland, Ohio: Cleveland Clinic Press, 2007. Perkins, Kenneth A., Cynthia A. Conklin, and Michele D. Levine. Cognitive-Behavioral Therapy for Smoking Cessation: A Practical Guidebook to the Most Effective Treatments. New York: Routledge, 2008. U.S. Department of Health and Human Services. The Health Benefits of Smoking Cessation: A Report of the Surgeon General. Washington, D.C.: Author, 1990.
u
Other Resources
American Cancer Society Tobacco and Cancer http://www.cancer.org/docroot/PED/PED_10.asp American Lung Association Quit Smoking http://www.lungusa.org/site/c.dvLUK9O0E/b.33484/ Nicotine Anonymous http://www.nicotine-anonymous.org Smokefree.gov http://www.smokefree.gov See also American Cancer Society (ACS); Chewing tobacco; Cigarettes and cigars; Coughing; Dry mouth; Family history and risk assessment; Geography and cancer; Medical marijuana; Occupational exposures and cancer; Personality and cancer; Pneumonia; Pregnancy and cancer; Prevent Cancer Foundation; Prevention; Psycho-oncology; Psychosocial aspects of cancer; Statistics of cancer; Tobacco-related cancers. 1095
Social Security Disability Insurance (SSDI)
u Social Security Disability
Insurance (SSDI) Category: Social and personal issues Also known as: DI, Title II Definition: Social Security Disability Insurance (SSDI) is a U.S. government income replacement program for persons who have paid taxes mandated by the Federal Insurance Contributions Act (FICA) and meet the guidelines for serious disabilities. History: SSDI can be traced to the Social Security Act of 1935, which established a retirement plan for older adults. At that time disability coverage was not included. In 1950 Congress passed a bill designating restrictive grants to the states to support lower-income disabled workers. In 1955 a disability program was proposed by the Social Security Administration (SSA). Politicians disagreed about this plan but made compromises to get the program passed. Many of the stipulations from that early program still exist today in SSDI. Cancer and SSDI: The cancer patient seeking SSDI must qualify for disability benefits like any other person with a disability. There is a basic five-step process to qualify: • Determine if the cancer patient is “working (engaging in a substantial gainful activity)” to meet the SSA guideline. • The cancer disability has to be severe enough that the patient cannot do most jobs. • The cancer disability either meets or equals the medical listing under neoplastic (malignant) diseases. The four factors of consideration are origin of the malignancy; extent of cancer involvement; response and duration of antineoplastic therapy, such as surgery, immunotherapy, bone marrow or stem cell transplantation, radiation, or chemotherapy; and the effects or magnitude of post-therapeutic residuals (lasting impact after cancer therapy). • The person cannot be able to do work he or she has done in the past. • SSA uses vocational guidelines on age, education, physical/mental ability, and past work experience to decide if the patient can perform any work. Experienced consultants recommend that cancer patients apply for SSDI as soon as possible, as the process takes time. The disability must be severe enough to be terminal (end in death) or to be continuous for at least twelve months. SSA acts on the assumption that cancer treatment will not meet the twelve-month duration guideline. However, patients can have unique responses to cancer thera1096
Salem Health: Cancer pies and treatments that would meet the twelve-month requirement. By law anyone who qualifies for Society Security benefits can file a claim, but the process is lengthy and difficult. An estimated 35 to 40 percent of all SSDI applications are approved when first filed. If benefits are denied, the applicant can appeal the decision by filing a Request for Reconsideration and try again. About 20 percent of appeals are successful. Some people hire an attorney to represent them to decrease the stress and increase the likelihood of an award. At the least, severely disabled cancer patients will need consistent support and assistance from family or friends to complete the application process and make appeals. If the cancer patient is successful in making a SSDI claim, there is a waiting period between the date the person stopped working and the date benefits are received. After twenty-four months on SSDI, the patient qualifies for Medicare A and B regardless of the person’s age. Tips for successful filing of application: Cancer patients should make application for SSDI benefits as soon as they can no longer work because of their illness and can establish that they will not be able to work for at least the next twelve months. Patients are responsible for assembling all information necessary to file for SSDI. With all documentation complete, the initial claims process may take up to six months to process, and an appeal can take longer. Collecting necessary documentation before applying may help move the process along. Patients are advised to purchase a portable file organizer and label the tabs for each category of information needed. Separate folders hold the following information: • Copies of social security card and a certified birth certificate • List of health care providers, such as doctors, hospitals, or clinics, with phone numbers and addresses • Copies of medical records from each health care provider • Copies of lab test results • List of current medications and known allergies • Copy of the last W-2 form or tax return • List of the names of spouses and dependents (from all marriages) • List of previous employment companies with dates of employment and explanation of the type of work done at each • Copies of applications or communications with any disability programs or workers’ compensation Alternative insurance should be maintained until the decision on the claim is final. COBRA health insurance
Salem Health: Cancer (mandated by the Consolidated Omnibus Budget Reconciliation Act) is available to employees after they are terminated from the company’s health plan. An application to the patient’s state Medicaid plan should be made in addition to the application for SSDI. If this process is too burdensome, patients should consider a disability lawyer to handle their claim. Otherwise, they can seek the counsel of a family or a trustworthy friend. Marylane Wade Koch, M.S.N., R.N. u For Further Information Morton, David. Nolo’s Guide to Social Security Disability: Getting and Keeping Your Benefits. 2d ed. Berkeley, Calif.: Nolo Press, 2003. Pfeiffer, David. “Social Security’s Disability Insurance Program: AHistory.” Ragged Edge 23, nos. 2/3 (2002). u
Other Resources
American Cancer Society Making End of Life Decisions http://www.cancer.org/docroot/MLT/content/ MLT_5_1x_Making_End_of_Life_Decisions .asp?sitearea=MLT Social Security Administration Benefits for People with Disabilities http://www.ssa.gov/disability See also Health maintenance organizations (HMOs); Hospice care; Insurance; Managed care; Medicare and cancer; Oncology social worker; Preferred provider organizations (PPOs).
u Soots Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Lampblack, carbon black Related cancers: Scrotal and other skin cancers, lung cancer, leukemia, esophageal cancer, lymphatic and hematopoietic cancers, bladder cancer Definition: Soots are dark, powdery deposits formed by the incomplete combustion of carbon-rich organic fuels, including gasoline and diesel fuel, coal, wood, fuel oil, paper, plastics, and household refuse. They are complex and variable mixtures of chemical compounds and differ depending on their source; soots from the same source can also differ depending on the conditions of their formation. Soots are composed primarily of elemental carbon; how-
Soots ever, particles may also contain sulfates, ammonium, nitrates, condensed organic compounds, and reactive gases and heavy metals such as arsenic, selenium, cadmium, and zinc. Exposure routes: Inhalation, ingestion, dermal contact Where found: Particulate emissions from any combustion source, including emissions from fireplaces and furnaces, and exhaust from gasoline and diesel engines; chemical products such as pigments in paints and inks, and in toners for xerography and laser printers; in the vulcanization process for rubber tires, imparting their typical black color At risk: Workers cleaning home and industrial chimneys and boilers, brick masons, building demolition personnel, insulators, firefighters, metallurgical workers, horticulturists, people exposed to gasoline or diesel engine exhaust, and anyone who is present where organic material is burned Etiology and symptoms of associated cancers: Compounds extracted from a number of soots cause mutations in standardized mutagenicity assays. Studies with laboratory animals demonstrated that soot from the same source produced skin tumors after dermal application and lung tumors when directed to the lungs. Soots are of concern when inhaled because their small size allows them to migrate deep into the lungs. History: Scrotal cancer was identified in chimney sweeps in 1775. More recently, studies in Sweden, Denmark, Germany, and the United Kingdom demonstrated a significantly increased risk of lung cancer among chimney sweeps. Research is ongoing to determine which components of soots and other small particles are responsible for their carcinogenicity and other health effects such as respiratory illnesses. Soots are in the general category of airborne particulate matter (PM). PM is classified as a criteria pollutant by the U.S. Environmental Protection Agency (EPA), meaning that it is an air pollutant for which the EPA has established a national ambient air-quality standard. These pollutants are measured in air-quality-control regions to determine whether the area meets federal air-quality standards. Bernard Jacobson, Ph.D. See also Air pollution; Arsenic compounds; Bronchial adenomas; Cadmium and cadmium compounds; Carcinogens, known; Carcinogens, reasonably anticipated; Esophageal cancer; Leukemias; Lung cancers; Lymphedema; Occupational exposures and cancer; Polycyclic aromatic hydrocarbons; Skin cancers. 1097
Soy foods
Salem Health: Cancer
u Soy foods
such as breast and prostate, this estrogen blocking could help reduce a person’s cancer risk.
Category: Lifestyle and prevention Definition: Soy foods or foods made from soybeans include tofu, tempeh, edamame, miso, and soymilk. Soy foods are an excellent source of protein and contain a number of substances that are being studied for the prevention of cancer. Background: Since the late 1990’s, researchers have conducted thousands of studies on the links between diet and cancer. Epidemiological studies (studies of populationwide patterns of disease) show that many cancers are less common in Asian than in Western countries. The Japanese breast cancer mortality rate, for instance, is only onefourth that of the women with breast cancer in the United States. Unfortunately, these types of studies are hard to interpret because they cannot account for many potential confounding factors. For example, the average person in Asia may have a more active lifestyle than a typical Westerner. Although it is not completely clear what factors are responsible for the lower rates of cancer in these countries, many researchers have focused on the potential influence of diet on cancer risks and outcomes. There are many differences between a traditional Asian diet and a modern Western diet, such as the amount of vegetables and fruits, processed foods, meat, fish, and whole grains consumed. However, one thing that is very common in traditional Asian cuisine and historically absent from the typical Western diet is soy foods. However, this may be changing—in the year 2000, more than 25 percent of Americans reported consuming soy products at least once a week. In addition, high-dose soy protein and isoflavone supplements are being marketed in the United States to healthy people to prevent cancer. How these compounds work: Soy products contain a number of anticarcinogenic (anticancer) compounds, including phytosterols and isoflavones. The two primary isoflavones in soybeans are genistein and daidzein. The National Cancer Institute classifies genistein (the main soybean isoflavone) as a key anticancer agent. Isoflavones act as weak estrogens, with less than 0.1 percent of the activity of estradiol (the main naturally occurring form of estrogen in humans). Isoflavones may act like antiestrogens in the body, because they can bind with the body’s estrogen receptors and block some of the body’s own estrogens. For cancers that have a hormonal basis, 1098
Research issues: About six hundred soy-related studies a year are published in the medical literature. There are three basic kinds of studies that have been conducted on the link between soy and cancer: population, animal, and laboratory. With population studies, there are always concerns about the accuracy of the methods used. For instance, food frequency questionnaires depend on study participants to remember what they ate over days, weeks, or even months. In addition, many of these studies have been conducted in small groups of people, so even when there is an apparent association, the link is often not statistically significant. Animal studies have shown many potential benefits (and some risks) of soy consumption, but there is controversy over how applicable these results are to humans, be-
Genistein, the main isoflavone in soybeans, is classified as a key anticancer agent by the National Cancer Institute. (U.S. Department of Agriculture)
Salem Health: Cancer cause animal biology, anatomy, and physiology are not the same as those of humans. Laboratory studies, such as those that use cultured human cells to investigate the biochemical response of specific human tissues to elements found in soy, can be similarly controversial because they cannot take into account the complexity of the whole human body and its systems. Possible risks: Although there have been more than one hundred published studies that suggest possible harm from eating soy, most are lab and animal studies, and this research represents only about 1 to 2 percent of all soy research published. One of the more prominently reported studies dealt with the interaction between soy compounds and drugs to treat breast cancer. One soy compound (genistein) was shown to decrease the effects of tamoxifen, a common breast cancer treatment, while another compound (daidzein) was shown to enhance tamoxifen’s effects. There is currently no consensus on whether high levels of soy foods are appropriate for current or former breast cancer patients. In addition, animal studies have found that soy (in supplement form or highly processed isolated proteins) can promote tumor growth under some circumstances, and one study showed that high levels of soy food intake are associated with an increased risk of bladder cancer, although this was based on sixty-one cases and depended on a food-frequency questionnaire. Possible benefits: Soy foods have been shown in many human and animal studies to be associated with statistically significant reductions in prostate, colorectal, breast, endometrial, and stomach cancer risk. Soy seems to have a particularly strong protective effect against prostate cancer. In fact, on a calorie-for-calorie basis, soy foods protect against prostate cancer at least four times more than any other dietary factor. The best estimate is that those who eat the most soy have a 30 percent lower risk of developing colorectal cancer than those who eat the least. Regarding stomach cancer, intake of at least 10 grams per day of unfermented soy foods such as tofu may result in lower risk, but there is some question about whether these results reflect other factors, such as fruit and vegetable consumption. As for breast cancer, modest reductions in risk have been shown for some groups of women, but most of the medical research suggests that soy intake protects against breast cancer mainly if consumed in childhood and adolescence. Postmenopausal women seem to receive little, if any, reduction in breast cancer risk. More research is needed for the effects of soy foods on cancer risk to be fully understood. Lisa M. Lines, M.P.H.
Spermatocytomas u
For Further Information Badger, T. M., M. J. Ronis, R. C. Simmen, and F. A. Simmen. “Soy Protein Isolate and Protection Against Cancer.” Journal of the American College of Nutrition 24, no. 2 (April, 2005): 146S-149S. Sun, C. L., et al. “Dietary Soy and Increased Risk of Bladder Cancer: The Singapore Chinese Health Study.” Cancer Epidemiology: Biomarkers and Prevention 11, no. 12 (December, 2002): 1674-1677. Trock, B. J., L. Hilakivi-Clarke, and R. Clarke. “Metaanalysis of Soy Intake and Breast Cancer Risk.” Journal of the National Cancer Institute 98, no. 7 (April 5, 2006): 459-471. Wu, A. H., D. Yang, and M. C. Pike. “A Meta-analysis of Soyfoods and Risk of Stomach Cancer: The Problem of Potential Confounders.” Cancer Epidemiology: Biomarkers and Prevention 9, no. 10 (October, 2000): 1051-1058. Yan, L., and E. L. Spitznagel. “Meta-analysis of Soy Food and Risk of Prostate Cancer in Men.” International Journal of Cancer 117, no. 4 (November 20, 2005): 667-669.
u
Other Resources
American Cancer Society Soybean page http://www.cancer.org/docroot/ETO/content/ ETO_5_3X_Soybean.asp?sitearea=ETO Memorial Sloan-Kettering Cancer Center Soy http://www.mskcc.org/mskcc/html/69383.cfm See also Antiestrogens; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Carcinogens, known; Carcinogens, reasonably anticipated; Childhood cancers; Epidemiology of cancer; Fruits; Isoflavones; Nutrition and cancer prevention; Nutrition and cancer treatment; Omega-3 fatty acids; Phytoestrogens; Prevention; Prostate cancer; Rectal cancer; Risks for cancer.
u Spermatocytomas Category: Diseases, symptoms, and conditions Also known as: Spermatocytic seminomas Related conditions: Germ-cell tumors, seminomas Definition: Spermatocytomas are a type of rare, germcell-derived testicular cancer. 1099
Spinal axis tumors Risk factors: No definitive genetic mutations or lifestyle habits have been identified that correlate with increased risk for developing spermatocytoma. Cryptorchidism, failure of the testes to descend by the time a boy reaches school age, is associated with increased risk of testicular cancer, as is a family history of testicular cancer. There is some suggestion that the presence of environmental estrogens may be related to an increased incidence of testicular pathologies, including spermatocytoma, but there is no definitive evidence for this hypothesis. Etiology and the disease process: The etiology is unknown. Spermatocytomas do not appear to arise from the same precursor cells as other germ-cell-derived testicular cancers. Some data indicate that spermatogonia (early sperm precursor cells) may be the cells from which spermatocytoma is derived. Spermatocytoma has a soft gray appearance on gross examination, with cystic areas in the tumor that do not show any hemorrhaged or necrotic areas. Microscopically, the tumor consists of tubular clusters of round cells that are highly variable in size. These cells are characterized by small, intermediate, and large nuclear regions. These are extremely slow-growing tumors, and metastasis of these tumors has been reported only anecdotally. Incidence: Spermatocytomas represent 2 to 3 percent of all testicular tumors, and approximately 10 percent occur in both testicles. They occur in older men, age forty-five to eighty. One retrospective study of 200 cases reported a single metastasis. Symptoms: These tumors generally manifest as a painless swelling in one testicle, although there are some reports of tenderness associated with the tumors. Screening and diagnosis: This cancer is diagnosed by physical exam. Spermatocytoma is most often confined to one or both testes (Stage I). In Stage II, the cancer has spread to lymph nodes, and in Stage III, it has metastasized. There are no specific chromosomal aberrations of the germ line or genetic mutation linked to this cancer. There are no specific blood markers for these tumors, although high expression of the tumor-suppressor gene TP53 has been reported. Treatment and therapy: Spermatocytoma is rarely metastatic and is usually contained within the testicle. Most often it is treated surgically by removing the affected testicle (orchidectomy). Prognosis, prevention, and outcomes: Since spermatocytoma is slow growing and rarely metastatic, the progno1100
Salem Health: Cancer sis is positive, with five-year survival rates of 80 to 100 percent reported after surgical treatment. Michele Arduengo, Ph.D., ELS See also Cancer clusters; Family history and risk assessment; Germ-cell tumors; Metastasis; Survival rates; Testicular cancer; TP53 protein; Tubular carcinomas; Tumorsuppressor genes.
u Spinal axis tumors Category: Diseases, symptoms, and conditions Also known as: Spinal tumors, osteoid osteomas, osteoblastomas, osteochondromas, giant cell tumors, chondroblastomas, vertebral hemangiomas, aneurysmal bone cysts, multiple myeloma, solitary plasmacytomas, osteosarcomas, Ewing sarcoma, softtissue sarcomas, chordomas, chondrosarcomas, central nervous system tumors Related condition: Central nervous system metastasis Definition: Spinal axis tumors are rare cancers of the spinal cord, an integral component of the central nervous system (CNS). Spinal tumors constitute between 10 and 19 percent of all primary neoplasms (tumors) in the central nervous system. The most common primary spinal axis tumors, which are usually benign, are schwannomas and meningiomas. The majority of spinal tumors are metastases from primary neoplasms elsewhere in the body, most commonly, the breast, prostate, and lung. Spinal cord tumors can be classified according to their location in the spinal column: Extradural tumors are those that occur outside the dura mater lining. Intradural tumors occur within the dural matrix, and intramedullary tumors occur inside the spinal cord. Risk factors: Vinyl chloride (also known as vinyl chloride monomer, or VCM, and cholorethene in International Union of Pure and Applied Chemistry literature) has been implicated in the development of gliomas. VCM is an industrial chemical chiefly used to produce its polymer, polyvinyl chloride (PVC). VCM is a toxic, colorless gas at room temperature with a sickly sweet odor. Once polymerized, it is stable and nonhazardous. Billions of pounds of PVC are produced per year and used in products such as PVC pipes (used in construction) and bottles. VCM was used as an anesthetic until its toxic effects were uncovered. Etiology and the disease process: Considerable advances have been made in the last several decades with regard to genetic and environmental factors involved in tumors in
Salem Health: Cancer
Spinal axis tumors
general; however, information pertaining to spinal tumors is still scant. Spinal tumors have been found to contain abnormal genes, but the causes of the genetic alterations remain unclear. Some of the better established hereditary (familial) models include neurofibromatosis 2 and von Hippel-Lindau (VHL) disease. Incidence: Spinal tumors are generally rare, with incidence ranging between 10 to 20 per 1 million people. However, incidence depends on age, with bimodal distribution. The first peak occurs among children age four and younger, and the second peak rises gradually from about age twenty-four and plateaus between the ages of sixtyfive and seventy-nine. The incidence for each type of spinal tumor is also age dependent. Low-grade astrocytomas (primary intracranial tumors derived from astrocyte cells of the brain) are common among children. Gliomas (tumors that arise from glial brain cells) tend to afflict adults, particularly those between the ages of forty and sixty. Certain spinal tumors are more common in one gender than the other. For example, the ratio of spinal meningioma is 10:1, women to men; for ependymoma it is 1.8:1, men to women.
Treatment and therapy: Surgery is usually the recommended treatment. Radiotherapy or chemotherapy is used in cases in which the tumor is incompletely resected or when malignant lesions are discovered. Although corticosteroids do not affect the tumors themselves, they are commonly administered to reduce inflammation following surgery or during radiation treatments. They are usually used for short durations to minimize the risk of osteoporosis, high blood pressure, diabetes, and infection. Prognosis, prevention, and outcomes: Prognosis varies depending on the type of tumor, extent of invasion, and how much of the tumor can be resected. For example, the prognoses for meningiomas and schwannomas are good, moderate for gangliomas, and poor for glioblastoma multi-
Symptoms: Clinical signs and symptoms reflect sequelae of spinal cord compression: Back pain in the middle and lower back, incontinence, and decreased sensitivity in the buttocks are warning signs of spinal nerve compression. The pain may spread beyond the aforementioned regions to the hips, legs, feet, or arms and may continue to worsen even with treatment. Depending on the location and type of tumor, other symptoms—loss of sensation including pain and temperature sensation, muscle weakness, difficulty with locomotion, and scoliosis (spinal deformity)—may develop. Screening and diagnosis: Spinal tumors are often overlooked because of their rarity and because their associated symptoms resemble more common conditions. Spinal magnetic resonance imaging (MRI) is commonly used for diagnostic purposes. Less commonly, computed tomography (CT) scans, either alone or in combination with contrast dyes as well as myelograms, are used. Biopsies (small tissue sampling technique) are conducted to determine the malignancy and grade (aggressiveness) of the tumor. In patients with known metastasis, particularly those with back pain, bone scans are used to confirm or exclude spinal metastasis.
A scan reveals a tumor in this patient’s spine. (©Howard Sochurek/ Corbis)
1101
Spinal cord compression
Salem Health: Cancer
Relative Survival Rates for Spinal Cancers, 1988-2001 Years
Survival Rate (%)
1 2 3 5 8 10
92.1 87.9 83.5 78.8 74.8 73.0
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) Note: Cancers of the spine made up 53.9 percent of the central nervous system cancers.
forme. A spinal tumor can impinge on nerves and cause pain, edema, ischemia, infarction, motor and sensory deficits including paralysis (below the level of the tumor), and death. Rena C. Tabata, M.Sc. u For Further Information Hackney, D. B. “Neoplasms and Related Disorders.” Topics in Magnetic Resonance Imaging 4 (1992): 37-61. Pascual Castroviejo, I. Spinal Tumors in Children and Adolescents. New York: Raven Press, 1990. Rossi, A., C. Gandolfo, G. Morana, and P. Tortori-Donati. “Tumors of the Spine in Children.” Neuroimaging Clinics of North America 17 (2007): 17-35. Sansur, C. A., et al. “Spinal-Cord Neoplasms: Primary Tumours of the Bony Spine and Adjacent Soft Tissue.” The Lancet Oncology 8 (2007): 137-147. Van Goethem, J. W., et al. “Spinal Tumors.” European Journal of Radiology 50 (2004): 159-176. u
Other Resources
Cord Foundation http://www.cordfoundation.org/ Spinal Cord Tumor Association http://www.spinalcordtumor.homestead.com/ See also Bone cancers; Bone scan; Computed tomography (CT) scan; Meningiomas; Metastasis; Schwannoma tumors; Spinal cord compression; Surgical biopsies; Symptoms and cancer; X-ray tests. 1102
u Spinal cord compression Category: Diseases, symptoms, and conditions Also known as: Nerve root compression, spinal column compression Related conditions: Primary spinal cord tumors, metastatic tumors Definition: Spinal cord compression occurs as a result of tumor invasion of the spinal canal or vertebrae, or from a primary tumor of the spinal cord pressing on the spinal cord and nerve roots. Occasionally, a malignant lymph node may grow to a size that can press on the cord. Metastasis, or spread of cancer cells from the primary tumor site, accounts for 85 percent of the cases of spinal cord compression. The spinal cord controls motor, sensory, and other functions, including walking, breathing, and bowel and bladder control. Compression may occur anywhere along the spinal cord from the neck to the lower back. Risk factors: The most significant risk factors are tumors that are in a higher stage, such as Stage III or Stage IV, because metastasis may already be present at diagnosis, or cancers that do not respond well to treatment, leading to metastases. Breast, lung, prostate, and renal cancers tend to have a greater risk of metastasis to the spinal cord. Gynecologic cancers tend to spread to the lower spine, and metastasizing breast and lung cancers affect higher areas in the spinal column. Primary tumors located in the spinal column, such as gliomas, pose a significant risk of cord compression. Etiology and the disease process: The cause of spinal cord compression is generally mechanical in nature, with a tumor pushing against the spinal cord’s thecal sac. The thecal sac surrounds the nerve roots and contains spinal fluid. When compression occurs, edema, inflammation, and nerve and circulation damage can result. Primary tumors of the spinal cord may originate inside the spinal column and cause pressure on the cord as the tumor expands. The vertebrae can be destroyed as the mass grows. Compression of the spinal cord begins with pain and weakness. If untreated, damage to the cord causes significant and permanent neurologic problems such as paralysis and an inability to control the bowel and bladder. If the compression is in the cervical area, where nerves control breathing, death can occur if a mechanical respirator is not employed until the compression is relieved. Incidence: Spinal cord compression may occur in up to 30 percent of cancer patients and in 12 to 15 percent of patients with primary central nervous system tumors. Men
Salem Health: Cancer tend to have a slightly higher incidence of cord compression from primary tumors. Older patients, usually age fifty and up, are more likely to experience cord compression from a metastatic tumor. Primary tumors affecting the spinal cord are seen more often in children and people between the ages of thirty and fifty. Symptoms: Symptoms often depend on the level of the spinal cord compression, but back pain is the main symptom regardless of site in 95 percent of patients. The pain can be local or radiating. As the tumor grows, progressive symptoms occur, including tenderness to touch, muscle weakness, tingling or numbness, inability to feel hot and cold, loss of bladder and bowel control, difficulty breathing, and paralysis. Screening and diagnosis: Patients at risk for spinal cord compression should be screened at each doctor’s visit for symptoms that indicate spinal cord compression. Educating the patient about symptoms that need to be reported to the doctor is critical to early intervention. Diagnosis is based on a careful history and physical examination to differentiate cord compression from other causes of symptoms. Back pain that does not get better with rest or lying down is diagnostic in nature. Laboratory tests are not usually helpful. Radiology studies, such as X rays to look for bone destruction and magnetic resonance imaging (MRI) to look at the entire spine, are more useful in identifying the site of damage. Staging is not used with spinal cord compression. Treatment and therapy: The goals of treatment are to relieve pain, restore nerve function, support the spine, and control or reduce the size of the tumor. Treatment includes dexamethasone, a corticosteroid, given intravenously over several days to reduce edema. Radiation therapy is the standard treatment when spinal cord compression is caused by tumor involvement. Treatments may range from five days to four weeks. Pain may be relieved in hours, but a return of spinal cord nerve function may take several weeks to months. Surgery may be used to stabilize the spine in a small group of patients, but recovery and healing are difficult, especially after radiation. If the tumor is sensitive to chemotherapy, drugs may be used to support other treatments. If the patient fails to respond to therapy, palliative care or hospice referral to include pain management and supportive care may be the only option. Prognosis, prevention, and outcomes: Because disease progression is the cause of spinal cord compression in 85 percent of cases, the prognosis for the patient is not good. Reversal of symptoms from spinal cord compression can occur with prompt intervention, leading to an im-
Splenectomy proved quality of life. Prevention is based on disease control when metastatic disease is involved. There is no prevention of a primary tumor. Outcomes depend directly on controlling the underlying cancer and early intervention to relieve spinal cord compression and alleviate symptoms. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Abrahm, J. L. “Assessment and Treatment of Patients with Malignant Spinal Cord Compression.” Journal of Supportive Oncology 2, no. 5 (2004): 377-388, 391. National Cancer Institute. Pain Control: A Guide for People with Cancer and Their Families. NIH Publication 03-4746. Bethesda, Md.: Author, 2003. Osowski, M. J. “Spinal Cord Compression: An Obstructive Oncologic Emergency.” Topics in Advanced Practice Nursing eJournal 2, no. 4 (2002). u
Other Resources
American Cancer Society http://www.cancer.org Merck Manuals Online Medical Library Compression of the Spinal Cord http://www.merck.com/mmhe/sec06/ch093/ ch093c.html See also Brain and central nervous systom cancers; External beam radiation therapy (EBRT); Non-Hodgkin lymphoma; Radiation therapies; Spinal axis tumors.
u Splenectomy Category: Procedures Also known as: Spleen removal Definition: A splenectomy is the surgical removal of the spleen. The spleen is located in the upper-left portion of the abdominal cavity. The function of the spleen is to filter the blood, removing old or damaged blood cells from the circulation and eliminating bacteria, parasites, and other organisms that can cause infection. The spleen also produces and stores blood. Cancers diagnosed or treated: Hodgkin disease (staging), non-Hodgkin lymphoma, chronic myelogenous leukemia, chronic B-cell leukemias (hairy cell leukemia and prolymphocytic leukemia) Why performed: A splenectomy is most commonly performed on a ruptured spleen, which, if not immediately 1103
Splenectomy
Salem Health: Cancer Splenectomy
Retractor Retractor Ligaments
Spleen Splenic artery
Stomach
Retractor Retractor Scissors
Clamps
treated, can cause life-threatening bleeding into the abdominal cavity. Splenectomies are also performed in patients with Hodgkin disease for staging the extent of disease; with non-Hodgkin lymphoma, leukemias, and splenomegaly for symptom control; or for correction of cytopenias (low blood cell counts) in patients with immunemediated destruction of one or more blood elements. Patient preparation: A few days before the procedure, blood and urine tests and X rays of the abdomen are performed. Immunizations against pneumococcal and meningococcal infections are administered, preferably a couple of weeks before the procedure (frequently this is not possible, particularly in the case of a ruptured spleen as a result of trauma or injury). If blood counts (red blood cells or platelets) are low, then a transfusion may be necessary before the procedure can be performed. Steps of the procedure: A splenectomy may be performed by the classic, open incision method or by laparoscopy. Before the procedure, anesthesia is administered and an airway tube is placed in the windpipe. In the classic surgery method, one incision is made in the abdomen over the spleen, and the blood vessels to and around the spleen are cut and tied off. This detaches the 1104
spleen from the rest of the body, and no further exchange of blood between the spleen and the rest of the body can occur. The spleen is then removed. If bleeding occurs, then it may be controlled with a cautery, which burns the tissue, or by tying the blood vessels. The incision is cleaned and closed with stitches or staples, which are generally removed approximately one week after surgery. During a laparoscopy, three to four small incisions are made in the abdomen. A laparoscope (a lighted tube with a small camera that projects a view of the internal structures to a video monitor) is inserted through one of these incisions. Specialized instruments are inserted through the two to three additional incisions for the doctor to perform the procedure. To provide more room for the doctor to work, carbon dioxide gas is pumped into the abdomen to inflate the abdomen. As with the classic surgery, blood vessels to the spleen are cut and tied off and the spleen is removed. The incisions are closed with stitches and covered with surgical tape. After the procedure: Blood tests and a pathology exam of the removed spleen may be performed. If necessary, a blood transfusion may be administered. Risks: Factors that may increase the risk for complications during the procedure include obesity, smoking, poor nutrition, recent or chronic illness, diabetes, advanced age, or a preexisting heart or lung disease. Complications that may be associated with a splenectomy include an increased risk for infection and, though rare, injury to surrounding organs (pancreas, stomach, or colon). Possible complications of any surgery include infection and excess bleeding. Additional complications that may occur with any surgery involving anesthesia include a collapsed lung, deep-vein blood clots, or thromboembolism (blockage of a blood vessel caused by a blood clot), especially in older adults. Results: Recovery time can vary depending on the underlying disease or condition. In general, however, complete healing from the procedure occurs in about four to six weeks. The results of splenectomy also vary according to the reason for the procedure: • Ruptured spleen: Once a ruptured spleen is removed, the risk of life-threatening bleeding is eliminated. • Splenomegaly: Pain and discomfort are effectively reduced if the patient was experiencing symptoms attributable to splenomegaly. • Chronic myelogenous leukemia: Asplenectomy significantly improves symptoms and simplifies management (by reducing transfusion requirements) in patients with chronic myelogenous leukemia.
Salem Health: Cancer
• Chronic B cell leukemia: A splenectomy may also be an effective secondary treatment for hairy cell leukemia and prolymphocytic leukemia, significantly reducing the tumor. • Cytopenias: Splenectomy has been shown to correct cytopenias in a large proportion of patients with immunemediated destruction of one or more cellular blood elements. Anita P. Kuan, Ph.D. u For Further Information Bridget, S. Wilkins, and Dennis H. Wright. Illustrated Pathology of the Spleen. New York: Cambridge University Press, 2000. “Guidelines for the Prevention and Treatment of Infection in Patients with an Absent or Dysfunctional Spleen.” BMJ 312 (1996): 430-434. Also available at http:// www.bmj.com. Hiatt, Jonathan R., Edward H. Phillips, and Leon Morgenstern, eds. Surgical Diseases of the Spleen. New York: Springer, 1997. Townsend, Courtney M., Jr., et al., eds. Sabiston Textbook of Surgery. 17th ed. Philadelphia: Elsevier Saunders, 2005. “Updated Guidelines: The Prevention and Treatment of Infection in Patients with an Absent or Dysfunctional Spleen.” British Committee for Standards in Haematology. BMJ, June 2, 2001. Also available at http://www .bmj.com. Uranus, S. Current Spleen Surgery. Munich: Zuckschwerdt, 1995. u
Other Resources
Cleveland Clinic http://www.clevelandclinic.org Familydoctor.org Splenectomy http://familydoctor.org/online/famdocen/home/ articles/655.html Lymphoma Research Foundation http://www.lymphoma.org National Institutes of Health http://www.nih.gov See also Chronic lymphocytic leukemia (CLL); Hairy cell leukemia; Hodgkin disease; Laparoscopy and laparoscopic surgery; Leukemias; Lymphomas; Myelofibrosis; Myeloproliferative disorders; Non-Hodgkin lymphoma.
Sputum cytology
u Sputum cytology Category: Procedures Definition: Sputum cytology is a screening for the presence of abnormal cells in sputum (saliva). Cancers diagnosed: Lung cancer Why performed: If a tumor is centrally located and has invaded the airways, then this procedure may allow visualization of tumor cells for diagnosis. It is a risk-free and inexpensive procedure. Patient preparation: A sputum sample may be collected from coughed-up mucus (sometimes induced by an inhaled saline mist) or by bronchoscopy, which uses a bronchoscope to examine the throat and airways. No special preparation is required if the sputum sample is to be collected by coughing with or without a saline mist at home or in the doctor’s office. If a sputum sample is to be obtained by bronchoscopy, then the patient may not eat or drink for eight to ten hours before the procedure. The patient may be given medications to dry the secretions in the mouth and airways. A chest X ray may also be done before bronchoscopy. Steps of the procedure: For simple coughing procedures, three sputum samples are usually collected over three days in a container with fixative to preserve the sample. Bronchoscopy is performed with a flexible or a rigid bronchoscope. Rigid bronchoscopy requires general anesthesia. In either case, the patient must sign a consent form. After the procedure: There are no requirements following sputum collection by coughing. A second chest X ray is taken after bronchoscopy, and the patient should be driven home. Patients should call immediately if they cough up more than two tablespoons of blood, have difficulty breathing, or have a fever for more than twenty-four hours. Risks: There is no risk in collecting sputum samples by coughing procedures. Bronchoscopy is usually a safe procedure, and complications are rare. Complications that may occur include spasms of the bronchial tubes, irregular heart rhythms, infections, hoarseness, and bubbles under the skin. Results: The most common screening tests for lung cancer are a chest X ray and sputum cytology. According to a 2007 report by the United States National Cancer Institute, the results of many studies have shown no evidence that screening for lung cancer using sputum cytology or chest X ray reduces lung cancer mortality. The institute also 1105
Squamous cell carcinomas concludes that screening could lead to false positive tests and unnecessary, invasive diagnostic procedures and treatments. Hence, these tests are not used for routine screening of healthy individuals but only when symptons indicate their use. Bernard Jacobson, Ph.D. See also Bronchial adenomas; Bronchoalveolar lung cancer; Carcinoid tumors and carcinoid syndrome; Coughing; Head and neck cancers; Hemoptysis; Infection and sepsis; Lung cancers; Mesothelioma; Pneumonia; Radon; Screening for cancer.
u Squamous cell carcinomas Category: Diseases, symptoms, and conditions Also known as: Skin cancer, SCC Related condition: Basal cell carcinomas Definition: Squamous cell carcinomas are malignant tumors that begin in the squamous cells that form the outer layer, or epidermis, of the skin. Risk factors: Risk factors for squamous cell carcinomas include exposure to sunlight and ultraviolet radiation, age above fifty years, male gender, light-colored skin that burns easily, blue or green eyes, blond or red hair, residence in a geographical area that receives high sun exposure, exposure to chemical carcinogens such as arsenic and tar, history of a large number of X rays, history of prior nonmelanoma skin cancer, and chronic immunosuppression. Etiology and the disease process: Cumulative lifetime sun exposure is the main cause of squamous cell carcinoma. The shorter-wavelength portion of the ultraviolet spectrum (known as UVB) is believed to be about one thousandfold more active in inducing skin cancer than the longer-wavelength portion (known as UVA). Squamous cell carcinoma spreads faster than basal cell carcinoma (skin cancer that originates from basal keratinocytes in the top layer of the skin, the epidermis) but still may be relatively slow growing. A subset of high-risk squamous cell carcinoma is capable of infiltrating the local area and metastasizing to regional lymph nodes as well as to distant locations and internal organs, most often to the lungs. This subset accounts for most of the morbidity and mortality associated with squamous cell carcinoma. The overall risk of metastasis for squamous cell carcinoma is 2 to 6 percent and as high as 47 percent for certain high-risk lesions. 1106
Salem Health: Cancer Five-year survival rates as high as 73 percent have been reported for patients with squamous cell carcinoma that has metastasized to the lymph nodes and has been treated with surgery and radiation therapy. Incidence: The annual incidence of squamous cell carcinoma in the United States is estimated to be 107 cases per 100,000 people in the general population. Because health registries often exclude squamous cell carcinoma from their databases and the rate of this cancer varies based on geographical location, this number is difficult to determine with accuracy. Squamous cell carcinoma is the second most common form of skin cancer after basal cell carcinoma in whites. In people of African and Asian descent, squamous cell carcinoma, although relatively rare, is the most common form of skin cancer. Squamous cell carcinoma carries a higher mortality rate in blacks than in whites, probably because of delayed diagnosis, and occurs at a two to three times higher frequency in men than in women, presumably because of a higher cumulative exposure to sunlight. There has been an apparent dramatic increase in the incidence of squamous cell carcinoma over the past several decades in the United States. This has been attributed to an increase in sun exposure in the general population, the advancing age of the population, and earlier diagnosis because of increased public awareness of skin cancer. Symptoms: Squamous cell carcinoma may manifest as a variety of primary morphologies. The main symptom is a growing bump that may have a rough, scaly surface and flat, reddish patches. A sore that does not heal can be a sign of squamous cell carcinoma. Squamous cell carcinomas typically occur on portions of the skin that have been exposed to sunlight over a period of years; approximately 70 percent of lesions occur on the head and neck, and about 15 percent occur on the arms and hands. Histologically, a squamous cell carcinoma lesion involves the full thickness of the epidermis, the outer layer of the skin, but without involvement of the dermis, the deep vascular inner layer of the skin. Screening and diagnosis: Screening for squamous cell carcinoma involves regular skin examinations for new lesions or changes in an existing lesion. Suspicious changes in an existing lesion include a change in appearance, color, size, or texture; pain; inflammation; bleeding; or itching. A lesion that is asymmetrical, has irregular or diffuse borders, has multiple colors, or is larger than six millimeters (mm) in diameter should be examined by a doctor. The appearance of a skin lesion may indicate a squamous cell carcinoma, but a skin biopsy is required for a de-
Salem Health: Cancer finitive diagnosis. The common types of biopsy are shave biopsy, punch biopsy, incisional biopsy (removes only a portion of the suspicious tissue), and excisional biopsy (removes the entire suspicious region). A biopsy for squamous cell carcinoma is normally done in the doctor’s office after the patient is given a local anesthetic. Biopsy samples must be deep enough to reach the mid-dermis to allow for determination of the presence or absence of invasive disease. For high-risk lesions, a larger tissue sample may be taken to assess the extent of invasion into nerves and to look for other features that would indicate a greater risk of metastasis. Squamous cell carcinoma is staged according to the TNM (tumor/lymph node/metastasis) classification system. Because most squamous cell carcinomas are not metastatic at the time of diagnosis, the stage (T1-T4) is based on the size and characteristics of the lesion. Treatment and therapy: Most squamous cell carcinomas are treated in the doctor’s office by cryotherapy, electrodesiccation and curettage, excision with conventional margins, or Mohs micrographic surgery. It is important to remove the lesion completely in the first treatment because it can recur, metastasize, and cause death. More advanced or more invasive squamous cell carcinomas may require more aggressive treatment, including surgical management, radiation therapy, or both. Cryotherapy with liquid nitrogen is a safe and low-cost procedure. For appropriate lesions and with good technique, the five-year cure rate for squamous cell carcinoma is 95 percent. Electrodesiccation and curettage, which may be used to treat squamous cell carcinoma on the trunk and extremities, is a simple procedure involving scraping and burning the tissue in the lesion. Its effectiveness is considered to be very dependent on technique; cure rates improve with a doctor’s experience. Excision with conventional margins (4 mm for lower-risk lesions is recommended) is highly effective for many squamous cell carcinomas, with a five-year cure rate of 92 percent for primary squamous cell carcinoma and 77 percent for recurrent squamous cell carcinoma. This technique commonly involves removal of a greater amount of normal tissue than is necessary for complete tumor removal. Mohs surgery, performed by dermatologic surgeons, has the highest cure rate for squamous cell carcinoma (94 to 99 percent) and is the procedure of choice when it is desirable to remove as little tissue as possible (such as on the face) and for highrisk squamous cell carcinoma. Unlike with simple excision, Mohs surgery allows for examination of the entire surgical margin during the procedure and the removal of the tumor in a step-wise procedure until clear margins are
Squamous cell carcinomas
A Few Facts About Ultraviolet Light Ultraviolet light is part of the invisible spectrum of sunlight. It has a wavelength shorter than visible light and longer than that of X rays. It can be divided into three wavelengths: UVA, UVB, and UVC. • UVA, with a wavelength of 320-400 nanometers (nm), has the least energy of the three. It penetrates glass and clouds. It is responsible for long-term skin damage and aging of the skin and decreases the amount of vitamin A in the skin. Because it produces indirect damage to deoxyribonucleic acid (DNA), it also plays a role in causing cancer. • UVB, with a wavelength of 290-320 nm, causes sunburns. It directly damages DNA and therefore results in skin cancers. It decreases the amount of vitamin A in the skin and can damage the eye and lead to cataracts. On the positive side, it causes the body to produce vitamin D and is an important source of this vitamin. It also is used to treat some skin conditions such as psoriasis. • UVC, with a wavelength of 200-290 nm, has the most energy of the three types. Although UVC is the most carcinogenic, it generally does not penetrate the atmosphere as it is absorbed by the ozone layer. Exposure to ultraviolet light is believed to alter people’s immune response and make them more susceptible to infection as well as to activate certain viruses, including the human immunodeficiency virus (HIV). The levels of ultraviolet light radiation vary by time of day, peaking at the solar noon, when the sun reaches its highest point in the sky, and by time of year, peaking in the Northern Hemisphere in June and ebbing in December. Geography also plays a part in people’s exposure to ultraviolet light. The nearer the equator, the higher the levels, as the sunlight passes through less atmosphere, and people who live in places such as Australia and Arizona, where there are many days of sunshine, are exposed to more ultraviolet rays. Because of the thinner air, the higher the elevation, the higher the intensity of the ultraviolet light, rising 4 percent with every 1,000 feet of elevation. Proximity to reflective surfaces—fresh snow, water, sand, and pavement—also increases the intensity, while air pollution and a thick cloud layer decrease the intensity. Sources: Skin Cancer Foundation, Ohio State University Extension Fact Sheet CDFD-199-07
obtained. Mohs surgery is routinely performed as an outpatient procedure with the patient under local anesthesia and is widely available in the United States. Nonsurgical treatment options for squamous cell carcinoma include topical chemotherapy and immune response modifiers (generally used for premalignant lesions), photo1107
Staging of cancer dynamic therapy, radiation therapy (generally used in patients for whom surgery is not feasible and as an adjuvant therapy for patients with metastatic or high-risk squamous cell carcinoma), and systemic chemotherapy (for patients with metastatic disease). Prognosis, prevention, and outcomes: Localized squamous cell carcinoma of the skin has a high cure rate if treated early. The overall three-year survival rate is estimated to be 85 percent. For patients with no high-risk factors, this rate approaches 100 percent, and for patients with at least one high-risk factor, it decreases to 70 percent. Risk factors associated with higher rates of recurrence and metastasis include tumors on the lips or ears; tumor size greater than 2 centimeters; an invasive, poorly differentiated, or recurrent tumor; nerve involvement; being an organ transplant recipient; having received chronic immunosuppressive therapy; and being infected with the human immunodeficiency virus (HIV) or having acquired immunodeficiency syndrome (AIDS). Patients who develop one squamous cell carcinoma have a 40 percent risk of developing additional squamous cell carcinomas within the next two years and therefore should receive a complete skin examination every six to twelve months. Patients with high-risk tumors should receive complete skin and lymph node examinations every three to six months for at least two years. The most important preventive measure is limiting exposure to sunlight. Skin should be protected by wearing protective clothing such as hats, long-sleeved shirts, long skirts, or pants. A high-quality broad-spectrum sunscreen that blocks UVA and UVB light should be applied at least thirty minutes before going outside and reapplied frequently. Exposure to the sunlight at midday when the sun is most intense should be limited. Jill Ferguson, Ph.D. u
For Further Information Aboutalebi, S., and F. M. Strickland. “Immune Protection, Natural Products, and Skin Cancer: Is There Anything New Under the Sun?” Journal of Drugs in Dermatology 5 (2006): 512-517. Alam, M., and D. Ratner. “Cutaneous Squamous-Cell Carcinoma.” New England Journal of Medicine 344 (2001): 975-983. Clayman, G. L., et al. “Mortality Risk from Squamous Cell Skin Cancer.” Journal of Clinical Oncology 23 (2005): 759-765. Green, A., and R. Marks. “Squamous Cell Carcinoma of the Skin (Non-Metastatic).” Clinical Evidence 14 (2005): 2086-2090. 1108
Salem Health: Cancer Takata, M., and T. Saida. “Early Cancers of the Skin: Clinical, Histopathological, and Molecular Characteristics.” International Journal of Clinical Oncology 10 (2005): 391-397. u
Other Resources
National Cancer Institute Squamous Cell Carcinoma of the Skin http://www.cancer.gov/cancertopics/pdq/treatment/ skin/HealthProfessional/page6 Skin Cancer Foundation Squamous Cell Carcinoma http://www.skincancer.org/squamous/index.php See also Basal cell carcinomas; Carcinomas; Dermatology oncology; Epidermoid cancers of mucous membranes; Eye cancers; Eyelid cancer; Geography and cancer; Itching; Lip cancers; Melanomas; Moles; Recurrence; Skin cancers; Sunlamps; Sunscreens; Ultraviolet radiation and related exposures.
u Staging of cancer Category: Procedures Also known as: Clinical staging, pathological staging, restaging Definition: Staging is the process in which the location, extent, and degree of metastasis (spread) of a primary, or original, cancerous tumor is determined. Cancers diagnosed or treated: Essentially all solid tumor cancer diagnoses are staged similarly. Nonlocalized leukemias are staged in unique ways according to the specific diagnosis. The diagnostic processes used to stage a specific case vary somewhat according to cancer type and location. Why performed: Cancer staging plays an integral role in determining overall disease prognosis as well as influencing treatment modality choices. Stage assessment also plays an important role in assuring effective communication among the patient’s medical team and accurate disease surveillance and epidemiology efforts. Patient preparation: Patient preparation will vary according to the technique, or supporting procedures, used to help stage the cancer. These procedures range from physical examination and imaging—X rays, ultra sounds, computed tomography (CT), magnetic resonance imaging (MRI) scans—to laboratory tests, biopsies, and surgical
Salem Health: Cancer excisions with subsequent pathological examination of the tumor. Any preparation normally required of these supporting procedures will apply to the process. Steps of the procedure: Cancer staging is composed of three distinct phases: clinical staging, pathological staging, and restaging. Clinical staging is accomplished by nonpathologic means based on physical examination and imaging technology such as X ray, MRI, and CT, as well as immunologic and molecular blood tests to detect and measure cancer markers where applicable. Pathological staging is accomplished following tissue removal by biopsy in which surgical tumor excision is assessed as a sound treatment option. The biopsied tissue and/or removed tumor, surrounding tissue, and nearby lymph nodes are examined microscopically and histologically to determine the type and extent of the cancer from a pathologic perspective. Because treatment considerations and survival statistics are based on the stage of a patient’s cancer, the initial stage assessment remains static throughout the course of the disease regardless of progression and/or response to treatment. Should a cancer patient enter remission but subsequently present with a recurrence, restaging may be accomplished if additional treatment is planned. The restaging process is identical to the original one, including both clinical and pathological staging, but is now designated with a lowercase r. For example, a restaged Stage IV grouping would be recorded as Stage rIV. In order to maintain terminology consistency, a limited number of classification systems are utilized, and efforts toward additional interpretive continuity are ongoing. Although the type of cancer dictates which specific categorization is applied, common elements include tumor location, size and number, lymph node involvement, and degree of metastasis (spread). The most prevalent systems used include tumor-node-metastasis (TNM) and overall group staging. The tumor-node-metastasis (TNM) classification is adapted by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer/ International Union Against Cancer (UICC). The category T, for tumor, provides information about the original tumor such as measurement (in millimeters, centimeters) at the site of origin and its degree of invasion into nearby tissues and organs. • TX: Cannot be measured/evaluated • T0: No evidence of primary tumor • Tis: In situ tumor (tumor limited to cell layers of the original site) Beyond Tis, numerical tumor categorization offers a
Staging of cancer relative degree of severity, with higher numbers reflecting a larger tumor and/or more aggressive invasion. • T1: Smaller tumor, least aggressive • T2 • T3 • T4: Larger tumor, most aggressive The tumor grade is the degree of abnormality (amount of differentiation from normal cells) and is determined pathologically—by microscopic analysis. Typically, welldifferentiated, or low-grade, tumors are considered the least aggressive and are associated with the best outcomes overall. • GX: Cannot be determined • G1: Tumor cells well differentiated from surrounding tissue • G2: Tumor cells moderately well differentiated from surrounding tissue G3: Tumor cells poorly differentiated from surrounding tissue G4: Tumor cells undifferentiated from surrounding tissue Special cases are prostate cancer and central nervous system (CNS) cancers. The most common approach to classification of prostate cancer is the Gleason system, which is based on the degree of glandular change, including size, shape, and pathologic differentiation. The Gleason Score or Sum (GS) represents the sum of the primary and secondary grade of the prostate tumor. Based on a ranking from G2 (least aggressive, best prognosis) to G10 (most aggressive, poorest prognosis), the higher the sum is, the more severe is the disease. There are several, similar classification systems used to grade CNS/brain cancers: World Health Organization (WHO), Kernohan, or Ringertz. Rather than tumor size, grading is based on tissue differentiation and degree of vascularity and necrosis. Classification is made based on a three- or four-grade system, with the higher number associated with more aggressive cancer. The category N, for node, describes the degree that lymph nodes have been affected by cancer. This is typically accomplished by a process termed “sentinal node biopsy.” The (nearby) sentinal node or nodes are detected by injection of a radioactive or colored dye solution at the tumor site. The indicator solution will travel a path within the lymph system that circulating cancer cells would be expected to follow. The area is then scanned to detect the presence of the indicator solution in nearby, or sentinal, lymph nodes. One or more lymph nodes are then removed and examined pathologically for the presence of cancer cells. Positive findings will typically result in further removal and testing of nearby lymph nodes to determine extent. 1109
Staging of cancer
• •
NX: Cannot be measured/evaluated N0: Nearby lymph nodes are clear of cancer Beyond N0, numerical categorization describes the size, location, and number of lymph nodes affected. The higher the number, the more lymph nodes are involved. • N1: Fewer lymph nodes affected • N2 • N3: More lymph nodes affected The M category, for metastasis, describes the degree to which the primary tumor has spread (metastasized) into surrounding tissues and/or organs. • MX: Cannot be measured/evaluated • M0: No cancer metastasis detected • M1: Cancer metastasis detected Although the TNM metrics are relatively universal, each cancer type has a customized version of this classification system. In some instances, there may be many additional subcategories to refine tumor classification and offer additional prognostic information to the provider. In other cases, the staging classification may be simplified by means of truncated categorization. Based on the established TNM categories, an overall cancer group stage is determined. Although criteria for stage assignment varies somewhat according to cancer type, the following provides a top-level overview of stage groupings: • Stage 0: Carcinoma in situ (cancer is limited to the site of origin) Stages I through III classify cancer where higher numbers indicate more extensive and aggressive disease. Some cancers types utilize subcategories in staging to provide more specific information about type, behavior, and prognosis. • Stage IV: Distant metastatic cancer (cancer has spread to another, distant organ) Special cases are female reproductive cancers, Hodgkin disease/lymphoma, colorectal cancer, and leukemia. Female reproductive cancers are stage according to the International Federation of Gynecologists and Obstetricians (FIGO). Although FIGO staging classification guidelines generally follow the general TNM/group staging approach, many of the female reproductive cancers, including those of the breast, cervix, and uterus, are subclassified in great detail. Hodgkin disease and other cancers of the lymphoid system are staged using the Ann Arbor classification system. Stages I through IV are defined by the anatomical location of affected lymph nodes. The higher the stage number, the more lymph nodes are affected and the more aggressive is the disease. Each stage assignment is then subclassified as either “A” (asymptomatic) or “B” (symptomatic). 1110
Salem Health: Cancer Colorectal cancer uses the Dukes’ staging classification, an older system that corresponds closely to group staging. Dukes’ A through D colorectal cancer stages effectively translate to group Stages I through IV. Because leukemia involves the bone marrow and has often affected many organs, including the liver, spleen, and lymph nodes, staging is based primarily on the patient’s survival outlook according to disease progression. Although not all forms of leukemia utilize a formal staging system, each form that does has a dedicated staging classification system. For example, chronic myelogenous leukemia (CML) is classified into three phases (as opposed to stages): • Chronic: Fewer than 5 percent immature cells in circulation/bone marrow; mildly symptomatic, readily responsive to treatment • Accelerated: 5 to 30 percent immature cells in circulation/bone marrow; more symptomatic, less responsive to treatment • Acute/blast phase: Less than 30 percent immature cells in circulation/bone marrow; very aggressive, acute disease Additional staging classifications, such as Rai (Stages 0-IV; U.S. predominant) and Binet (Stages A, B, and C; European predominant), are used for chronic lymphocytic leukemia (CLL). Still other systems are applied to different leukemia types such as the Stage 1 through Stage 3 classification based on level of anemia and spleen size for hairy cell leukemia (HCL). In addition to providing information on the size, extent, and prognostic status of each cancer case, staging plays a vital role in epidemiology and treatment studies. The National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program and other cancer registries such as the National Program of Cancer Registries (NPCR) use summary staging classification in their surveillance and epidemiology efforts. For these purposes, all cancers are grouped into one of the following five summary categories: • In situ: Early-stage cancer, present only in the cell layers where first detected • Localized: Cancer localized to tissue/organ where first detected; no evidence of metastasis • Regional: Cancer metastasized to nearby lymph nodes, tissues, organs • Distant: Cancer metastasized to distant lymph nodes, tissues, organs • Unknown: Insufficient data available to classify Data collected are made available to clinical and research professionals so that they may better understand and address the cancer burden according to a variety of demographics and metrics, including cancer stage.
Salem Health: Cancer Results: Cancer staging is a vital component of the diagnostic process. Accurate stage assessment will guide the medical team in making optimal treatment recommendations for patient care according to prognostic expectations. Because the epidemiologic value of the original stage is significant, the classification remains constant throughout the course of disease. Restaging occurs only if treatment is planned following a recurrence. Pam Conboy, B.S. u For Further Information Benedet, J. L., et al. “FIGO Staging Classifications and Clinical Practice Guidelines in the Management of Gynecologic Cancers.” International Journal of Gynecology and Obstetrics 70 (2000): 209-262. Greene, F. L. “Updates to Staging System Reflect Advances in Imaging, Understanding.” Journal of the National Cancer Institute 22 (2002): 1664-1666. _______. “Updating the Strategies in Cancer Staging.” American College of Surgeons Bulletin 87 (2002): 13-15. Greene, F. L., et al., eds. American Joint Committee on Cancer Staging Manual. 6th ed. New York: Springer, 2002. O’Dowd, G. J., et al. “The Gleason Score: A Significant Biologic Manifestation of Prostate Cancer Aggressiveness on Biopsy.” PCRI Insights 4, no. 1 (January, 2001). Wittekind, C., et al. “TNM Residual Tumor Classification Revisited.” Cancer 94 (2002): 2511-2516. u
Other Resources
American Cancer Society http://www.cancer.org American Joint Committee on Cancer (AJCC) http://www.cancerstaging.org/ CancerCare http://www.cancercare.org Centers for Disease Control and Prevention (CDC) National Program of Cancer Registries (NPCR) http://www.cdc.gov/cancer/npcr/ CureSearch http://www.curesearch.org International Federation of Gynecologists and Obstetricians (FIGO) http://www.figo.org International Union Against Cancer http://www.uicc.org/
Statistics of cancer Lung Cancer Online Foundation http://www.lungcanceronline.org National Cancer Institute http://www.cancer.gov See also Biopsy; Cancer care team; Carcinomas; Chemotherapy; Childhood cancers; Dukes’ classification; Epidemiology of cancer; Gleason grading system; Leukemias; Lymphomas; Medical oncology; Metastasis; National Cancer Institute (NCI); Oncology; Sentinel lymph node (SLN) biopsy and mapping; Statistics of cancer; TNM staging.
u Statistics of cancer Category: Social and personal issues Definition: Cancer statistics are numerical values regarding aspects of cancer that characterize the population or sample from which the data was taken. Common statistics: Statistics provide a good estimate of the impact of cancer on the general population. The most common way to show this impact is to report the incidence, death or mortality, and survival rates. Incidence is the number of newly diagnosed, or found, cancer cases in a given time period. Mortality is the number of deaths from cancer during a certain time period. Incidence and death rates are reported as a specific number for every 100,000 people in the general population, per year. Survival looks at the length of time patients live after their cancer is diagnosed. Relative survival compares cancer patients still living after a certain period of time (for example, five years) to a similar group of people in age, sex, and race without diagnosed cancer. Relative survival rates are useful for group predictions but not individual survival predictions, because this rate does not account for an individual’s medical condition, such as other medical illnesses. Some rates will be age-adjusted to give a more accurate statistic, which is often done when comparing populations where the age distributions are very different. Data used for the general population come from the U.S. Census. Description of the population: Cancer statistics take a look at cancer’s impact by dividing the population by sex, age, and race and ethnicity. The U.S. Census divides race into five groups. White is any person whose origin can be traced to Europe, the Middle East, or North Africa. Black or African American is any person whose origin can be traced to the black groups of Africa. American Indian and Alaska Native refer to any person whose origins can be traced to the native peoples of North, South, and Central 1111
Statistics of cancer America and who remains affiliated with the tribe or community. Asian is any person with origins in the Far East, Southeast Asia, or the Indian subcontinent. Native Hawaiian and other Pacific Islander refer to any person whose origins can be traced back to Hawaii, Guam, Samoa, or another Pacific island. Incidence, death, and survival statistics: In 2007 the American Cancer Society estimated that about 1,444,920 Americans would be diagnosed with an invasive cancer (called incidence), and 559,650 would die from an invasive cancer. Invasive means the cancer has spread beyond the site where it developed. An example of an invasive cancer would be a breast tumor that has spread to surrounding tissue or lymph nodes. Cancer is the second leading cause of death after heart disease. A person’s risk, or chance, of developing cancer increases as he or she ages; about 77 percent of all cancer diagnoses occur in persons fifty-five years and older. According to the Surveillance Epidemiology and End Results (SEER) Cancer Statistics Review, the average age of diagnosis for all cancer sites per year between 2000 and 2004 was sixty-seven years. Broken down into age ranges, about 10 percent were under age forty-four; 35 percent were between forty-five and sixty-four; 48 percent were between sixty-five and eighty-four; and 7 percent were eighty-five years or older. The average age at death for all cancer sites for 2000 to 2004 was seventy-three years of age. By age ranges, about 4 percent were under age fortyfour; 26 percent were between forty-five and sixty-four; 56 percent were between sixty-five and eighty-four; and 14 percent were eighty-five years of age or older. The American Cancer Society reported the following age-adjusted rates for men and women per year between 1999 and 2003 (numbers in parentheses are per 100,000 people from the general population). Men had a higher incidence of cancer (562) and death from cancer (244) than women (415 incidence; 164 deaths). The major cancers diagnosed among men were prostate (165), lung and bronchial area (90), colon and rectum (64), urinary bladder (38), and non-Hodgkin lymphoma (23). The highest incidence of cancer in women occurred as breast cancer (128), lung and bronchial area cancer (55), colon and rectum cancer (47), non-Hodgkin lymphoma (16), and urinary bladder cancer (10). Men died most often from lung and bronchial cancers (75), prostate cancer (29), colon and rectum cancers (24), pancreatic cancer (12), and nonHodgkin lymphoma (10). Women died most often from lung and bronchial cancers (41), breast cancer (26), colon and rectum cancers (17), pancreatic cancer (9), and nonHodgkin lymphoma (6). 1112
Salem Health: Cancer By race and ethnicity for the same time period, ageadjusted cancer incidence for all sites per 100,000 people was highest among African Americans (1,024), followed by whites (976), Hispanics and Latinos (771), Asian Americans and Pacific Islanders (689), and finally American Indians and Alaska Natives (665). Cancer incidence among African Americans occurred most often in the prostate (243), lung and bronchial area (161), colon and rectum (124), female breast (112), kidney and renal pelvis (28), and stomach (26). Cancer incidence among whites occurred most often in the prostate (156), lung and bronchial area (145), female breast (131), colon and rectum (110), kidney and renal pelvis (27), and stomach (14). Cancer incidence among Asian Americans and Pacific Islanders occurred most often in the prostate (104), female breast (91), colon and rectum (91), lung and bronchial area (85), stomach (31), and liver and bile duct (30). Cancer incidence among American Indians and Alaska Natives occurred most often in the colon and rectum (95), lung and bronchial area (89), female breast (74), prostate (71), stomach (34), and kidney and renal pelvis (31). Cancer incidence among Hispanics and Latinos occurred most often in the prostate (141), female breast (93), colon and rectum (90), lung and bronchial area (79), kidney and renal pelvis (26), and stomach (25). African Americans were at the top of the list relative to deaths from cancer (523), followed by whites (403), Hispanics and Latinos (275), American Indians and Alaska Natives (265), and finally Asian Americans and Pacific Islanders (244). By racial group, and six cancer sites with highest rates, cancer deaths among African Americans occurred in the lung and bronchial area (138), prostate (65), colon and rectum (57), female breast (34), stomach (18), and liver and bile duct (13). Cancer deaths among whites occurred in the lung and bronchial area (116), colon and rectum (40), prostate (27), female breast (25), liver and bile duct (9), and kidney and renal pelvis (9). Cancer deaths among Asian Americans and Pacific Islanders occurred in the lung and bronchial area (58), colon and rectum (26), liver and bile duct (22), stomach (18), female breast (13), and prostate (12). Cancer deaths among American Indians and Alaska Natives occurred in the lung and bronchial area (70), colon and rectum (27), prostate (18), female breast (14), liver and bile duct (12), and stomach (11). Cancer deaths among Hispanics and Latinos occurred in the lung and bronchial area (52), colon and rectum (29), prostate (22), female breast (16), liver and bile duct (16), and stomach (14). In comparing race and ethnic groups, African American men had a 38 percent higher death rate and African American women a 17 percent higher death rate than
Salem Health: Cancer whites from colorectal, lung (male), breast (women), and prostate cancers. In addition, African Americans had higher incidence for all cancers except for female breast cancer when compared with whites. Hispanics had a higher incidence of uterine cervix, liver, and stomach cancers than whites. Asian Americans and Pacific Islanders had the highest incidence and death rates from stomach and liver cancers when compared with all racial and ethnic groups, with the exception of death rates from stomach cancer in men of this minority group. Within the Asian American and Pacific Islander group, Vietnamese women were four times more likely to be diagnosed with cervical cancer than other women in this minority group. Finally, American Indians and Alaska Natives appear to have the highest incidence and death rate from kidney cancer. As available data for American Indians and Alaska Natives are limited, this last statement should be viewed as a rough estimate. The SEER Program looked at trends in five-year relative survival rates for several time periods using data from nine regions of the United States. The five-year relative survival rate for all cancers diagnosed per year between 1996 and 2002 for all races was 66 percent, which increased from 51 percent for the years 1975 to 1977. Comparing the two largest race populations, whites had a higher five-year relative survival rate for all cancers (68 percent) than African Americans (57 percent) between 1996 and 2002. By cancer sites for 1996 and 2002, prostate cancer had the highest five-year relative survival rate (100 percent) and pancreatic cancer the lowest survival rate (5 percent). Finally, the five-year relative survival rates for some of the more familiar cancers were breast, 89 percent; lung and bronchial area, 16 percent; and skin cancer, 92 percent. Risk statistics: The major risk factors for developing cancer among all populations are tobacco use, obesity or overweight, physical inactivity, poor nutrition, infectious agents (for example, human immunodeficiency virus, or HIV, and human papillomavirus, or HPV), sun exposure, irregular or no cancer screenings, carcinogens (for example, asbestos and pollution), inherited genes, and age. Of the 559,650 cancer deaths expected in 2007, about 30 percent were estimated to be tobacco-related, and 33 percent related to poor diet, overweight or obesity, and no exercise. More than 1 million skin cancer diagnoses were expected in 2007; most of these could be prevented with proper sunscreen use. Occupational and environmental exposure to carcinogens account for about 6 percent of cancer deaths. Only about 5 percent of cancers are hereditary (meaning an altered gene that conveys a significant chance of developing cancer is passed from parent to
Statistics of cancer child). Age is a main risk factor for cancer in general and closely associated with breast cancer (age fifty and older), prostate cancer (65 percent of cases diagnosed after age sixty-five), and colorectal cancer (age fifty and older). In addition, poverty, lack of health insurance, geographic location, and cultural and language barriers are some of the main factors that prevent minorities from accessing health care services. Some 12 percent of whites, 18 percent of African Americans, and 35 percent of Hispanics and Latinos have no health insurance. In addition, 24 percent of African Americans and 23 percent of Hispanics and Latinos live below the poverty line compared with 11 percent of whites. Perspective and prospects: The five-year relative survival rate for all races and all cancer sites increased 16 percent between 1977 and 1996. Improvements in prevention, earlier detection of cancer, and advances in cancer treatments helped lower incidence and deaths from cancer. Screenings are available for breast, cervix, colon, rectum, prostate, mouth, and skin cancers. About half of newly diagnosed cancer cases are found through a screening; the five-year relative survival rate for these cancers is about 86 percent. For example, breast cancer is the most frequently diagnosed cancer among women, but death rates have steadily decreased since 1990 largely because of earlier detection and improved treatments. However, cancer is still the second leading cause of death, with 75 to 80 percent of cancer cases and deaths caused by lifestyles and behaviors, such as smoking and not exercising. Lung and bronchial cancer is the numberone cause of cancer death among all Americans. Men have the highest incidence and death rates from cancer, as do African American men and women. The American Cancer Society attributes higher death rates for minorities to lower socioeconomic status and poorer-quality health care than whites. Issues to address in the future to reduce the incidence of cancer and deaths from cancer are smoking cessation, eating right, exercising, and improved health care for all Americans. Christine G. Holzmueller, B.L.A. u
For Further Information American Cancer Society. Cancer Facts and Figures 2008. Atlanta: Author, 2008. National Cancer Institute. SEER Cancer Statistics Review, 1975-2004. Bethesda, Md.: Author, 2006. U.S. Department of Commerce. U.S. Census Bureau. Profiles of General Demographic Characteristics: 2000 Census of Population and Housing. Washington, D.C.: Author, 2001. 1113
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Other Resources
National Cancer Institute Cancer Statistics http://www.cancer.gov/statistics/ National Program of Cancer Registries United States Cancer Statistics http://apps.nccd.cdc.gov/uscs North American Association of Central Cancer Registries, http://www.naaccr.org See also African Americans and cancer; Africans and cancer; Aging and cancer; Alcohol, alcoholism, and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Cancer clusters; Developing nations and cancer; Elderly and cancer; Epidemiology of cancer; Ethnicity and cancer; Genetics of cancer; Insurance; Latinos/Hispanics and cancer; Native North Americans and cancer; Poverty and cancer; Psycho-oncology; Risks for cancer; Survival rates.
u Stem cell transplantation Category: Procedures Also known as: Bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), umbilical cord blood stem cell transplant Definition: A stem cell transplant is the infusion of healthy stem cells into the body. Stem cells are early blood-forming cells, also referred to as hematopoietic cells, that grow and mature in the bone marrow but can circulate in blood as well. Hematopoietic cells are immature cells capable of dividing and developing into all blood cell types, including cells of the immune system. Stem cell transplantation involves replenishing hematopoietic cells following highdose chemotherapy and radiation by infusing stem cells into the patient’s body. Stem cell transplants are classified based on the source of stem cells, including where they are collected. Stem cells may be collected from the bone marrow, peripheral blood, or umbilical cord. To represent the source of stem cells, the terms “bone marrow transplantation,” “peripheral blood stem cell transplantation,” and “umbilical cord transplantation” are utilized. There are important advantages and disadvantages associated with using stem cells from these different sources. Stem cell transplants are also classified by who donates them. If stem cells come from the patient, they are termed autologous. They may also come from an identical twin, called syngeneic, or from someone other than the patient, 1114
Salem Health: Cancer called allogeneic. Allogeneic stem cells are then further classified by whether the individual donating the stem cells is related or unrelated to the patient. The best-known stem cell therapy is bone marrow transplantation (BMT). While most blood stem cells reside in bone marrow, a small number are present in the blood. These multipotent peripheral blood stem cells (PBSCs) can be used similarly to bone marrow stem cells to treat leukemia and other cancers. PBSC transplants are less invasive than BMT because PBSCs can be collected from blood, although the difficulty arises in collecting sufficient numbers to perform a transplant. Stem cells from umbilical cords can also be used in stem cell transplants. Newborns no longer need umbilical cords, a tissue that has traditionally been discarded during birth. Recently it was realized that umbilical cord blood is rich in multipotent stem cells and thus useful against health problems similar to those treated with bone marrow and peripheral blood stem cells. An important advantage of umbilical cord stem cell transplants is reduced rejection, probably because the cells have not yet developed features that can be recognized by the recipient’s immune system. Similarly, because umbilical cord blood lacks well-developed immune cells, there is less chance that transplanted cells will attack the recipient’s body, a problem called graft-versus-host disease (GVHD). Bone marrow or PBSC transplants can be either autologous or allogeneic. An autologous transplant requires infusion of the patient’s own hematopoietic cells to restore the body’s ability to make blood cells. In an autologous stem cell transplant, stem cells are collected from the patient’s bone marrow or blood before high-dose chemotherapy is administered. An allogeneic stem cell transplant combines high-dose therapy with immunotherapy. Highdose therapy is administered to treat the cancer as in autologous transplants but is followed by an infusion of stem cells from a donor’s blood or bone marrow. The donor cells supply the patient with new blood cells as well as a new immune system, which helps eliminate any residual disease, a process called immunotherapy. Allogeneic transplants can vary based on intensity. A stem cell transplant that utilizes high-dose chemotherapy combined with radiation to stop bone marrow function to allow donor cells to engraft, or grow, is referred to as myeloablative. A non-myeloablative transplant, sometimes called a minitransplant, uses lower radiation and chemotherapy doses to allow the bone marrow to function until donor cells replace the patient’s marrow. Cancers treated: Hematological (blood) malignancies such as chronic leukemias, lymphomas, and myelomas;
Salem Health: Cancer
Stem cell transplantation
This sample of stem cells from a donated umbilical cord is to be used in research on cancers and blood diseases. (Tek Image/Photo Researchers, Inc.)
also cancers such as neuroblastoma and selected solid tumors Why performed: High-dose chemotherapy is the best treatment for certain types of cancers. One of the major side effects of high-dose chemotherapy is the destruction of bone marrow stem cells. Stem cell transplants can help restore or replace these cells. Using stem cell transplants in cancer treatment makes it possible for patients to receive very high doses of chemotherapy and/or radiation therapy. In addition, immune factors in the transplanted cells may help destroy any cancer cells remaining in the bone marrow. Patient preparation: Usually, patients remain at home until the time that the transplant is scheduled. During this time, the patient is often encouraged to build strength and maintain a healthy diet. An important part of patient preparation is researching insurance coverage in order to maxi-
mize care. If not nearby, the patient should make arrangements to stay closer to the hospital. It is also necessary to make arrangements for caregiving for up to four months. Caregiving will be needed for help with household chores, grocery shopping, food preparation, medications, central venous catheter care, monitoring of food and fluid intake, companionship, and transportation. Steps of the procedure: Once donor stem cells become available, many tests and procedures are conducted to ensure that the patient is healthy enough to receive the transplant. A catheter, called a central line, is inserted intravenously in the chest area near the neck. The central line remains in place for duration of the treatment and will be used for the infusion of stem cells. The central line is also used to collect blood samples, administer chemotherapy, and provide blood transfusions and nutrition. 1115
Stent therapy
Salem Health: Cancer
The next step in the procedure is called conditioning and occurs the week before the transplant. During conditioning, the patient undergoes chemotherapy and possibly radiation in order to destroy cancer cells and suppress the immune system to prevent the patient’s body from rejecting transplanted stem cells. Conditioning may be conducted in the hospital or on an outpatient basis. Even if it is conducted as an outpatient, hospitalization for side effects may be required. Numerous side effects may occur, including nausea and vomiting, diarrhea, hair loss, mouth sores or ulcers, infections, bleeding, infertility, sterility, premature menopause, anemia, fatigue, cataracts, organ failure, and secondary cancers. Medications may help reduce side effects. After the patient is treated with high-dose anticancer drugs and/or radiation during the conditioning process, stem cells are introduced into the patient’s bloodstream intravenously. If the transplant is successful, then the stem cells will migrate into the patient’s bone marrow and begin producing healthy cells.
skin, liver, and intestines. GVHD is treated with steroids or other immunosuppressive agents.
After the procedure: After entering the bloodstream, stem cells travel to the bone marrow, where they produce new white blood cells, red blood cells, and platelets. This process occurs within about two to four weeks and is known as engraftment. Until the new stem cells begin functioning, transplant recipients will be at risk for complications such as infections and bleeding. Complete recovery of immune function can take several months for autologous transplant recipients and up to two years for patients receiving allogeneic or syngeneic transplants. Doctors conduct various tests to confirm that cancer cells have been eliminated and new blood cells are being produced. Bone marrow aspiration, the removal of a small sample of bone marrow, may be conducted to determine whether the transplant is working. Some patients can leave the hospital within three to five weeks, but others may require longer hospitalization.
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Risks: Stem cell transplants are associated with many risks and complications, some potentially fatal. Complications that can arise include stem cell failure, organ and blood vessel damage, cataracts, secondary cancers, and death. Other major risks associated with stem cell transplants are increased susceptibility to infection and bleeding. Stem cell transplant recipients may experience shortterm side effects such as nausea, vomiting, fatigue, loss of appetite, mouth sores, hair loss, and skin reactions. A very serious complication known as graft-versushost disease (GVHD) may occur when immune cells from the donor attack the patient’s cells. Generally, the most commonly damaged organs in a GVHD response are the
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Results: Stem cell transplants can extend the lives of transplant recipients and cause some cancers to go into remission. Many transplant recipients enjoy a good quality of life and are able to resume their normal activities. Side effects and transplant success vary among recipients, with some patients experiencing very few complications, while others experience numerous problems. C. J. Walsh, Ph.D. u
For Further Information Cant, A. J. Practical Hematopoietic Stem Cell Transplantation. New York: John Wiley & Sons, 2007. Stewart, Susan K. Bone Marrow and Blood Stem Cell Transplants: A Guide for Patients. Highland Park, Ill.: BMT Newsletter, 2002. _______. Bone Marrow Transplants: A Book of Basics. Highland Park, Ill.: BMT Newsletter, 1995. Other Resources
Cancer Backup http://www.cancerbackup.org.uk Mayo Clinic http://www.mayoclinic.com National Cancer Institute http://www.cancer.gov See also Blood cancers; Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Childhood cancers; Graft-versus-host disease (GVHD); Hematologic oncology; Leukemias; Lymphomas; Multiple myeloma; Myeloma; Umbilical cord blood transplantation; Young adult cancers.
Category: Procedures Definition: Stent therapy is the placement of a rigid plastic or expandable metal tube to open a blocked airway, a stenosed blood vessel, the colon, or the esophagus. Cancers treated: Lung cancer, esophageal cancer, colon cancer, gastric carcinoma, vena cava syndrome Why performed: When cancerous growth constricts or occludes an airway or major blood vessel, a stent can be an important option if removal of tissue alone is not effective.
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Stent therapy
Stents can be used to strengthen a weakened airway or blood vessel. Stents made by the Schneider company are used as an entro-endo prosthesis for colonic stenting and also for gastroduodenal stenting. Such stents are used for two purposes: preoperative relief of obstruction and palliative treatment. Stricture formation can be a major problem among patients who have an anastomosis between the esophagus and stomach or jejunum following subtotal or total gastrectomy. Although first used as a simple adjunct to radiotherapy, stenting of the superior vena cava can be an effective first-line procedure for immediate relief in patients with malignancy. Growth of malignant lesions surrounding the vena cava often causes stenosis or obstruction of the vena cava and symptoms of venous congestion result, the so-called vena cava syndrome. Stent therapy can be effective to treat such cases and to improve quality of life for patients with advanced malignant disease. Patient preparation: Patients diagnosed with This metallic mesh stent holds open the duodenum of a woman with a pansuperior vena cava (SVC) syndrome caused by creatic carcinoma. (David M. Martin, M.D./Photo Researchers, Inc.) severe stenosis secondary to mediastinal malignancy may be referred for stent insertion. Most placement is usually achieved in lesions of the sigmoidal cases of SVC syndrome are attributable to an underlying colon, descending colon, and transverse colon. The stent primary thoracic malignancy, lymphoma, or metastatic tudelivery system is quite flexible and can be maneuvered mor. Symptoms include venous congestion and edema in into the transverse colon if necessary. the upper half of the body. These symptoms are associated Effective symptom relief can be achieved with an exwith dyspnea, dysphagia, and cognitive dysfunction as a pandable stent. The rigid plastic tube stent, on the other result of cerebral venous hypertension. In these cases, pahand, is shoved through the distal tumor with the use of a tients must decide along with their doctors whether to unpusher-tube device. The newest type of stent treatment is dergo stent therapy or instead proceed with radiotherapy the self-expanding metal stent, which was first modified and chemotherapy. for esophageal use in 1991. One example is the Schneider Prior to SVC stent therapy, patients undergo a bilateral Wallstent, which can be mounted onto a delivery catheter arm venography to determine the site and degree of stenowhere it is held in check with a sheath. sis. Patients in which the SVC is severely stenosed and the Percutaneous access can be achieved via the right comobstruction involves confluence of the brachiocephalic mon femoral vein for SVC stent insertion. An angled veins may be candidates for stent therapy. Patients with guidewire is inserted, dilatation is achieved with a small very extensive total occlusions involving both SVC and balloon, and a self-expanding stent (such as produced by subclavin veins may be referred to other therapy. Short ocBoston Scientific) is inserted. clusions can also be treated with thrombolysis and then stented. After the procedure: The duration of palliative stent therapy, when placed properly, averages seventeen weeks and Steps of the procedure: For preoperative relief of colon can extend as long as sixty-four weeks. Stent insertion is obstruction, the stent is placed across the acute obstrucsuccessful for most patients receiving treatment for SVC tion, with the intent of decompressing and cleaning the syndrome, with patients experiencing symptomatic relief colon, which may allow a single-stage procedure. In studies of stent treatment of colon cancer, successful stent within a few hours of the procedure. Few major complica1117
Stereotactic needle biopsy tions are reported, and most patients are able to start radiotherapy the next day after stenting. During the procedure, heparin is administered to prevent clotting. Risks: Insertion of a self-expanding metallic stent into an esophagojejunal anastomotic stricture can be a successful and uncomplicated therapy. The risks of palliative stent therapy for treatment of colon cancer include migration in the colon with colonic motility. Especially when the stent is placed at an anatomical curve such as the splenic flexure, these stents are much more likely to migrate. Migration in the treatment of colon cancer occurs in about 20 percent of cases. Perforation can occur, although this outcome is often the result of balloon dilation performed before the stent is placed. Results: Stent therapy to treat SVC syndrome usually results in patients being able to undertake an ideal radiotherapy course, which maximizes the quality and length of their lives. Michael R. King, Ph.D. u For Further Information Altman, Arnold J., ed. Supportive Care of Children with Cancer: Current Therapy and Guidelines from the Children’s Oncology Group. Boston: Johns Hopkins University Press, 2004. Boyiadzis, Michael, et al. Hematology-Oncology Therapy. New York: McGraw-Hill, 2006. Talamonti, Mark S., and Sam G. Pappas, eds. LiverDirected Therapy for Primary and Metastatic Liver Tumors. New York: Springer, 2001.
Salem Health: Cancer different positions and the images are combined with a computer, much the way the eyes capture the same object with two slightly different images that the brain then unites to form the final three-dimensional image. Cancer diagnosed: Breast cancer Why performed: Stereotactic needle biopsy is used to determine whether a suspicious lesion is cancer. Patient preparation: Before stereotactic needle biopsy, sterile technique is observed, and a topical anesthetic is administered. Steps of the procedure: The doctor obtains the informed consent of the patient and verifies the correct breast to be biopsied. A stereotable is used, whereby the patient is prone with the affected breast hanging down through an opening in the table. A stereo pair of the breast is generated and the relative shift in the lesion’s position between the two X-ray pictures, called parallax shift, allows the computer to determine the exact location of the lesion in three dimensions. The skin surface of the breast to be biopsied is cleaned with antiseptic and local anesthetic is given. The needle is inserted into the breast lesion through a tiny nick in the skin under computer guidance. Several samples of the lesion are then obtained. Adhesive skin closures (SteriStrips) are applied to close the nick in the skin, and a sterile dressing is then applied. The samples are labeled and sent to pathology.
Library of the National Medical Society http://www.medical-library.org
After the procedure: The patient is given discharge instructions, including to avoid the use of aspirin or ibuprofen and to instead take acetaminophen (Tylenol) for pain, to apply cold compresses over the biopsy site that evening to reduce swelling, to avoid exercise for seventy-two hours, and to monitor for any sign of fever or infection.
See also Colorectal cancer; Esophageal cancer; Gastrointestinal cancers; Lung cancers; Palliative treatment; Superior vena cava syndrome.
Risks: The risks of this procedure, although minimal, include infection, bleeding at the biopsy site, and bruising and/or scarring.
u Stereotactic needle biopsy Category: Procedures Also known as: Breast biopsy, image-guided biopsy
Results: The pathology results are usually available within forty-eight hours postprocedure, and if the lesion is benign, then no further workup is usually necessary. If the lesion is cancer, however, an open surgical biopsy may then be necessary to ensure complete removal. Debra B. Kessler, M.D., Ph.D.
Definition: Stereotactic needle biopsy is an outpatient procedure, usually performed by a radiologist or breast surgeon, in which a biopsy is obtained following imaging of a breast lesion using X rays. A stereo pair of the breast to be biopsied is generated using an X-ray tube at two slightly
See also Acoustic neuromas; Astrocytomas; Biopsy; Cordotomy; Core needle biopsy; Craniopharyngiomas; Gamma Knife; Medulloblastomas; Microcalcifications; Needle biopsies; Needle localization; Radiation oncology; Stereotactic radiosurgery (SRS); Surgical biopsies.
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(SRS) Category: Procedures Also known as: Fractionated stereotactic radiosurgery Definition: Stereotactic radiosurgery (SRS) is a noninvasive procedure that uses multiple beams of radiation to treat a selected target, such as a brain tumor or a difficultto-reach tumor in the chest or abdomen. The radiation comes from either cobalt or a linear accelerator. Cancers treated: Benign and malignant brain tumors, acoustic neuroma, metastases, head and neck cancers, lung cancer, pancreatic cancer, gynecological cancers, liver cancer, spinal cancer, other cancers that are difficult to reach Why performed: SRS is the most precise in tumor targeting of the radiation therapy interventions. While stereotactic radiosurgery is noninvasive and similar to radiation therapy, it is so accurate that it is considered surgical in nature. Most often, SRS is used to reach tumors that are not
Stereotactic radiosurgery (SRS) candidates for surgery or near structures that could be damaged by a surgical approach. SRS provides the option for an outpatient procedure rather than a traditional surgery that may require several days or weeks of hospitalization. In some instances, SRS may be used when patients have had previous radiation. Patient preparation: Stereotactic radiosurgery preparation depends on the site of the tumor and the type of equipment used. The traditional approach to SRS in the head uses a lightweight halo frame attached to the skull with four small screws and cobalt radiation beams for treatment. Another option for SRS is a robotically controlled linear accelerator that delivers multiple beams and uses a variety of techniques to hold the patient still. A facial mask or a body frame is fitted for each patient when the robotically controlled linear accelerator is used. Since treatments may last thirty minutes to two hours, positioning devices help the patient lie still during the treatment. A computed tomography (CT) scan with contrast dye, a magnetic resonance imaging (MRI) scan, or an angiogram, all very accurate radiology procedures, may be done
A man undergoes stereotactic radiosurgery for a brain tumor. (AP/Wide World Photos)
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Sterility to determine the size and location of the tumor or blood vessels to be treated. If treatment is in the head, then a neurosurgeon will work with a radiation oncologist to review the images and other patient data to determine the site to be treated. Other physician specialists may be involved in planning the SRS treatment for other body sites along with the radiation oncologist. Information is loaded into a treatment-planning computer that calculates how much radiation the patient is to receive and precisely where to direct the beams. The patient may receive a mild drug to be more comfortable during the treatment. Steps of the procedure: For a stereotactic radiosurgery treatment of the head using a cobalt radiation source, the patient lies down on the treatment table and the halo head frame is attached to the equipment, securing the position of the head to prevent movement that might cause the radiation beams to stray onto normal tissue. Up to 201 separate beams may be used to shape the treatment area. The treatment may last two to forty-five minutes during the session. There is no pain during the treatment. For a stereotactic radiosurgery treatment using a robotically controlled linear accelerator, the patient lies down on the treatment table and the premade positioning devices are adjusted to hold the patient in one position for the treatment. One beam of radiation is used as the linear accelerator moves around the patient in a circle to shape the treatment area. A single treatment or a daily treatment of one or two sessions for five or more days may be used. Regardless of equipment, the patient is awake and can talk with the radiation therapy staff using an intercom. The staff watches the patient on closed-circuit television. The patient may hear noises from the equipment as adjustments of the beam are made to move around the tumor. After the procedure: If a head frame was used, then it is removed. Depending on the procedure and the site treated, the patient may be able to go home in just a few hours or may stay overnight in the hospital. The patient may need to lie still for a while after the procedure. The doctor will provide information about when the patient may resume normal activities, but it is usually in just a few days. It is safe for patients to be around others, including children and pregnant women, because no radiation is in the body. Risks: Side effects depend on the site treated but may include headache, swelling as the tumor cells die, minor swelling where the head frame was attached to the skin, nausea, skin irritation, diarrhea, or bladder problems. There is a slight chance of paralysis or other deficits, such as weakness or difficulty with speech or hearing, when the brain or spine receives radiation. 1120
Salem Health: Cancer Results: Stereotactic radiosurgery does not work immediately but causes cell death over time. The tumor decreases in size over time based on the type of tumor and its growth rate before treatment. Malignant tumors and metastatic tumors usually respond more rapidly because their growth rate is faster. The patient sees the physician frequently to monitor the tumor destruction and to be sure that side effects are not developing as the cells die. Patricia Stanfill Edens, R.N., Ph.D., FACHE u
For Further Information Le, Q. T., B. W. Loo, A. Ho, et al. “Results of a Phase I Dose-Escalation Study Using Single-Fraction Stereotactic Radiotherapy for Lung Tumors.” Journal of Thoracic Oncology 1, no. 8 (October, 2006): 802-809. National Cancer Institute. Radiation Therapy and You: A Guide to Self-Help During Cancer Treatment. NIH Publication 01-2227. Bethesda, Md.: National Institutes of Health, 2001. Also available at http://www .cancer.gov. Slotman, B. J., T. D. Solberg, and D. Verellen. Extracranial Stereotactic Radiotherapy and Radiosurgery. New York: Taylor and Francis, 2006.
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American Cancer Society http://www.cancer.org International Radiosurgery Association http://www.irsa.org See also Acoustic neuromas; Afterloading radiation therapy; Astrocytomas; Cobalt 60 radiation; Craniopharyngiomas; Gamma Knife; Linear accelerator; Medulloblastomas; Radiation oncology; Radiation therapies; Stereotactic needle biopsy.
u Sterility Category: Diseases, symptoms, and conditions Also known as: Intractable infertility, azoospermia, menopause Related condition: Infertility Definition: Sterility is the inability to achieve pregnancy due to the absence of viable sperm in the testicles (azoospermia) or an absence of mature, viable eggs in the ovaries (menopause). Sterility is often diagnosed when conception does not occur even after assisted reproductive technology treatments. Sterility can be caused by some cancer treatments.
Salem Health: Cancer
Stomach cancers
Risk factors: The risk of sterility depends on the type of cancer and its location, the specific cancer treatment, and the use of any fertility-preservation or -sparing procedures before or during treatment. The risk of sterility is also affected by the person’s age, general health, and pretreatment fertility status.
See also Alkylating agents in chemotherapy; Amenorrhea; Chemotherapy; Fertility issues; Infertility and cancer; Klinefelter syndrome and cancer; Pregnancy and cancer; Selfimage and body image.
Etiology and the disease process: Sterility can be caused by chemotherapy, especially alkylating agents; high doses of radiation to the entire body, cranium, abdomen, or pelvis; and surgical treatments that remove or damage reproductive structures.
u Stomach cancers
Incidence: The occurrence of sterility is highly variable based on patient- and treatment-related factors. The frequency of sterility across all cancer patients is unknown.
Related conditions: Peptic ulcers, gastritis, Helicobacter pylori infection, lymphoma, adenomatous polyps, pernicious anemia
Symptoms: Sterility is not often detected until a person attempts to conceive. Azoospermia is not evident without medical screening, but the inability to ejaculate or produce semen during ejaculation may be a symptom of sterility. The absence or cessation of menstruation is symptomatic of menopause.
Definition: Stomach cancers are malignant tumors of the stomach, about 95 percent of which are adenocarcinomas that develop from the glandular epithelial cells of the innermost lining of the stomach (mucosa). Others are stomach lymphoma (about 4 percent of stomach cancers), carcinoid tumors of the hormone-producing cells (3 percent), and rare gastrointestinal stromal tumors (GISTs) of the interstitial cells of Cajal (part of the autonomic nervous system controlling stomach muscle movement).
Screening and diagnosis: Male sterility is diagnosed through semen analysis and sometimes testicular biopsy to assess the presence of sperm. Female sterility is diagnosed by assessing hormone levels and an ultrasound examination for ovulation, usually after ovulation induction with fertility medications. Treatment and therapy: There are no known treatments for sterility due to azoospermia or menopause. Sterility related to cancer treatments, such as surgery and chemotherapy, is often of less concern than addressing the cancer itself. Prognosis, prevention, and outcomes: It is advised that cancer patients consider fertility-preservation or -sparing options before treatment and consult a fertility specialist. Before treatment, men can have healthy sperm frozen for future use. Researchers are testing whether frozen testicular tissue or sperm stem cells transplanted back into the testicles can restore sperm production. Women can have their eggs collected and fertilized in the laboratory, with the resulting embryos frozen for future use. The possibility of freezing unfertilized eggs for later use or ovarian tissue for transplantation is being researched. Patients may benefit from fertility-sparing options during treatment, which include protecting reproductive organs from radiation, using conservative surgery when possible, and engaging in experimental hormonal therapy. Amanda McQuade, Ph.D.
Category: Diseases, symptoms, and conditions Also known as: Gastric cancer, esophageal cancer, adenocarcinoma
Risk factors: Long-term infection with the bacterium Helicobacter pylori causes inflammation that can cause precancerous changes in the stomach lining. Age and gender are also risk factors, because most people who develop stomach cancer are older than the age of fifty, and men develop stomach cancers at double the rate of women. Familial cancer syndromes, inherited disorders, and having a parent or sibling with the disease increase the risk of stomach cancer. Pernicious anemia (inability to absorb vitamin B12), obesity, and having type Ablood are also risk factors. Rates of stomach cancer, especially at the esophagusstomach junction, are doubled in cigarette smokers. High alcohol intake contributes to increased risk. A diet high in foods preserved by smoking, salting, or pickling; large amounts of red meat, particularly if barbecued or welldone; and foods that contain nitrites and nitrates (that can form N-nitroso carcinogens), such as bacon, ham, hot dogs, and processed meats, increase the risk. People with part of their stomach and pyloric valve removed as a treatment for peptic ulcers also are at increased risk. After stomach surgery, bile or pancreatic juices can accumulate, causing gastritis. The amount of protective stomach acid also decreases while nitrite-producing bacteria may increase, leading to stomach cancer. The risk is greatest for the first twenty years after the initial surgery. 1121
Stomach cancers
Salem Health: Cancer of stomach cancer is higher in men older than the age of forty. Hispanics, Native Americans, Asian Americans, and African Americans are roughly twice as likely to develop gastric cancer as whites. The incidence of stomach cancer has declined by 50 percent in the United States and Western Europe since the 1930’s, probably because of better, more balanced diets; the frequent use of antibiotics that reduce H. pylori and childhood infections; and refrigeration, which reduces nitrate-producing bacteria in food. The disease remains a serious problem in many parts of the world, however, because of infection with H. pylori and diets high in meat or smoked, cured, heavily salted, or pickled foods. Stomach cancer is therefore more common in Japan, Korea, parts of Eastern Europe, and Latin America. Stomach cancer incidence rates decrease in Chinese who have immigrated to the United States, but not if they maintain their traditional diet. Gastric cancer affects all races, but unexplained geographic and cultural differences in incidence occur, with higher mortality in Japan, Chile, Austria, and Iceland.
Small growths (polyps) in the stomach lining, especially adenomatous polyps, may also be precancerous. Etiology and the disease process: Most stomach cancers start in the innermost mucosal layer of the stomach, where stomach acid and digestive enzymes are made, and develop slowly over many years. Before a true cancer develops, precancerous changes occur in the lining of the stomach, such as atrophic gastritis, a condition in which the acid-producing glands are slowly destroyed. Low acid levels prevent cancer-causing toxins from being properly broken down or flushed out of the stomach. Stomach cancers can spread in different ways: through the wall of the stomach to invade nearby organs; through the bloodstream to the lungs, bones, and ovaries; or to the lymph vessels and lymph nodes slowly or aggressively. Carcinoid tumors grow less quickly and metastasize less frequently. Incidence: In the United States, about 21, 260 people were expected to be diagnosed with stomach cancer in 2007, and 11,210 were expected to die of it. The rate of incidence
Incidence of Stomach Cancer per 100,000 People, by Gender 14 Women
Men 12
11.9 10.5
10
9.6
9.1
8
6
5.8
6.2 5.5
5.1
5.2
4 2.6 2
0 Black
Asian/Pacific Islander
American Indian/ Alaska Native
Hispanic
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
1122
White
Salem Health: Cancer
Stomach cancers
Symptoms: Stomach cancer rarely produces initial symptoms and is usually detected in advanced stages. Depending on their location in the stomach, cancers may have different symptoms and outcomes. One early sign is microscopic internal bleeding, which is detected only by tests that check the stool for blood. Other early symptoms are heartburn and abdominal pain, which can be mistaken for other common problems such as peptic ulcers. Advanced cases produce discomfort in the upper or middle region of the abdomen that may not be relieved by food or antacids; abdominal discomfort aggravated by eating; chronic abdominal pain; swelling; black, tarry stools; indigestion; nausea; vomiting blood; vomiting after meals; weakness and fatigue; unintended weight loss; and a full feeling after meals, even when eating less than normal. Screening and diagnosis: Early diagnosis of stomach cancer is hindered by its initial vague symptoms; the disease can easily be mistaken for less serious problems such as a stomach virus or heartburn. Diagnosis includes a complete medical history and physical examination, barium X rays of the gastrointestinal tract with fluoroscopy showing changes, gastroscopy with fiber-optic endoscopy that helps rule out other diffuse gastric mucosal abnormalities, photogA section of a stomach showing a cancerous tumor (triangular shaped area). raphy with a fiber-optic endoscope that pro(St. Bartholomew’s Hospital/Photo Researchers, Inc.) vides a permanent record of gastric lesions, and biopsy for microscopic examination to confirm Depending on the extent of the cancer, the doctor may recancer when abnormal cells are discovered. move part of the stomach (via subtotal, or partial, gastrecScreening of serum sample glycoprotein antigens protomy) or all of the stomach (via total gastrectomy) as well duced by cancer cells reveals undetected cancer and monias surrounding tissue and lymph nodes. After subtotal gastors established cancer. trectomy, the remaining part of the stomach is connected Polymerase chain reaction (PCR) kits, which amplify to the esophagus and small intestine. For total gastrecand detect altered deoxyribonucleic acid (DNA) base sequences in minute samples of cells, facilitate the diagnosis tomy, the esophagus is connected directly to the small inof cancer types that are difficult to categorize by conventestine. tional pathology. Prognosis and treatment for stomach lymphoma depend on the extent of aggressiveness. Individuals who Treatment and therapy: Stomach cancer is treatable if have H. pylori-associated gastric lymphomas may be cured caught early. Less than one in five stomach cancers are diby antibiotic therapy that eliminates the bacteria. In some agnosed before spreading outside the stomach. Pain is ofadvanced cases, a laser beam directed through an endoten relieved by food or acid-buffering medications in the scope can vaporize most of the tumor without an operaearly stages. The kind of treatment for stomach cancer detion. pends on the location of the cancer, how advanced it is, and Radiation therapy, chemotherapy, or a combination of the patient’s overall health and personal preferences. The both is used to completely destroy all remaining cancer most common treatment for stomach cancer is surgery. cells after surgery. 1123
Stomatitis Prognosis, prevention, and outcomes: The prognosis for stomach cancer depends on the stage of the disease at the time of diagnosis and is dim if the cancer has grown deeper into layers of the stomach or has spread to the lymph nodes. The general five-year survival rate for stomach cancer is about 20 percent because it is often detected at an advanced stage but rises to 60 percent when the disease is diagnosed early. A 2006 study suggested that chemotherapy before and after surgery improves outcomes for some people. It is estimated that diet could prevent 70 percent of stomach cancers in 1 million global instances of the disease. To help prevent cancer, people should eat plenty of fresh fruits and vegetables with antioxidant vitamins and polyphenols, especially those high in vitamin C and betacarotene and those that are red, deep green, orange, or deep yellow—such as mango, cantaloupe, strawberries, carrots, tomatoes, red bell peppers, Swiss chard, bok choy, spinach, acorn and butternut squash, and sweet potatoes— and vegetables from the cabbage family, including broccoli, brussels sprouts, and cauliflower. People following the diet should avoid nitrites and nitrates in processed and cured meats; consume more fish or poultry instead of red meat; limit smoked, pickled, and heavily salted foods; avoid smoking; and limit or avoid alcohol consumption. Samuel V. A. Kisseadoo, Ph.D. u For Further Information Beers, Mark H., ed. The Merck Manual of Medical Information. 2d home ed. Whitehouse Station, N.J.: Merck Research Laboratories, 2003. King, R. J. B. Cancer Biology. 2d ed. New York: Prentice Hall, 2000. Shah, Manish A. Dx/Rx. Upper Gastrointestinal Malignancies: Cancers of the Stomach and Esophagus. Sudbury, Mass.: Jones and Bartlett, 2006. u
Other Resources
American Cancer Society Detailed Guide: Stomach Cancer http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_stomach_cancer_40.asp National Cancer Institute Stomach (Gastric) Cancer http://www.cancer.gov/cancertopics/types/stomach/ See also Achlorhydria; Adenocarcinomas; Adenomatous polyps; Bacteria as causes of cancer; Barium swallow; Carcinomatous meningitis; Colon polyps; Diarrhea; Elderly and cancer; Esophageal cancer; Fiber; Fruits; Gas1124
Salem Health: Cancer trointestinal cancers; Gastrointestinal complications of cancer treatment; Gastrointestinal stromal tumors (GISTs); Helicobacter pylori; Hereditary diffuse gastric cancer; Krukenberg tumors; Nausea and vomiting; Obesityassociated cancers; Polyps; Small intestine cancer.
u Stomatitis Category: Diseases, symptoms, and conditions Also known as: Mucositis Related condition: Esophagitis Definition: Stomatitis is a general term used to describe injury or inflammation to the tissues of the mouth such as the gums, tongue, roof or floor of the mouth, lips, and cheeks. Risk factors: This inflammation can be caused by many things, such as poor oral hygiene, medications, infections, or poorly fitted dentures. Many cancer treatments, such as chemotherapy drugs and radiation, can cause stomatitis. Etiology and the disease process: Chemotherapy and radiation treatments stop the growth of cancer cells and all other rapidly dividing cells. As the cells in the lining of the mouth also divide rapidly, some of the treatments for cancer make it difficult for the lining of the mouth to repair itself. Cancer treatments can also weaken the immune system and make it easier for a person to develop an infection. Incidence: Stomatitis occurs in approximately 40 percent of the patients receiving chemotherapy and cancer treatments, such as radiation to the head and neck. Stomatitis can affect a patient’s cancer treatment and quality of life. Symptoms: The symptoms of stomatitis can vary depending on the causes. Generally, redness, swelling, and pain in the mouth are common. Ulcers can develop and make eating and drinking difficult. This can lead to dehydration and weight loss. Bleeding in the mouth, fever, and irritability can also occur. Screening and diagnosis: Stomatitis can be diagnosed by a careful examination of the patient’s mouth, tongue, and lips. A blood test may be done to detect infection. Sometimes a scraping of the lining of the mouth may be sent to the laboratory to identify a specific organism causing the infection. Treatment and therapy: Treatment is also based on the cause of stomatitis. The most important part of treatment is to keep the mouth and teeth clean. A soft toothbrush and
Salem Health: Cancer mild toothpaste can be used, brushing carefully to prevent any further damage to the gums. Patients should consume soft foods and liquids and avoid acidic foods and alcoholbased mouthwashes. Pain medicine in the form of a topical anesthetic such as lidocaine gel, systemic inflammatory or narcotic pain medications, or both may also be used. Prognosis, prevention, and outcomes: One way to prevent or lessen the severity of stomatitis is to find and treat oral problems before cancer treatment begins. In addition, eating a well-balanced diet can help the body tolerate the stress of treatment and fight infection. Keeping the mouth and teeth clean and having regular dental checkups are also important. Michelle Kasprzak, R.N., B.S.N., O.C.N. See also Chemotherapy; Cobalt 60 radiation; Dry mouth; Esophagitis; Fever; Herpes simplex virus; Infection and sepsis; Mucositis; Side effects; Stress management; Weight loss.
u Stress management Category: Social and personal issues Definition: Stress management reduces and controls tensions rising from emotional and physical stress. Emotional stress can occur in response to situations that seem out of control or difficult to manage, such as a diagnosis of or treatment for cancer. Physical stress, such as nausea, vomiting, and hair loss occurring as side effects of chemotherapy, can lead to emotional distress. Physiology: The physiology of stress is oftened referred to as the “fight-or-flight response.” Faced with an immediate physical threat, the body gears up for physical confrontation or rapid retreat with the following physiological responses: • Neurotransmitters are released by the sympathetic nervous system • Catecholamines and epinephrine surge, increasing body metabolism • Heart and breathing rates increase • Blood pressure rises • Blood-clotting increases • Digestive activities are suspended Stress hormones: Catecholamines, epinephrine, and cortisol—the “stress hormones”—prepare the heart to beat harder and faster, cause the lungs to inhale more oxygen, and tense muscles in preparation for fight or flight. The
Stress management blood levels of these hormones remain elevated for hours and have lingering effects on the body. Cortisol, a steroid hormone, stays at high levels for several hours and is particularly troublesome. One effect of this hormone is to reduce the immune response (which is why hydrocortisone creams can address the itchy symptoms of skin rashes and inflammations; hence, it is important not to use these creams on infections, which may become worse in the presence of cortisol). People who are chronically or often stressed therefore are likely to have suppressed immune systems, resulting in more infections like colds or sinus infections. Chronic stress: Problems arise when the stress response occurs in reaction to emotional problems, such as concerns over chronic illnesses, financial difficulties, criticism, traffic jams, or deadlines. Repetitive and prolonged stress leads to physical problems, including immune system dysfunction, digestive tract problems such as diarrhea or constipation, and cardiovascular difficulties including palpitations (heart pounding) or irregular heartbeats. Sleep disturbances such as insomnia or lack of restful sleep can occur. Increased blood clotting contributes to heart attacks and strokes. Hence, stress feeds on itself, creating problems that in turn place more stress on human physiology. One of the greatest stressors human beings face is that of a chronic illness, such as cancer. Not only does the diagnosis of cancer increase stress, but also the ongoing decisions, treatments, medical bills, insurance paperwork, and the simple coping with normal stresses of daily life escalate in the face of a cancer diagnosis and treatment. Moreover, the plethora of treatment options for different types of cancer has made it possible to live with many types of cancer for months or years. The ability of medical pharmacology and technology to increase the life span, while positive overall, also prolongs the period of time patients must cope with their disease, in turn increasing stress. Stress reduction: Any chronic and repetitive stress must be recognized and met with stress reduction methods. Managing stress is as important for healthy people as it is for those facing cancer: Most people think of calming situations such as watching the sun set, curling up with an interesting book, or meditating. Although these relaxing situations may be good for some, others may need a thrilling situation, like a vigorous aerobic workout or a competitive game of tennis. Sometimes seeking balance is a good approach. A job that requires a great deal of thinking, decision making, and problem solving may be counterweighted by physical activity, such as a walking to work or a basketball game after work. Those with physical jobs, on the other hand, may re1125
Stress management
Salem Health: Cancer
Exercise may help some people reduce stress. (PhotoDisc)
duce their stress by engaging in more intellectual pursuits, such as playing cards or learning a foreign language. Managing stress improves not only the immune system but also one’s quality of life and may well help protect against the physiological vulnerabilities that open the door to precancerous and cancerous conditions. For those diagnosed with cancer, stress management is equally if not more important: Social support systems, like meeting with friends or associating with groups that have interests similar to one’s own, can help reduce stress and anxiety. Helpful support groups are usually available in most communities. Patients are also advised to seek advice from their personal health care provider, who is in the best position to offer it. In one study, volunteers who wrote about “the most stressful event they had ever undergone” for twenty minutes on three consecutive days showed significant improvement compared with those who spent the same amount of time writing about neutral topics. Researchers theorize that writing may help patients make sense of what has happened to them and come to terms with its impact, thus reducing stress. 1126
Making an effort to maintain a healthy diet can also reduce stress. Although some medical situations, such as postchemotherapy nausea and vomiting, may require vitamin supplementation and management with other medications, the best way to obtain necessary minerals and vitamins during most stressful episodes is via fresh, whole fruits and vegetables. Minerals and vitamins in this natural state are more bioavailable, meaning they are more readily absorbed and utilized by the body than supplements in pill or powder forms. Fortunately, a number of medications can relieve pain, alleviate nausea, and lessen anxiety. Music, deep breathing, caring for pets, and allowing oneself to engage in enjoyable activities with family and friends are some other well-known stress relievers. Many cancer patients report that they discover a new appreciation for life and do not delay activities they find rewarding. Among the best stress relievers for cancer patients is the sense of well-being and purpose friends and family can bring by simply visiting and reminding patients of their value as a friend and human being. Richard P. Capriccioso, M.D.
Salem Health: Cancer u For Further Information Hales, D. An Invitation to Health. 10th ed. Belmont, Calif.: Wadsworth/Thomson Learning, 2003. Sobel, D. S., and R. E. Ornstein. The Healthy Mind, Healthy Body Handbook. New York: Time Life Medical-Time Warner, 1996. Whitney, E., and F. Sizer. Nutrition: Concepts and Controversies. 9th ed. St. Paul, Minn.: West, 2003. u
Other Resources
American Institute of Stress http://www.stress.org MedlinePlus Stress Management http://www.nlm.nih.gov/medlineplus/ency/article/ 001942.htm See also Aids and devices for cancer patients; Anxiety; Caregivers and caregiving; Complementary and alternative therapies; Counseling for cancer patients and survivors; Depression; Diarrhea; Exercise and cancer; Financial issues; Infection and sepsis; Insurance; Journaling; Living with cancer; Nausea and vomiting; Nutrition and cancer prevention; Nutrition and cancer treatment; Personality and cancer; Prayer and cancer support; Psychooncology; Relationships; Self-image and body image; Support groups.
u Sunlamps Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2000 Also known as: Ultraviolet radiation (UVR), ultraviolet A (UVA), ultraviolet B (UVB), artificial ultraviolet radiation, nonsolar ultraviolet radiation Related cancers: Skin cancer, squamous cell carcinoma, basal cell carcinoma, nonmalignant melanoma, malignant melanoma, intraocular melanoma Definition: Sunlamps are lamps that produce ultraviolet radiation. Exposure routes: Through skin Where found: Sunlamps, sunbeds, tanning salons, tanning booths, home tanning lamps At risk: People who use artificial sources of ultraviolet radiation such as sunlamps or tanning salons
Sunlamps Etiology and symptoms of associated cancers: Sunlamps or other artificial sources of ultraviolet radiation are used primarily for cosmetic reasons, such as to obtain a suntan, as well as for treatment of certain medical conditions. Approximately 25 million people in the United States use sunbeds each year, with 1 to 2 million people visiting tanning facilities as often as one hundred times a year. Teenagers and young adults, usually female, use sunlamps most often. Epidemiological studies report that exposure to sunlamps increases the risk of skin cancer. A person’s risk of skin cancer is related to lifetime exposure to ultraviolet (UV) radiation, with greater incidence observed with increasing duration of exposure, especially in those using sunlamps before the age of thirty and in those who readily sunburn. Ultraviolet radiation from sunlamps can affect all skin types, but people with fair skin that freckles or burns easily, a skin type generally associated with red or blond hair and light-colored eyes, are at greater risk. Sunlamps increase the risk of skin cancer because they involve exposure to ultraviolet radiation. Although ultraviolet radiation emissions vary substantially according to the device, the radiation exposure can be similar to or greater than that from the sun. Depending on the frequency of use, commonly used sunlamps deliver several times the annual ultraviolet A dose. Newer indoor tanning units may emit ultraviolet A and ultraviolet B radiation at levels as much as fifteen times greater than solar ultraviolet radiation. Ultraviolet radiation damages deoxyribonucleic acid (DNA) in skin cells, which can lead to skin cancer. Skin cancers that have been associated with use of a sunlamp include basal and squamous cell carcinomas as well as melanoma. Most basal cell and squamous cell skin cancers can be cured if found and treated early. Both basal and squamous cell skin cancers occur on parts of the skin frequently exposed to the sun, such as the face. Basal cell carcinoma grows slowly and rarely spreads to other parts of the body. Squamous cell carcinoma is more aggressive and sometimes spreads to lymph nodes and organs inside the body. Although much less prevalent than other types of skin cancer, melanoma is the most serious. Melanoma occurs in pigment cells in the skin called melanocytes. When melanoma becomes cancerous, it can become invasive and spread to other parts of the body. When melanoma starts in the skin, it is called cutaneous melanoma. Melanoma may also occur in the eye and is then called ocular melanoma or intraocular melanoma. Not all skin cancers look the same, but a change on the skin is the most common sign of skin cancer. Some skin changes that may occur include a new growth, a sore that 1127
Sun’s soup does not heal, a change in an existing growth, or red or brown spots that are rough, dry, and scaly. Melanoma usually begins in a mole, with the first symptom typically a change in size, shape, or color of an existing mole or the appearance of a new mole. Melanomas vary in their appearance, but most melanomas have a black or blue-black area and usually appear abnormal or “ugly looking.” History: Sunlamps have been used for many years to treat a range of skin conditions, vitamin D deficiency, and neonatal jaundice. Sunlamps have also been used increasingly for cosmetic tanning in commercial salons or at home. Ultraviolet emissions from artificial tanning devices have changed over time. Before the mid-1970’s, sunlamps were primarily used in the home, except for medical use, and mostly emitted ultraviolet B and with a small amount of ultraviolet C. In the early 1980’s sunlamps that emitted ultraviolet A radiation were developed and used mainly at commercial tanning salons. Sunlamps in use in the twentyfirst century emit mostly ultrlaviolet A radiation and some ultraviolet B radiation. The U.S. Food and Drug Administration (FDA) Center for Devices and Radiological Health developed regulations concerning ultraviolet lamps in sunlamps that specify requirements for performance, protective eyewear, and labeling, and require tanning salons to post warnings about the dangers associated with exposure to artificial ultraviolet radiation. The American Medical Association, the American Academy of Dermatologists, and the Centers for Disease Control and Prevention have all issued statements discouraging the use of sunlamps for nonmedical purposes. Catherine J. Walsh, Ph.D.
Salem Health: Cancer u
Other Resources
American Academy of Dermatology http://www.aad.org Centers for Disease Control and Prevention Skin Cancer http://www.cdc.gov/cancer/skin/ National Cancer Institute What You Need to Know About Skin Cancer http://www.cancer.gov/cancertopics/wyntk/skin National Toxicology Program FDA Radiological Health Program http://www.fda.gov/cdrh/radhealth/products/ sunlamps.html See also Basal cell carcinomas; Electromagnetic radiation; Melanomas; Moles; Skin cancers; Squamous cell carcinomas; Ultraviolet radiation and related exposures; Young adult cancers.
u Sun’s soup Category: Lifestyle and prevention; complementary and alternative therapies Also known as: Selected Vegetables (SV) Definition: Sun’s soup is a nutritional supplement consisting of plant nutrients containing phytochemicals believed to enhance immune properties and disease prevention. Cancers treated or prevented: Cancerous tumors; effectiveness not scientifically verified Delivery routes: Oral by diet
u
For Further Information Chen, Y. T., et al. “Sunlamp Use and the Risk of Cutaneous Malignant Melanoma: A Population-Based CaseControl Study in Connecticut, USA.” International Journal of Epidemiology 27 (1998): 759-765. Gallagher, R. P., J. J. Spinelli, and T. K. Lee. “Tanning Beds, Sunlamps, and Risk of Cutaneous Malignant Melanoma.” Cancer Epidemiology Biomarkers and Prevention 14, no. 3 (2005): 562-566. Swerdlow, A. J., et al. “Fluorescent Lights, Ultraviolet Lamps, and Risk of Cutaneous Melanoma.” British Medical Journal 297 (1988): 647-650. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Eleventh Report on Carcinogens. Research Triangle Park, N.C.: Author, 2005. 1128
How this agent works: Sun’s soup is believed to boost the immune system, although how it works and whether it is effective are considered unverified scientifically. In the late 1980’s, Dr. Alexander Shihkaung Sun (1939-2006), a Taiwanese American biochemist with a Ph.D. from the University of California, Berkeley, investigated the use of specific foodstuffs, mainly shiitake mushrooms, mung beans, and Chinese herbs associated with reinforcing immune systems, to aid his mother after she became ill with lung cancer. Affiliated professionally with Mount Sinai Medical Center and the Yale University School of Medicine, Sun chose ingredients with phytochemicals that Asian physicians had incorporated into treatments. Sun freeze-dried his concoction, which he initially called Selected Vegetables (SV), as a supplement to medi-
Salem Health: Cancer cal treatments to extend the life spans of patients with cancerous tumors. In the early 1990’s, he conducted trials with mice to assess the impact of SV on tumors. He then tested SV in humans, focusing on patients diagnosed with non-small-cell lung cancer, who orally consumed one ounce of hydrated SV powder daily and a control group who did not ingest SV. Everyone in the trial simultaneously received chemotherapy, radiation, or surgery. Sun revised his recipe for a frozen version, which included soy and legumes, and conducted a second clinical study for sixty months in which patients ate ten ounces of Sun’s soup every day. Applying for a U.S. patent, Sun sought protection of his recipe to mitigate cancerous conditions and received a patent on August 1, 1995. Sun, who established the Connecticut Institute for Aging and Cancer, summarized his results with colleagues in two Nutrition and Cancer articles published in 1999 and 2001. He hypothesized that some aspect of SV battled cancer and extended lives but did not address or control for the impact of chemotherapy. Sun’s testing was flawed because of the limited number of subjects, most of whom volunteered, knowing about his soup’s anticancer possibilities and not representing a random test group. Also, the freeze-dried powder and frozen soup thawed for consumption in the two trials differed chemically. Researchers acknowledged that Sun’s soup needed more scientific trials before definitive results regarding its ability to impede cancer could be determined. Sun stated that his mother was free of cancerous growths fifteen years after he created his first soup, crediting it for her health. Founding Sun Farm Soup Company at Milford, Connecticut, Sun oversaw the production of Sun’s soup for commercial sale. The anticancer benefits of Sun’s soup remain scientifically unproven. The U.S. Food and Drug Administration (FDA) does not endorse Sun’s soup because it is advertised as a supplement, and by law the FDA does not regulate supplements in the stringent way that it does drugs. Side effects: There are no known side effects to ingesting Sun’s soup, other than a bloated sensation felt by those who participated in Sun’s early studies. Later study participants who ingested a frozen, rather than the earlier freezedried, formulation of SV did not report bloating. Elizabeth D. Schafer, Ph.D. See also Bronchial adenomas; Cancell; Chemotherapy; Cobalt 60 radiation; Complementary and alternative therapies; Herbs as antioxidants; Lung cancers; Nutrition and cancer prevention; Nutrition and cancer treatment.
Sunscreens
u Sunscreens Category: Lifestyle and prevention Also known as: Avobenzone, oxybenzone, mexoryl, zinc oxide, titanium dioxide Definition: Sunscreens are lotions or sprays that, when applied correctly, can help prevent sunburn and other kinds of skin damage from the sun’s ultraviolet (UV) rays. Using sunscreen can lower a person’s risk for skin cancer. Cancers treated or prevented: Skin cancers Delivery routes: Topical via lotions and creams How these agents work: There are two types of UV light from the sun, UVA and UVB. UVA rays damage the skin with long-term effects such as premature wrinkles and skin aging because they penetrate deep into the skin. UVB radiation causes sunburns and most likely contributes to skin cancers. Most sunscreens do not block UVA as well as they do UVB rays. It is recommended that a broadspectrum sunscreen be used to protect against both types of UV rays. Sunscreens contain both organic and inorganic ingredients such as avobenzone, oxybenzone, mexoryl, zinc oxide, and titanium dioxide. They work by absorbing, reflecting, or scattering UVA and UVB rays from the sun. Most sunscreens contain a combination of these ingredients, which work together to have a synergistic effect in protecting the skin. The newest Food and Drug Administration (FDA)-approved ingredient is mexoryl, which has proven to be more photostable than other ingredients and therefore retains its stability when exposed to sunlight. Sunscreens have a sun protection factor (SPF) number that refers to how long the sunscreen is effective on the skin. The higher the SPF, the more sun protection the sunscreen offers. This number is only an estimate, however, because many additional factors—such as how much and how often the sunscreen is applied, how much sunscreen is absorbed, and the person’s activity (for example, sleeping in the sun, swimming, or exercising)—affect how the sunscreen works. Sunscreen works best when applied fifteen to thirty minutes before sun exposure, followed by a reapplication fifteen to thirty minutes after being out in the sun. Sunscreen then needs to be applied every two to three hours to remain effective. Most people do not apply enough sunscreen. Studies have shown that 1 ounce or 2 tablespoons is needed to cover the average body adequately. In reality, no matter what sunscreen is used, some UV still gets through to the skin. A total program is needed to decrease the sun’s harmful effects: 1129
Superior vena cava syndrome
Salem Health: Cancer
u Superior vena cava syndrome Category: Diseases, symptoms, and conditions Also known as: Superior vena cava (SVC) obstruction Related conditions: Fibrosing mediastinitis, lung cancer Definition: Superior vena cava syndrome is puffiness of the face, swelling of the eyelids and arms, and enlargement of the neck that results from obstruction of the superior vena cava (the vein connecting the upper half of the body and right atrium of the heart, formed by brachiocephalic veins) from any number of causes, including malignancy, infection, or an iatrogenic cause (inadvertently caused during the course of medical treatment).
Sunscreens work by absorbing, reflecting, or scattering UVA and UVB rays from the Sun. (©Stephen Coburn/Dreamstime.com)
• Use sunscreen with an SPF of 15 or higher every day, even on cloudy days • Avoid the sun during the hours of 10:00 a.m. to 4:00 p.m. • Wear a hat, sunglasses, and long-sleeved protective clothing when out in the sun • Select a sunscreen that contains some combination of avobenzone, oxybenzone, mexoryl, zinc oxide, and titanium dioxide—products that also provide UVAprotection Side effects: Occasionally, some people develop a mild to moderate allergic reaction or rash in reaction to some of the active ingredients in sunscreens. Discontinuing that sunscreen and switching to another type usually corrects this problem. Michelle Kasprzak, R.N., B.S.N., O.C.N. See also Basal cell carcinomas; Bowen disease; Carcinomas; Eyelid cancer; Lip cancers; Melanomas; Premalignancies; Prevention; Skin cancers; Squamous cell carcinomas; Sunlamps; Ultraviolet radiation and related exposures; Young adult cancers. 1130
Risk factors: The most common cancer that causes superior vena cava syndrome is bronchogenic carcinoma, responsible for 65 to 80 percent of cases. Other types of cancers that can cause this syndrome include small-cell lung cancer, primary mediastinal neoplasms such as thymoma and lymphoma, and metastases, especially from breast carcinoma. The most common infectious cause is histoplasmosis-induced fibrosing mediastinitis, most often seen in the midwestern part of the United States. This syndrome can also be caused by idiopathic fibrosing mediastinitis. Central venous catheters are the most common iatrogenic cause, followed by pacemaker electrodes and hyperalimentation lines. Etiology and the disease process: When the superior vena cava is obstructed, there is an increase in venous pressure to between 20 and 50 millimeters of mercury (mmHg), which is diagnostic. In about 40 percent of patients, the obstruction occurs above the azygous vein and is responsible for the most disabling symptoms. Obstruction between the azygous vein and the right atrium is less serious, as the azygous vein can provide collateral venous decompression. Incidence: Although superior vena cava syndrome is considered a rare disease, affecting less than 200,000 people in the U.S. population, the incidence of superior vena cava syndrome due to iatrogenic causes has been reported in 2 per 1,000 implantation procedures for pacemakers and defibrillators, and it is a well-described complication of both device implantation and central venous catheter placement. Symptoms: The symptoms of superior vena cava syndrome vary depending on the degree of increase in venous pressure that develops, as well as the level of obstruction, the rate at which it developed, and the cause. If extrinsic compression of the superior vena cava is caused by a be-
Salem Health: Cancer nign process such as fibrosing mediastinitis, the obstruction is gradual, allowing time for collateral circulation to develop, and therefore the symptoms are milder. With mild obstruction, symptoms include headache, puffiness of the face, and swelling of the eyelids or neck. Patients quickly find that severity is related to posture, with symptoms often worsening when they lie down or bend over. If invasion of the superior vena cava or thrombosis occurs, the obstruction develops rapidly, and the symptoms are more acute. If acute obstruction occurs because of hemorrhage into a rapidly growing neoplasm, cerebral edema with blurring of vision and drowsiness occur. As the majority of cases are caused by rapidly growing bronchogenic lung cancer, pulmonary symptoms such as shortness of breath, orthopnea, cough, hemoptysis, and chest pain predominate. Other symptoms include hoarseness, stridor, and laryngeal edema from laryngeal obstruction. Screening and diagnosis: In the past, superior vena cava syndrome was diagnosed by upper extremity venography; however, with the advent of contrast computed tomography (CT), helical CT scanning is now the most common modality used for diagnosis. CT scanning can show not just the extent of the obstruction but also the likely cause, a distinct advantage over venography. Direct CT signs of superior vena cava obstruction include nonopacification of the superior vena cava with or without intraluminal filling defects or encasement, or extrinsic compression of the superior vena cava by tumor. Indirect signs of superior vena cava obstruction include opacification of venous collateral circulation. The five major routes of collateral circulation include internal mammary veins, azygous or hemiazygous veins, paravertebral veins or Batson’s plexus, anterior jugular veins, and lateral thoracic and thoracoepigastric veins. Additional collaterals include the superior intercostal veins, parascapular veins, superficial thoracoabdominal and epigastric veins, and the vertebral veins. The location and extent of the obstruction determine the collaterals that opacify during the contrast CT exam. Sometimes marked focal enhancement of the liver is seen in cases of superior vena cava obstruction and is thought to represent low-resistance collateral flow from the superior vena cava through the liver to the inferior vena cava. In patients with contraindications to CT intravenous contrast, magnetic resonance imaging (MRI) can be performed; however, MRI occasionally fails to differentiate complete obstruction from incomplete obstruction because of marked narrowing and slow flow. An advantage of MRI over CT involves the ability to clear up confusion regarding flowrelated artifacts seen on CT because of the mixing of opacified and unopacified blood.
Superior vena cava syndrome Treatment and therapy: Because most cases involve a malignant process that precludes surgical resection, standard therapy includes radiation therapy (often in combination with diuretics and corticosteroids to reduce cerebral edema) and chemotherapy. Some 80 to 90 percent of patients are relieved of superior vena cava syndrome; however, approximately 50 percent of patients relapse, even in benign disease because, although collaterals develop, thrombosis will continue to propagate and occlude even these collaterals over time. Thrombolytic therapy has been used for selected cases of acute thrombosis. Superior vena cava bypass with composite autogenous vein grafts has also been used for patients with a benign process in whom collateral circulation is inadequate to relieve symptoms. Prognosis, prevention, and outcomes: With benign causes, symptoms will improve or subside as collateral circulation develops. With malignant causes, an improvement in symptoms varies with the type of tumor involved but most patients improve rapidly within a few weeks from the decrease in edema after the intensive radiation therapy, steroids, diuretics, and chemotherapy. Death from the cancer within the next several months is inevitable, however, with rare survivors beyond two years. Debra B. Kessler, M.D., Ph.D. u
For Further Information Abner, A. “Approach to the Patient Who Presents with Superior Vena Cava Obstruction.” Chest 103 (1993): 394S-397S. Hagga, John R., and Charles F. Lanzieri. Computed Tomography and Magnetic Resonance Imaging of the Whole Body. 4th ed. St. Louis: Mosby, 2003. Schwartz, Seymour I. Principles of Surgery. New York: McGraw-Hill, 1984.
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Other Resources
American Society of Clinical Oncology http://opl.asco.org Cancer.Net http://www.cancer.net/portal/site/patient National Cancer Institute Cardiopulmonary Syndromes http://www.cancer.gov/cancertopics/pdq/ supportivecare/cardiopulmonary/Patient/page5 See also Lung cancers; Risks for cancer; Stent therapy; Thymomas. 1131
Support groups
u Support groups Category: Social and personal issues Definition: Cancer support groups are designed to provide comfort, information, and education within a confidential group setting. They are intended to provide a safe place for individuals with common cancer-related concerns to experience mutually provided emotional support. The need for support: At critical points in the course of cancer, such as designation of high-risk status, diagnosis, initiation or cessation of treatment, and recurrence, patients face challenges that can be overwhelming. They may find that their usual ways of coping are ineffective and find it difficult to talk to family and friends. Commonly, patients want to protect their family and friends from their pain or are reluctant to admit how scared they feel. Support groups can help patients feel less isolated, improve their coping skills, and afford the opportunity to express concerns to others who share similar problems. The group format provides multiple perspectives on many issues; thus, participants can acquire new information, learn new skills, and observe, firsthand, better ways to manage problems that they would not have thought of on their own. Cancer support groups can also assist with managing practical aspects of cancer, such as providing patients with knowledge of innovative ways to manage treatment effects or tips about returning to work after treatment. In the United States, there are more than 450 cancer-related patient support and advocacy groups, and many have been instrumental in providing assistance to people affected by cancer. Goals of groups: General goals of cancer support groups include the following: • Provision of support among homogeneous groups affected by cancer • Improvement of morale and self-esteem • Enhancement of coping skills, personal control, and problem-solving abilities • Reduction of emotional distress • Provision of education regarding cancer and treatmentspecific issues • Clarification of medical information that may be missed in other settings because of anxiety • Clarification of misconceptions and misinformation regarding cancer and its treatment • Normalizing emotional reactions that occur throughout the course of the patient’s cancer 1132
Salem Health: Cancer Attainment of group goals is often enhanced by the disease-specific or role-specific membership of cancer support groups and the nonmedical environment in which they meet. Types of groups and therapeutic approaches: Cancer support groups employ a variety of psychotherapeutic approaches. They vary widely in structure, focus, and activities. Some are time limited with specific content and goals, or teach a specific skill targeted to improving quality of life. In general the these types are called psycho-educational groups. Other cancer groups may be ongoing, patient-centered, and focused on general expression of fears and concerns that may be too painful for patients to reveal to family and friends. These groups are called psychotherapy groups. Psychotherapy groups should be run by a professional with special training in both mental health and group intervention modalities relevant to patients with cancer. Some cancer support groups include a combination of education, group interaction, support, and behavioral training. Behavioral training teaches new skills such as progressive muscle relaxation, meditation, or biofeedback, which can be effective in reducing stress and minimizing treatment side effects. The fact that behavioral skills are learned and self-administered is of benefit in improving symptom management, self-efficacy, and quality of life. Cancer-specific versus general support groups: General psychotherapy groups tend to explore a range of life experiences, often promote confrontation among members in an effort to identify and eradicate maladaptive communication styles and relationship patterns, and may focus on past rather that current experiences to examine the origin of destructive relationship patterns. However, groups specifically for people with cancer typically maintain a focus on the cancer diagnosis, including its meaning and implications, and offer education and support specific to cancer-related topics. They are usually time limited and use a brief therapy, supportive, or crisis-intervention model. Normalizing emotional distress, providing realistic reassurance, bolstering strengths and positive coping skills, and gently suggesting behavioral alternatives to replace destructive methods of coping are essential components of the cancer support group’s process and goals. Cancer support groups offer participants a range of perspectives about cancer-specific topics within the context of guidance, protection, and boundaries provided by a knowledgeable leader. Confrontational communication, exploration of past trauma, and problems not directly relevant to current issues are usually not addressed. Obviously, the rationale
Salem Health: Cancer for this approach is based on the goal of enhancing coping skills and keeping stress within manageable limits. Group composition: Cancer support groups exist for a range of individuals affected by cancer. Usually membership is limited to individuals with similar characteristics and problems. For example, new genetic technologies have given rise to groups for those at risk but not yet diagnosed with cancer. These groups offer multiple perspectives and education about issues such as genetic testing, risks and benefits of testing, and various prevention and screening practices. Membership may be centered on characteristics including cancer site, point in the course of cancer, and relationship to patient (for example, parents with an affected child, children with an affected parent). The benefit of a homogeneous group is the focus on similar content and themes that are relevant to all participants; thus members are protected from painful experiences that do not pertain to them and could overwhelm and undermine rather that enhance their coping skills.
Support groups Groups for cancer caregivers: Family and friends may benefit from participating in a cancer support group, especially if they love, depend on, or take care of the affected person. Family members may need help in dealing with stresses such as family disruptions, financial worries, and changing roles. To help meet these needs, some support groups are designed just for family members of cancer patients. There has been an increase in the number of groups designed for family cancer caregivers that combine education, support, and links to community services, although far more caregiver resources are needed. This rapidly growing need is based on changes in health care financing and delivery and resultant trends that have displaced a large burden of cancer care onto family members. Patients are discharged from hospitals while still needing some care; they often require highly technical, complex care that at one time was performed by professionals in a clinical setting. For example, it has become common practice for a breast cancer patient to be discharged from the hospital on
Cancer survivors can find comfort by participating in support groups and events such as this cancer walk. (AP/Wide World Photos)
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Support groups the day of a mastectomy. Drains are still in place, pain management and risk for infection are primary concerns, and the need for monitoring, direct care, functional assistance, and support is constant. Coupled with dramatic reductions in third-party reimbursement for home health services, the burden of this complex care falls to family and friends who typically are not equipped, from an educational or emotional standpoint, to manage it. Stress may be compounded among caregivers who work and depend on maintenance of their income, have others who depend on them such as children or other ill or elderly family members, have limited finances or people available to provide assistance and respite, are ill themselves, or are experiencing countless other issues. Caregiver burden and the need for additional services promise to be critical well into the future. The practical and emotional needs of family caregivers and the farreaching impact of these issues on the social and economic welfare of the United States and its citizens are immense. There are support groups specific to the needs of professional caregivers, although more resources are needed in this area. Professional caregiver support groups are valuable for countless reasons, not the least of which are validation of the stressful nature of the work and stress management in the service of maintaining professional morale and promoting and maintaining high-quality oncology care. Research regarding efficacy: One of the most important predictors regarding the efficacy of any behavioral or group technique is whether the person receiving the treatment believes it will be helpful. That is a major limitation to studies examining efficacy of cancer support group treatments. Although several studies have demonstrated positive outcomes, from increased survival time to improved quality of life among support group members, subjects are largely self-selected, meaning that they participate in the support group because they start out with the belief that it will benefit them. The consensus among researchers is that cancer support groups enhance quality of life by providing information, reducing isolation and helplessness, and normalizing emotions. Studies have shown that participation in cancer support groups promotes positive coping; reduces symptoms such as tension, anxiety, fatigue, and confusion; and improves compliance with cancer treatment. One of the most widely publicized studies regarding efficacy of cancer support group treatment was a 1989 clinical trial of women with metastatic breast cancer conducted by physician David Spiegel. Study findings suggested that women who participated in a cancer support group lived eighteen months longer than a control group of women 1134
Salem Health: Cancer who did not participate. The study was later criticized because average rather than median survival was the statistic used to compare group survival differences. Averages can be dramatically skewed in one direction or another by just one early death or long-term survivor in a particular group; therefore it was concluded that study findings were misleading. A subsequent clinical trial that followed a sample of women with breast cancer found no survival differences between support group participants and nonparticipants, and yet another study reported that patients with malignant melanoma who had taken part in a psycho-educational cancer group lived longer than those who did not take part. A 2005 review of four studies of women with breast cancer found no relationship between support group participation and survival other than that reported in Spiegel’s study. Limitations of studies that have examined the link between support group participation and survival include the self-selective nature of research samples and the group’s impact on treatment compliance, which directly impacted survival. One study at the Ontario Cancer Institute found that women with breast cancer who lacked support from their families and friends were helped the most by support groups; therefore there may be factors that predispose some patients to benefit from participation in support groups. Finally some data link cancer support group participation with negative consequences. At this point, there is insufficient evidence to support the efficacy of cancer support group interventions. Nonetheless there is abundant anecdotal evidence to support the benefits of attending if participants believe the experience will help and are not unduly stressed by exposure to the feelings and problems of others, and their needs are met by the group’s content, goals, and activities. Internet-based groups: Recent years have seen an explosion of Internet sites designed to provide information, support, and education for individuals affected by cancer. They usually involve interaction in real time among individuals who communicate via computer in chat rooms. Other sites are informational in nature. Questions can be posed and answers received at a future time, or individuals may be directed to a number of question-specific predetermined resources. Internet-based groups vary widely in content, process, and quality. Some are led by moderators; others are not moderated or monitored at all. At present, there is scant empirical evidence supporting the efficacy of Internetbased cancer support. Even more problematic is that there are no quality control measures to ensure accuracy of information, nor are there procedures to screen or assist those who may be upset or otherwise harmed by content.
Salem Health: Cancer Tension between patient advocacy groups, clinicians, and groups devoted to freedom of information has prevented the limitation of the content of Internet sites or access to sites by specific vulnerable populations. Although many cancer-related sites provided by respected institutions and organizations such as the American Cancer Society and the National Cancer Institute are of excellent quality and aim to assist patients in every way, the Internet has provided a breeding ground for unscrupulous practices. Vulnerable patients—especially those with progressive illness or those not faring well with conventional treatment— can fall prey to false hope and financial as well as psychological exploitation, whether visiting an unmonitored support group or other Web site. The virtual explosion of technology, Web sites, unclear laws, and the ability of Internet sites to disappear and emerge overnight under new names makes their regulaton difficult. Further, the technological expertise of unscrupulous Web site administrators often surpasses that of law enforcement, although that gap is closing. Therefore, the safety, accuracy, and ethics of Internet support groups and the validity of their informational content will remain a formidable challenge. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u
For Further Information Breitbart, W. “Spirituality and Meaning in Supportive Care: Spirituality- and Meaning-Centered Group Psychotherapy Interventions in Advanced Cancer.” Journal of Supportive Care in Cancer 10, no. 4 (2002): 272280. Cunningham, A. J., et al. “A Randomized Controlled Trial of the Effects of Group Psychological Therapy on Survival in Women with Metastatic Breast Cancer.” Psychooncology 7 (1998): 508-517. Edmonds, C. V., G. A. Lockwood, and A. J. Cunningham. “Psychological Response to Long-Term Group Therapy: A Randomized Trial with Metastatic Breast Cancer Patients.” Psycho-oncology 8 (1999): 74-91. Fawzy, F. I., N. W. Fawzy, L. A. Arndt, and R. O. Pasnau. “Critical Review of Psychosocial Interventions in Cancer Care.” Archives of General Psychiatry 52 (1995): 100-113. Goodwin, Pamela J. “Support Groups in Advanced Breast Cancer.” Cancer 104, suppl. 11 (December 1, 2005): 2596-2601. _______. “Support Groups in Breast Cancer: When a Negative Result Is Positive.” Journal of Clinical Oncology 22, no. 21 (November 1, 2004): 4244-4246. Zabalegui, A., S. Sanchez, P. D. Sanchez, and C. Juando. “Nursing and Cancer Support Groups.” Journal of Advanced Nursing 51, no. 4 (2005): 369-381.
Surgical biopsies u
Other Resources
Association of Cancer Online Resources http://www.acor.org National Cancer Institute Cancer Support Groups: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Support/support-groups The Wellness Community http://www.thewellnesscommunity.org/ See also Anxiety; Caregivers and caregiving; Case management; Complementary and alternative therapies; Counseling for cancer patients and survivors; Long-distance caregiving; Oncology social worker; Prayer and cancer support; Psychosocial aspects of cancer; Relationships; Self-image and body image; Stress management; Young adult cancers.
u Surgical biopsies Category: Procedures Also known as: Tissue sampling, incisional biopsy, excisional biopsy, endoscopic or laparoscopic biopsy, open biopsy, transvenous biopsy Definition: A surgical biopsy is the removal of tissue through an incision during an open or laparoscopic surgical procedure. A pathologist examines the tissue sample in the laboratory to detect the presence of cancer cells and determine the grade of the tumor. There are several types of surgical biopsy procedures. The one performed is dependent on the type of suspected cancer and the area of the body being examined. In incisional biopsy, a scalpel or similar instrument is used to remove a portion of the suspected cancerous tissue through an incision made in the skin. Incisional biopsies are most commonly used to remove soft tissue, such as skin, connective tissue, breast tissue, muscle, and fat. For skin lesions, an incisional biopsy may be performed with a hollow, circular-shaped instrument (punch biopsy), or a razor may be used (shave biopsy). Depending on the type of procedure, general or local anesthesia may be used. In excisional biopsy, a whole lump, tumor, or organ and a margin of normal tissue around it are removed. Some open surgical biopsy procedures include laparotomy, thoracotomy, or mediastinotomy. General anesthesia is used for excisional and open biopsy procedures. In endoscopic or laparoscopic biopsy, an endoscope (small camera on a thin tube) is used to view an internal 1135
Surgical biopsies area and identify the tissue for removal. The endoscope transmits magnified images of the area onto a video monitor to guide the physician during the procedure. The endoscope can be inserted through a natural body opening (endoscopy), such as the throat to remove esophageal tissue, or through a small abdominal incision (laparoscopy). When the laparoscope is used to view the inside of the chest cavity, the procedure is called a thoracoscopy and the scope is called a thoracoscope. When the laparoscope is used to view the mediastinum (space between and in front of the lungs), the procedure is called a mediastinoscopy, and the scope is called a mediastinoscope. Surgical instruments attached to the endoscope or inserted through other small incisions are used to remove the tissue. Laparoscopic biopsy procedures are the most common type of biopsies and are often used when a tissue sample is needed from more than one area or when a larger tissue sample is needed. Depending on the biopsy site, the patient may be under general or local anesthesia. Cancers diagnosed or treated: Various, including breast cancer, bone cancer, carcinoid tumors, germ-cell tumors, liver cancer, lung cancer, sarcoidosis, Hodgkin disease, myasthenia gravis, neurogenic tumors, thymic cancer and thymomas, malignant mesothelioma, mediastinal tumors, pericardial tumors, lymphoma, skin cancer, and thyroid cancer Why performed: Surgical biopsies are performed to diagnose a variety of conditions and to assess the degree of organ damage (disease staging). Surgical biopsies may be performed when abnormalities are found during other tests such as an ultrasound, computed tomography (CT) scan, magnetic resonance imaging (MRI), or a nuclear scan. Surgical biopsies also may be performed to determine the cause of unexplained symptoms or to match organ tissue before a transplant. An excisional biopsy may be used to remove some types of tumors or suspected cancers that need to be entirely removed for an accurate diagnosis, such as the removal of lymph nodes to accurately diagnose lymphoma. A surgical biopsy procedure also may be recommended when other, less invasive biopsy procedures do not provide conclusive results for an accurate diagnosis to be made. Patient preparation: Preprocedure tests may include a chest X ray, electrocardiogram (EKG), CT, MRI, and other imaging tests. Urine tests and blood tests are performed before the procedure to evaluate the patient’s blood count, platelet count, and blood clotting ability. Depending on the type of surgical biopsy procedure to be performed, additional tests may be required. 1136
Salem Health: Cancer The patient preparation for a biopsy procedure varies, depending on the type of procedure and biopsy location. One week before the procedure, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician. Other anticoagulant medications may be prescribed as needed. In most cases, the patient must not eat or drink for eight to twelve hours beforehand. The patient will receive specific preparation instructions from the health care team. Patients at most health care facilities must sign a form stating their willingness to permit diagnosis and medical treatment, a process called informed consent. Steps of the procedure: An intravenous (IV) line is inserted into a vein in the patient’s arm to deliver medications. For some surgical biopsy procedures, such as liver biopsy and some laparoscopic procedures, the patient is given a sedative and the procedure is performed under conscious sedation. With conscious sedation, the patient is awake but relaxed and able to respond to the physician’s instructions during the procedure. The majority of surgical biopsy procedures, however, are performed while the patient is under general anesthesia. The biopsy site is cleansed, and sterile drapes may be placed around the area. A local anesthetic is injected into the area. In some cases, such as with sentinel node biopsy, a radioactive substance or dye is injected into the tumor, and a scanner is used to locate the lymph node or tissue containing the radioactive substance or stained with the dye. During a laparoscopic biopsy, a laparoscope is inserted into a small abdominal incision. The laparoscope transmits magnified images onto a video monitor to guide the physician as laparoscopic instruments are inserted through additional small abdominal incisions to remove tissue samples. Ultrasound or CT guidance may be used to aid the surgeon during the procedure. Transvenous biopsy is a technique used to remove a tissue sample via a catheter inserted into a vein in the neck. This technique is not common, but it may be used for certain high-risk patients, including those who have a bloodclotting disorder, fluid in the abdomen, or liver failure or who are morbidly obese. During an incisional biopsy, the surgeon uses a scalpel to remove a sample of tissue from the area. During an excisional biopsy, the lesion and surrounding margin of normal tissue are removed. During an open surgical biopsy, an incision is made in the abdomen (laparotomy), upper chest (thoracotomy or mediastinoscopy), or breast, allowing visualization of the area. The location and size of the tumor are identified, and a tissue sample or lymph
Salem Health: Cancer nodes can be removed for analysis. Ultrasound or CT guidance may be used to aid the surgeon during the procedure. After the tissue has been removed, a pathologist sends it to a laboratory for microscopic analysis to determine how much the tissue sample differs from normal tissue. A variety of methods can be used to process tissue samples. Histologic sections involve preparing stained, thin “slices” of tissue mounted on slides. The histologic method may take up to forty-eight hours to produce results. With this method, the tissue sample is placed in a machine that replaces all water in the sample with paraffin wax. The sample is embedded into a larger block of paraffin and is then sliced into very thin sections and stained with dye to aid microscopic analysis. Frozen tissue analysis involves freezing the tissue, slicing it into thin sections, and staining the sections to aid analysis. Smears are tissue samples that are spread onto a slide for examination. The results of smears can usually be obtained very quickly, although the smear technique cannot be used on all types of biopsy samples. After the procedure: The length of a patient’s recovery and the steps for recovery vary depending on the type of biopsy procedure, biopsy location, and type of anesthesia. The patient may stay in an intensive care unit (ICU) or recovery room for a certain amount of time after the procedure. The incision is closed with sutures, and the biopsy site is usually covered with a bandage or dressing. A catheter may remain after surgery to drain urine. Drains or chest tubes may remain in place at the incision site to remove fluid or air that may have accumulated during the procedure. Pain medication is prescribed as needed for relief of pain, which may include discomfort at the biopsy site or muscle pain. The patient usually stays in the hospital overnight but may need to recover in the hospital three to four days, depending on the biopsy site, type of procedure, and type of anesthesia given during the procedure. Specific instructions for driving, activity, incision care, medications, nutrition, and managing emergencies and a follow-up care schedule are provided to the patient, as applicable. In most cases, the patient is not permitted to drive home after the procedure, and driving or operating machinery may be limited for a certain amount of time. Depending on the physician’s instructions, the patient may be required to stay on bed rest at home for a certain amount of time after the procedure. The patient should avoid vigorous physical activity and heavy lifting after the procedure, as directed by the physician. For one week after the procedure, the patient should avoid aspirin and products containing aspirin, ibuprofen, and anticoagulants, as these medications decrease blood
Surgical biopsies clotting, which is necessary for healing. Other anticoagulant medications may be prescribed if necessary after the procedure. The patient may take acetaminophen (Tylenol) to relieve pain as needed. Risks: The risks of biopsy procedures are dependent on the type of procedure performed and the biopsy location. Possible risks of all surgical biopsy procedures include allergic reaction to the anesthetic, bleeding, infection, and scarring, and these risks are greater with open surgical biopsy procedures. The risk of death associated with biopsy procedures is generally very low. The physician can discuss specific mortality rates and risks with the patient, depending on the type of procedure performed. Results: Biopsy results are available either right away or within twenty-four to forty-eight hours after the tissue removal, depending on the type of biopsy analysis that is being performed. The tissue sample removed during the procedure is either normal, which means it is benign or noncancerous, or abnormal, which means it has unusual characteristics and may be malignant or cancerous. The grade of tumor may also be determined from the biopsy sample, indicating how quickly the tumor is likely to grow and spread. Surgical biopsy procedures remove a larger tissue sample than other biopsy methods, increasing the accuracy of a diagnosis. The type of cancerous cells and extent of disease will help guide the patient’s treatment. Angela M. Costello, B.S. u
For Further Information DeVita, Vincent, Jr., Samuel Hellman, Steven A. Rosenberg, et al., eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. McPhee, Stephen J., Maxine A. Papadakis, and Lawrence M. Tierney, eds. Current Medical Diagnosis and Treatment 2008. New York: McGraw-Hill Medical, 2007. Ota, D. M. “What’s New in General Surgery: Surgical Oncology.” Journal of the American College of Surgeons 196, no. 6 (2003): 926-932. Skandalakis, John E., Panajiotis N. Skandalakis, and Lee John Skandalakis. Surgical Anatomy and Technique: A Pocket Manual. 2d ed. New York: Springer, 2000.
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Other Resources
American Cancer Society http://www.cancer.org American Pathology Foundation http://www.apfconnect.org 1137
Surgical oncology College of American Pathologists http://www.cap.org National Cancer Institute http://www.cancer.gov Radiology Info, provided by the American College of Radiology and the Radiological Society of North America http://www.radiologyinfo.org Society of Interventional Radiology http://www.sirweb.org Society for Hematopathology http://socforheme.org See also Biopsy; Liver biopsy; Needle biopsies; Needle localization; Stereotactic needle biopsy.
u Surgical oncology Category: Medical specialties Definition: Surgical oncologists are doctors who have been trained in general surgery techniques and practices and then completed additional training in surgical techniques specific to cancer treatment. They may perform various diagnostic surgeries, such as removing a lymph node to see if skin cancer has spread, or may perform treatment surgeries such as the removal of tumors and surrounding cancerous tissues. Surgical oncologists work closely with other allied health professionals to ensure that the patient receives the best possible care. Subspecialties: Surgical oncologists generally specialize in cancers that occur in certain areas of the body. Some specializations include breast, lung, kidney, skin, gastrointestinal tract, and colorectal, and endocrine system cancers. Surgical oncologists may also specialize in either patient treatment or research. Research specialists do treat patients, but instead of consulting with patients and doing surgeries during the majority of their time, they spend a significant portion of their time working to develop new and better diagnostic procedures and treatments. Improved procedures are generally intended to improve positive patient outcomes or reduce the number of side effects generally experienced. Cancers treated: Nearly all forms of cancer Training and certification: After completing medical school, surgical oncologists must successfully complete a 1138
Salem Health: Cancer five-year residency in surgery. After completing the residency, they must then complete a fellowship in surgical oncology. These fellowships generally last from two to four years and must be completed at one of the fourteen schools accredited by the Society of Surgical Oncology. There is no board certification for surgical oncology, but upon completion of the fellowship, a certificate is usually awarded. During their training, surgical oncologists generally receive instruction in both commonly accepted, frequently performed surgeries, such as a lumpectomy for breast cancer, and very new or experimental procedures, such as cryosurgery, a treatment procedure that involves killing the cancerous cells through freezing them with liquid nitrogen or argon gas, or isolated limb perfusion, a treatment for cancers involving the limbs that is considered an alternative to amputation in some cases. Research techniques can also be an important part of the training received by surgical oncologists. Many are involved in research and the development of new procedures and techniques for diagnosis and treatment. Often the development of new procedures focuses on techniques to treat rare or unusual forms of cancer or those believed to provide a better outcome or have a lower incidence of side effects. Doctors trained in research techniques can participate in research or be better equipped to recommend clinical trials or experimental procedures to their patients if appropriate. Services and procedures performed: Surgical oncologists perform many different diagnostic procedures as well as procedures intended to remove or otherwise treat the cancer. Depending on the location of the cancer, a surgical oncologist may be required to take a sample from the area in which cancer is suspected or some cells from a tumor that is believed to be malignant. For this type of procedure, the surgeon will often insert a small instrument into the patient, guided by X ray or other images, and remove tissue from the area in question. An important procedure that surgical oncologists commonly perform is the removal of tumors. During this type of procedure, the surgeon makes the smallest incision possible to allow access to the tumor and the area around the tumor. Then the tumor is removed, along with adjoining tissue that is also believed to be cancerous. This type of treatment may be used alone, or it may be used along with other treatment options. Radiation and chemotherapy may actually be delivered during the surgery, when the cancerous area is exposed and it is possible to apply radiation or chemotherapeutic agents very accurately to the cancerous area.
Salem Health: Cancer
Surgical oncology
Surgical oncologists specialize in both the therapeutic and palliative removal of cancerous tumors. (Digital Stock)
Surgery can also be performed for reasons that are not directly intended to cure the cancer, such as to reduce the size of the tumor or to remove it from a specific area where it is causing damage. It is not always possible to completely surgically remove a tumor, because it may have invaded areas that are necessary for the body to function. In this case, surgery may be performed to remove as much of the tumor as possible, with the hope that radiation therapy or chemotherapy will be able to combat what remains. Palliative surgery may also be performed by a surgical oncologist. This type of surgery is done when the cancer has metastasized extensively, and the surgery is not expected to provide a cure. If a tumor is causing the patient pain, some or all of the tumor may be surgically removed to provide pain relief and improve the patient’s quality of life. Related specialties and subspecialties: The surgical oncologist works closely with many different members of the health professions. The surgical oncologist may have a patient referred by a primary physician, gynecologist, der-
matologist, or other doctor, and will work closely with the referring physician throughout the cancer treatment process. During the process of diagnosis, the surgical oncologist may perform surgery to take a sample from the area where cancer is suspected and send it to a pathologist for evaluation. The pathologist can then determine if cancer is in fact present, and if it is, which type of cancer is present. The surgical oncologist will also work closely with nurses, medical technologists, and members of the office or hospital staff. During cancer treatment, the surgical oncologist will work with various other health professionals depending on the type and extent of the cancer being treated and the treatment option chosen. During surgery, nurses and medical technologists will assist the surgical oncologist by providing various services such as patient and equipment monitoring. Nurses will prepare the patient for surgery by communicating necessary information and instructions and administering any medications necessary preoperatively. The anesthesiologist is present at surgery to ensure that the patient is fully and safely anesthetized using the 1139
Survival rates minimum level of anesthesia. Depending on the type of treatment, the surgical oncologist may work with additional professionals during surgery. For example, if targeted chemotherapeutic agents are being introduced to treat residual cancer cells during surgery, a chemotherapy expert will be present to oversee and administer the chemotherapeutic treatment. After surgery, another set of health care professionals will work with the surgical oncologist. Nurses will provide aftercare for the incision or wound site; administer pain, anti-inflammatory, and other medications; and communicate information to the patient about self-care. Physical or occupational therapists may be necessary to assist patients in recovering skills and mobility lost through surgery. A prosthetist may be required to make a prosthetic for any body part removed during the surgery, and a plastic or reconstructive surgeon may be necessary to repair damage or scarring caused by the surgery or the cancer itself. A psychological counselor or therapist may help the patient with any emotions brought about by the surgery or the cancer itself. Throughout the process, the surgical oncologist may also work closely with a case manager who oversees and organizes the patient’s care and treatment. Helen Davidson, B.A. u
For Further Information Damron, Timothy A., ed. Oncology and Basic Science. Philadelphia: Lippincott Williams & Wilkins, 2008. Lyons, Lyman. Diagnosis and Treatment of Cancer. New York: Chelsea House, 2007. Sabel, Michael S., Vernon K. Sondak, and Jeffrey J. Sussman, eds. Surgical Foundations: Essentials of Surgical Oncology. Philadelphia: Mosby Elsevier, 2007. Stroszczynski, E., ed. Minimally Invasive Tumor Therapies. New York: Springer, 2006. Wrightson, William R., ed. Current Concepts in General Surgery: A Resident Review. Georgetown, Tex.: Landes Bioscience, 2006. u
Organizations and Professional Societies
American Society of Clinical Oncology http://www.asco.org 1900 Duke Street, Suite 200 Alexandria, VA 22314 Society of Surgical Oncology http://www.surgonc.org 85 West Algonquin Road, Suite 550 Arlington Heights, IL 60005 1140
Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org MayoClinic.com Cancer Surgery: Physically Removing Cancer http://www.mayoclinic.com/health/cancer-surgery/ CA00033 See also Bilobectomy; Biopsy; Cholecystectomy; Colectomy; Cordectomy; Cordotomy; Core needle biopsy; Electrosurgery; Esophagectomy; Glossectomy; Hysterectomy; Hystero-oophorectomy; Laparoscopy and laparoscopic surgery; Laryngectomy; Lobectomy; Loop electrosurgical excisional procedure (LEEP); Lumbar puncture; Lumpectomy; Lymphadenectomy; Mastectomy; Mohs surgery; Oophorectomy; Oral and maxillofacial surgery; Orchiectomy; Pancreatectomy; Pneumonectomy; Polypectomy; Prostatectomy; Salpingectomy and salpingooophorectomy; Splenectomy; Stereotactic radiosurgery (SRS); Surgical biopsies; Vasectomy and cancer.
u Survival rates Category: Social and personal issues Also known as: Mortality rates Definition: Survival rate is a statistic that states the percentage of people with a disease who live a specified length of time after diagnosis (such as one year, five years, or ten years). Types of survival rates: The overall or observed survival is the percentage of a group of people diagnosed with a disease who are alive after a specified time period, often five years. Overall survival rates do not distinguish between different causes of death—deaths from cancer and car accidents are both included. The net survival filters out deaths from causes other than the disease of interest, by calculating either relative survival or cancer-specific survival. Relative survival compares the overall survival rate of a group of people after diagnosis with a disease to the survival rate of a similar (age- and sex-matched) group without the disease. Cancer-specific survival includes only deaths by cancer, usually determined using death certificates. Overall and relative survival rates do not always give a clear picture. For example, there is no way to tell whether cancer survivors are still undergoing treatment at five years or if they have gone into remission. Two other types of survival rates can give more information: progressionfree survival and disease-free survival. The progression-
Salem Health: Cancer free survival rate is the percentage of people who survive without their cancer spreading, such as the proportion of people who have had partial treatment success—their diseases are not in remission, but the tumors are not growing. Disease-free survival represents the proportion of patients during a specified time period who achieve remission or are completely cancer-free. One of the newer methods of calculating survival is period survival, which uses only the most recent information available. This method is believed to take newer treatment regimens and modalities into account more effectively than other methods. However, restricting the analysis to a relatively short, recent time period (such as the most recent calendar year for which cancer registry data are available) results in a loss of precision in the estimate. Although surviving is the opposite of dying, mortality rates are not always the inverse of survival rates. The mortality rate is often defined as the proportion of the entire population that died from a disease in a specified period, often reported as deaths per 1,000 or 100,000 (for example, 89 per 100,000 persons rather than 0.089 percent). Population-based mortality rates do not help to measure advances in treating cancers because they reflect changes in incidence. For example, death rates from lung cancer have declined since 1990, but that is more related to the reduction in tobacco use over the past forty years than to any improvement in treatments for lung cancer. When the mortality rate is defined as the proportion of people diagnosed with a disease who died from that disease during a specific period, then its value is simply the inverse of the survival rate. How survival rates are used: Survival rates are important in determining prognosis, or the prediction of the course of the disease. Survival rate estimates are used in health services research for studying trends over time, such as the effect of a new therapy or the effect of stage at diagnosis or socioeconomic status. Survival statistics are also important in clinical research to measure the efficacy of treatments for cancer. On an individual patient level, survival rates can give patients a better understanding of their disease and help them evaluate different treatment plans in consultation with their medical providers. How survival rates are calculated and reported: Cancer survival rates are usually calculated based on observations of hundreds or thousands of people, often using cancer registries or other databases. Survival rates can be reported in simple percentages, or in life tables, survival curves, or Kaplan-Meier survival curves. Life tables show the actual observed survival over time, and although they are one of the oldest techniques in biostatistics, they are no
Survival rates longer seen much outside of government reports. Survival curves are graphical presentations of the probabilities for surviving different lengths of time, often derived from life tables. In the actuarial method, they present the probabilities of surviving to set, specific intervals, such as one year or one month. Kaplan-Meier survival curves also graphically represent survival probabilities, but unlike the actuarial survival curve, the Kaplan-Meier method (named for its originators) identifies the exact point in time when each death occurred and uses those timepoints as the intervals. The goal is to produce the most accurate survival curve possible, taking into account all the information available. The Kaplan-Meier method allows researchers to analyze complex data, such as data from a study in which patients have been diagnosed or started treatment at different times and have varying lengths of follow-up. The Kaplan-Meier method is so widely used and so well known that, more often than not, research papers will refer to survival curves as Kaplan-Meier curves. Limitations of survival rate statistics: It is well known that statistics can be both accurate in general and completely wrong in particular. Survival rates are no different from other statistics in this regard. Statistics cannot predict the course of an individual’s disease. Because statistics are based on many different people and every person is different, they cannot give the exact chances of remission or progression in a particular case. Even when survival rates can be calculated for smaller groups—even very specific groups, such as fifty-five- to sixty-four-year-old white women in Texas with Stage II breast cancer—the differences between people in that subpopulation in genetics, body type, lifestyle, and socioeconomic factors means that the survival rates can vary considerably. It is always important to remember that survival rates represent an average and cannot reflect a person’s individual experience. Because of this limitation, many cancer patients choose to disregard survival rate statistics. In addition, survival rates usually do not reflect the latest treatment options. Because there is a lag between when cancer patients die and when this information is reported, the data are usually at least several years old. In other words, the effects of new treatments are not seen in the statistics for a number of years after the treatment becomes commonplace. Another limitation of survival rates has to do with improvements in screening. When screening is widespread, a higher five-year survival rate may be observed not because people live longer but only because an earlier diagnosis has been made. 1141
Survival rates
Salem Health: Cancer
Age-Adjusted Five-Year Relative Survival Rates in the United States, 1996-2003 Site
Total Men
Women
All Sites Prostate Thyroid Testis Melanoma of the skin Breast Hodgkin disease Corpus uteri Urinary bladder Cervix uteri Kidney and renal pelvis Rectum Colon Non-Hodgkin lymphoma Larynx Oral cavity and pharynx Kaposi sarcoma Leukemia Ovary Brain and nervous system Myeloma Stomach Esophagus Lung and bronchus Liver and bile duct Mesothelioma Pancreas
64.9 98.4 96.7 95.4 91.1 88.6 84.9 83.9 79.5 71.6 65.5 65.0 63.5 63.4 62.9 59.1 56.3 49.6 44.9 33.9 33.7 24.3 15.6 15.0 10.8 8.4 5.0
65.2 – 97.5 – 93.5 88.6 87.0 83.9 75.3 71.6 66.3 66.2 63.1 66.4 58.3 62.6 63.7 49.4 44.9 36.0 31.7 26.9 16.8 17.4 11.7 13.8 5.1
64.6 98.4 93.9 95.4 89.1 85.0 83.0 – 80.9 – 65.1 64.1 64.0 60.8 64.1 57.6 55.8 49.7 – 32.2 35.5 22.6 15.3 13.0 10.4 6.8 4.9
and physicians. However, earlier diagnosis does not necessarily imply longer survival. If one person is diagnosed when symptoms appear in 2005 and survives until 2007, while another is diagnosed while still asymptomatic in 2003 and survives until 2007, the survival statistics will seem to be improved even though both people died at the same time. From the point of view of the cancer patient, there may even be negative consequences of earlier diagnosis—the patient’s emotional well-being may worsen or there may be longer exposure to the side effects of treatment.
Source: Data from L. A. G. Ries et al., SEER Cancer Statistics Review, 1975-2004 (Bethesda, Md.: National Cancer Institute, 2007)
Survival rates by cancer site and stage: The most upto-date survival rates for different cancers are available through the National Cancer Institute. Among different types of cancer, the highest relative five-year survival rate is seen in prostate cancer, at 98.4 percent, while the lowest is seen in cancer of the pancreas, at 5.0 percent. Survival rates can vary greatly based on how early the cancer is diagnosed. For example, for patients diagnosed with Stage I (local) lung cancer, the five-year relative survival rate is 56 percent, while the rate is only 2 percent for those with Stage IV disease. Only 12 percent of lung cancers are diagnosed at Stage I, and the overall relative survival rate is very low. Even so, it is unlikely that the survival rate would increase significantly if all lung cancer were diagnosed at Stage I or II, since treatment options are limited and the disease spreads rapidly. Such is not the case for cancers that can be cured relatively easily with surgery if caught early, such as melanoma. Prostate cancer, on the other hand, has a high survival rate because it is generally a very slow form of cancer, and most men with prostate cancer will die of other causes before the cancer has a chance to spread.
Survival rate trends: The five-year survival rate is commonly used to report progress in the so-called war against cancer. Experts disagree as to whether cancer patients are living longer than cancer patients did in the past. Although survival rates have increased for many cancers since the 1970’s, this could be because of a number of different factors (or combinations of factors), including improvements in surgical treatment or chemotherapy, changes in definitions of diseases, diagnoses of cases that would have been undetectable in years past, improvements in access to care, and earlier diagnoses through advances in screening. Many cases of cancer are diagnosed earlier than they would have been even in the late 1990’s because of improvements in imaging technology, advancements in genetic screening, and increasing awareness among patients
Survival rates in different populations: Survival rates can vary greatly between different groups of people. For instance, women have better relative survival rates than men, both overall and in most of the major types of cancer, although these differences are generally not large. In addition, age at diagnosis has been shown to influence survival rate, since older people are less likely to be treated aggressively. This may be related to their perceived or actual lowered capability of withstanding severe side effects from treatment, or it may be an example of age-related bias on the part of medical providers. Compared with non-Hispanic whites, African Americans, and American Indians, Hispanic whites have poorer survival rates both overall and for nearly every type of cancer. This is attributed to the fact that they are more likely to be diagnosed with advanced cancer, as a result of disparities in access to and receipt of health care services. In
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Salem Health: Cancer breast cancer, it has been shown that American women of Japanese and Chinese descent have better survival rates and Hawaiians have worse survival rates relative to nonHispanic whites. Some studies suggest that most of these racial and ethnic disparities are actually socioeconomic disparities, and that when nonwhite people receive cancer treatment and medical care similar to that received by whites, their survival rates also are similar. This is supported by the fact that higher income has been shown to be a predictor of better survival. Lisa M. Lines, M.P.H. u For Further Information Dickman, P. W., and H. O. Adami. “Interpreting Trends in Cancer Patient Survival.” Journal of Internal Medicine 260, no. 2 (August, 2006): 103-117. Gordis, L. Epidemiology. Philadelphia: Elsevier/Saunders, 2004. Jemal, A., et al. “Cancer Statistics, 2007.” CA: A Cancer Journal for Clinicians 57, no. 1 (January/February, 2007): 43-66. Welch, H. G., L. M. Schwartz, and S. Woloshin. “Are Increasing Five-Year Survival Rates Evidence of Success Against Cancer?” Journal of the American Medical Association 283, no. 22 (June 14, 2000): 2975-2978. u
Other Resources
Centers for Disease Control and Prevention Health Disparities in Cancer http://www.cdc.gov/Features/ CancerHealthDisparities/ MayoClinic.com Cancer Survival Rate: A Tool to Understand Your Prognosis http://www.mayoclinic.com/health/cancer/CA00049 National Cancer Institute Overview of Population-Based Cancer Survival Statistics http://srab.cancer.gov/survival See also African Americans and cancer; Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Bronchial adenomas; Chemotherapy; Chewing tobacco; Childhood cancers; Elderly and cancer; Epidemiology of cancer; Imaging tests; Lung cancers; Melanomas; National Cancer Institute (NCI); Prevention; Prostate cancer; Psychooncology; Statistics of cancer; Survivorship issues; Tobacco-related cancers; Young adult cancers.
Survivorship issues
u Survivorship issues Category: Social and personal issues Definition: A survivor is anyone who remains alive and continues to function after being treated for cancer. Survivors face many issues—financial, physical, and emotional—as they return to everyday living. Cancer survival: The survival rate for various types of cancer is the number of people who are alive for a given period of time after diagnosis (usually defined as five years). As of 2009, more than 10 million people in the United States had survived cancer. The overall death rate from cancer began to decline in 1992 and continues to decline. Reasons for the decline include the availability of more effective treatments and more people being diagnosed at earlier, treatable stages of cancer. Also, more people are reducing their cancer risk by stopping smoking, using sun protection, and undergoing screening tests. The number of people being diagnosed with some cancers (lung, bladder, and prostate), however, is increasing. Issues facing cancer survivors: With increasing survival rates, those involved in cancer care are realizing the importance of addressing the unique needs of cancer survivors. For many patients, enduring and surviving cancer and its treatment become the sole focus of life. Once treatment is over, patients often are faced with worries about the future and decisions about how to transition to life as a survivor. Survivors may face financial issues, difficulties obtaining or returning to employment, or discrimination in obtaining health and life insurance or in finding employment. The experience of surviving cancer also may create emotional reactions, such as depression, guilt, or anxiety, that can evolve into significant emotional difficulties without appropriate help. Resuming daily life: Cancer affects very basic aspects of patients’ lives, such as their daily routines. Those undergoing treatment are faced with a daily, often painful battle simply to survive the illness. Their entire lives and those of their families are consumed by treatments, doctor visits, and hospitalizations. Suddenly, they no longer lead a “normal” life, and daily activities such as going to work or school, buying groceries, or simply visiting with friends become things of the past. Life no longer seems to stretch out in a straight line before them; it no longer is as predictable as it once was. After treatment, this time line changes, often just as suddenly. Patients may be left wondering what to do. Their daily lives may begin to resume their precancer patterns. Survivors may expect to resume life exactly as it was be1143
Symptoms and cancer fore cancer but may be impeded by fatigue or other physical changes. It also is possible that survivors will expect the world (jobs, school, and relationships) to be the same as it was before cancer, and they may be disappointed to learn that some things have changed while they were absorbed in cancer treatment. This change in a person’s perception of time can create feelings of anxiety, frustration, anger, sadness, and fear. Feelings of vulnerability, uncertainty, and fear about the future may cause the survivor to feel lost, abandoned by others, and depressed. Physical changes: After cancer treatment, some patients must face permanent physical changes, such as loss of a limb or a breast. Others may gain significant weight because of medications. Some people must cope with damage to other parts of the body as a result of their treatment. Radiation treatment, for example, not only destroys cancer cells but also can damage organs such as the thyroid gland or the liver. Certain types of chemotherapy may cause toxic effects, such as eye damage or bone degeneration. Women may experience early menopause or infertility resulting from treatment. Survivors simply may look fatigued, with sallow skin and dark circles under the eyes. Some changes, such as hair and nail loss, may be temporary. Experiencing such physical changes may affect survivors psychologically and emotionally. Seeing their changed appearance in the mirror may affect the self-image, selfconfidence, and self-identity of survivors. Disruptions in relationships with others: After surviving cancer, people may expect more from their relationships with spouses or children. They may approach relationships with more intensity if they feel that their lives may be shortened. Likewise, fears that they may not survive for long can cause the survivor to break off relationships with others, to push others away through anger or other behaviors, and to withdraw from social activities. To address these issues, some treatment centers offer coordinated recovery programs for survivors that include continued medical care and help with exercise, nutrition, counseling, and advocacy services. Amy J. Neil, M.S., M.A.P. u
For Further Information Feuerstein, Michael, and Patricia Findley. The Cancer Survivor’s Guide: The Essential Handbook to Life After Cancer. New York: Marlowe, 2006. Hunter, Brenda. Staying Alive: Life-Changing Strategies for Surviving Cancer. Colorado Springs, Colo.: WaterBrook Press, 2004. Levine, Margie. Surviving Cancer: One Woman’s Story 1144
Salem Health: Cancer and Her Inspiring Program for Anyone Facing a Cancer Diagnosis. New York: Broadway Books, 2001. Nessim, Susan. Can Survive: Reclaiming Your Life After Cancer. Boston: Houghton Mifflin, 2000. u
Other Resources
American Cancer Society Cancer Survivors Network http://www.acscsn.org Candlelighters Childhood Cancer Foundation http://www.candlelighters.org Lance Armstrong Foundation http://www.livestrong.org National Coalition for Cancer Survivorship http://www.canceradvocacy.org See also Advance directives; Anxiety; Depression; Donot-resuscitate (DNR) order; End-of-life care; Financial issues; Insurance; Living will; Living with cancer; Psychosocial aspects of cancer; Psycho-oncology; Psychosocial aspects of cancers; Relationships; Self-image and body image; Survival rates; Transitional care.
u Symptoms and cancer Category: Diseases, symptoms, and conditions Definition: Symptoms are the outward signs—such as swellings, lumps, pain, shortness of breath, rashes, and any number of other unusual conditions—that a person may experience as a result of an underlying disease or other pathology. With regard to cancer, symptoms may be warning signs for undiagnosed, site-specific cancers. Their early or timely recognition is key to treatment and relief of symptoms. As a result of rapid scientific advances, it has become increasingly important that symptoms be managed comprehensively as a vital component of the cancer treatment plan. The notion that quality of life and its maintenance through aggressive symptom management efforts are as important, as maintenance and length of survival is of considerable interest as science and technology can keep individuals alive for lengthening periods albeit often with marginal quality of life. It is also important to differentiate discrete symptoms through refined and evolving assessment strategies, so that treatments aimed at promoting quality of life may be symptom specific. Symptoms as warning signs: For symptoms to function as warning signs of undiagnosed, site-specific cancers,
Salem Health: Cancer well-documented, established symptoms and symptom clusters or profiles must be well publicized, using a range of methods that are understandable and palatable to an increasingly diverse American population. Public information should make it easy for people to receive timely medical attention, consisting of a diagnostic workup, definitive medical or surgical recommendations, and timely intervention. Public education regarding signs and symptoms of cancer is vital to promote early diagnosis, not only to promote cure and survival but also to minimize disability and health care costs. Several reliable Internet sites deliver information regarding early symptoms and warning signs for a range of cancer diagnoses. The fact that this information can be accessed in a private, confidential manner may facilitate action among individuals who would otherwise be hesitant to seek medical advice in a timely manner. Nevertheless, attention needs to be paid to recognizing and addressing common psychological issues such as depression, fear, and anxiety that prevent some people from seeking medical attention even when they are aware of symptoms. Cancer symptoms: The following symptoms may be early warning signs for site-specific cancers and, if experienced, are reason to seek medical attention for a definitive diagnosis: • Bladder cancer: Blood in the urine, pain or burning upon urination, frequent urination, or cloudy urine • Bone cancer: Pain in the bone or swelling around the affected site, fractures in bones, weakness, fatigue, weight loss, repeated infections, nausea, vomiting, constipation, problems with urination, weakness or numbness in the legs, bumps and bruises that persist • Brain cancer: Dizziness; drowsiness; abnormal eye movements or changes in vision; weakness or loss of feeling in arms or legs or difficulties in walking; fits or convulsions; changes in personality, memory, or speech; headaches that tend to be worse in the morning and ease during the day, which may be accompanied by nausea or vomiting • Breast cancer: A lump or thickening of the breast, discharge from the nipple, change in the skin of the breast, a feeling of heat, enlarged lymph nodes under the arm • Colorectal cancer: Rectal bleeding (red blood in stools or black stools), abdominal cramps, constipation alternating with diarrhea, weight loss, loss of appetite, weakness, pallid complexion • Kidney cancer: Blood in urine; dull ache or pain in the back or side; lump in kidney area, sometimes accompanied by high blood pressure or abnormality in red blood cell count
Symptoms and cancer
•
Leukemia: Weakness; paleness; fever and flulike symptoms; bruising and prolonged bleeding; enlarged lymph nodes, spleen, or liver; pain in bones and joints; frequent infections; weight loss; night sweats • Lung cancer: Wheezing; persistent cough for months; blood-streaked sputum; persistent ache in chest; congestion in lungs; enlarged lymph nodes in the neck • Melanoma: Change in mole or other bump on the skin, including bleeding or change in size, shape, color, or texture • Non-Hodgkin lymphoma: Painless swelling in the lymph nodes in the neck, underarm, or groin; persistent fever; feeling of fatigue; unexplained weight loss; itchy skin and rashes; small lumps in skin; bone pain; swelling in the abdomen; liver or spleen enlargement • Oral cancer: A lump in the mouth; ulceration of the lip, tongue or inside of the mouth that does not heal within a couple of weeks; dentures that no longer fit well; oral pain or bleeding; foul breath; loose teeth; changes in speech • Ovarian cancer: Abdominal swelling; in rare cases, abnormal vaginal bleeding; digestive discomfort • Pancreatic cancer: Upper abdominal pain, unexplained weight loss, pain near the center of the back, intolerance of fatty foods, yellowing of the skin, abdominal masses, enlargement of liver and spleen • Prostate cancer: Urination difficulties due to blockage of the urethra; bladder retains urine, creating frequent feelings of urgency to urinate, especially at night; bladder not emptying completely; burning or painful urination; bloody urine; tenderness over the bladder; dull ache in the pelvis or back • Stomach cancer: Indigestion or heartburn, discomfort or pain in the abdomen, nausea and vomiting, diarrhea or constipation, bloating after meals, appetite loss, weakness or fatigue, vomiting blood, or blood in the stool • Uterine cancer: Abnormal vaginal bleeding, a watery bloody discharge in postmenopausal women, painful urination, pain during intercourse, pain in pelvic area Symptoms after cancer diagnosis: Identification and treatment of distressing symptoms that occur as a result of cancer or its treatment are paramount so that quality of life and comfort are optimized for the cancer patient. As people live longer following cancer diagnosis, symptom management is an increasingly important aspect of treatment. However, many factors interfere with prompt recognition and treatment of these symptoms. The period between diagnosis and the start of treatment is marked by medical evaluation, the development of new relationships with unfamiliar medical personnel, and the need to integrate a barrage of information that, at best, is 1145
Symptoms and cancer frightening and confusing. Patients and families experience heightened responsibility, concern, and isolation during this period. They are particularly anxious and fearful when receiving initial information regarding diagnosis and treatment. Consequently, care should be taken by professionals to repeat information over several sessions and to inquire about patients’ and families’ understanding of facts and options. Early assessment by clinicians can help identify individuals at risk for medical or psychological adjustment problems and particularly those who are in the greatest need of ongoing psychosocial support and symptom management. Patients who have ongoing involvement with medical personnel and repeatedly receive accurate and consistent information about what to expect will have less uncertainty and be less likely to develop maladaptive coping strategies based on erroneous beliefs. Although many studies document the devastating emotional impact of a cancer diagnosis, many individuals cope effectively, experience minimal distress, and have a high quality of life throughout most aspects of the cancer experience. Effective coping strategies, such as taking action and finding favorable aspects of the situation, have been associated with positive treatment experiences. Contrary to the beliefs of many clinicians, denial has been found to assist patients to cope effectively, unless sustained and used to the point that it interferes with obtaining recommended treatment. Health care providers play a vital role in monitoring physical comfort and psychosocial adjustment and managing problems as they arise. As cancer progresses, patients often report an upsetting scenario that includes frequent pain, disability, increased dependence on others, and diminished functional ability, which often results in psychological symptoms. Investigators studying quality of life in cancer patients have demonstrated a clear relationship between the presence of discomfort and a patient’s perception of quality of life. As uncomfortable symptoms increase, perceived quality of life diminishes. Therefore, an important goal in the psychosocial treatment of patients with advanced cancer focuses on symptom control. Patients who are diagnosed with late-stage disease or have aggressive illnesses with no hope for cure are often the most vulnerable to psychological distress, particularly anxiety, depression, and family problems, and physical discomfort, including pain, fatigue, shortness of breath, and confusion. When physicians cannot offer patients hope for cure, helping them maintain comfort and control promotes adaptation and improved quality of life. One of the highest levels of psychological distress, with an increase in depression, anxiety, and thoughts of suicide, oc1146
Salem Health: Cancer curs in patients who have a recurrence of their cancer, which is often associated with a negative outcome or advanced disease. The patient’s culture has a significant influence on perception of distressing symptoms such as pain. Some researchers have found that the best predictors of pain intensity are ethnic affiliation and locus of control style. For example, an individual’s stoic attitude, which serves to minimize or negate discomfort, may be related to a cultural value learned and reinforced through years of family experiences. Similarly, an individual’s highly emotional response to routine events may become exaggerated during the terminal phase of illness and not necessarily signal maladjustment but rather a cultural norm. Knowledge of an individual’s response to illness and symptom expression is enhanced through awareness of the person’s family traditions and culture. Understanding a patient’s cultural, religious, ethnic, and socioeconomic underpinnings is key to understanding that person’s beliefs, attitudes, practices, and behaviors related to illness and death. Cultural patterns play a significant role in determining how patients cope with terminal stages of cancer when symptoms such as delirium, depression, thoughts of suicide, and severe anxiety are common. When severe, these symptoms require aggressive treatment using up-todate pharmacological and psychotherapeutic treatment strategies. In spite of the seemingly overwhelming nature of physical discomfort and psychosocial stress associated with cancer, most patients can be relatively symptom free and cope effectively throughout the experience. Differentiating psychiatric complications from adaptive coping and differentiating normal from pathological emotional distress can be challenging. For example, anxiety and depression are normal responses to traumatic events such as a cancer diagnosis or progression of a life-threatening illness and are typical and expected at transitions throughout the cancer experience. Clinicians can distinguish between patients who need aggressive psychiatric intervention and those needing routine support and information by looking at factors such as whether the patient has a prior psychiatric history including hospitalization and has used or is using psychopharmacologic treatments, and the intensity and duration of symptoms and how much they diminish functioning. These factors can also help clinicians determine whether the patient has a lasting psychiatric disorder or transient psychological symptoms that will dissipate without specific treatment. Psychological symptoms may also emerge when physical discomfort escalates or is not well controlled and diminish following treatment of physical discomfort. Health
Salem Health: Cancer
Syndrome of inappropriate antidiuretic hormone production (SIADH)
professionals and family and friends can monitor the patient’s symptoms to determine what is normal for the patient and what indicates the need for intervention. They can also observe whether the patient’s usual patterns of coping remain effective. In general, when psychological stress worsens over time and does not respond favorably to the usual supports, aggressive psychiatric assessment and management should be instituted. Jeannie V. Pasacreta, Ph.D., A.P.R.N. u
For Further Information Groenwald, Susan L., et al. Cancer Symptom Mangement. Boston: Jones and Bartlett, 1996. Kelvin, Joanne Frankel, and Leslie B. Tyson. One Hundred Questions and Answers About Cancer Symptoms and Cancer Side Effects. Sudbury, Mass.: Jones and Bartlett, 2005. Lyman, Gary H., and Jeffrey Crawford, eds. Cancer Supportive Care: Advances in Therapeutic Strategies. New York: Informa Healthcare USA, 2008. New England Medical Center EPC. Management of Cancer Symptoms: Pain, Depression, and Fatigue. Rockville, Md.: U.S. Department of Health and Human Services, Public Health Service, Agency for Healthcare Research and Quality, 2002. u
Other Resources
American Cancer Society http://www.cancer.org Cancer.Net http://www.cancer.net/portal/site/patient CureSearch http://www.curesearch.org Lance Armstrong Foundation http://www.livestrong.org National Cancer Institute http://www.cancer.gov Oncology Tools http://www.fda.gov/cder/cancer See also Bone pain; Coughing; Depression; Diarrhea; Fatigue; Fever; Infection and sepsis; Itching; Lumps; Moles; Nausea and vomiting; Palpation; Personality and cancer; Psychosocial aspects of cancer; Screening for cancer; Weight loss.
u Syndrome of inappropriate
antidiuretic hormone production (SIADH) Category: Diseases, symptoms, and conditions Also known as: Hyponatremia Related conditions: Dehydration, water intoxication Definition: Syndrome of inappropriate antidiuretic hormone (SIADH) was first described by Frederic C. Bartter and William B. Schwartz in 1957 when their patient, diagnosed with oat cell carcinoma, was experiencing symptoms related to a low sodium level. Sodium is an electrolyte that is important for the function of many cells within the body. SIADH occurs when there is an excessive release of antidiuretic hormones (ADH, or vasopressin), which causes an increase in fluid retention by the kidneys. Risk factors: Patients who have small-cell lung cancer are at high risk for developing SIADH. Other cancers that may place the patient at high risk for developing this syndrome are pancreatic cancer, colon adenocarcinoma, olfactory neuroblastoma, lymphoma, and leukemia. Chemotherapy drugs, pain medications, tricyclic antidepressants, general anesthesia, and other drugs used to treat cancer side effects can also cause SIADH. Etiology and the disease process: Antidiuretic hormone (ADH) is normally produced in the hypothalamus and stored in the posterior pituitary, which are both located in the brain. ADH is released by the pituitary gland but also can be released from a few cancer tumors. It works with the kidneys to regulate the amount of fluid that either remains in the body or is released in the urine. An increase in ADH can cause the kidney to retain fluid, which in turn causes fluid volume overload and dilutes the sodium as well as other electrolytes in the body. Incidence: SIADH is a rare condition that is the most common cause of hyponatremia. Approximately 1 in 100,000 people are diagnosed with SIADH every year. Symptoms: Symptoms are related more to the sudden changes in the sodium level than to the sodium level itself. Early signs and symptoms of SIADH include weakness and lethargy, confusion, irritability, altered mental status, nausea, vomiting, increased thirst, abdominal cramping, decreased urine output, and weight gain. Unresponsiveness, muscle cramping, and seizures are symptoms of progressively low sodium levels. Normal blood sodium levels are 135 to 145 milliequivalents of solute per liter of solvent 1147
Syndrome of inappropriate antidiuretic hormone production (SIADH)
Asymptomatic cases are treated by treating the underlying cause. Symptomatic patients will be initially treated by being placed on fluid restrictions that allow for one half to one liter of fluid every twenty-four hours. Patients may also be placed on a high-protein, high-salt diet. Loop diuretics, such as furosemide (Lasix), may be given to help the body excrete more urine while retaining the sodium. Demeclocycline, a form of tetracycline antibiotic, may also be used to increase urine output. Demeclocycline is a pill that stops the kidneys from responding to the increased ADH, allowing the body to excrete large amounts of urine. For more severe cases, hypertonic saline (3 percent saline) is given intravenously to increase sodium levels within the serum. Furosemide can also be given with the hypertonic saline to help balance the fluid levels.
Common Causes of SIADH Cancers • small-cell lung cancer • bladder cancer • prostate cancer • ovarian cancer • lymphoma • Hodgkin disease • oral cancers • pancreatic cancer • exocrine cancer • stomach cancer • laryngeal cancer • nasopharyngeal cancer • thymoma • brain cancer
• • •
central nervous system cancers breast cancer melanoma
Chemotherapy drugs cisplatin cyclophosphamide vincristine
• • •
Drugs to Treat Side Effects of Cancer • levamisole • morphine • amitriptyline • carbamazepine
(mEq/l). Symptoms usually start occurring when the sodium level in the blood decreases to 120 to 125 mEq/l. Screening and diagnosis: Initial blood tests should be taken to evaluate sodium levels. The blood test of a patient with SIADH will commonly reveal low serum (blood) sodium levels. Urine levels will show an increase in sodium levels and an increase in osmolarity. Patients will typically show no edema or volume depletion (dehydration). The patient will have normal renal, adrenal, and cardiac function. The decrease in sodium levels can be a slow gradual process or may have rapid onset. Additional blood tests include a complete blood count, electrolytes, urea, creatinine, glucose, and serum (blood) osmolarity. Urine can also be tested for electrolytes. Tests that may also be considered are thyroid-stimulating hormone (TSH) levels, cortisol level, and liver function tests (LFTs). A chest X ray and a computed tomography (CT) scan of the head may also be completed to assist with diagnosis. Treatment and therapy: SIADH will need to be corrected slowly. Sodium levels that rise too quickly can cause central pontine myelinolysis (CPM), a type of nerve damage caused by the destruction of the layer covering the nerve cells in the brain stem. Symptoms of CPM are mental status changes, weak muscles, and cranial nerve abnormalities. There is no known cure. Patients with SIADH will be assessed by medical personnel to evaluate for any signs of swelling, increase in thirst, intake and output, urine concentration, daily weights, and what they are currently consuming. 1148
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Prognosis, prevention, and outcomes: Outcomes for SIADH are related to the underlying disease. Prompt treatment of the underlying condition may improve the outcomes for the patient. The more rapid the increase of the sodium levels, the higher the risk of mortality. Patients may have to limit fluid intake for an extended period to ensure that the SIADH does not return if the underlying condition does not improve. Katrina Green, R.N., B.S.N., O.C.N. u
For Further Information Itano, J. K., and K. N. Toaka. Core Curriculum for Oncology Nursing. 4th ed. Philadelphia: Elsevier/Saunders, 2005. Johnson, B. L., and J. Gross. Handbook of Oncology Nursing. 3d ed. Sudbury, Mass.: Jones and Bartlett, 1998. Lenhard, R. E., R. T. Osteen, and T. Gansler. The American Cancer Society’s Clinical Oncology. Atlanta: American Cancer Society, 2001. Otto, S. E. Oncology Nursing. 4th ed. St. Louis: Elsevier, 2001. Yarbro, C. H., M. H. Frogge, and M. Goodman. Cancer Nursing: Principles and Practice. 6th ed. Sudbury, Mass.: Jones and Bartlett, 2005. _______. Cancer Symptom Management. 3d ed. Sudbury, Mass.: Jones and Bartlett, 2005.
u
Other Resources
American Cancer Society http://www.cancer.org
Salem Health: Cancer National Cancer Institute http://www.cancer.gov See also Chemotherapy; Colorectal cancer; Craniotomy; Leukemias; Lung cancers; Lymphomas; Pain management medications; Pancreatic cancers; Paraneoplastic syndromes.
u Synovial sarcomas Category: Diseases, symptoms, and conditions Related conditions: Soft-tissue sarcomas Definition: Soft-tissue sarcomas are cancers that begin in fat, cartilage, blood vessels, and muscles. A synovial sarcoma is a distinct type of soft-tissue tumor that arises from tissues that are associated with a joint. Almost all synovial sarcomas are found within 2 inches (5 centimeters, or cm) of a joint. The tumor can be composed of all epithelial cells, all spindle cells, or a mix of the two cell types. These cells form distinct pink, fleshy masses. Risk factors: Synovial sarcomas appear to develop because of a genetic mutation. About 90 percent of these tumors show a specific genetic defect that is different from that found in all other sarcomas. This defect involves a switch in a small amount of material on chromosome 18 and the X chromosome. As a result, an incorrect protein is formed. Etiology and the disease process: Exactly why the genetic mutation occurs or how the resulting protein causes cells to become cancerous is not known. About half of synovial sarcomas develop in the legs. The knee joint is the most common tumor location, followed by the ankle and the foot. Primary synovial sarcomas can also develop in arm, wrist, and hand joints and less frequently in the joints of the trunk, head, and neck. Only rarely are primary tumors found in the lungs or abdomen. Synovial sarcomas tend to grow slowly. Often these tumors exist for a long time as hard nodules and then begin to grow suddenly. Sometimes calcium deposits develop in the tumors. Tumors with calcium tend to grow more slowly than those without calcium. Tumors may invade nearby tissues, and about half metastasize to distant sites. Incidence: Synovial sarcomas account for 8 to 10 percent of all soft-tissue sarcomas and are the fourth most common type of soft-tissue sarcoma. In absolute terms, however, they are quite rare, with only about 800 new cases of
Synovial sarcomas synovial sarcoma diagnosed each year in the United States. Synovial sarcomas are about 1.5 times more common in men than women. They can develop in people of any age, but the median age of diagnosis is about thirty years, with fewer than 30 percent of new cases reported in people younger than twenty. Symptoms: Most often, the first symptom a person with a synovial sarcoma notices is a swelling that may or may not be painful. Since synovial sarcomas grow slowly, the person may have a hard mass for quite a while, especially if it is not painful, before consulting a doctor. Other symptoms are specific to the location of the tumor. For example, a tumor near a joint may cause pain similar to bursitis or arthritis, or a tumor pressing on a nerve may cause the person to feel numbness and tingling in the surrounding area. Screening and diagnosis: There are no screening tests specific to synovial sarcoma; however, people who have unexplained swellings or lumps anywhere in the body should consult a physician immediately. Often diagnosis is delayed because these swellings seem nonthreatening and are not painful, so that by the time they are diagnosed, they have already spread to the lymph nodes or beyond. Exploration of the tumor begins with a magnetic resonance imaging (MRI) scan. However, a definitive diagnosis can be made only by a biopsy (tissue sample) of the tumor. Depending on the location of the tumor, the biopsy process may be complex (for example, a tumor of the hand). The biopsied tissue is examined under the microscope, where a distinctive pattern of cells identifies it as a synovial sarcoma. The tissue also may be tested for the specific chromosomal abnormalities associated with this cancer. Staging is done using MRI and computed tomography (CT) scans to determine if the sarcoma has metastasized to distant sites. Treatment and therapy: The treatment of choice is always surgery regardless of the stage of the tumor. These tumors tend to spread along the tissues surrounding joints, and it may be necessary to amputate the entire limb to remove all traces of the sarcoma cells. Surgery is supplemented by radiation therapy before and after tumor removal. The use of chemotherapy in addition to surgery and radiation therapy is controversial, with some studies reporting improved survival rates and others reporting no differences in survival when compared with radiation therapy alone. Clinical trials of biological therapies that use man-made antibodies to target sarcoma cells are under way. 1149
Synovial sarcomas Prognosis, prevention, and outcomes: There is no known way to prevent synovial sarcoma. Outcomes are better with early diagnosis, when tumors are less than 2 inches (5 cm) in diameter, when tumors contain calcium deposits, and when they are located farthest away from the trunk. Recurrence is common, usually within two years of surgery. Amputation of a limb is often necessary. The fiveyear survival rate is about 50 percent. Martiscia Davidson, A.M. u For Further Information Pappo, Alberto S., ed. Pediatric Bone and Soft-Tissue Sarcomas. New York: Springer, 2005. Thompson, Lester D. R., and Gretchen S. Folk. “Synovial Sarcoma (Disease Overview).” Ear, Nose, and Throat Journal 85 (2006): 418-419.
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Salem Health: Cancer Verweij, J., and Herbert M. Pinedo. Targeting Treatment of Soft-Tissue Sarcomas. Boston: Kluwer Academic, 2004. u
Other Resources
National Cancer Institute Synovial Sarcoma: Questions and Answers http://www.cancer.gov/templates/doc.aspx?viewid= 5B6A9BCC-80A4-4FBF-B7C2-7E07D5BD4798 Sarcoma Foundation of America http://www.curesarcoma.org See also Amputation; Fibrosarcomas, soft-tissue; Limb salvage; Sarcomas, soft-tissue.
Salem Health: Cancer
u Taste alteration Category: Diseases, symptoms, and conditions Also known as: Taste change, taste dysfunction, dysgeusia, hypogeusia, ageusia Related conditions: Anorexia (loss of appetite), xerostomia (dry mouth), thrush (a fungal disease of the mouth), zinc deficiency, increased levels of calcium Definition: As the phrase suggests, taste alteration is a change in the way people perceive tastes, or flavors. People can recognize four main tastes: sweet, sour, salty, and bitter. Any one or all four taste sensations can be affected. Taste alteration is a symptom or side effect, not a disease. Infection in the mouth, cancer, and certain cancer treatments can change a person’s sense of taste. Taste alteration may emerge as one of three medically recognized abnormalities: dysgeusia (changes in how foods normally taste), hypogeusia (a decreased ability to taste foods), or ageusia (the complete loss of the ability to taste foods). In addition, many cancer patients complain of a medicinelike or metallic taste in the mouth that affects their sense of taste. Risk factors: Risk factors include having cancer of the mouth, tongue, lips, or throat; receiving radiation treatments to the head or neck; receiving chemotherapy involving certain cancer-fighting drugs; and undergoing surgery to the head or neck. Etiology and the disease process: Although the exact causes of taste alteration in cancer patients are not known, doctors suspect three principal sources: the disease itself, radiation treatments, and certain cancer-fighting drugs. Many cancerous tumors, found anywhere in the body, release substances that change the taste of foods or even take away people’s desire to eat. Radiation treatments, especially to the head or neck, can damage taste buds, which changes the way food tastes to a patient. For instance, sour or bitter foods may taste especially strong, or sweet foods may not taste as sweet as they once did. Radiation can also damage the salivary glands, causing them to produce less saliva, which results in a dry mouth. Saliva contributes to the sense of taste by mixing with food particles and carrying them to the tongue. This process stimulates the taste receptors on the tongue, allowing people to experience and distinguish among the four tastes. Taste alteration from radiation may not show up until several weeks after treatment begins. Chemotherapy seems to change the sense of taste in some patients. Researchers believe that some cancer-
Taste alteration fighting drugs affect certain taste cells on the tongue and cause an imbalance of taste, changing the way things normally taste. These changes may result from damage to the cells in the mouth from chemotherapy or by the spread of the drug to the tissues of the mouth. Taste alteration in itself is normally not a serious problem. Nevertheless, it can lead to problems when patients change their eating habits. Each patient’s sense of taste changes differently. Some patients with taste alteration may avoid certain nutritious foods because their taste has changed; others may lose their appetite altogether. Taste alteration is one of the leading causes of malnutrition in cancer patients. Incidence: Although taste alteration appears to be common among cancer patients receiving radiation treatment or chemotherapy, few studies have confirmed the degree of prevalence. Research may be lacking because the condition usually does not last long and often takes place in the early stages of cancer. When this condition arises in patients in the later stages of cancer, treatment and research focus more on other aspects of care, such as pain relief. Symptoms: Taste alteration itself is a symptom or a side effect. It can, however, lead to complications in a cancer patient’s nutritional status, which causes such symptoms as mouth sores, anorexia, nausea and vomiting, diarrhea, constipation, lack of energy, and weight gain or loss. Screening and diagnosis: Nutritional screening and assessments are done for nearly all cancer patients before starting radiation therapy or chemotherapy. Screenings identify patients who may be undernourished. Assessments establish the nutritional status of patients and determine which patients need nutritional therapy. Patients who are well nourished are better able to tolerate aggressive cancer treatments.
Chemotherapy Drugs That Can Cause Taste Alteration
• • • • • • •
carboplatin cisplatin cyclophosphamide dacarbazine dactinomycin doxorubicin fluorouracil
• • • • • •
levamisole mechlorethamine methotrexate nitrogen mustard paclitraxel vincristine
Source: Cleveland Clinic Cancer Center
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Teratocarcinomas Treatment and therapy: There is no treatment for taste alteration. Results of some studies suggest that increased zinc may be of some benefit. Care management focuses on nutrition therapy to help cancer patients avoid malnutrition, tolerate treatment, maintain their energy and strength, fight infection, heal and recover, and improve their quality of life. In addition, dietitians suggest the following for patients who may have lost their desire to eat: • Eat with plastic utensils. • Use sweet marinades or strong sauces with foods. • Eat chilled rather than hot foods. • Use extra seasonings, spices, and herbs. • Drink citrus juices, especially lemon, to stimulate saliva. • Keep the mouth clean with frequent tooth brushing and rinsing. Prognosis, prevention, and outcomes: Fortunately, for many cancer patients, taste alteration lasts only a short time and is hardly ever permanent. Normal taste returns within a few weeks up to a few months after treatment ends. In terminal patients, however, taste alteration can cause or exacerbate existing anorexia and cachexia. Wendell Anderson, B.A. u For Further Information Bloch, A. Nutrition Management of the Cancer Patient. Sudbury, Mass.: Jones and Bartlett, 1990. Keane, M., and D. Chace. What to Eat If You Have Cancer: A Guide to Adding Nutritional Therapy to Your Treatment Plan. New York: McGraw-Hill, 1996. Whittington, E. “Food for Thought: A Waste of Taste.” CURE (Fall, 2006). u
Other Resources
American Cancer Society Changes in Taste and Smell http://www.cancer.org/docroot/MBC/content/ MBC_6_2X_When_Things_Arent_Tasting_Right .asp?sitearea=MBC
Salem Health: Cancer
u Teratocarcinomas Category: Diseases, symptoms, and conditions Also known as: Teratomas Related conditions: Germ-cell tumors, nonseminomatous germ-cell tumors (NSGCTs), choriocarcinomas, yolk sac tumors, seminomas, embryonal cell carcinomas, dermoid cysts Definition: Teratocarcinomas are malignant testicular cancers whose cells are derived from primordial germ cells (spermatozoa precursor cells). The term “teratoma” is sometimes used to refer to a benign form seen in prepubescent boys and may also refer to a benign cancer in the ovary (dermoid cyst), in which cells are derived from all three primitive embryonic tissue layers. Teratocarcinomas contain embryonic stem cells in addition to these cells. Risk factors: One of the risk factors for the development of a teratocarcinoma is undescended testes (cryptorchidism) during infancy. Anomalies in testicular development such as that found in Klinefelter syndrome may increase the risk of malignancy. Family history, age of descent or correction, location, single or bilateral undescended testes, premature birth, and previous history of testicular cancer have also been implicated. Etiology and the disease process: The exact mechanisms by which teratocarcinomas develop remain unknown. Studies suggest that primordial spermatozoa cells (gonocytes) in the seminiferous tubules of the testes retain their embryonic characteristics of being able to differentiate into different mature tissues as well as divide uncontrollably when testicular development is interrupted. Incidence: A history of cryptorchidism increases the risk of testicular malignancy by a factor of 1.6 to 17 times irrespective of prior removal, where carcinoma can still develop in the remaining testis. The incidence of teratocarcinoma in particular is estimated at 7 percent of testicular cancers in male adults and 40 percent in prepubescent boys, although these figures may be grossly underestimated.
National Cancer Institute Overview of Nutrition in Cancer Care http://www.cancer.gov/cancertopics/pdq/ supportivecare/nutrition/patient
Symptoms: Symptoms may include an often painless, palpable mass within the scrotal area. The mass may also be firm and, at times, fixed. Discovery of the mass may be incidental, with no other signs of disease present.
See also Anorexia; Appetite loss; Cachexia; Calcium; Chemotherapy; Dry mouth; Gastrointestinal complications of cancer treatment; Nausea and vomiting; Nutrition and cancer treatment; Salivary gland cancer.
Screening and diagnosis: Diagnosis is primarily clinical. If twisting of the testicle or its blood supply is suspected (causing discoloration and pain), Doppler ultrasound is done to assess blood flow as well as visualize the mass.
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Teratomas
Abdominal computed tomography (CT) or magnetic resonance imaging (MRI) is carried out to look for spread outside the scrotum.
nervous system); and the mesoderm (which produces the heart, kidney, ovaries, testes, and the connective tissues, including bone, muscles, and blood).
Treatment and therapy: Surgical resection of the entire tumor; chemotherapy with cisplatin, bleomycin, and vinblastine; and irradiation are the treatments of choice.
Incidence: Sacroccocygeal teratoma (found at the base of the spine in fetuses) affects 1 in 40,000 births, with 80 percent occurring in girls. In adults, teratomas occur in the neck, brain, ovaries, testes, mediastinum (chest), and retroperitoneum (back of the abdominal cavity). Teratomas of the chest are most commonly diagnosed in young men in their twenties.
Prognosis, prevention, and outcomes: Prognosis is generally excellent with optimal treatment, approaching 90 percent. However, infertility may occur and should be understood by the patient as a possible side effect of therapy. Aldo C. Dumlao, M.D. See also Benign tumors; Carcinomas; Childhood cancers; Choriocarcinomas; Computed tomography (CT) scan; Cryptorchidism; Embryonal cell cancer; Family history and risk assessment; Germ-cell tumors; Infertility and cancer; Magnetic resonance imaging (MRI); Teratomas; Testicular cancer; Yolk sac carcinomas.
u Teratomas Category: Diseases, symptoms, and conditions Also known as: Germ-cell tumors Related conditions: Teratocarcinomas, seminomas Definition: Teratomas are tumors containing cells derived from more than one of the three embryonic germ layers. Risk factors: Risk factors are unclear. In young men, teratomas in the chest may be associated with other cancers, including acute myelogenous leukemia and small-cell undifferentiated carcinoma. Metastasis risk increases with a tumor stage greater than II and vascular invasion. Etiology and the disease process: Teratomas can contain structures such as teeth, hair, and bone. They arise from abnormal development of pluripotent cells (cells that have not assumed their final form and function) or germ cells (cells that produce the sperm or eggs) and contain cells from more than one of the three embryonic germ layers. The early embryo has three germ layers: the endoderm (which produces the lining of the digestive tube and its associated organs); the ectoderm (which produces the cells of the epidermis and
Symptoms: Symptoms of teratoma vary with the location of the tumor. Teratomas of the brain in children can produce vision problems, developmental delays, headaches, nausea, and vomiting. Teratomas of the chest may be associated with difficulty breathing, chest pain, cough, and fatigue upon exercise. Ovarian teratomas are associated with abdominal pain. Screening and diagnosis: Sacroccocygeal teratomas are diagnosed by fetal ultrasound. Other teratomas are diagnosed by physical exam and imaging such as a computed tomography (CT) scan. Teratomas are staged as 0, mature; I, immature; II, immature, possibly malignant; and III, malignant, or teratoma with malignant transformation. Solid teratomas are composed mostly of tissue, and cystic teratomas have pockets of fluid. Mixed teratomas are composed of cysts and tissue. Nonmalignant teratomas can still be highly aggressive and grow quickly. Treatment and therapy: Sacrococcygeal teratoma is treated surgically. Stage I teratoma is usually treated with a combination of surgery and radiation therapy. Teratoma
A dermoid cyst (a cystic teratoma that contains developmentally mature skin) in an eye. (Biophoto Associates/Photo Researchers, Inc.)
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Testicular cancer with malignant transformation is treated surgically, followed by radiation, chemotherapy, or both. Prognosis, prevention, and outcomes: With sacrococcocygeal teratoma, prognosis is determined by the size and histology of the tumor. These tumors can result in fatalities from secondary effects. Some 20 to 30 percent of adult metastatic teratomas are cured with chemotherapy. Michele Arduengo, Ph.D., ELS See also Carcinomas; Childhood cancers; Choriocarcinomas; Cryptorchidism; Embryonal cell cancer; Family history and risk assessment; Germ-cell tumors; Klinefelter syndrome and cancer; Mediastinal tumors; Teratocarcinomas; Testicular cancer; Yolk sac carcinomas.
u Testicular cancer Category: Diseases, symptoms, and conditions Also known as: Germ-cell tumors, testicular tumors Related conditions: Testicular tumors, cryptorchidism, germ-cell tumors, decreased fertility Definition: Testicular cancer is the development of tumors in the testicles, or male sex glands. Risk factors: The primary risk factor associated with testicular cancer is a history of an undescended testicle (cryptorchidism). Some 5 to 10 percent of patients with this abnormality, which is resolved with surgery, may develop testicular cancer. Research has shown that men who have any type of abnormal development of the testicles are at an increased risk of developing testicular cancer. Additionally, a hypothesized link between some pollutants and testicular cancer has been noted, because of an increase in the diagnoses linked with industrial growth and waste. Although research has not confirmed a link between a hormone taken by mothers during pregnancy, there is an abnormally high rate of testicular cancer in men exposed to diethylstilbestrol (DES) during fetal development. Etiology and the disease process: In men under the age of sixty, 95 percent of testicular tumors originate in the germ cells, or embryonic cells that develop into sperm cells. These tumors can be divided into seminomas or nonseminomas. Seminomas are responsible for 40 percent of all testicular cancer and are slow to grow and usually remain in the testicle. These types of tumors are very responsive to both radiation therapy and chemotherapy. Nonseminomas are cancers that occur in combination with other types of cancers and arise from more mature germ cells. These can1154
Salem Health: Cancer cers are more aggressive in growth and respond well to chemotherapy. Rarely tumors leading to testicular cancer include Leydig and Sertoli cell tumors, leiomyosarcoma, rhabdomyosarcoma, and mesothelioma. Incidence: Approximately 1 in 100,000 men develop testicular cancer each year, and it is the most common malignancy in men between the ages of fifteen and thirtyfive. Whites are more likely to be diagnosed than are Hispanics, and the incidence in African Americans has doubled since the 1980’s. Male infants and men over sixty have also been diagnosed with the disease. Symptoms: Symptoms of testicular cancer most often include a lump in one testis or a hardening of the testis and pain or tenderness in the testicles. Some 50 percent of men diagnosed with testicular cancer complain of swelling in the testicles or enlarged testicles. Other symptoms include an increase in fluid in the scrotum, loss of sexual activity, a feeling of heaviness in the scrotum, a dull ache in the groin or lower abdomen, shrinking of the testicle, and enlargement or tenderness of the breasts. Screening and diagnosis: The most effective screening mechanism for testicular cancer is the testicular selfexam. It involves a manual exam of the testicles to feel for any suspicious lumps and can be performed monthly at home. If testicular cancer is suspected, the physician conducts a medical history and physical exam. In addition to carefully examining the scrotum, the physician will order an ultrasound, chest X ray, and blood and urine tests.
Age at Diagnosis for Testicular Cancer, 2001-2005 Age Group
Percentage Diagnosed
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
5.8 46.3 29.2 13.3 3.3 1.2 0.6 0.2
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of diagnosis from 2001 to 2005 was thirty-four, with an age-adjusted incidence rate of 5.4 per 100,000 men per year.
Salem Health: Cancer
Testicular cancer
A procedure called a serum marker test may be performed to measure the amounts of certain substances released into the blood by organs, tissues, or tumor cells in the blood. Certain substances, called tumor markers, are linked to specific types of cancer when found in increased levels in the blood. Three tumor markers are used in staging testicular cancer: alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), and lactate dehydrogenase (LDH) if ultrasound reveals a solid mass in the testicle. It is important to note that nearly one-third of all patients diagnosed with testicular cancer are misdiagnosed the first time because testicular cancer is so rare. If there is a lump or mass on A malignant tumor in a sliced open testicle. (CNRI/Photo Researchers, Inc.) the testicle, it is very important to rule out testicular cancer early on. This intion, and most men will receive this therapy for their lymph volves obtaining a second opinion if the patient is not ofnodes following surgery. Radiation is ineffective with fered an ultrasound at the first discovery of a lump in the nonseminomas. testicle. Chemotherapy is a treatment whereby drugs are inA procedure called a lymphangiography may also be serted into the bloodstream (either via a vein or taken used to X-ray the lymph system. In this procedure, a dye is orally) to treat the entire body. This treatment is used if injected into the lymph vessels in the feet to observe any the physician suspects cancer cells have spread, or if the possible blockages. This test helps determine whether cancells are suspected to remain after surgery or radiation cer has spread to the lymph nodes. therapy. The only way to confirm diagnosis of testicular cancer Tumor-marker levels are measured again, after radical is by removal of the testis (orchiectomy). Biopsy of the inguinal orchiectomy and biopsy, to determine the stage of tumor is not an option because of the risk of malignancy the cancer. This helps to show if all the cancer has been of any remaining cancerous cells in the testis. removed or if more treatment is needed. Tumor-marker After removal of the suspicious testicle, the tumor is levels are also measured during follow-up as a way of staged by a pathologist. The size of the tumor is irrelevant checking if the cancer has come back. to the stage of the cancer. Stage I: Cancer is only in the testis. • Prognosis, prevention, and outcomes: Although testic• Stage II: Cancer is in the testis and lymph nodes. ular cancer is the most common malignancy in men beStage III: Cancer in the testis has spread to remote sites • tween the ages of fifteen and thirty-five, it is the cancer in the body (for example, the lungs, brain, liver, or bones). with the highest cure rate. It is almost always curable if discovered early on. It responds well to treatment even Treatment and therapy: Almost all treatment involves when it has spread to other parts of the body. surgically removing the testicle (orchiectomy). This is The most effective method of prevention is the tesnecessary because of the risk of any remaining cancer cells ticular self-exam, which can be performed monthly by becoming malignant and spreading to other parts of the men in their own homes. This simple, risk-free exam inbody. The risk of surgery is very low, and most men can volves manually examining each testicle for any suspimaintain a normal reproductive life with one testicle. cious lumps, swelling, or hardness. Sometimes surgery will include removing the lymph nodes Men diagnosed with Stage I seminoma have a survival in the abdomen if the cancer has spread. rate of 99 percent. The survival rate of men diagnosed with Radiation therapy uses high-energy rays to kill localStage I nonseminoma is about 98 percent. Cure rates for ized cancer cells. Seminomas are highly sensitive to radia1155
Testicular self-examination (TSE)
Salem Health: Cancer
Stage II tumors range above 90 percent, while cure rates for Stage III tumors can fall between 50 and 80 percent. Generally after removal of one testis, a man can lead a life of normal fertility because the remaining testis increases production of testosterone and sperm cells. In the case of men who have decreased fertility before surgery, it may be prudent to consider sperm banking (freezing sperm for later use) if he wants to have children. Fewer than 5 percent of those diagnosed will have a recurrence in the other testicle. If this occurs, the patient will need to take hormone supplements such as testosterone (produced in the testes) and will be infertile but otherwise will lead a normal life. Robert J. Amato, D.O. u For Further Information Johanson, Paula. Frequently Asked Questions About Testicular Cancer. New York: Rosen, 2008. Kurth, K. H., G. H. J. Mickisch, and Fritz H. Schroder, eds. Renal, Bladder, Prostate, and Testicular Cancer: An Update. New York: Parthenon, 2001. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Testicular Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. u
u Testicular self-examination
(TSE) Category: Procedures Definition: Testicular self-examination (TSE) is a procedure done by the patient as a screening tool for early diagnosis of any testicular disorders. The exam is performed by manually examining the scrotum and testes. Cancers diagnosed: Testicular cancer Why performed: A self-exam of the testicles is an effective way of becoming familiar with this area of the body and thus enabling the early detection of abnormalities that can lead to testicular cancer. It can be the first line of defense against cancer because testicular cancer comes with virtually no obvious symptoms or pain. Testicular cancer primarily develops in younger men, and it is the most common form of cancer developed by men between the ages of twenty and thirty-five. Therefore, monthly performance of the testicular self-exam is recommended for men over age fourteen.
Other Resources
American Cancer Society Do I Have Testicular Cancer? http://www.cancer.org/docroot/PED/content/ PED_2_3X_Do_I_Have_Testicular_Cancer.asp National Cancer Institute Testicular Cancer http://www.cancer.gov/cancertopics/types/ testicular/ The Testicular Cancer Resource Center http://tcrc.acor.org/ See also Cryptorchidism; Desmoplastic small round cell tumor (DSRCT); Diethylstilbestrol (DES); Embryonal cell cancer; Germ-cell tumors; Infertility and cancer; Orchiectomy; Organochlorines (OCs); Paraneoplastic syndromes; Penile cancer; Peutz-Jeghers syndrome (PJS); Renal pelvis tumors; Sertoli cell tumors; Spermatocytomas; Teratocarcinomas; Teratomas; Testicular self-examination (TSE); Urologic oncology; Vasectomy and cancer; Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome and cancer; Yolk sac carcinomas; Young adult cancers. 1156
Rolling and palpating the testis in a self-examination. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
Salem Health: Cancer Patient preparation: Because heat relaxes the scrotum, a TSE is best performed after a warm bath or shower. Steps of the procedure: The first step in TSE is to stand in front of a mirror and observe any possible swelling on the scrotal skin. Next, the patient should elevate one leg for better access and examine each testicle with both hands. With the index and middle fingers under the testicle and the thumbs placed on top, the testicle should be rolled gently between the thumbs and fingers. This process should not be painful, but if pain or tenderness is experienced, the patient should notify a physician. The testicles should feel firm and round, but not hard, and it is normal for one testicle to be slightly larger than the other. It is important to feel for any lumps on the testicle, which can range in size from a pea to a golf ball and are frequently very hard. If any lumps are detected, then it is critical for the patient to see a physician as soon as possible to determine if the lumps are benign (noncancerous) or malignant (cancerous). The next step in the TSE is to locate the epididymis, a soft, tubelike structure behind the testicle that collects and carries sperm. It is important to become familiar with this structure to avoid mistaking it for a lump or mass. After the procedure: No aftercare is required. Risks: There are no risks with this procedure if the patient performs the exam without inflicting pain. Results: If any abnormalities (swelling, change in color, lumps, hardness, pain) are detected during the testicular self-exam, a physician (urologist) should be consulted. Generally any suspicions can be confirmed or ruled out by the physician with an exam and/or ultrasound. Robert J. Amato, D.O. u For Further Information Johanson, Paula. Frequently Asked Questions About Testicular Cancer. New York: Rosen, 2007. Kurth, Karl H., Gerald H. J. Mickisch, and Fritz H. Schröder. Renal, Bladder, Prostate, and Testicular Cancer: An Update. New York: Parthenon, 2001. Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Testicular Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002.
See also Embryonal cell cancer; Lumps; Risks for cancer; Symptoms and cancer; Testicular cancer; Ultrasound tests.
Thermal imaging
u Thermal imaging Category: Procedures Also known as: Digital infrared thermal imaging (DITI) Definition: Thermal imaging is a procedure to measure the skin surface temperature by detecting infrared radiation emitted from the circulation. Since tumors have higher metabolic rates than normal tissues, they tend to recruit and/or create more surrounding blood vessels than normal tissues. This process provides nutrients and oxygen for tumor cell survival and increases surface temperature. Cancers diagnosed: Primarily breast cancer Why performed: Thermal imaging is an extremely sensitive test performed to detect and monitor cancers. It is an alternative to other screening options that carry the risk of radiation exposure. Additionally, multiple images over time may aid in analyzing responses to treatment. Patient preparation: Because thermal imaging measures temperature changes, patients should maintain normal circulation and body temperature prior to the imaging, including the avoidance of excessive sun exposure one week prior to testing. Also, patients should avoid hot water exposure and the use of topical analgesics two hours prior to testing, as well as nicotine, caffeine, alcohol, strenuous physical exercise, and hot or cold beverages four hours prior to testing. Medications affecting the sympathetic nervous system may need to be withheld twelve to twentyfour hours prior to the evaluation as well. Steps of the procedure: Patients will wear a hospital gown and lay on an examination table in a temperaturecontrolled room (68 degrees Fahrenheit) for approximately ten minutes to equilibrate the patient to the room temperature. Both sides of the body will be scanned with a thermal camera, also called an imaging radiometer, and the scans will be used as a thermal reference because of the body’s natural thermal symmetry. After the procedure: After thermal images are taken, no more action is required by the patient. The emitted infrared radiation will be detected and converted into a monochrome or multicolored image, known as a thermogram, and displayed on a monitor screen. Risks: The risks of this procedure are negligible, since it is noninvasive and does not use tracer dyes, radiation, or chemicals. Results: The thermal images are analyzed with the assistance of software programs, where shades or colors repre1157
Thiotepa sent thermal patterns. The test result would be normal if the sides of the body are mirror images, indicating a symmetrical thermal pattern. Areas of increased heat, however, would indicate a potentially cancerous mass as a result of increased local blood vessels emitting more infrared radiation. Because thermal imagers cannot pinpoint specific tumor sites, an abnormal result would likely be followed up with other imaging or clinical laboratory tests. Elizabeth A. Manning, Ph.D. See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Imaging tests; Risks for cancer.
u Thiotepa Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1998 Also known as: TESPA, triethylenethiophosphoramide, TSPA, thio-TEPA Related cancers: Leukemia Definition: Thiotepa is a colorless or white crystalline solid that is odorless. Exposure routes: Some cancer patients are exposed to thiotepa when it is used as a chemotherapy treatment. It is typically administered intravenously. It may be injected into muscle tissue, directly into a tumor, or through a catheter into a body cavity. Potential exposure by direct contact can occur to workers who are involved in the formulation, packaging, preparation, and administration of thiotepa for use in chemotherapy treatments. Where found: Thiotepa is found at sites where it is manufactured, packaged, and supplied. It can be found at medical facilities where it is prepared and administered during cancer treatments. During the 1970’s it was found in some polymeric flame retardants for cotton and in some insecticides. At risk: Patients who are treated with thiotepa for various cancers, including bladder cancer, ovarian cancer, breast cancer, bronchial cancer, mesotheliomas, and lymphomas, are at high risk. Workers at locations where thiotepa is manufactured, packaged, and supplied for chemotherapy treatments are at risk for contamination. Health care professionals who prepare and administer thiotepa for cancer therapy risk contamination. 1158
Salem Health: Cancer Etiology and symptoms of associated cancers: Thiotepa is an alkylating agent that slows or stops the growth of cancer cells in the human body. It can induce deoxyribonucleic acid (DNA) damage, changes in chromosome structure or number, addition or deletion of chromosomes, and cell transformation. It can also control the accumulation of fluids in body cavities that results from various cancers. Side effects of thiotepa chemotherapy include low white and red blood cell counts, decrease in platelets, hair loss, mouth sores, loss of appetite, tightness of the throat, nausea and vomiting, hives, rash, bladder irritation, and painful urination. History: Thiotepa was first used in cancer therapy treatment of lymphomas and malignant tumors in 1953. Between 1970 and 1978, a link was established between the secondary development of leukemia and exposure to thiotepa. In the Second Report on Carcinogens (RoC; 1981), it was listed as a highly probable human carcinogen. By the 1990’s, it was produced only in Japan. In the Eighth Report on Carcinogens (1998), thiotepa was listed as a known human carcinogen. To a large extent, it has been replaced by nitrogen mustard gas derivatives for chemotherapy treatments. It is still used in combination with other chemotherapy drugs for lymphomas and for bladder, ovarian, breast, lung, and brain cancers. Alvin K. Benson, Ph.D. See also Alkylating agents in chemotherapy; Antineoplastics in chemotherapy; Chemotherapy; Leukemias; Occupational exposures and cancer.
u Thoracentesis Category: Procedures Also known as: Thoracocentesis, pleural tap Definition: Thoracentesis is the removal of pleural fluid from the layers of the pleura, the membranes lining the lungs and chest cavity. The pleural fluid is removed through a needle inserted through the chest wall, between the ribs, and is analyzed in a laboratory to determine the underlying cause of the fluid accumulation. Cancers diagnosed or treated: Lung cancer, breast cancer, lymphoma, leukemia Why performed: A thoracentesis is performed as a diagnostic procedure to determine the cause of a pleural effusion, the abnormal collection of excess fluid between the layers of the pleura. Normally, only a small amount of
Salem Health: Cancer fluid is present in the pleural cavity to lubricate the pleural surfaces. This procedure is also performed as a therapeutic procedure to remove excess fluid and help reduce pressure on the lungs when an effusion is large and causing symptoms, such as shortness of breath or other breathing problems. A thoracentesis may be used as a palliative treatment to relieve symptoms of advanced cancers. Patient preparation: Tests performed before the procedure include a chest X ray to confirm the presence of the pleural effusion and identify its location, ultrasound of the chest, and blood tests, such as a complete blood count, to exclude any blood-clotting abnormalities. One week before the procedure, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician. Other anticoagulant medications may be prescribed if necessary before the procedure. There are no specific eating or drinking guidelines in preparation for a thoracentesis. Steps of the procedure: The patient usually sits upright on the edge of a chair or bed with the head and arms resting on a table. Sedating medications are not usually given for this procedure. The skin around the procedure site between the ribs and back of the chest is cleansed, and sterile drapes are placed around the area. A local anesthetic is injected into the skin to numb the area. The thoracentesis needle is inserted into the pleural space. Ultrasound guidance may be used to direct the biopsy needle into the effusion. Fluid is withdrawn through a syringe attached to the biopsy needle and collected for analysis in the laboratory. Sclerosing agents such as talc, doxycycline, bleomycin, and quinacrine may be inserted through a chest tube during thoracentesis to prevent recurring, symptomatic malignant effusions. The patient may experience mild pain or discomfort at the puncture site. The patient should not cough or breathe deeply during the procedure and must remain as still as possible to prevent injury to the lung. If the patient develops a cough or chest pain during the procedure, then the procedure should be stopped immediately. After the procedure: Pressure is applied at the site where the needle was inserted. A dressing or adhesive bandage is placed over the site to help prevent infection. Supplemental oxygen may be given to the patient. The patient’s breathing will be monitored after the procedure. A chest X ray is performed to ensure that the lung was not injured during the procedure. The patient should immediately report chest pain, shortness of breath, or difficulty breathing to the nurse. After the patient goes home within a few hours of the procedure, he or she should seek emergency
Thoracentesis treatment if these symptoms occur. A follow-up chest X ray may be scheduled within two to four weeks. Risks: The risks of a thoracentesis are decreased when the procedure is performed with ultrasound guidance. In most cases, there are few complications. The risks, however, include reaccumulation of fluid in the pleural space or fluid in the lungs (pulmonary edema), bleeding, infection, respiratory distress, or collapse of the lung (pneumothorax). Pneumothorax occurs when air has built up in the pleural space because of a leak in the lung. Pneumothorax often does not require treatment, but in some cases it may require placement of a chest tube thoracostomy, a procedure to drain air from the space around the lungs to allow the lung to reexpand. Rarely, damage to the spleen or liver may occur as a result of a puncture from the thoracentesis needle. Results: The fluid sample that was removed during the procedure is first examined for color and consistency by the physician and is then analyzed in a laboratory. The fluid may be exudative (protein-rich) or transudative (watery, protein-poor). Pleural fluid analysis is useful in determining the cause of the effusion such as infection, pneumonia, blood in the pleural space (hemothorax), cancer, heart failure, cirrhosis, or kidney disease. It may also help identify other conditions such as pancreatitis, pulmonary embolism, or thyroid disease. The goals of therapeutic thoracentesis include draining excess fluid, treating infection, fully reexpanding the lung, and relieving symptoms such as shortness of breath, chest pain, or dry cough. If a large amount of fluid was removed, then the patient will experience a relief of symptoms soon after the procedure. A repeat thoracentesis procedure may be needed if the effusion reaccumulates, which often occurs when the underlying cause is a malignancy. Angela M. Costello, B.S. u
For Further Information Colice, Gene L., et al. “Medical and Surgical Treatment of Parapneumonic Effusions: An Evidence-Based Guideline.” Chest 118 (2000): 1158-1171. Ferrer, Jaume. “Predictors of Pleural Malignancy in Patients with Pleural Effusion Undergoing Thoracoscopy.” Chest 127 (2005): 1017-1022.
u
Other Resources
American College of Chest Physicians http://www.chestnet.org American Thoracic Society http://www.thoracic.org 1159
Thoracoscopy Society of Thoracic Surgeons http://www.sts.org/sections/patientinformation See also Bronchoalveolar lung cancer; Lung cancers; Mesothelioma; Needle biopsies; Pleural biopsy; Pleural effusion; Pleurodesis; Radiofrequency ablation; Thoracentesis; Thoracoscopy; Ultrasound tests.
Salem Health: Cancer the surgical area onto a computer screen to guide surgeons during the procedure. Compared to open-chest surgery that requires one 6- to 8-inch incision, thoracoscopy uses several small, 1-inch incisions to access the chest, thereby minimizing trauma, decreasing postoperative pain, and promoting a shorter hospital stay and a quicker recovery. Cancers diagnosed or treated: Pleural effusion, malignant mesothelioma, lung cancer, thymomas, and mediastinal and pericardial tumors
u Thoracoscopy Category: Procedures Also known as: Pleuroscopy, minimally invasive or video-assisted thoracic surgery Definition: Thoracoscopy is an endoscopic procedure used to view inside the chest cavity with a thoracoscope (small videoscope). The thoracoscope transmits images of
Why performed: Thoracoscopy may be used as a diagnostic procedure to determine the cause of a pleural effusion, perform a lung biopsy, or evaluate tumors. Thoracoscopy may be used to perform therapeutic procedures including thoracoscopic pneumonectomy, lobectomy, or wedge resection for lung cancer treatment; thoracentesis to drain excess pleural fluid; and removal of tumors in the esophagus, mediastinum, pericardium, or thymus.
A doctor performs a thoracoscopy. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Salem Health: Cancer
Thoracotomy
Patient preparation: Preprocedure tests may include a chest X ray and ultrasound, pulmonary function test, computed tomography (CT) scan, electrocardiogram (EKG), and blood tests. In general, patients must not eat or drink for eight hours before the procedure. Depending on the type of procedure to be performed, additional tests or patient preparations may be required. Steps of the procedure: General anesthesia is used in most cases. The thoracoscope and surgical instruments are inserted through three or four small chest incisions between the ribs. The thoracoscope is manipulated to view the area, and the surgical instruments may be used to remove tissue. After the procedure: A chest tube drains fluid and removes air that may have accumulated during the procedure. Cardiac Incisions in a left anterolateral thoracotomy. (LifeART© 2008 Wolters Kluwer function and blood oxygen levels are Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.) monitored, and daily chest X rays evaluate lung reexpansion and chest tube placement. The hospital recovery is about three to four days. u Thoracotomy The chest tube is removed. and the patient receives a follow-up schedule and homegoing instructions. The paCategory: Procedures tient can generally return to normal activities three to four Also known as: Lung surgery weeks after discharge. Definition: A thoracotomy is the surgical opening of the chest wall so that the lungs, esophagus, or heart may be acRisks: The risks of thoracoscopy include accumulation of cessed. It can be performed on the right or left side or the fluid in the pleural space, fluid in the lungs (pulmonary midline of the chest. edema), bleeding, infection, respiratory distress, or collapse of the lung (pneumothorax). The risk of death is rare Cancers diagnosed or treated: Lung cancer, esophageal and occurs in about 0.24 percent of patients. cancer, cancer of the heart Results: Pleural fluid removed during the procedure is analyzed in the laboratory, and the biopsy tissue is examined for malignancy. The type and extent of disease will help guide the patient’s treatment. Angela M. Costello, B.S. See also Bronchoalveolar lung cancer; Endoscopy; Gastrointestinal oncology; Hematologic oncology; Lung cancers; Medical oncology; Mesothelioma; Pediatric oncology and hematology; Pleural effusion; Pleurodesis; Surgical biopsies; Thoracentesis; Thymomas.
Why performed: A thoracotomy is performed to biopsy and/or remove a tumor, to close a bleb (blister) in the external wall of the lung, or to drain an abscess. Patient preparation: Several days before the thoracotomy, the patient will require blood work and an electrocardiogram (EKG). The patient will have to fast after midnight the day of the procedure. Steps of the procedure: Before the thoracotomy, the patient will have an intravenous (IV) line inserted and be hooked up to a heart monitor. After the patient is sedated, an endotracheal tube is placed through the patient’s nose 1161
Throat cancer or mouth into the trachea and attached to a ventilator, which breathes for the patient. A midline thoracotomy is performed for surgery on the heart or esophagus. The patient lies on the back, and the surgeon splits the sternum to gain access to the chest. A right or left thoracotomy is used for surgery on the lungs. The patient lies on the opposite side with the arm over the head, and the surgeon makes an incision over the fifth intercostal (between the ribs) space. After the surgery and before the chest wall is closed, one or two chest tubes are placed through the chest wall into the pleural space. They are necessary to reestablish the negative pressure in the chest. The chest tubes are attached to a drainage unit, which has a water seal to keep air from entering the pleural space. After the procedure: The patient is sent to an intensive care unit (ICU) for close monitoring of vital signs, breathing, heart rhythm, and chest drainage. The patient will remain in the hospital for five or ten days. Usually the chest tubes can be removed after three to five days. Risks: The risks of a thoracotomy are pneumothorax (collapse of the lung), air leaks, infection, bleeding, local nerve damage, and respiratory failure. After a thoracotomy, the patient may have severe pain with breathing. Results: The lungs should be fully inflated. The tumor should be removed and the local lymph nodes evaluated. Christine M. Carroll, R.N., B.S.N., M.B.A. See also Bilobectomy; Biopsy; Bronchial adenomas; Bronchoalveolar lung cancer; Esophageal cancer; Esophagectomy; Lung cancers; Pleural effusion; Pleurodesis; Pneumonectomy; Surgical biopsies.
u Throat cancer Category: Diseases, symptoms, and conditions Also known as: Oropharyngeal cancer, laryngeal cancer, pharyngeal cancer, nasopharyngeal cancer Related conditions: Thyroid cancer, vocal cord cancer, cancer of the glottis, adenoid cystic carcinoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma Definition: Throat cancer is a malignant tumor in the pharynx (part of the alimentary canal from behind the nose to the top of the esophagus) or in the larynx (voice box). The pharynx is divided into the nasopharynx (upper part behind the nose), oropharynx (middle part including the 1162
Salem Health: Cancer soft palate, base of tongue, and tonsils), and hypopharynx (lower part). Risk factors: Studies have found that as many as 90 percent of people with head and neck cancers, particularly of the oropharynx, hypopharynx, and larynx, have a history of smoking cigarettes or chewing tobacco, and as many as 80 percent have a history of drinking alcohol. Risk increases with the frequency, duration, and number of “pack-years” of cigarette smoking, independent of alcohol consumption. (One pack-year is defined as equivalent to smoking one pack, or twenty cigarettes, per day for one year.) One study indicated that smoking or chewing tobacco in conjunction with excess drinking of alcohol increases the risk beyond that for those who use either tobacco or alcohol alone. In a study among those who never smoked, only those with excessive amounts of alcohol consumption (three or more drinks per day) were at increased risk of head and neck cancers. Other factors vary by tumor site and include Chinese ancestry, consumption of preserved and salted foods, wood dust exposure, and infection with the Epstein-Barr virus for nasopharyngeal cancer; poor oral hygiene, a diet low in fruits and vegetables, chewing betel quid, and infection with the human papillomavirus (HPV) for oropharyngeal cancer; Plumner-Vinson syndrome, a disorder characterized by severe anemia and trouble swallowing, for hypopharyngeal cancer; and asbestos exposure for laryngeal cancer. East Asians who drink alcohol and possess a genetic mutation that prevents effective elimination of acetaldehyde, a carcinogen created by metabolism of alcohol, are at greater risk for oropharyngeal cancer. Etiology and the disease process: Most throat cancers begin in squamous cells lining mucosal surfaces in the throat. Squamous cell cancers grow aggressively. They begin as carcinomas in situ, abnormal cells lining the cells in the epithelieum, before they progress to invasive squamous cell cancers. Salivary gland tumors can develop in the mucosal lining of the oropharynx and oral cavity. What makes squamous cells become cancerous is unknown, but it is believed that tobacco and alcohol use damage the deoxyribonucleic acid (DNA) in the cells of the mouth and throat, causing changes that lead to cancer. Incidence: According to the National Cancer Institute, in 2008, there will be an estimated 12,250 new cases of laryngeal cancer and 12,410 new cases of pharyngeal cancer. Some 3,670 people will die of laryngeal cancer, and 2,200 will die of pharyngeal cancer. Cancers of the throat occur more often in men than in women, with men making up 78 percent of those with hypopharyngeal cancer and 69 per-
Salem Health: Cancer cent of those with nasopharyngeal cancer. The incidence of head and neck cancers has declined since the 1980’s, attributable in part to a drop in the number of people smoking cigarettes. However, the incidence of throat cancers has remained steady and some studies indicate an increase of throat cancer among young adults.
Throat cancer
Relative Survival Rates for Throat Cancer by Site, 1988-2001 Survival Rates (%) Site
1-Year 2-Year 3-Year 5-Year 8-Year 10-Year
Nasopharynx Oropharynx and tonsils Hypopharynx Larynx
84.1 79.8 67.4 87.9
73.2 65.9 47.9 78.4
65.3 58.8 38.3 72.7
56.6 49.8 29.5 65.2
48.3 43.5 22.0 57.6
44.7 39.3 18.2 53.1
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. Symptoms: Symptoms of throat cancer SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. may be mild or absent but may include a No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007) lump or sore that does not heal or becomes larger, sore throat, trouble swallowing, and a change in voice such as hoarseness. Patients with cancer of the of the tumor; magnetic resonance imaging (MRI); posioropharynx or hypopharynx may experience ear pain, and tron emission tomography (PET) to see if the cancer has those with cancer of the nasopharynx may have ear pain and spread to nearby lymph nodes; and a barium swallow, a sedifficulty hearing, headaches, and difficulty breathing or ries of X rays to determine if the cancer has spread to the talking. Symptoms of cancer of the larynx may include esophagus in the digestive tract and to see if the cancer afsore throat, hoarseness, ear pain, or a lump in the neck. fects swallowing. Screening and diagnosis: There are no screening tests for throat cancer. If throat cancer is suspected, the physician Treatment and therapy: If cancer is present, the physiwill take a complete medical history for risk factors and cian will discuss treatment options, taking into considerperform a physical exam. During the physical exam, the ation the patient’s overall health, prognosis, staging, psyphysician will palpate for lumps in the throat to rule out chosocial supports, treatment side effects, and the impact other conditions related to the symptoms, look for signs of of the cancer and treatment on functions such as swallowmetastasis, and determine the patient’s overall health. ing, talking, and chewing. The patient’s medical team may Then, the physician will most likely perform an endoscopy consist of otorhinolaryngologists, oral surgeons, patholoto view areas that are not visible during a physical exam gists, plastic surgeons, prostodontists, and radiation and and to look for lesions. (A laryngoscope examines the larmedical oncologists. Other allied health professionals— ynx; a nasopharyngoscope examines the nasal cavity and such as dieticians, speech pathologists, physical theranasopharynx.) During this procedure, the physician will pists, and social workers—may be involved as needed. excise tissue for examination. Depending on the location Surgery and radiation therapies are commonly used for of the tumor, the biopsy can be one of three types: an treating throat cancers, particularly when the tumor is exfoliative biopsy, incisional biopsy, or fine needle aspirasmall and can be destroyed before spreading to other areas tion biopsy (commonly done to stage oropharyngeal canof the body. Radiation therapy may follow surgery if not cer). The physician may recommend a panendoscopy, a all the cancer has been removed, or radiation may be used diagnostic procedure done under general anesthesia durbefore surgery to preserve the voice. Individuals receiving ing surgery to thoroughly examine the nose, throat, voice radiation therapy may experience side effects including box, esophagus, and bronchi to look for areas of lesions nausea, irritation and sores in the mouth, decreased appeand obtain a biopsy. tite, earaches, and stiffness in the jaw. If cancer is present, it will be staged, from Stage 0, loIf a larger tumor is involved or if the cancer has spread, calized cancer, to Stage IV, metastasized cancer. Staging a combination of radiation and chemotherapy is often sucdepends not only on the pathology results but on clinical cessful and can preserve the voice box. Rarely will a laryndata such as results of the endoscopy, findings on physical gectomy be recommended and only in cases in which the examination, and results of any imaging studies. Imaging larynx and primary tumor must be removed. Palliative studies may include an X ray to determine if there is cancer care is needed for individuals whose primary throat cancer in the lungs; computed tomography (CT) scans for a crosshas spread to other organs or distant parts of the body and sectional picture of the size, location, shape, and position cannot be treated.
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Thrombocytopenia Prognosis, prevention, and outcomes: The overall fiveyear survival rate for laryngeal cancer is 65.2 percent; for nasopharyngeal, 56.6 percent; for cancer of the oropharynx and tonsils, 49.8; and for hypopharyngeal cancer, 29.5 percent. If detected early, five-year survival rates climb to 82.5 percent for cancer of the larynx, 78.4 for cancer of the nasopharynx, 56.0 percent for cancer of the oropharynx and tonsils, and 48.7 percent for cancer of the hypopharynx. However, these rates drop when these cancers are detected after metastasis: the larynx to 19.1 percent, the nasopharynx to 46.7 percent, the oropharynx and tonsils to 43.4 percent, and the hypopharynx to 23.2 percent. If the tumor has spread to lymph nodes, it often cannot be controlled with surgery, radiation, or combined treatments. Even when the primary tumor is controlled, distal spread often cannot be avoided. Rehabilitation is often a critical component in caring for patients treated for throat cancers. Many patients need therapy for assistance in speaking and swallowing following treatment. Patients may need dietary counseling as well. Those who receive a laryngectomy will have a stoma, a surgical opening in the throat, and will need to learn how to care for it and how to speak again if the stoma is permanent. Follow-up care for those treated for throat cancer is essential to ensure that the cancer does not recur. Individuals with a prior diagnosis of throat cancer are at the highest risk of recurrence of the cancer within two to three years of initial diagnosis. During follow-up visits, the physician will perform a physical exam and sometimes order X rays, blood tests, and imaging studies. Regular dental exams may be necessary as well. If patients received radiation therapy, the physician may monitor functioning of the thyroid and pituitary glands. The treating physician will also urge patients to stop smoking and drinking alcohol, as doing so has been shown to compromise treatment and increase the risk that a second cancer will develop. Second primary tumors, particularly in the aerodigestive tract, have been reported in as many as 25 percent of patients whose initial throat lesions are controlled. It has been reported that daily administration of moderate doses of isotretonin for one year following initial treatment significantly reduces the incidence of second tumors of the oropharynx and larynx. However, survival advantages to this treatment have not yet been demonstrated. Susan H. Peterman, M.P.H. u
For Further Information Gordon, Serena. “Oral Sex Implicated in Some Throat and Neck Cancer.” Washington Post, August 27, 2007. Hashibe, Mia, et al. “Alcohol Drinking in Never Users of 1164
Salem Health: Cancer Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium.” Journal of the National Cancer Institute 99 (2007): 777-789. Lydiatt, William M., and Perry J. Johnson. Cancers of the Mouth and Throat: A Patient’s Guide to Treatment. Omaha: Addicus Books, 2001. Spitz, M. R. “Epidemiology and Risk Factors for Head and Neck Cancer.” Seminars in Oncology 31, no. 6 (2004): 726-733. u
Other Resources
MayoClinic.com Oral and Throat Cancer http://www.mayoclinic.com/health/oral-and-throatcancer/DS00349/DSECTION=1 National Cancer Institute Throat (Laryngeal and Pharyngeal) Cancer http://www.cancer.gov/cancertopics/types/throat/ See also Chewing tobacco; Cigarettes and cigars; Esophageal speech; Head and neck cancers; Hypopharyngeal cancer; Laryngeal cancer; Oral and oropharyngeal cancers; Tobacco-related cancers.
u Thrombocytopenia Category: Diseases, symptoms, and conditions Also known as: Bleeding disorders Related conditions: Anemia, neutropenia, pancytopenia Definition: Thrombocytopenia is any disorder in which the number of platelets (thrombocytes, or blood cells that facilitate clotting) is below average. Risk factors: Patients who are receiving large doses of chemotherapy, sometimes referred to as dose-dense therapy, or radiation therapy are at risk of developing thrombocytopenia, as are patients with leukemias, myeloma, and lymphomas. As aspirin is a drug known to act against platelets, patients who take aspirin often may be at risk. Serious infections and sepsis also can cause thrombocytopenia. Etiology and the disease process: Platelets, small cells without a nucleus, are formed from hematopoietic stem cells that develop into megakaryocytes. Megakaryocyte formation is stimulated by the endogenous hormone thrombopoietin. Other hematopoietic growth factors, including
Salem Health: Cancer interleukin-11 and interleukin-6, are involved in the production of megakaryocytes. Platelets are formed when the megakaryocyte shatters into small pieces. It takes approximately five days for a new platelet to differentiate and mature from a hematopoietic stem cell, which means that a patient receiving chemotherapy or radiation therapy can have a low number of platelets for days; platelets have a life span of only ten days. The role of platelets is to allow blood to clot normally. Clotting occurs when a platelet encounters and adheres to a rough or jagged edge of damaged tissue. Other platelets adhere to this platelet in the process of platelet aggregation and formation of a plug. Finally, fibrin is released, forming a mesh that traps other platelets and completes the clot. Chemotherapy and radiation therapy target the rapidly dividing cancer cells as well as other rapidly dividing cells, including hematopoietic stem cells, and reduce the numbers of platelets available for clotting and maintenance of normal blood consistency. Patients with thrombocytopenia can have severe bleeding because of routine blood draws, stiff toothbrushes, vigorous nose blowing, shaving, and ingestion of sharp foods, such as popcorn and peanuts. Under healthy circumstances, tiny ruptures in blood vessels are immediately repaired; when thrombocytopenia is present, this bleeding can go unchecked. Incidence: At least 25 percent of patients who are receiving chemotherapy or radiation therapy develop thrombocytopenia. Thrombocytopenia makes a patient more susceptible to internal bleeding and stroke and may lead to anemia. Symptoms: Symptoms of thrombocytopenia include unexplained bruises, nosebleeds, bleeding gums, prolonged bleeding from minor cuts and blood draws, pink or reddish urine, and black or bloody stools. Screening and diagnosis: Thrombocytopenia is usually confirmed by a blood test. Normal platelet count is 200 × 109/liter to 400 × 109/liter. Sometimes, a bone marrow biopsy is needed to determine the cause of the thrombocytopenia. At 50 × 109/liter, a patient is at great risk of bleeding, and at 20 × 109/liter, at severe risk for bleeding; at this level, thrombocytopenia is a life-threatening condition. Besides measuring the number of platelets in circulation, platelet function tests also may be done. In the past, the primary test for platelet dysfunction was bleeding time, but this test has fallen out of favor as it is not very sensitive or precise. Normal bleeding time, which requires small, thin cuts on a patient’s forearm to assess, is generally 3 to 9.5 minutes but can be affected by aspirin and by
Thrombocytopenia the skill of the laboratory technician. Other tests that may be done on a blood sample include prothrombin time, a measure of how long it takes blood to clot, which normally is 10 to 13 seconds. A partial prothrombin time test is usually done in conjunction with the prothrombin time to measure the function of several clotting factors. Other tests include platelet aggregation studies that measure the response of blood or platelet-rich blood to specific agents known to induce aggregation (clumping) of platelets. Treatment and therapy: Transfusions of platelets can be used to treat life-threatening thrombocytopenia. Most oncologists, however, prefer not to use transfusions excessively because of the small but inherent risks of infections and immune system complications. Transfusions often involve platelets from a number of volunteer donors. Patients who receive platelets pooled from a number of donors run the risk of developing antibodies to the various proteins on the platelet membranes. If antibodies develop, the patient may no longer respond to transfusions. The risk of immune system reactions can be reduced if a patient who requires platelet transfusions can arrange to receive platelets from one specific donor, preferably a sibling. If antibodies do develop from transfusions of pooled platelets, it may be critical for a patient to receive platelets only from a sibling. A recombinant version of the naturally occurring protein that is responsible for the growth and development of platelets has received marketing approval from the Food and Drug Administration. This product, a recombinant human interleukin-11 (oprelvekin, or Neumega), is administered as a subcutaneous injection and stimulates the bone marrow to produce more platelets. Prognosis, prevention, and outcomes: Recombinant growth factors and platelet transfusions are standard care for the treatment of severe thrombocytopenia at many cancer centers. Transfusion in particular can rapidly, that is, within hours in some cases, increase platelet counts. Left untreated, the patient is at risk for serious and possibly lifethreatening internal bleeding and stroke. Because chemotherapy and radiation therapy carry a risk of thrombocytopenia, the only way to prevent thrombocytopenia is to delay or reduce the amount of chemotherapy or radiation therapy, which is not advised as it lessens the success of the treatments. MaryAnn Foote, M.S., Ph.D. u
For Further Information Kuter, D. J., P. Hunt, W. Sheridan, and D. Zucker-Franklin, eds. “Thrombopoiesis and Thrombopoietins.” In Molecular, Cellular, Preclinical, and Clinical Biology. Totowa, N.J.: Humana Press, 1997. 1165
Thymomas
Salem Health: Cancer
McCrae, Keith R., ed. Thrombocytopenia. New York: Taylor & Francis, 2006.
•
u
Incidence: Thymomas and thymic cancers are rare. The American Cancer Society reports about 500 to 700 new cases of malignant thymomas diagnosed annually. The incidence of nonmalignant thymomas is unknown. Thymomas usually affect people aged fory to sixty years.
Other Resources
MayoClinic.com Thrombocytopenia (Low Platelet Count) http://www.mayoclinic.com/health/ thrombocytopenia/DS00691 MedlinePlus Thrombocytopenia http://www.nlm.nih.gov/medlineplus/ency/article/ 000586.htm See also Anemia; Angiogenesis inhibitors; Aplastic anemia; Azathioprine; Chemotherapy; Computed tomography (CT)-guided biopsy; Hypercoagulation disorders; Infection and sepsis; Interleukins; Leukemias; Lymphomas; Matrix metalloproteinase inhibitors; Myelosuppression; Neutropenia; Proteasome inhibitors; Topoisomerase inhibitors.
u Thymomas Category: Diseases, symptoms, and conditions Also known as: Epithelial tumors of the thymus, thymic tumors Related conditions: Thymic cancer, carcinoid tumors, germ-cell tumors, lymphomas Definition: Thymomas are abnormal tissue masses on the outside of the thymus, a small organ in the upper chest. Risk factors: Myasthenia gravis is the primary risk factor, occurring in about half of patients with thymomas. Red cell aplasia and hypogammaglobulinema are tumor-related conditions that may occur with thymomas. Autoimmune diseases increase the risk. Etiology and the disease process: The World Health Organization’s letter grade system identifies thymomas based on their microscopic appearance: • Type A: Spindle-shaped endothelial cells, few lymphoctyes • Type AB: Features of type A plus lymphocytes • Types B1 and B2: Numerous lymphocytes, thymus cells normal (B1) or abnormal (B2) • Type B3: Few lymphocytes, normal thymus epithelial cells 1166
Type C (thymic carcinomas): Mature lymphocytes mixed with plasma cells, invasion of surrounding tissues
Symptoms: Symptoms are often related to other coexisting conditions. Thymomas may cause shortness of breath, coughing, and angina when there is added pressure on the nearby airways or blood vessels. About 40 percent of patients do not experience symptoms, but the thymoma is found during examination for another medical condition. Screening and diagnosis: A needle biopsy may be performed, but thymomas are usually diagnosed, staged, and treated during surgery. • Stage I: Noninvasive, within thymus boundary • Stage II: Spread beyond the thymus, affecting fatty tissue or mediastinum • Stage III: Extending to the pleura, pericardium, lungs, nerves, or superior vena cava • Stage IVA: Spread throughout the pleura and pericardium • Stage IVB: Spread to distant organs Treatment and therapy: Surgical removal of the thymus (thymectomy) and some of the surrounding tissue is recommended. Removal of nearby structures affected by the malignancy may be necessary for Stage III or IV thymomas. Chemotherapy, radiation therapy, or both may decrease the size of the tumor before surgery and may be given after surgery. Prognosis, prevention, and outcomes: The prognosis depends on the stage of the disease, with the highest survival rates for patients with Stage I and II thymomas that undergo thymectomy. About 25 percent of patients with thymic carcinomas are cured, with a five-year survival rate of 35 percent. There is no known prevention for thymomas. Angela M. Costello, B.S. See also Carcinoid tumors and carcinoid syndrome; Carcinomas; Germ-cell tumors; Hemolytic anemia; LambertEaton myasthenic syndrome (LEMS); Lymphomas; Mediastinal tumors; Mediastinoscopy; Myasthenia gravis; Superior vena cava syndrome; Surgical biopsies; Thoracoscopy; Thymus cancer.
Salem Health: Cancer
u Thymus cancer Category: Diseases, symptoms, and conditions Also known as: Thymic cancer, thymoma, thymic carcinoma, thymic carcinoids Related conditions: Myasthenia gravis, red cell aplasia, autoimmune disorders (including lupus and rheumatoid arthritis) Definition: Thymus cancer is a malignant tumor in the thymus, a small organ in the upper chest where the body makes and matures T lymphocytes (a type of white blood cell involved in immune responses). When thymic cells acquire mutations, normal cells may be replaced by cancerous ones. About 90 percent of thymic cancers are thymomas, with thymic carcinoma and thymic carcinoids being much less common. Risk factors: Thymic tumors are most prevalent in middleaged or elderly populations (between fifty and eighty years of age). Men and women have similar incidence rates. There is some evidence that thymomas may be hereditary, although specific gene mutations have not yet been identified. There are several disorders that predispose one to developing thymic cancer. For instance, myasthenia gravis, characterized by severe muscle weakness, develops in about 30 to 50 percent of people with thymoma, and 15 percent of patients with myasthenia gravis have thymomas. Red cell aplasia, characterized by a lack of red blood cell formation, also develops in about 30 to 50 percent of people with thymoma and occurs in 5 percent of thymoma patients. Additionally, people with autoimmune disorders, in which the immune system incorrectly targets the body’s own tissues, also have an increased risk of thymic cancers. Etiology and the disease process: Two major cell types in the thymus include lymphocytes and epithelial cells. When lymphocytes are transformed into cancerous cells, this may lead to Hodgkin disease and non-Hodgkin lymphomas. Thymic cancers arise from either the cortical or medullary epithelial cells. One of the early events in the development of thymomas is a TP53 mutation. The protein produced by this gene is involved in regulating the cell cycle, and loss-offunction mutations can allow damaged or abnormal cells to divide and replicate. Another genetic mutation in thymic cancer is the overexpression of the epithelial growth factor receptor (EGFR), which is involved in signal transduction pathways that activate proteins and transcription factors to subsequently turn on genes involved in survival and proliferation.
Thymus cancer The World Health Organization’s classification system of thymic cancers is based on their microscopic appearance. The types and prevalence follow: • Type A (about 5 percent): Cells are spindle-shaped or oval epithelial cells, and they do not appear to be malignant. • Type AB (about 30 percent): Cells look like Type A, except that there are also some lymphocytes mixed in with the tumor. • Type B1 (about 10 to 20 percent): Cells look like Type A, except that there are many lymphocytes mixed in with the tumor. • Type B2 (about 20 to 35 percent): Epithelial cells appear abnormal and have large nuclei, and there are several lymphocytes. • Type B3 (10 to 15 percent): This type has few lymphocytes and mostly consists of thymic epithelial cells that look pretty close to normal. While Types A-B3 describe thymomas, Type C thymic cancers are known as thymic carcinomas. Thymic carcinomas have abnormal cells and are likely to spread outside of the thymus. They are divided into low-grade and highgrade carcinomas based on how aggressive the tumor is and how likely it is to spread. Thymic carcinoids are often associated with disorders of the endocrine system. These tumors are aggressive and can spread outside the thymus. Incidence: The American Cancer Society estimates 500 to 700 new cases of thymic cancers are diagnosed each year in the United States. Thymomas make up 90 percent of all cases, while the remaining 10 percent are thymic carcinomas and carcinoid tumors. Symptoms: In about 40 percent of cases, there are no symptoms. However, when they occur, signs include longlasting coughs, chest pain, and trouble breathing. These symptoms are often the result of thymic tumors constricting air passages or blood vessels. Obstructing blood flow may also lead to swelling in the arms or face. Other symptoms include low levels of red blood cells, fatigue and muscle weakness, and an increased risk of infection. Screening and diagnosis: An X ray of the chest is often the first procedure performed to detect thymic cancer. Follow-up imaging tests include computed tomography (CT), which is a more sensitive X ray that produces crosssectional images. CT scans provide information regarding the size, shape, and position of a tumor, as well as identify enlarged lymph nodes that may also have cancerous cells. Magnetic resonance imaging (MRI) scans, which use radio waves and magnets instead of X rays, are another 1167
Thymus cancer
Salem Health: Cancer
Relative Survival Rates for Thymus Cancer by Gender, 1988-2001 Survival Rate (%) Gender
1-Year 3-Year 5-Year 10-Year
Men Women Total
88.9 85.5 87.4
75.0 73.9 74.5
68.5 63.4 66.3
54.4 46.8 51.3
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
sensitive test that provides sectional scans of the body. Finally, positron emission tomography (PET) is a newer form of imaging that scans the entire body. PET generally uses radioactive glucose (a form of sugar) as a tracer. The radioactivity is absorbed by the cancer cells and then detected with a special camera. The most definitive procedure to diagnose thymic cancer is a biopsy, in which a piece of the tumor tissue from the thymus is removed by either a needle or surgery, and then analyzed under the microscope. Thymomas are staged using the Masaoka system. Since thymic carcinomas and thymic carcinoid tumors are rare (about 10 percent of thymic cancers), there is not a separate staging system for these cancer types. However, the Masaoka system is sometimes used for thymic carcinomas. The stages of the Masaoka system are as follows: • Stage I: The cancer remains within the thymus. • Stage II: The cancer has spread into the outer layer of the lung or into nearby fat tissue. • Stage III: The cancer has spread to areas within the chest, including the outer layer of the heart, lungs, or blood vessels. • Stage IVA: The cancer has spread throughout the heart, lungs, or both. • Stage IVB: The cancer has spread to organs in other parts of the body. Treatment and therapy: For Stage I thymoma, surgical removal of the thymus is the standard treatment. In other stages, the thymus and any tissues to which the cancer may have spread are removed. Radiation therapy may be performed if patients are unable to undergo surgery, if the tumor has spread to too many tissues, if there is still a residual tumor mass after surgery, or if the tumor is inoperable because it is next to major arteries or veins in the chest. In the later stages, radiation therapy may also be 1168
given after surgery to decrease the risk of recurrence or spreading. Chemotherapy drugs used to treat thymic cancers include doxorubicin, cisplatin, cyclophosphamide, etoposide, and ifosfamide. These drugs may be used either alone or in combination and may be administered before surgery to reduce tumor size or after surgery if tumor cells still remain. For tumors where surgery cannot be performed, and patients have not responded to radiation, corticosteroids may be used. A newer therapy for advanced thymic cancers is the drug octreotide. Octreoide blocks the ability of cancerous thymic cells to bind the hormone somatostatin, and this leads to cell death or slower rates of proliferation. After surgery or therapy, patients should have checkups including blood work and chest X rays every six to twelve months to monitor for recurrence. Prognosis, prevention, and outcomes: Survival rates depend on the stage of the cancer at diagnosis. Results from a study published in 2000 showed that the average five-year survival rates for thymomas are 96 percent for Stage I, 86 percent for Stage II, 70 percent for Stage III, and 50 percent for Stage IV (staging based on the Masaoka system). However, up to 30 percent of survivors can experience a recurrence. For thymic carcinomas, the five-year survival rates are around 35 percent, and they are approximately 60 percent for thymic carcinoids. There are no specific guidelines for preventing thymic cancers. However, following a healthy diet, which is high in fruits and vegetables and low in fat, has been shown to prevent the development of many cancers. Elizabeth A. Manning, Ph.D. u
For Further Information Bogot, N. R., and L. E. Quint. “Imaging of Thymic Disorders.” Cancer Imaging 5 (December 15, 2005): 139-149. Detterbeck, F. C. “Clinical Value of the WHO Classification System of Thymoma.” Annals of Thoracic Surgery 81, no. 6 (June, 2006): 2328-2334. Johnson, S. B., T. Y. Eng, G. Giaccone, and C. R. Thomas, Jr. “Thymoma: Update for the New Millennium.” Oncologist 6, no. 3 (2001): 239-246. Nishino, M., et al. “The Thymus: A Comprehensive Review.” Radiographics 26, no. 2 (March/April, 2006): 335-348. Suster, S. “Diagnosis of Thymoma.” Journal of Clinical Pathology 59, no. 12 (December, 2006): 1238-1244. Suster, S., and C. A. Moran. “Thymoma Classification: Current Status and Future Trends.” American Journal of Clinical Pathology 125, no. 4 (April, 2006): 542-554.
Salem Health: Cancer u
Thyroid cancer
Other Resources
The Thyroid Gland
American Cancer Society Detailed Guide: Thymus Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=42 Medline Plus Thymus Cancer http://www.nlm.nih.gov/medlineplus/ thymuscancer.html
Thyroid cartilage
See also Carcinoid tumors and carcinoid syndrome; Carcinomas; Computed tomography (CT) scan; Hodgkin disease; Immune response to cancer; Lymphomas; Thymomas. Thyroid gland
u Thyroid cancer Category: Diseases, symptoms, and conditions Also known as: Malignant neoplasm of the thyroid
Trachea
Related conditions: Autoimmune thyroiditis, sarcoma of the thyroid, Gardner syndrome, Cowden syndrome Definition: Thyroid cancer is a malignant tumor in the thyroid gland, a butterfly-shaped gland in the neck that makes a hormone essential for normal body function. The thyroid contains cells that grow and divide to form new ones as needed; however, when this process goes awry, tissue masses called nodules develop; these may be benign or malignant (cancerous). There are several types of thyroid cancer: papillary, the most common type (over 70 percent), has a very high cure rate. It usually appears in people thirty to fifty years old and accounts for 85 percent of thyroid cancers resulting from radiation exposure. About 10 to 15 percent of thyroid tumors are follicular carcinoma. This cancer is more aggressive, occurs in a slightly older age group, and rarely occurs after radiation exposure but is more common in an iodine-deficient environment. Hurthle cell carcinoma is a rare variant. Medullary thyroid cancer (about 5 to 8 percent) is not associated with radiation exposure and is inherited. Anaplastic carcinoma is the rarest type (about 0.5 to 1.5 percent) but the most deadly; it may appear many years following radiation exposure. Thyroid lymphomas account for less than 5 percent of thyroid cancers. Risk factors: Increased risk of papillary carcinoma is associated with external-beam irradiation to the head and neck areas, especially during childhood. Exposure to ingested radioactive isotopes and radioactive fallout also poses a cancer risk. Having a parent with multiple endo-
crine neoplasia (MEN) types 2A or 2B or familial medullary cancer increases the chance of having the genetic mutation that causes thyroid cancer by as much as 50 percent. Women are two to three times as likely as men to develop thyroid cancer; women whose last pregnancy occurs at or later than age thirty are also at greater risk. Whites are more susceptible than are blacks, and being Asian or California Asian increases the risk. Other risk factors include dietary iodine deficiency; ingestion of goitrogenic (goitercausing) or cruciferous vegetables (such as cabbage) and seafood and shellfish, especially when fished from sites near active volcanoes, as in Hawaii and Iceland; and chronic elevation of thyroid-stimulating hormone (TSH). Etiology and the disease process: In many cases, the etiology, or cause, of thyroid cancer is unknown. Thyroid cancers are either differentiated or undifferentiated. Differentiated cells look and act like normal ones and actually assist in making thyroxine. They reproduce more slowly than undifferentiated ones do. Papillary and follicular carcinoma are two types of differentiated cancer. Around 85 percent of papillary thyroid cancers are caused by radiation exposure. Follicular cancer is more prevalent in countries where people are iodine deficient. Undifferentiated cancer is made up of very primitive cells that do nothing but reproduce; this produces the rare 1169
Thyroid cancer
Salem Health: Cancer neck; swallowing or breathing difficulty; and pain in the throat or neck.
anaplastic cancer that is not effectively treatable and therefore has a high mortality rate. Even rarer is medullary thyroid carcinoma (MTC), which is inherited. A specific cell, the C cell, is involved. It makes the hormone calcitonin, which helps regulate calcium in the body, but when it overproduces, medullary carcinoma must be suspected.
Screening and diagnosis: More often than not, a nodule felt in the thyroid during a routine physical examination or found incidentally during an imaging test for some other condition signals a tumor’s presence. When symptoms suggest thyroid cancer, a number of tests may be performed: An ultrasound scan outlines a growth but does not rule out malignancy. That determination is made with biopsy. Biopsy may be fine needle aspiration (FNA) biopsy, in which a needle is inserted in different parts of a nodule to remove cell samples that are analyzed in a laboratory, or surgical biopsy to remove the nodule and check the tissue for cancer cells. Blood tests may also be done to detect abnormal levels of thyroid-stimulating hormone in the blood. If a physician suspects medullary cancer, blood tests are run to check for abnormally high levels of calcitonin in the blood or to detect an altered gene (RET gene), which aids diagnosis. Radionuclide scanning involves administering a small
Incidence: Compared with other types of cancer, thyroid cancer is uncommon; only about 0.6 percent of men and 1.6 percent of women in the United States are diagnosed with it, and the mortality rate is even lower. The incidence of thyroid carcinoma, especially in women, has been on the rise, due in part to improved diagnosis, but earlier detection, improved treatment, and a decline in the very aggressive anaplastic type have resulted in fewer deaths. Symptoms: In its early stages, thyroid cancer often does not exhibit symptoms. As the disease progresses, however, the affected person may develop a nodule (lump) in the front of the neck; hoarseness or changes in the normal speaking voice; swollen lymph nodes, especially in the
Incidence of Thyroid Cancer per 100,000 People, by Gender 14 Women
Men
12.6
12.5 12
11.6
10 7.8
8
7.3
6 4.3 4
3.9 3.3 2.7
2.4
2
0 White
Asian/Pacific Islander
Hispanic
American Indian/ Alaska Native
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: Based on cases diagnosed in 2000-2004
1170
Black
Salem Health: Cancer amount of radioactive material to make thyroid nodules show up on a picture. When thyroid cancer is diagnosed, tests are done to determine whether the cancer has spread; this process is called staging. Tests such as ultrasonography, computed tomography (CT) scanning, and magnetic resonance imaging (MRI) can help the doctor determine if the cancer has spread to the lymph nodes or to other areas. A special scan may be used to check for the spread of medullary cancer. Staging is essential to choose treatment options and predict odds for cure and long-term survival. A common staging system is that of the American Joint Committee on Cancer (AJCC), called the TNM (tumor/ lymph node/metastasis) system. This system looks at the size of the tumor, whether it has spread to the lymph nodes, and whether it has metastasized to distant organs. Stages are described in Roman numerals from I to IV, with values assigned to each one. In the case of papillary or follicular thyroid carcinoma, age is also taken into account. All anaplastic thyroid cancers are considered Stage IV to reflect the poor prognosis of this particular kind of thyroid cancer. Treatment and therapy: Treatment for thyroid cancer includes surgery, thyroid hormone therapy, radiation, and chemotherapy. Total or near-total surgical removal is the treatment of choice in most cases. Following surgery, thyroid hormone medication is required for life to supply the hormone the thyroid would normally produce. Frequent blood tests are done until the proper dosage can be established. Radioactive iodine may be used for follow-up screening to detect remaining normal or abnormal tissues. Moderate doses can eliminate the normal tissue, and larger doses destroy any cancerous cells. External beam radiation also destroys cancer cells. Chemotherapy may be used when the cancer has metastasized, especially for the medullary type, which does not respond to radioiodine therapy. Other follow-up care includes blood tests for thyroglobulin levels that would indicate recurrence, and imaging such as ultrasonography. Prognosis, prevention, and outcomes: The type of thyroid cancer affects the prognosis to a large extent. In papillary and follicular cancer, Stages I and II have a 100 percent five-year survival rate. Stage III decreases to 96 percent for papillary and 79 percent for follicular types. Stage IV drops to 45 percent in papillary cancer and 47 percent for follicular. Stage I medullary thyroid cancer has a 100 percent five-year survival rate, then drops to 97 percent and 78 percent, respectively, for Stages II and III; however, the rate falls to only 24 percent for Stage IV. The five-year survival rate for anaplastic thyroid cancer is around 9 percent. Thyroid cancer prevention measures are limited. How-
Thyroid cancer ever, certain steps can be taken in situations in which there is heightened risk. A genetic test can determine if there is increased risk for medullary thyroid cancer. If the results are positive, thyroid gland removal may prevent development of cancer later in life. Also, government guidelines recommend that people living within ten miles of a nuclear power plant take potassium iodide tablets just before or immediately after exposure to fallout. Anyone who has received radiation to the head and neck during childhood should be examined carefully every year or two. More general measures include diets high in fruit and vegetables and low in animal fats and consumption of unsaturated fats, which contain omega-3 fatty acids. Maintaining a healthy weight may also help. Victoria Price, Ph.D. u
For Further Information Braverman, Lewis E., and Robert D. Utiger, eds. Werner and Ingbar’s The Thyoid: A Fundamental and Clinical Text. 7th ed. New York: Lippincott-Raven, 1991. Foley, John R., Julie M. Vose, and James O. Armitage. Current Therapy in Cancer. Philadelphia: W. B. Saunders, 1994. Lenhard, Raymond E., Jr., Robert T. Osteen, and Ted Gansler. The American Cancer Society’s Clinical Oncology. Atlanta: American Cancer Society, 2001. Rosenthal, M. Sara. The Thyroid Sourcebook: Everything You Need to Know. 3d ed. Los Angeles: Lowell House, 1998.
u
Other Resources
Endocrine Web Thyroid Cancer http://www.endocrineweb.com/thyroidca.html MedlinePlus Thyroid Cancer http://www.nlm.nih.gov/medlineplus/ thyroidcancer.html National Cancer Institute Thyroid Cancer http://www.cancer.gov/cancertopics/types/Thyroid See also Childhood cancers; Computed tomography (CT) scan; Cowden syndrome; Cruciferous vegetables; Fibrocystic breast changes; Gardner syndrome; Imaging tests; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Radionuclide scan; Surgical biopsies; Ultrasound tests; Young adult cancers; Zollinger-Ellison syndrome. 1171
Thyroid nuclear medicine scan
u Thyroid nuclear medicine
scan Category: Procedures Also known as: Thyroid scintiscan, technetium thyroid scan Definition: The thyroid nuclear medicine scan is an imaging technique using a gamma camera to help assess the health and anatomy of the thyroid gland following the administration of a radioisotope, a radiation-emitting form of an element. The radioisotopes most commonly used are iodine 123, iodine 131, and technetium pertechnetate. Other isotopes, such as gallium 67 and thallium 201, are also in use for their characteristic correlation in malignancy profiling. Still others are being scrutinized for better visualization of specific thyroid cancers. When radiation is given off during the procedure, it is recorded by the scanner on radiographic film or on a screen, which allows direct viewing or photographing of the thyroid image. The radioactive substance used often gives name to the procedure, such as a technetium thyroid scan or a radioactive iodine uptake scan (RAIU test). These studies are possible because of the thyroid’s special affinity for radioactive substances and its normal uptake of iodine in the production of thyroid hormones. Cancers diagnosed: Thyroid cancers (papillary, follicular, medullary, or anaplastic) Why performed: Thyroid scans are helpful in evaluating masses in the neck area, in defining specific types of hyperthyroidism, and in assessing thyroid nodules, metastatic tumors, and thyroid cancer. They are an important tool in determining the position, size, and structure of the thyroid gland and, together with other tests, help assess thyroid function. Scans are especially helpful in evaluating patients with suspected thyroid nodules. Thyroid nodules are either functioning (hot or warm) or nonfunctioning (cold), and this has important implications in assessing malignancy. The butterfly-shaped thyroid is an endocrine gland consisting of two lobes located on either side of the trachea connected by bridging tissue called an isthmus. Assessing thyroid health is critical because of its central role to basic human physiology. The iodine-laden hormone produced in the thyroid gland regulates oxygen consumption, body temperature, heart function, skeletal growth, skin function, and carbohydrate, lipid, and fat metabolism. Patient preparation: The scintiscan may be performed either in an outpatient X-ray center or a hospital radiol1172
Salem Health: Cancer ogy department. The patient is instructed to discontinue iodine-containing medications such as thyroid drugs, corticosteroids, phenothiazines, salicylates, anticoagulants, and antihistamines for several weeks to twenty-four hours prior to the scan, depending on the amount of time that the substance takes to clear from the body. If the radioisotope is to be administered orally, then the patient should fast after the midnight preceding the test. Fasting is not required for intravenous (IV) injection. Steps of the procedure: The patient will receive the radioisotope either intravenously or orally. The patient takes the oral medication (iodine 123 or iodine 131) as either a tasteless liquid or a capsule twenty-four hours prior to imaging or receives an IV injection (pertechnetate) twenty to thirty minutes before imaging. During the scan, the patient will be lying down with the face up. The camera is then positioned over the thyroid area in the neck, and the radioactive response is displayed on a monitor and recorded on X-ray film. The procedure is usually complete in less than thirty minutes. When evaluating thyroid function, the radioisotope iodine 123 or iodine 131 is measured at six hours and again at twenty-four hours after dosing. After the procedure: This is a noninvasive procedure, and there are no special precautions or instructions. Regular eating can continue two hours after imaging. Risks: The radioactive dose is very small and is generally considered harmless, but pregnant or lactating women, as well as patients allergic to iodine, shellfish, or the tracers used in the imaging, should not undergo the procedure. Results: Many types of thyroid pathology may be revealed through imaging, and fortunately most are not cancerous. One of the ways in which the scintiscan makes this distinction is through the assessment of thyroid nodules. A thyroid nodule is a nonspecific term for a swelling in the thyroid gland. It might be no more than an accumulation of thyroid cells or a cyst. Even though they are common, they might grow large enough to interfere with swallowing or breathing, or they can produce so much hormone that hyperthyroidism results. They can also become cancerous about 5 percent of the time. On scintiscan, the nodules are seen as hot, warm, or cold. An area of increased radionuclide uptake may be called a hot nodule, signifying that a benign growth has become overactive. An area of decreased radionuclide uptake, representing low thyroid activity, is a cold nodule. A variety of conditions, including cysts, nonfunctioning benign growths, localized inflammation, or cancer, may produce a cold spot. Hot or warm nodules are rarely malig-
Salem Health: Cancer nant, while almost all cancerous nodules are cold. A cold nodule is not exclusive to malignancy, however, as most benign nodules, cysts, and localized areas of inflammation are cold as well. Neoplasms are graded according to cell abnormality and for their potential for invasiveness and growth as a guide to treatment options and prognosis. The minimally invasive, encapsulated, and well-circumscribed growth is a grade I neoplasm. As the neoplasm becomes more aggressive and infiltrates the surrounding gland and the cells become more irregular and mitotic, the neoplasm is considered grade II. Grade III describes even more extensive growth, with possible invasiveness beyond the gland and increased cellular irregularity and mitosis. Further classification is done by anatomic staging, which defines the extent of the disease process. The results of a thyroid nuclear medicine scan serve as a guide and are almost always used in conjunction with other tests to establish a diagnosis. Richard S. Spira, D.V.M. u For Further Information Beers, Mark H., et al., eds. The Merck Manual of Medical Information, Second Home Edition. Whitehouse Station, N.J.: Merck Research Laboratories, 2003. Feld, Stanley. AACE Clinical Practice Guidelines for the Diagnosis and Management of Thyroid Nodules. New York: American Association of Clinical Endocrinologists, 1996. u
Other Resources
American Thyroid Association http://www.thyroid.org MedlinePlus http://www.nlm.nih.gov Thyroid Foundation of America http://www.allthyroid.org See also Cobalt 60 radiation; Cold nodule; Corticosteroids; Endocrine cancers; Imaging tests; Nuclear medicine scan; Pathology; Pregnancy and cancer; Radionuclide scan; Risks for cancer; Staging of cancer; Thyroid cancer; X-ray tests.
TNM staging
u TNM staging Category: Procedures Also known as: Tumor/nodes/metastases staging Definition: TNM (an abbreviation for tumor, node, and metastasis) staging is a system used to describe the extent and severity of solid malignant tumors and how much they have spread. Cancers diagnosed or treated: Solid tumors such as breast, colorectal, kidney, larynx, lung, and prostate cancers and melanoma Why performed: Staging of cancer is important because the stage at diagnosis is the most powerful predictor of survival. Doctors use staging information to help plan a patient’s treatment, to estimate a patient’s prognosis, to select changes in treatment, and to identify appropriate clinical trials for patients. TNM staging provides a common language with which oncologists and all other members of the health care team can communicate when discussing cancer patients, as well as evaluate and compare the results of clinical trials. Staging data, when collected over time, can be valuable to epidemiologists for analysis of similar types of cancer or for use in special studies. Patient preparation: Tissue samples are taken from a variety of tumors; patient preparation depends on the type of tumor and its location. Often, samples are taken as part of the surgical process to remove the tumor. Steps of the procedure: Staging is based on an understanding of the way in which cancer develops. A tumor is formed at the primary site as cancer cells grow and divide in an uncontrolled fashion. As a tumor grows, its cells can invade neighboring tissues or leave the tumor to migrate through the bloodstream or lymph system to new sites in the body, a process called metastasis. Staging systems for cancer have evolved over time and continue to be upgraded as cancer becomes better understood. The American Joint Committee on Cancer, established in 1988 to address the inadequacies of the traditional method of staging cancer using I-IV, created the TNM system for staging solid tumors throughout the body. Most types of solid tumors have TNM designations, although some do not (for example, cancers of the brain and spinal cord). As of 2008, the TNM system was in its sixth edition. In the TNM system, each factor is evaluated separately and given a number. For instance, a T1N1M0 cancer means that the patient has a T1 tumor, N1 lymph node involvement, and no metastases. 1173
Tobacco-related cancers The precise definitions of T, N, and M are specific to each type of cancer, but general definitions of each element are tumor, node, and metastasis. Tumor (T) describes the extent of the primary tumor and carries a number of 0 to 4, with 0 being a tumor that is entirely contained at the local site and 4 being a large primary tumor that has probably invaded other organs. Node (N) describes regional lymph node metastasis and can also be ranked from 0 to 4, with 0 being no lymph node involvement and 4 being extensive involvement. Metastasis (M) describes the presence or absence of distant metastases; it is 1 if distant metastases are present and 0 if not. For example, breast cancer T3N2M1 describes a large tumor that has spread outside the breast to nearby lymph nodes and to other parts of the body, whereas prostate cancer T2N0M0 describes a tumor located only in the prostate that has not spread to the lymph nodes or any other part of the body. The category X is used in each element where no assessment of that characteristic was made. For example, NX indicates that the status of lymph nodes was not assessed. It is important not to confuse this category with N0, which indicates that no lymph node involvement was found by the diagnostic tools used. The types of tests that are used for staging depend on the type of cancer but can include physical examination; imaging studies such as X rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), or positron emission tomography (PET) scans; laboratory values such as tests for liver function or tumor markers; pathology reports; and surgical reports. The TNM system has evolved as advances have been made in diagnosis and treatment of different types of cancer. For instance, endoscopic ultrasound imaging of esophageal and rectal tumors has improved the accuracy of the clinical T, N, and M classifications. Advances in treatment have necessitated more detail in some T4 categories. Clinical TNM staging and pathological TNM staging are distinct evaluations. Clinical staging is based on all available information obtained before pathology results are available. It may include information obtained by physical examination, radiologic examination, and endoscopy, for example. Pathologic staging includes information gained by microscopic examination of the primary tumor and regional lymph nodes. These two categories of staging are denoted by a small c or p before the stage, such as cT2N2M0 or pT3N4M1. It is also possible to stage a case at recurrence after a disease-free interval, at which time an r precedes the TNM designation. After the procedure: Aftercare depends on the type of biopsy taken and whether the patient was placed under 1174
Salem Health: Cancer anesthesia. For most types of biopsy for which a patient is not already hospitalized, patients will arrange transportation to and from the health care facility and will have a family member or friend’s supervision afterward. Often, a postsurgical hospital stay is required. Risks: The risks to patients are related to the type of sample taken and the disease involved. Results: Staging is an important aspect of understanding a patient’s cancer. It guides treatment decisions and provides insight into the patient’s prognosis. Jill Ferguson, Ph.D. u
For Further Information Bernick, P. E., and W. D. Wong. “Staging: What Makes Sense? Can the Pathologist Help?” Surgical Oncology Clinics of North America 9 (2000): 703-720. Kehoe, J., and V. P. Khatri. “Staging and Prognosis of Colon Cancer.” Surgical Oncology Clinics of North America 15 (2006): 129-146. Sobin, L. H. “TNM: Evolution and Relation to Other Prognostic Factors.” Seminars in Surgical Oncology 21 (2003): 3-7.
u
Other Resources
American Joint Committee for Cancer General Guidelines for TNM Staging http://training.seer.cancer.gov/module_staging_ cancer/unit03_sec03_part04_ajcc_guidelines.html National Cancer Institute Staging: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Detection/staging See also Biopsy; Blood cancers; Breast cancers; Epidermoid cancers of mucous membranes; Head and neck cancers; Imaging tests; Kidney cancer; Lung cancers; Melanomas; Metastasis; Risks for cancer; Staging of cancer; Surgical oncology; Thyroid cancer; Tumor markers; Ultrasound tests.
u Tobacco-related cancers Category: Diseases, symptoms, and conditions Definition: Tobacco-related cancers are malignant tumors that are caused wholly or in part by the direct use of or indirect exposure to tobacco and tobacco-based products. Related cancers: There are many types of cancer related to tobacco. The most well-known condition associated with tobacco is lung cancer. In the United States, lung can-
Salem Health: Cancer cer is the leading cause of cancer death, with 87 percent of these deaths related to tobacco. Other types of cancer related to tobacco include cancers of the bladder, breast, esophagus, kidney, larynx, liver, mouth, nasal cavity, pancreas, pharynx, stomach, and uterus. Tobacco also has been related to endometrial, cervical, and colon cancers, as well as myeloid leukemia. Tobacco-related products and their risks: Tobacco products include cigarettes, cigars, smokeless tobacco (such as snuff or chew), and pipe tobacco. Interestingly, nicotine is not considered carcinogenic, though it may play a role in cancer. It is the other chemicals in these products as well as what happens to them when vaporized through the process of smoking that are troublesome. For instance, the smoke may contain substances such as ammonia, carbon monoxide, cyanide, and even formaldehyde. Obviously, the way the products are used relates somewhat to the types of cancers produced. For instance, lung cancer is more associated with smoking, while use of smokeless tobacco products is typically linked to cancers of the mouth and throat. Incidence and statistics: Approximately 30 percent of all cancer deaths are said to be caused by tobacco use. Worldwide, more than three million people die each year from tobacco use. However, it is not just smokers who die, but also nonsmokers exposed to secondhand smoke. Estimates suggest that approximately 3,000 nonsmokers die of lung cancer each year because of secondhand smoke, and 35,000 people who are not current smokers will die each year of heart disease attributed to secondhand smoke exposure. For example, female nonsmokers exposed to secondhand smoke for as little as three hours per day on a regular basis have a threefold increase in risk for cervical cancer over female nonsmokers who are not exposed to secondhand smoke. Secondhand smoke also causes an increase in pet mortality due to cancer. Each year tobacco-related health problems cost Medicare and Medicaid $22.9 billion. In addition, over a lifetime, current and former smokers generate more than $500 billion in health care costs. Nancy A. Piotrowski, Ph.D. See also Acute myelocytic leukemia (AML); Air pollution; Bladder cancer; Blood cancers; Breast cancers; Cancer biology; Chewing tobacco; Cigarettes and cigars; Esophageal cancer; Head and neck cancers; Laryngeal cancer; Lung cancers; Malignant tumors; Metastatic squamous neck cancer with occult primary; Oral and oropharyngeal cancers; Pancreatic cancers; Personality and cancer; Prevention; Salivary gland cancer; Smoking cessation; Throat cancer; Uterine cancer.
Topoisomerase inhibitors
u Topoisomerase inhibitors Category: Chemotherapy and other drugs ATC code: 101XX, 101CB Definition: Topoisomerase inhibitors are a group of anticancer chemotherapeutic drugs. Topoisomerases are important in changing the topology of deoxyribonucleic acid (DNA), allowing for efficient DNA replication and subsequent cell proliferation. Inhibitors of topoisomerases primarily kill tumors by interfering with DNA replication, which results in both a decrease in tumor cell division and an increase in tumor cell death. Because tumors comprise rapidly dividing cells, cancer cells are particularly susceptible to the inhibitory actions of topoisomerase inhibitors. These drugs are often administered in combination with other chemotherapy agents but may also be given as a single-agent therapy. Cancers treated: Advanced colorectal cancer, testicular tumors, small-cell lung cancer, and acute lymphocytic leukemia; many other cancers that are refractory to first-line therapies Subclasses of this group: Epipodophyllotoxins, camptothecin and related analogs Delivery routes: Topoisomerase inhibitors are generally administered orally or intravenously (IV). The two main oral formulations used are either a solution or a soft gelatin capsule. Many of the topoisomerase inhibitors are not water-soluble and therefore to be administered by IV must be dissolved in a special solution of chemicals, including alcohol, polyethylene glycol, and polysorbate 80. This solution is responsible for the hypersensitivity reactions induced in some patients (less than 5 percent) following infusion, such as vasomotor changes in the gastrointestinal and pulmonary systems. Slowing the rate of infusion, as well as administration of steroids or antihistamines, can diminish these hypersensitivity reactions. How these drugs work: As a cell prepares to undergo division, the DNA must be replicated in order to provide a copy of DNA for each of the resulting cells. Doublestranded DNA is normally tightly coiled in the nucleus of nondividing cells. The supercoiled topology of the DNA strands makes it difficult for the replication protein complexes that are necessary to copy the DNA to properly localize on the DNA strand. Therefore, to properly duplicate the DNA, it must first be “unwound,” relaxing the structural topology and allowing access for the replication protein complexes. Topoisomerases are proteins located in 1175
Topoisomerase inhibitors
Salem Health: Cancer
Common Topoisomerase Inhibitors Drug
Brands
Subclass
Etoposide, etoposide phosphate
Etopophos, Epipodophyllotoxin VePeside (VP-16)
Delivery Mode
Cancers Treated
IV, oral
Refractory testicular tumors, small-cell lung cancer
Irinotecan hydrochloride Camptosar (CPT-11)
Camptothecin
IV
Metastatic colon cancer, metastatic rectal cancer
Teniposide
Vumon
Epipodophyllotoxin
IV
Childhood acute lymphocytic leukemia, glioma brain tumors
Topotecan
Hycamtin
Camptothecin
IV
Refractory ovarian cancer, small-cell lung cancer, advanced cervical cancer
the cell nucleus that can act to unwind the DNA. These proteins are enzymes, meaning that they have an intrinsic catalytic activity that allows them to perform a certain function in the cell. Topoisomerases relax the supercoiled DNA by making transient breaks within the DNA strand, allowing it to unwind. Once the topoisomerase cleaves the DNA and relieves the DNA topology, the enzyme then reseals the breakage. Two types of topoisomerases have been identified, mainly differentiated by how they cleave double-stranded DNA. Type I topoisomerases alter DNA supercoiling by cleaving only one DNA strand. Type II enzymes are capable of cleaving both DNA strands. The current model of both types I and II topoisomerase activity predicts that the enzyme breaks the DNA phosphate backbone, and in an intermediate reaction step, a covalent linkage is formed between the DNA and the enzyme. For type I topoisomerases, the nicked DNA strand is then free to rotate around the unnicked strand, relieving the DNA supercoil. Type II topoisomerases relax the DNA by cleaving the entire DNA strand, inducing the passage of one DNA double-strand through a loop in another DNA double-strand. Without the action of topoisomerases, normal cell division would not be possible. However, these enzymes also play a major role in the growth of cancer cells. Many natural compounds act to poison topoisomerases. Inhibitors to both types of topoisomerases have shown clinical activity against tumors. The primary mechanism of action of topoisomerase inhibitors is thought to be stabilization of the enzyme while it is bound to the cleaved DNA. By stabilizing this complex, the topoisomerase enzyme is unable to religate the DNA back together, resulting in cleaved DNA strands. Prolonged DNA cleavage induces apoptosis, or cell death. These drugs therefore are thought to kill cells either by increasing the rate of 1176
DNA breakage or by decreasing the rate of DNA religation. Although some of these drugs may also intercolate between DNA bases, DNA binding has been shown not to be a critical component of topoisomerase activity inhibition, as neither camptothecin nor etoposide binds DNA. Two main groups of topoisomerase inhibitors are currently in clinical use, epipodophyllotoxins and camptothecin analogs. Epipodophyllotoxins, which target topoisomerase II, were synthesized in an effort to chemically improve the efficacy of the antimicrotubule drug podophyllotoxin, isolated from the mandrake plant. The epipodophyllotoxins include etoposide and teniposide. Camptothecin, an inhibitor of topoisomerase I, was discovered in an extract from the Chinese tree Camptotheca acuminate. The extreme side effects induced by camptothecin induced the creation of two main derivatives that cause fewer side effects, topotecan and irinotecan. Resistance to topoisomerase inhibitors can occur through many mechanisms, including changes in the accumulation of these drugs, changes in the topoisomerase enzyme, and changes in the cellular response to the damage induced by these drugs. Because many topoisomerase inhibitors are naturally occurring substances, they are particularly susceptible to natural cellular efflux mechanisms. Cellular efflux results in a “pumping out” of the drugs, causing less total concentration of drug to be available inside the cell. By means of in vitro laboratory techniques, several cancer cell lines have been shown to display resistance to topoisomerase inhibitors. Laboratory studies have found that one mechanism of this resistance is the development of point mutations within the topoisomerase enzyme, genetic alterations that may change the target binding site where these drugs bind to the enzyme, inhibiting the ability of the drug to bind. Another way in which cells evade the effects of topoisomerase inhibitors is by increasing the
Salem Health: Cancer expression of DNA repair enzymes, which can repair the cleavage induced by the topoisomerases. Side effects: Topoisomerase inhibitors are generally well tolerated in most patients. The main toxicity resulting from topoisomerase inhibitors is bone marrow suppression, also known as myelosuppression. This is primarily manifested as leukopenia, or a decrease in the number of circulating white blood cells, and thrombocytopenia, a decrease in the number of blood platelets. The decrease in white blood cells increases the risk of patients developing infections, while the decrease in blood platelets may increase the risk of bleeding. Typically, the onset of myelosuppression occurs within five to seven days after the initiation of therapy, peaks within the next week, and is returned to normal approximately twenty-one to twentyeight days after the original administration. Because of the potential seriousness of myelosuppression, patients receiving topoisomerase inhibitor therapy are required to be closely monitored by a clinician. Patients can effectively manage myelosuppression by avoiding interaction with infected people and by minimizing the risk of cuts and bruises. Other side effects that result from drug administration mainly involve the gastrointestinal system, including diarrhea, nausea, and vomiting. Many patients often experience hair loss. These side effects can be controlled by reducing the dosage of therapy administered and by administering drugs to control the side effects, such as antinausea agents. Most of these side effects are reversible after drug therapy is stopped. Despite the powerful effects that these drugs have in inducing tumor cell death, the use of topoisomerase inhibitors has also been linked with the development of secondary cancers in rare cases. For example, use of epipodophyllotoxins such as etoposide has been associated with an increased risk of developing secondary leukemia, at an incidence ranging from 0.7 to 3.2 percent. The reason for this increase is currently unknown. Lisa M. Cockrell, B.S. u
For Further Information Adams, Val R., and Thomas G. Burke, eds. Camptothecins in Cancer Therapy. Totowa, N.J.: Humana Press, 2005. Andoh, Toshiwo, ed. DNA Topoisomerases in Cancer Therapy: Present and Future. New York: Kluwer Academic/Plenum, 2003. Kantarjian, Hagop M., et al. The M. D. Anderson Manual of Medical Oncology. New York: McGraw-Hill, 2006. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006.
TP53 protein Pratt, William B., et al. The Anticancer Drugs. 2d ed. New York: Oxford University Press, 1994. Skeel, Roland T. Handbook of Cancer Chemotherapy. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007. u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Acute lymphocytic leukemia (ALL); Antineoplastics in chemotherapy; Chemotherapy; Drug resistance and multidrug resistance (MDR); Infusion therapies; Leukemias; Lung cancers; Myelosuppression; Plant alkaloids and terpenoids in chemotherapy; Rectal cancer; Testicular cancer.
u TP53 protein Category: Cancer biology Also known as: Tumor protein 53, p53, cellular tumor antigen p53, tumor suppressor p53, phosphoprotein p53 (pp53), antigen NY-CO-13, guardian of the genome Definition: The TP53 protein is the product of the TP53 tumor-suppressor gene. As the molecular weight appears to be 53,000 when electrophoresed in a sodium dodecyl sulfate (SDS) polyacrylamide gel, it is referred to as TP53. The TP53 protein functions as a transcription factor that controls the activity of other genes. The TP53 gene is often referred to as the “guardian of the genome” because if the cell detects damage to its deoxyribonucleic acid (DNA), TP53 protein prevents the replication of the damaged DNA, stimulates DNA repair, or stimulates cell death (apoptosis) so that damaged DNAis not passed to daughter cells. It also seems to be important in the process of suntanning. Biological function: The TP53 tumor-suppressor gene is located on chromosome 17 at 17p13.1 and is essential for cell function. The TP53 protein’s anticancer activity is exhibited by one of several mechanisms, many of which have not been clearly elucidated: activating mechanisms that repair DNA, arresting the cell cycle and preventing it from entering the DNA synthesis phase and passing damaged DNA on to daughter cells until damaged DNA can be re1177
TP53 protein paired, and initiating apoptosis to prevent damaged DNA from being replicated and distributed to its daughter cells. One well-characterized pathway involves the CDKN1A (p21) gene, so called because its product is a protein of 21,000 daltons. Normally, TP53 is sequestered in the nucleus by the protein HDM2. When bound to HDM2, TP53 is inactive and targeted for breakdown, keeping its cellular concentration low. If the cell detects damage to its DNA, oxidative stress, or membrane damage, TP53 becomes phosphorylated on its N-terminus by enzymes called kinases. These kinases include DNA-PK, CHK1, CHK2, ATM, ATR, CAK, and members of the MAPK (mitogenactivated protein kinase) family. When phosphorylated, TP53 dissociates from HDM2, becomes more stable, increases in concentration, changes its conformation, and becomes an active transcription factor that stimulates transcription of several genes including the CDKN1A gene. The CDKN1A protein binds to and inactivates polypeptides that are required for the cell to enter the DNA synthesis phase of the cell cycle. Thus, the cell is prevented from replicating damaged DNA that could cause cancer and passing it on to its daughter cells. The TP53 protein can also activate genes that stimulate apoptosis of cells with damaged DNA, activate genes necessary for the repair of damaged DNA, and stimulate genes involved with the tanning reaction to protect cells from damaging ultraviolet (UV) light. By these and other mechanisms TP53 prevents cell growth and even causes cell death to suppress the formation of cancer. Structure of the protein: Active TP53 protein is a tetramer consisting of four identical polypeptides of 393 amino acids each. Many of the amino acid residues can be assigned to distinct functional domains. The 39 amino acid residues at the N-terminus are involved with HDM2 binding and activation of transcription of the CDKN1A gene. Residues 80 to 94 are responsible for TP53’s apoptosis activity, while amino acid residues 101 to 306 are responsible for TP53’s DNA-binding activity, an activity essential to its role as a transcription activator. The ability of TP53 monomers to polymerize into tetramers depends on amino acid residues 307 to 355. The C-terminus amino acids (356 to 393) are responsible for TP53’s localization in the nucleus and nonspecific binding to damaged DNA. Cancer involvement: Mutations, usually simple amino acid replacement (missense) mutations, and deletions in the TP53 gene that alter the function of its product can severely limit its tumor-suppressor activity. People who inherit one defective TP53 gene are highly predisposed to developing Li-Fraumeni syndrome, which is characterized by cancer in a variety of tissues. More than 50 per1178
Salem Health: Cancer cent of all human cancers involve the TP53 gene, including 60 percent of head and neck cancers, 50 percent of ovarian and lung cancers, 45 percent of colon cancers, 35 percent of stomach cancers, and 30 percent of bladder cancers. Of the mutations in TP53 that result in cancer, 90 percent affect the DNA-binding domain (amino acids 101 to 306). These mutations result in the inability of TP53 to bind to the CDKN1A gene and stimulate its expression. Mutations in the TP53 gene affecting amino acid residues 307 to 355 are in the domain that allows TP53 to form tetramers with other TP53 molecules, a function necessary for its activity. TP53 molecules with one of these mutations form dimers with normal TP53 molecules, preventing their activity. Thus, these mutations are referred to as dominant loss-of-function mutations. Charles L. Vigue, Ph.D. u
For Further Information Hainaut, Pierre, and Klas G. Wiman. Twenty-five Years of p53 Research. New York: Springer, 1999. Mukhopadhyay, Tapas, Steven A. Maxwell, and Jack A. Roth. p53 Suppressor Gene. New York: Springer, 1995. Zambetti, Gerald, ed. Protein Reviews: The p53 Tumor Suppressor Pathway and Cancer. New York: Springer, 2005.
u
Other Resources
Cornell University Tumor Suppressor Genes: Guardians of Our Cells http://envirocancer.cornell.edu/FactSheet/Genetics/ fs6.TSgenes.cfm HUGO Gene Nomenclature Committee Symbol Report: TP53 http://www.genenames.org/data/hgnc_data .php?hgnc_id=11998 International Agency for Research on Cancer IARC TP53 Mutation Database http://www-p53.iarc.fr p53 Knowledgebase http://p53.bii.a-star.edu.sg/index.php The p53 Web Site http://p53.free.fr See also Adenoid cystic carcinoma (ACC); Ataxia telangiectasia (AT); Bowen disease; BRAF gene; Breast cancer in pregnant women; Cancer biology; Cytogenetics; Dilation and curettage (D&C); Drug resistance and multidrug resistance (MDR); Endocrine cancers; Endometrial cancer;
Salem Health: Cancer Fallopian tube cancer; Family history and risk assessment; Fibrosarcomas, soft-tissue; Free radicals; Gene therapy; Genetics of cancer; Giant cell tumors (GCTs); Gynecologic cancers; Li-Fraumeni syndrome (LFS); Liver cancers; Mutagenesis and cancer; MYC oncogene; Nasal cavity and paranasal sinus cancers; Neuroectodermal tumors; Oncogenes; Sarcomas, soft-tissue; Simian virus 40; Spermatocytomas; Thymus cancer; Tumor-suppressor genes; Virus-related cancers; Vulvar cancer.
u Tracheostomy Category: Procedures Also known as: Tracheotomy, trach tube Definition: Tracheostomy is a surgical procedure performed to aid breathing. An incision is made in the neck, just below the larynx (voice box), to directly access the trachea (windpipe). A tracheostomy tube is inserted through the opening, called a stoma, to keep the airway open. The tracheostomy tube may be connected to oxygen or mechanical ventilation.
Tracheostomy patient’s chest, are attached via wires to an electrocardiograph (EKG) machine to monitor the patient’s heart rhythm. The patient receives general anesthesia through the IV. The neck is cleaned, and sterile drapes are placed around the surgical area. Incisions are made in the neck and through the second and third tracheal rings to create an opening in the trachea. The tracheostomy tube is inserted into the opening. Tape or stitches hold the tube in place. A newer technique, called tube-free tracheostomy, may be performed when a long-term tracheostomy is anticipated. A permanent opening in the trachea is created with skin and muscle flaps. After a one-month recovery period, the patient is usually able to talk efficiently by contracting the neck muscles, without the use of valves or devices. After the procedure: The patient will not be able to talk or eat by mouth immediately after the procedure and while remaining on mechanical ventilation. Most patients will need several days to adjust to breathing through the trach tube. Nutrition is given directly into the stomach through a
Cancers treated: Neck, laryngeal, thyroid, and some congenital cancers Why performed: A tracheostomy is performed for patients who have an upper airway obstruction, difficulty breathing, or excess secretions in the airway. It is also performed for patients recovering after tracheal or laryngeal surgery and for patients who are having difficulty being weaned from mechanical ventilation. Patient preparation: With a planned tracheostomy, patients must stop taking aspirin and products containing aspirin, ibuprofen, and anticoagulants, as directed by the physician, one week before the procedure. Patients must not eat or drink for eight hours beforehand. Steps of the procedure: The procedure is usually performed by a surgeon in an operating room while the patient is under general anesthesia. In emergent cases, the procedure may be performed at the patient’s bedside in an emergency room or an intensive care unit (ICU). If the procedure is emergent, then the patient lies on the back with a rolled-up towel between the shoulders. A local anesthetic is injected and the procedure is performed. In nonemergent cases, an intravenous (IV) line is inserted into the patient’s arm to deliver medications. A small clip placed on the patient’s finger is attached to an oximeter monitor to check the patient’s blood oxygen level during the procedure. Electrodes, placed on the
A tracheostomy tube placed in the trachea. (LifeART© 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.)
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Transfusion therapy percutaneous endoscopic gastrostomy tube until the tracheostomy tube is removed. The patient will communicate with others by writing and nonverbal communication in response to questions. With training and an adaptive valve on the tracheostomy, patients are able to resume speaking as they adjust to the tracheostomy. A speech therapist can help the patient learn to speak with the tube in place. Antibiotics may be given to reduce the risk of infection. A nurse or respiratory therapist will remove secretions from the trach tube using a suction device to clear the breathing passages. A tracheostomy is not necessarily permanent. The patient’s condition and the purpose of the tracheostomy will determine when and if the tube can be removed. If the tube is eventually removed, then the area heals quickly, leaving a small scar. The patient and caregiver will learn how to care for the tracheostomy before leaving the hospital. The patient is usually able to go home in three to five days after the procedure, depending on his or her medical condition and rate of recovery. Some patients go home with mechanical ventilation, depending on their condition. A nurse will teach the patient and caregiver how to care for the equipment; suction, clean, and change the tube; and manage emergencies. Routine tracheostomy care must be performed at least once daily at home. Aloose covering or tracheostomy cover is recommended to prevent foreign particles from entering the stoma. The patient must take precautions to avoid getting water in the opening. The patient will feel some pain and discomfort in the neck area for about one week after the procedure, and pain medication will be prescribed as needed. It may take up to one month for the patient to heal completely. Most activities can eventually be resumed within six weeks after the procedure. Risks: Like all surgeries, the tracheostomy procedure has risks. Complications are rare but may include bleeding, damage to the larynx or airway with a permanent change to the voice, need for further surgery, infection, scarring of the airway or neck, or impaired swallowing function. The health care team will discuss the potential risks of the procedure with the patient and his or her family or caregiver beforehand if the tracheostomy is not being performed as an emergent procedure. Results: A tracheostomy can help the patient breathe more easily and allows the health care provider to clear secretions from the patient’s breathing passages. In many cases, the tracheostomy is temporary and is removed when the patient is able to breathe without the help of a ventilator. Angela M. Costello, B.S. 1180
Salem Health: Cancer u
For Further Information Cooper, Sue, ed. Tracheostomy Care. Hoboken, N.J.: John Wiley & Sons, 2006. Lewarski, Joseph. “Management of the Tracheostomy Patient in the Home.” RT for Decision Makers in Respiratory Care, August, 2006. Available online at http:// www.rtmagazine.com. Pierson, D. J., S. K. Epstein, C. G. Durbin, Jr., et al. “Twentieth Annual New Horizons Symposium: Tracheostomy from A to Z.” Respiratory Care 50 (2005): 473-549. See also Infection and sepsis; Laryngeal cancer; Laryngeal nerve palsy; Laryngectomy.
u Transfusion therapy Category: Procedures Also known as: Blood transfusion, red cell transfusion, platelet transfusion, plasma transfusion, cryoprecipitate transfusion, granulocyte transfusion Definition: Transfusion therapy is the infusion of blood components. Cancers treated: All Why performed: Cancer patients may need transfusion of blood components because of the disease itself or as a result of cancer treatments. Some cancers, such as those of the digestive system, may cause loss of blood through internal bleeding. Patients with cancers affecting the production or storage of blood cells may need transfusion if blood counts become too low. Treatments such as chemotherapy and radiation may destroy enough cells that patients need transfusion. Patients having surgery for cancer may need blood to replace blood loss during the procedure. Patient preparation: The physician admits the patient to an inpatient or outpatient facility. The physician discusses benefits and risks of transfusion with the patient or legal guardian and asks him or her to sign an informed consent for transfusion. Patients experiencing previous allergic reactions to blood components are given a pretransfusion medication such as diphendydramine (Benedryl). Steps of the procedure: A phlebotomist collects a sample of blood. In some facilities, a special transfusion armband is placed on the patient’s arm at the time that the blood sample is collected. Other facilities use the standard hospital patient armband for identification. The sample is sent to transfusion services.
Salem Health: Cancer Transfusion services staff test the sample to determine the patient’s blood type. An antibody screening is also done to detect any unusual antibodies, proteins that may cause adverse reactions if the corresponding antigen is present on the donor cells. These antibodies may be naturally occurring, formed from exposure to a blood cell antigen during previous blood transfusions, or, in females, during childbirth. If unusual antibodies are present, then donor units that lack the corresponding antigen are used for transfusion. Transfusion services staff select appropriate components from storage. If the component is red cells, then a crossmatch is performed to ensure compatibility between the patient’s serum and the donor red cells. Platelets, fresh frozen plasma, or cryoprecipitate do not need to be crossmatched. The selected components are tagged with the patient’s name and identification number, the component unit number, blood type of the patient and the donor, results of antibody screening, and any special needs. Special needs that the physician may order are leukoreduction and/or irradiation of cellular components (red cells and platelets). Leukoreduction is the removal of white cells, which decreases exposure to leukocyte antigens and cytomegalovirus (CMV). Irradiation is done to prevent graft-versus-host disease. A nurse inserts an intravenous (IV) line into the patient’s arm. Two nurses verify identification of the patient and that information on the component tag matches the patient and donor information. Before starting the transfusion, the nurse checks and records the patient’s temperature, pulse, and blood pressure. During the first fifteen minutes of the transfusion, the nurse stays at the bedside and observes the patient for any signs of adverse reaction. At the end of fifteen minutes, the nurse again checks and records pulse, temperature, and blood pressure. Transfusion of blood components takes as little as fifteen minutes to as long as four hours, depending on the component and the rate of transfusion that the physician orders. At the end of the transfusion, the nurse again checks and records the pulse, temperature, and blood pressure, comparing them with the beginning rates. Changes that are greater than established standards at any time or adverse patient symptoms may result in stopping the transfusion. The physician reviews the information and may order a reaction workup. In the event of a reaction workup, any remaining component and the transfusion tubing are sent to transfusion services. A phlebotomist collects a new sample of blood and sends it to transfusion services. Nursing staff and transfusion services staff review all patient identification, paperwork, and donor information. Repeat testing is performed on pretransfusion and posttransfusion blood samples and the donor sample. Additional tests such as a cul-
Transfusion therapy
Cancer patients may require blood transfusions because of either the disease itself or cancer treatments. (PhotoDisc)
ture for bacteria or other blood and chemistry tests may be done. A pathologist reviews the results of the transfusion reaction workup and determines the cause. The patient will not be transfused with additional components until the completion of the workup. After the procedure: The IV line is removed. The nurse advises the patient about signs and symptoms to watch for and report. Blood samples may be collected to test for hemoglobin, platelet count, or clotting factors. If transfusion is done on an outpatient basis, then the patient may be discharged shortly after completion of the transfusion. Risks: The risks of transfusion are allergic reactions, transmission of viruses or infectious diseases, fever iron overload, lung injury, acute hemolytic reaction, delayed hemolytic reaction, and graft-versus-host disease. Results: Red cells are given to replace blood loss or correct anemia. Platelet transfusions are given to replace 1181
Transitional care platelets to prevent bleeding. Plasma and cryoprecipitate are given to correct coagulation factors. Rarely, granulocytes are given to increase the white blood cell count. Wanda E. Clark, M.T. (ASCP) u For Further Information Abeloff, Martin D., et al. Clinical Oncology. 3d ed. Philadelphia: Churchill Livingstone Elsevier, 2004. Klein, Harvey G., and David J. Anstee. Mollison’s Blood Transfusion in Clinical Medicine. 11th ed. Malden, Mass.: Blackwell, 2005. u
Other Resources
American Association of Blood Banks, America’s Blood Centers, and the American Red Cross Circular of Information for the Use of Human Blood and Blood Components http://www.fda.gov/cber/gdlns/crclr.pdf American Cancer Society Why Cancer Patients Might Need Blood Product Transfusions http://www.cancer.org/docroot/ETO/content/ ETO_1_4x_Why_Cancer_Patients_Might_Need_ Blood_Product_Transfusions.asp?sitearea=ETO National Heart and Lung and Blood Institute Diseases and Conditions Index What Is a Blood Transfusion? http://www.nhlbi.nih.gov/health/dci/Diseases/bt/ bt_whatis.html See also Anemia; Aplastic anemia; Autologous blood transfusion; Biological therapy; Blood cancers; Bone marrow aspiration and biopsy; Fanconi anemia; Hematemesis; Hematologic oncology; Hemochromatosis; Hemolytic anemia; Hepatitis B virus (HBV); Hepatitis C virus (HCV); Infusion therapies; Pathology; Risks for cancer.
u Transitional care Category: Social and personal issues Definition: Transitional care consists of the needs, services, and resources to consider when helping a person with cancer adjust, as the disease shifts from one phase to another. The importance of transitions: The course of treatment for cancer can be long and difficult, with many changes in disease state and in treatments. As these changes occur, the 1182
Salem Health: Cancer needs of the patient and the patient’s family or caregivers also change. For example, the patient may move from hospital care to home care, or from home care to hospice care. In other situations, the patient may shift frequently between home care and hospital care, or may require care at a rehabilitation facility or a nursing home. Whatever the case may be, it is important that the patient’s (and family’s) needs remain the primary consideration and that each transition occurs as smoothly as possible to ensure continuity of care. What to consider in planning: Ideally, a nurse will develop a comprehensive care plan addressing every aspect of the patient’s life that will be affected by the forthcoming transition. This plan should include a detailed assessment of the following: • The patient’s current physical status • Specific needs of the patient and family if the patient is cared for at home • The patient’s and family’s emotional and psychological adjustment • Requirements for extra support at home • Transferring records and other information with the patient if health care providers change • Financial issues, such as insurance coverage, the patient’s ability to work, and how the costs of care will be covered • Spiritual needs of the patient and family • Legal issues, such as advance directives, a living will, health care proxy, durable power of attorney, and do-notresuscitate (DNR) orders The patient (or the patient’s caregivers) should receive all legal documents, which should accompany the patient through different stages of care. This helps ensure that the patient’s wishes are respected during all stages of care. Who does the planning: Many people may be involved in planning for transitional care, depending on the needs of the patient and family. Those involved might include the patient and patient’s family or caregivers, the patient’s doctors and primary nurse, a social worker, psychologist or other mental health professional, advocacy or support personnel from community agencies or cancer support organizations, pastoral counselor or other spiritual adviser, physical therapist, and occupational therapist. Services available: A variety of services are available, depending on the needs of the patient and family and on available local resources. For example, patients may require specific services, such as visiting nurses, housekeeping or cleaning services, medical equipment and supply services, a home infusion agency, financial or legal con-
Salem Health: Cancer sultation, transportation services for medical appointments, counseling, spiritual care, employment services that can help with employment transitions or skills retraining, special services to enable the patient to return to school, and other community services that can assist with various needs, such as home meal delivery and errands. Other patients may be transferred to a hospice, to a nursing home, or to a rehabilitation center. Many of these facilities provide a social worker, nurse, or other personnel to help the patient and family adjust to the new surroundings, to access needed services, and to ensure that the patient’s medical care (including medication) is coordinated among previous and current care providers. Transition to the patient’s or caregiver’s home: In this case, health care staff are advised to assess the following aspects of home care: • Issues of safety and access (stairs, bathing facilities, and the like) that may require modification (ramps, handle bars, lifts) • If special equipment (hospital beds, medical devices) will be required in the home • If the home can physically accommodate such equipment • If the patient or caregiver is able to operate the equipment • If the patient or caregiver will require physical help (such as with the patient’s hygiene or personal care) • If the patient or caregiver understands and can safely give medications • If the patient or caregiver can handle the emotional stress of home care • If the patient or caregiver understands pain control and how to manage symptoms of pain. The person performing this assessment (for example, an occupational therapist, social worker, or home health nurse) can then work with the patient and appropriate staff to ensure the patient’s needs are met. Amy J. Neil, M.S., M.A.P. u
For Further Information Bellenir, Karen, ed. Cancer Survivor Sourcebook. Detroit: Omnigraphics, 2007. Brennan, James. Cancer in Context: A Practical Guide to Supportive Care. New York: Oxford University Press, 2004. Houts, Peter, ed. Home Care Guide for Cancer. Philadelphia: American College of Physicians, 1996. Stern, Theodore, and Mikkael Sekeres. Facing Cancer: A Complete Guide for People with Cancer, Their Families, and Caregivers. New York: McGraw-Hill, 2004.
Transitional cell carcinomas u
Other Resources
Hospice Foundation of America http://www.hospicefoundation.org International Association for Hospice and Palliative Care http://www.hospicecare.com National Cancer Institute Transitional Care Planning http://www.cancer.gov/cancertopics/pdq/ supportivecare/transitionalcare/patient National Care Planning Council http://www.longtermcarelink.net National Family Caregivers Association http://www.nfcacares.org National Patient Advocate Foundation http://www.npaf.org Patient Advocate Foundation http://www.patientadvocate.org See also Advance directives; Caregivers and caregiving; Do-not-resuscitate (DNR) order; Financial issues; Home health services; Hospice care; Infusion therapies; Insurance; Living will; Occupational therapy; Oncology social worker; Psychosocial aspects of cancer; Rehabilitation.
u Transitional cell carcinomas Category: Diseases, symptoms, and conditions Also known as: Transitional cell cancer, bladder cancer, renal pelvic tumors, TCCs Related conditions: Bladder cancer, kidney cancer, renal cell carcinoma Definition: Transitional cell carcinoma is a cancer that forms in transitional cells in the lining of the bladder, kidney, or ureter (tube connecting the kidney to the bladder). Risk factors: Common risk factors for this disease include smoking, misusing certain pain medicines for an extended period of time, and exposure to some chemicals and dyes used in the textile, leather, plastic, and rubber industries. Etiology and the disease process: The lining of the bladder, ureter, and kidney contain transitional cells, which can change shape and stretch without breaking apart as needed in organs that expand in the urinary tract. Transitional cell carcinoma begins in these cells and can move 1183
Transitional cell carcinomas
Salem Health: Cancer
Stage at Diagnosis and Five-Year Relative Survival Rates for Bladder Cancer, 1996-2004 Stage a
Localized Regionalb Distantc Unstaged
Cases Diagnosed (%)
Survival Rate (%)
75 19 4 3
92.1 44.6 6.4 59.3
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 a Cancer still confined to primary site b Cancer has spread to regional lymph nodes or directly beyond the primary site c Cancer has metastasized
from the lining of the organs to invade the internal areas of the organ, as well as other nearby organs. Transitional cell carcinoma that begins as a superficial tumor may grow through the lining and into the muscular wall of the bladder, kidney, or ureter. This invasive cancer may extend into a nearby organ such as the uterus, vagina, or prostate gland or to nearby lymph nodes, in which case cancer cells may have spread to other lymph nodes or other sites, such as the lungs, liver, or bones. Incidence: The incidence of transitional cell carcinoma is equivalent to that of bladder and kidney cancer, though almost 90 percent of bladder and ureter cancers are caused by transitional cell carcinoma. According to the National Cancer Institute, bladder cancer is the fourth most common type of cancer in men and the eighth most common in women. Whites get bladder cancer twice as often as blacks and Hispanics. People with family members who have bladder cancer are more likely to get the disease, as well as people who have previously had bladder cancer. Symptoms: The most common symptom is blood in the urine (hematuria). Some patients experience pain or burning during urination or a change in urinary habits, such as painful urination or a frequent urge to urinate. Other symptoms include back pain, lethargy, and weight loss. Screening and diagnosis: Diagnosis of transitional cell carcinoma is confirmed with a physical exam, urinalysis, and urine cytology tests. The urinalysis determines if abnormalities such as blood, protein, sugar, and solids exist 1184
in the urine. Urine cytology is a microscopic examination of urine to detect any abnormal cells that have sloughed off the walls of the bladder or kidney and been released in the urine. If necessary, cytoscopy is performed; a very narrow tube with a light and camera is inserted through the urethra to examine the inside of the bladder and ureter. Further imaging studies can help determine if the cancer has spread to other layers of the organs, as well as outside the urinary tract. If bladder or kidney cancer is suspected, a physician may order a computed tomography (CT) scan, pyelography, or biopsy. The CT scan is helpful for a three-dimensional view of the urinary tract to determine if any masses or tumors exist in the bladder or if the cancer has spread to other organs. Pyelography involves injecting a special dye into the vein or urethra and examining a series of timedinterval X rays of the urinary system to determine if abnormalities exist. The biopsy is typically performed during cytoscopy, and abnormal cells can be detected with a microscope. Treatment and therapy: Treatment for transitional cell carcinoma depends on the stage and location of the cancer. Typically surgery to remove the entire kidney, the ureter, and the bladder cuff (connecting the ureter to the bladder) will be performed. When the cancer is superficial and in the lower third of the ureter, another procedure called a segmental resection of the ureter is performed. In this surgery, part of the ureter is removed and the ends of the ureter are reattached. Radiation therapy uses high-energy rays to kill localized cancer cells to shrink the tumor before surgery or if surgery is not an option. Chemotherapy uses one drug or a combination of drugs to kill cancer cells. Superficial bladder cancer can be treated with local chemotherapy by inserting a catheter through the urethra and leaving it in the bladder for several hours, once per week for several weeks. If the cancer has deeply invaded the bladder or spread to lymph nodes or other organs, chemotherapy may be used to treat the entire body. Prognosis, prevention, and outcomes: The outcome of transitional cell carcinoma varies depending on the exact location of the cancerous cells and whether the cancer has metastasized. Cancer localized to the kidney or ureter can be cured with surgery. Cancer that has metastasized to other organs is usually not curable, though there are exceptions. Preventive measures include not smoking, wearing protective equipment if exposed to toxic chemicals, and following the physician’s advice concerning the use of all pain medications, including over-the-counter pain medications. Treatment given after the primary treatment to in-
Salem Health: Cancer crease the chances of a cure is called adjuvant therapy and may include chemotherapy, radiation therapy, hormone therapy, or biological therapy. Robert J. Amato, D.O. u
For Further Information Ellsworth, Pamela. One Hundred Questions and Answers About Bladder Cancer. Sudbury, Mass.: Jones and Bartlett, 2005. Raghavan, Derek. Bladder Cancer: A Cleveland Clinic Guide—Information for Patients and Caregivers. Cleveland: Cleveland Clinic Press, 2008. Schrier, Robert W., ed. Diseases of the Kidney and Urinary Tract. 8th ed. Philadelphia: Wolters Kluwer Health/ Lippincott Williams & Wilkins, 2007. u
Other Resources
American Cancer Society Detailed Guide: Bladder Cancer http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=44
Transrectal ultrasound American Urological Association UrologyHealth.org http://www.urologyhealth.org National Cancer Institute Bladder Cancer http://www.cancer.gov/cancertopics/types/bladder See also Bladder cancer; HRAS gene testing; Kidney cancer; Phenacetin; Urethral cancer; Urinary system cancers.
u Transrectal ultrasound Category: Procedures Also known as: Prostate sonography Definition: Transrectal ultrasound is a procedure that uses ultrasonic waves to evaluate the prostate gland, primarily by acting as a guide for prostate biopsies. Cancers diagnosed: Prostate cancer
A doctor performs a transrectal ultrasound of a patient’s prostate gland. (©Yoav Levy/Phototake—All rights reserved)
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Transvaginal ultrasound
Salem Health: Cancer
Why performed: Since the sensitivity of transrectal ultrasound is only 60 to 70 percent for the detection of prostate cancer, it is not a screening test. Therefore, the primary role of transrectal ultrasound is to guide prostate biopsies. The sonographic appearance of prostate cancer is variable, with approximately 70 percent of cancer appearing hypoechoic (lower in density) compared to the peripheral zone. The remainder of prostate cancer can appear hyperechoic (higher in density) or a mixture of both and can be either nodular or infiltrative. Cystic cancer is rare. Although classically cancer of the prostate presents as a hypoechoic nodule in the peripheral zone, only 20 to 30 percent of such nodules actually represent cancer. Benign conditions that can be visualized on transrectal ultrasound include prostatitis, atrophy, fibrosis, infarct, and benign prostatic hyperplasia (BPH).
See also Benign prostatic hyperplasia (BPH); Endorectal ultrasound; Prostate cancer; Prostate-specific antigen (PSA) test; Prostatitis; Screening for cancer; Ultrasound tests.
Patient preparation: The scan is usually performed as an outpatient procedure, and patients are not asked to perform any special preparation.
Why performed: Transvaginal ultrasound is a diagnostic procedure used to evaluate women with dysfunctional uterine bleeding to detect pelvic masses, ectopic pregnancy, and pelvic inflammatory disease. In postmenopausal women, the thickness of the endometrium is evaluated to check for overgrowth (hyperplasia) or cancer. Since the ovaries shrink after menopause, a gynecologist cannot feel them during a routine pelvic examination. The ovaries can be examined by transvaginal ultrasound.
Steps of the procedure: The patient is placed on his side on a table, and the technologist or the radiologist applies a water-based conducting gel to the probe in order to study the organ or body part of interest, in this case the prostate gland. The transducer is designed to be inserted inside the rectum, and it may feel uncomfortable. The sonographer then rubs the handheld probe or transducer across the surface of the the prostate gland. There will be some discomfort from pressure, but the ultrasound waves themselves are painless. After the procedure: The scan is generated by the computer attached to the ultrasound probe and read by the radiologist the same day. The patient will need to contact his doctor or health care provider for the radiology report and for any follow-up therapy, Risks: The study is painless and relatively harmless, as no radiation is involved. Use of the transrectal probe is a decision made by the health care provider, not the sonographer or radiologist. The patient should consult his health care provider if he has any questions or concerns regarding use of the transrectal probe and talk to his health professional about any concerns regarding the need for the ultrasound, its risks, how it will be done, and what the results indicate. Results: The results are dependent on the type of scan performed and the reason for the study. If evidence of cancer is found, additional tests will be ordered to confirm the diagnosis and suggest a course of treatment. Debra B. Kessler, M.D., Ph.D. 1186
u Transvaginal ultrasound Category: Procedures Also known as: Transvaginal sonogram Definition: Transvaginal ultrasound is a diagnostic procedure that uses an internal probe or transducer to enter the vagina. Cancers diagnosed: Uterine, ovarian, and endometrial cancers; noncancerous fibroids
Patient preparation: Little preparation is needed for the transvaginal ultrasound. The patient undresses from the waist down and lies face-up on the examination table. Either the patient will place her feet in stirrups or a bolster is placed under the hips to tilt the pelvis upward for insertion of the probe as well as the examination. The bladder is empty. Steps of the procedure: Often the woman inserts the probe herself (similar to inserting a tampon). Warm gel is used to lubricate the probe. There may be slight pressure when the transducer is inserted. A transducer is used to transmit high-frequency sound waves, which bounce back to produce images that can be seen on a video monitor or recorded on X-ray film. There is no radiation exposure during transvaginal ultrasound, and the results are available immediately. The procedure is performed by a radiological technician or physician radiologist and read by a physician radiologist. After the procedure: The patient can resume normal activities immediately. There may be a small amount of leakage from the gel used, which can be absorbed by using a sanitary pad. Risks: No risks are associated with this procedure.
Salem Health: Cancer Results: The results of a transvaginal ultrasound may be normal or abnormal. Normal results mean that no abnormal areas are found in the uterus. It is normal in shape and size with no abnormal thickness, masses, or growths. Abnormal results include growths (masses or cysts) and unanticipated thickness. Because there is a risk of false positive results, abnormal findings should be evaluated and confirmed by magnetic resonance imaging (MRI) or biopsy. Marcia J. Weiss, J.D. See also Endometrial cancer; Gynecologic cancers; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Imaging tests; Pelvic examination; Ultrasound tests; Uterine cancer.
u Trichilemmal carcinomas Category: Diseases, symptoms, and conditions Related conditions: Trichilemmomas, Cowden syndrome Definition: Trichilemmal carcinomas are rare and slowgrowing malignant tumors that start in the outer sheath of a hair root; they most often occur on skin that has had a lot of exposure to the sun, such as the face or arms. Risk factors: There are no known risk factors, although exposure to the sun may be a reason for development of trichilemmal carcinoma. Etiology and the disease process: The cause of trichilemmal carcinoma is not known. The carcinoma is slowgrowing and does not cause pain. Incidence: Trichilemmal carcinoma usually occurs in individuals over the age of fifty, with equal incidence in men and women. Symptoms: A trichilemmal carcinoma appears as a small (approximately ¼-inch to ¾-inch in diameter) tan, fleshcolored, or purplish spot on the face, scalp, trunk, or extremities; usually it is a single spot. The tumor may look like a wart and may have a hair in it. Less likely, the trichilemmal carcinoma may be on a part of the body that is not exposed to the sun, and it may appear as multiple spots. There are no other symptoms of a trichilemmal carcinoma. Screening and diagnosis: Any spot on the skin that fits the description of a trichilemmal carcinoma should be looked at by a dermatologist. Trichilemmal carcinoma is diagnosed by biopsy and histological examination (when
Tuberous sclerosis the tissue is viewed under a microscope by a pathologist). Trichilemmal carcinoma is probably the malignant form of a noncancerous tumor called a trichilemmoma. A trichilemmal carcinoma is not the same as a malignant proliferating trichilemmal tumor (usually seen on the scalp or the back of the neck). Treatment and therapy: The trichilemmal carcinoma spot is usually easily removed by a surgeon during an outpatient surgical procedure; the procedure is considered low risk, and additional therapy is not necessary. It is possible that the spot may recur in the same location, and surgical removal should be repeated. Spread (metastasis) of a trichilemmal carcinoma is very unlikely. Prognosis, prevention, and outcomes: The prognosis for individuals who have had a trichilemmal carcinoma removed is very good. There are no recommended preventive strategies for trichilemmal carcinoma since the underlying cause is not known. Vicki Miskovsky, B.S., R.D. See also Carcinomas; Cowden syndrome; Family history and risk assessment; Metastasis; Sunscreens.
u Tuberous sclerosis Category: Diseases, symptoms, and conditions Also known as: Tuberous sclerosis complex (TSC), Bourneville disease, epiloia Related conditions: Benign tumors Definition: Tuberous sclerosis is a genetic disease characterized by the growth of benign tumors in the brain and other organs. Risk factors: Tuberous sclerosis develops because of a genetic mutation, but only 35 percent of tuberous sclerosis cases are known to be inherited; the other 65 percent are the result of spontaneous genetic mutations. The cause of these spontaneous mutations is unknown. Etiology and the disease process: Two genes have been shown to be important in the development of tuberous sclerosis: the hamartin gene (TSC1) and the tuberin gene (TSC2). Both of these genes are tumor suppressors, and mutations that suppress their function have been linked with uncontrolled cell growth. Because these genes are thought to act in concert together, inactivation of only one gene is sufficient to produce symptoms of tuberous sclerosis. 1187
Tubular carcinomas Incidence: Tuberous sclerosis is a relatively rare disease, affecting all ethnicities and both genders equally. Currently, nearly 1 million people worldwide are estimated to be afflicted with the disease; approximately 50,000 of these cases are in the United States. Symptoms: The growth of benign, tumor-like nodules is a common feature of tuberous sclerosis. These growths, also termed hamartomas, have the potential to form in almost every organ, resulting in distinct consequences. For example, brain growths can lead to seizures and mental retardation, while hamartomas that form in and around the heart, called cardiac rhabdomyomas, can lead to valve dysfunction and arrhythmia. Kidney growths, or renal angiomyolipomas, may eventually grow so large that the normal kidney function is compromised. Many children with tuberous sclerosis exhibit small, reddish facial growths, called angiofibromas. Screening and diagnosis: There is no particular hallmark sign used to diagnosis tuberous sclerosis. Instead, the recognition of a combination of major and minor symptomatic features is used to establish a clinical diagnosis. Treatment and therapy: Currently no cure exists for tuberous sclerosis. Surgery has become an important approach to remove harmful nodule growths and preserve the function of the affected organ. Drugs to alleviate the symptoms may also be used, including antiepileptic drugs to control seizures. Prognosis, prevention, and outcomes: The prognosis for individuals with tuberous sclerosis depends on the severity of symptoms. Many patients with mild tuberous sclerosis lead productive lives with a normal life span. However, if these patients are not treated appropriately, complications arising from hamartoma growth in vital organs can result in premature death. Lisa M. Cockrell, B.S. See also Benign tumors; Brain and central nervous system cancers; Fibrosarcomas, soft-tissue; Sarcomas, softtissue.
u Tubular carcinomas Category: Diseases, symptoms, and conditions Also known as: Pure or mixed tubular carcinomas, tubulolobular carcinomas Related conditions: Infiltrating ductal carcinomas Definition: Tubular carcinomas are a type of invasive ductal carcinoma, a well-differentiated form of breast can1188
Salem Health: Cancer cer, characterized by invasion of the stroma by small epithelial tubules. Risk factors: The risk factors for the development of tubular carcinoma may be the presence of a radial scar, lobular proliferative lesions, and ductal carcinoma. Etiology and the disease process: Tubular breast carcinoma is estrogen dependent and human epidermal growth factor receptor 2/neu (HER2/neu) negative. The tumor varies in size and cell division time. Tubular carcinomas are a genetically distinct group of breast cancers. In particular, pure tubular carcinomas are a separate morphologic entity and have more than 70 percent tubularity. Carcinomas with less than 70 percent tubularity are often ductal and aggressive, and are referred to as mixed tubular carcinomas. Another type of tubular carcinoma is tubulolobular carcinoma, which consists of tubular and infiltrating lobular elements. Tubular carcinoma is usually a unicentric lesion, but in about 20 percent of the cases, it exhibits multifocality. Multifocality is found in more than 30 percent of mixed tubular or tubulolobular carcinomas. Contralateral development of cancers, such as infiltrating ductal tumors, has been reported in 10 percent of patients with tubular carcinoma. Incidence: Although invasive cancers containing tubular elements are common, tubular carcinoma is rare and accounts for less than 2 percent of all breast cancers. It occurs most frequently in women between the ages of forty and sixty. Symptoms: Tubular carcinoma often manifests as a palpable mass. Infiltrating ductal carcinoma is characterized by a hard lump with irregular borders, and the skin over the area or the nipple may retract. Screening and diagnosis: Tubular carcinoma is usually detected by mammography, appearing as a small mass and spicules or microcalcifications when the mass is less than 1 centimeter (cm) in diameter. The spicules are often due to malignant cells and fibrous stroma. Under a microscope, the cancer cells in tubular carcinoma resemble tiny tubes that are well differentiated. Treatment and therapy: Treatment for tubular carcinoma resembles that for estrogen-responsive breast cancer, and it may include mastectomy. Prognosis, prevention, and outcomes: Pure tubular carcinoma typically does not metastasize, and patients with this disease have an excellent survival rate. However, the differentiation between the types of tubular carcinomas is important for more precise prognosis. With the increase of
Salem Health: Cancer nontubular elements in a tumor, the likelihood of metastatic spread and multifocality also increase. Anita Nagypál, Ph.D. See also Breast cancer in children and adolescents; Breast cancer in men; Breast cancer in pregnant women; Breast cancers; Calcifications of the breast; Ductal carcinoma in situ (DCIS); Invasive ductal carcinomas; Invasive lobular carcinomas.
u Tumor flare Category: Diseases, symptoms, and conditions Also known as: Hormone flare, hormonal flare Related conditions: All cancers Definition: Tumor flare is a sudden and temporary worsening of symptoms or markers, which can include an increase in the size a tumor, heightened pain, and abnormal blood chemistry values. Tumor flare can occur in all types of cancer and often follows administration of a cancer therapy. This can be considered a positive sign that the cancer is responding to the treatment; however, tumor flare can be life-threatening. Risk factors: Risk factors for tumor flare depend on the type of tumor and the stage of the cancer. Etiology and the disease process: The cause of tumor flare varies depending on the type of cancer and the tumor. Tumor flare typically involves intense exacerbation of symptoms followed by diminished symptoms. Incidence: Tumor flare is a common adverse reaction to chemotherapy in patients with cancer. Symptoms: Symptoms of tumor flare can include but are not limited to an increase in the size of the tumor, bone and tumor pain, paralysis (depending on the location of the tumor), and wide variations in blood laboratory values that can lead to life-threatening conditions. Screening and diagnosis: Tumor flare typically is not difficult to diagnose, as many of the symptoms are detectable by the patients. Further evaluation, however, can also include blood tests and biopsy. Treatment and therapy: Treatment for tumor flare includes supportive therapy for the symptoms, such as pain medications and treatments that counteract the potential variation in blood chemistry values. Hormonal therapy can also be used to reduce the symptoms of tumor flare.
Tumor lysis syndrome Prognosis, prevention, and outcomes: Prognosis for tumor flare depends on the type of cancer exacerbated by the flare. As a flare can be life-threatening but is not in every case, it is not possible to predict a prognosis. Tumor flare can be prevented by administration of antiandrogen therapy in some cases. Anna Perez, M.Sc. See also Androgen drugs; Antiandrogens; Chemotherapy; Hormonal therapies; Malignant tumors; Metastasis.
u Tumor lysis syndrome Category: Diseases, symptoms, and conditions Related conditions: Acute renal failure, cardiac arrhythmia, metabolic acidosis Definition: Tumor lysis syndrome is a potentially lifethreatening metabolic emergency caused when tumor cells are destroyed and broken down faster than the body can get rid of them. This causes an increase in various electrolyte levels in the blood. The rapid increase of uric acid and phosphate may also cause acute renal failure. These cells are destroyed by chemotherapy, radiation, or the disease process itself. Tumor lysis syndrome can occur up to seven days after the initiation of treatment. The increase in destroyed cells can occur rapidly and cause patient death. Risk factors: People at risk are those who are diagnosed with a rapidly growing cancer that responds well to chemotherapy. Common cancers that place patients at risk for tumor lysis syndrome are leukemia, non-Hodgkin lymphoma, breast cancer, testicular or germ-cell cancer, soft-tissue sarcoma, small-cell lung cancer, and medulloblastomas. The more involved or aggressive the disease is, the more the risk for developing tumor lysis syndrome. People who have preexisting kidney failure and are diagnosed with a cancer that involves rapidly growing cells are also at increased risk for developing tumor lysis syndrome. Etiology and the disease process: Chemotherapy causes the patient’s cancer cells to lyse, or break down, releasing the contents of the cancer cell into the bloodstream. This causes an increase in the serum potassium, phosphate, and uric acid levels and a decrease in the calcium levels. The levels change at such a rapid rate that the body is unable to maintain a balance and lethal symptoms arise. Incidence: The exact incidence of tumor lysis syndrome is not known. Patients who are diagnosed with leukemia in 1189
Tumor lysis syndrome blast crisis have a higher incidence of tumor lysis syndrome. Symptoms: Symptoms include the following changes in blood values: • Hyperkalemia: Increased levels of potassium in the blood. Normal potassium levels are about 3.5 to 5.0 millimoles/ deciliter (mmol/dl). In tumor lysis, the potassium will increase to greater than 7 mmol/dl. Symptoms commonly associated with an increase in potassium levels are muscle weakness, muscle cramps, and paralysis. High potassium levels also contribute to cardiac problems including a racing heart rate, decrease in heart rate, and sudden death. Additional symptoms associated with high potassium levels include nausea, vomiting, diarrhea, and loss of appetite. • Hyperphosphatemia: Increased levels of phosphorus in the blood. Cancer cells contain about four times more phosphorus than normal cells. When the cancer cells are killed, the phosphorus is released into the blood. This increased level of phosphate can cause the kidneys to misfunction and can cause acute renal failure. The increase in the phosphorus combines with the increased calcium levels and affects the kidney and muscle tissue. This causes a rapid decrease in calcium levels, which can then cause the patient to experience severe muscle cramping and twitching, and problems with the heart. • Hypocalcemia: Decreased levels of calcium in the blood. When phosphate increases, the calcium decreases. Symptoms of hypocalcemia can include seizures, Parkinsonlike movements, swelling of the optic disk, agitation or anxiety, painful muscle spasms, and muscle weakness. • Hyperuricemia: Increased levels of uric acid in the blood. This can cause acute renal failure. Symptoms may include nausea, vomiting, diarrhea, and loss of appetite. Screening and diagnosis: Patients who are at high risk of developing tumor lysis syndrome should have baseline labs drawn before therapy begins. Many times patients may not exhibit any signs and symptoms but will begin to have altered lab values. It is important that the patient who is at risk have frequent blood tests taken to monitor for changes. Blood tests should be drawn at least every two to six hours to monitor the calcium, potassium, phosphate, magnesium, and uric acid levels. Treatment and therapy: The best treatment is prevention. Treatment is targeted to the altered laboratory value as well as symptoms as they arise. Intravenous (IV) fluids should be initiated in patients before therapy begins and continue to be infused throughout therapy. If high flow rate is used for IV fluids, then a diuretic, such as furosemide (Lasix), may be added to assist with urine excretion. 1190
Salem Health: Cancer Patients are also given allopurinol, an antigout medication, to stop the formation of uric acid. Urine alkalization may be done by adding sodium bicarbonate to the IV fluids. More severe cases of tumor lysis syndrome may require kidney dialysis to help support the patient through the crisis. The dialysis helps remove the excess potassium and phosphorus when the patient’s kidneys are unable to do so. Patients who have increased potassium levels are treated with sodium polystyrene (Kayexalate). Sodium polystyrene draws the potassium into the bowel to be excreted. Diuretics can also be used to help eliminate the potassium in the urine. In severe cases of elevated potassium, patients are treated with insulin and dextrose, which causes the cells to take in more potassium, decreasing the potassium levels in the blood. Increased phosphorus is treated with oral doses of aluminum hydroxide. Aluminum hydroxide will draw the phosphorus into the bowel to be excreted. Diuretics can also be given to increase the amount of phosphorus excreted in the urine. Decreasing the phosphorus level causes the calcium level to increase. Low calcium levels are not typically treated unless the patient becomes symptomatic and then the patient receives calcium gluconate. Prognosis, prevention, and outcomes: Tumor lysis may be prevented by administering intravenous fluids and allopurinol. Tumor lysis syndrome can occur rapidly, within hours, and have a poor prognosis. As lab values can start changing before the patient experiences side effects, patients who are at risk for tumor lysis syndrome should be hospitalized with preventive therapy initiated, allowing for aggressive treatment to start before the patient’s condition worsens. Katrina Green, R.N., B.S.N., O.C.N. u
For Further Information Itano, J. K., and K. N. Toaka. Core Curriculum for Oncology Nursing. 4th ed. Philadelphia: Elsevier/Saunders, 2005. Johnson, B. L., and J. Gross. Handbook of Oncology Nursing. 3d ed. Sudbury, Mass.: Jones and Bartlett, 1998. Lenhard, R. E., R. T. Osteen, and T. Gansler. The American Cancer Society’s Clinical Oncology. Atlanta: American Cancer Society, 2001. Otto, S. E. Oncology Nursing. 4th ed. St. Louis: Elsevier, 2001. Yarbro, C. H., M. H. Frogge, and M. Goodman. Cancer Nursing: Principles and Practice. 6th ed. Sudbury, Mass.: Jones and Bartlett, 2005.
Salem Health: Cancer Yarbro, C. H., M. H. Frogge, and M. Goodman. Cancer Symptom Management. 3d ed. Sudbury, Mass.: Jones and Bartlett, 2005. u
Other Resources
American Cancer Society http://www.cancer.org National Institutes of Health http://www.nlm.nih.gov See also Calcium; Chemotherapy; Cobalt 60 radiation; Diarrhea; Gastrointestinal complications of cancer treatment; Medical oncology; Nausea and vomiting; Oncology.
u Tumor markers Category: Procedures Also known as: Biomarkers, cancer markers, tumorassociated antigens, tumor-specific antigens Definition: Tumor markers are molecules whose presence or abnormal concentration in body fluids or tissue samples is associated with malignancy. They are most often individual, well-characterized proteins or nucleic acids. Increasingly, multiple tumor markers are interpreted in combination. Cancers identified: Many, notably prostate, ovarian, and gastrointestinal cancers How tumor markers are used: Tumor markers have been sought for every type of cancer, and tumor-marker determinations can be used in several contexts. In risk assessment, mutations in the BRCA1 and BRCA2 genes confer an increased risk of breast and ovarian cancer, and mutations in the APC gene are associated with increased colorectal cancer risk. Knowledge of increased risk can motivate more frequent screening procedures or more aggressive treatment decisions if cancer is eventually diagnosed. In early detection efforts, three serum tumor markers are widely used: • Cancer antigen 125 (CA 125) for ovarian cancer • Carcinoembryonic antigen (CEA) for gastrointestinal cancer • Prostate-specific antigen (PSA) for prostate cancer Because of the need for very high specificity, only one tumor marker (PSA) is recommended for screening of asymptomatic individuals; most early detection efforts focus on clinical and radiological findings. In diagnostic con-
Tumor markers firmation procedures, markers such as alpha-methylacylCoA racemase (AMACR) can be interrogated on biopsy specimens; the presence of AMACR in prostate tissue helps rule out benign mimickers of prostate cancer. In molecular classification efforts, tumor markers can resolve different types of cancer that might otherwise be misdiagnosed. Four malignancies appearing histologically as small round blue cell tumors—neuroblastoma, nonHodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma—fall into this category; tumor markers are needed to distinguish among them. Therapy selection can also be guided by tumor markers, such as the ABCB1 (more commonly known as MDR1) protein and the estrogen and progesterone receptors (ER/ PR). Low levels of MDR1 correlate with better response to treatment in ovary and lung cancer patients, whereas presence of the ER/PR tumor marker in advanced breast cancer patients correlates with a high response rate to endocrine ablation. Breast cancer patients whose tumors overexpress the HER2/neu (also known as ERBB2, c-erb-B2) protein are another important subgroup identified by tumor-marker analysis, since these patients are uniquely appropriate for therapy with anti-HER2-based therapies such as trastuzumab. Tumor-marker concentrations often correlate with tumor burden or activity, providing information on the effectiveness of treatment. Rapid normalization of serum CA 125 levels following ovarian cancer treatment, for example, has favorable prognostic significance. The next important application of tumor markers is in long-term follow-up of patients with previously diagnosed and treated cancer, because early detection of recurrent or metastatic disease can hasten intervention and improve outcome. The tumor markers CA 15-3 (breast), CEA (colorectal), CA 125 (ovary), and PSA (prostate) are used in this context. Finally, scientists performing cancer research are seeking improved diagnostic assays and clues to novel therapies; tumor markers are an integral part of these efforts. Overexpression of fatty acid synthase, for example, was noted in several types of tumors; subsequent efforts to inhibit the enzyme demonstrated this to be a promising therapeutic modality. Significant barriers exist to more extensive use of tumor markers in oncology. Primarily, the clinical value of the marker must be proven; that is, the result should trigger or remand a treatment decision that benefits patients, this benefit must be demonstrated in a large and rigorous trial, and the benefits must outweigh the costs of implementation and follow-up. After this is accomplished, oncologists must be convinced of the need to change their established practices by incorporating the marker. 1191
Tumor markers Data analysis: After the appropriate material is obtained from the patient, several options exist for tumor-marker determination and data analysis. The method for tumormarker quantification depends both on the marker and on the specimen; the method of analysis depends largely on the form and amount of data present. Serum protein markers are typically measured with specific antibody-based assays. A popular immunoassay format is the enzyme-linked immunosorbent assay (ELISA), which provides a numerical readout of the marker’s concentration. Protein markers can also be determined in tissue biopsy slices or individual cells by immunohistochemistry (IHC) or immunocytochemistry (ICC). In contrast to the ELISA, samples analyzed by IHC or ICC must be assessed visually for an estimate of tumor-marker abundance. However, IHC and ICC allow precise localization of the tumor marker within the cell. IHC and ICC are appropriate for tumor markers that are not shed into the extracellular space. Enzymes such as lactate dehydrogenase are sometimes employed as tumor markers; their concentration is inferred from their catalytic activity. Highly complex protein mixtures present in body fluids such as serum or urine can be analyzed by protein chips coupled with surfaceenhanced laser desorption ionization/time-of-flight mass spectrometry (SELDI/TOF-MS). In this case, the relative abundance of hundreds to thousands of proteins in a sample is determined in a single run. Tumor markers that are products expressed by genes (messenger ribonucleic acid, or mRNA, molecules) can be measured by the reverse transcriptase polymerase chain reaction (RT-PCR) or on a larger scale by oligonucleotide microarrays. In reverse transcriptase polymerase chain reaction, the mRNA sample is first reverse-transcribed into deoxyribonucleic acid (DNA), then amplified by standard polymerase chain reaction. Relative quantification is achieved by monitoring the abundance of the polymerase chain reaction products spectrophotometrically during the thermal cycling process. Messenger RNA-based tumormarker assays can estimate the risk of breast cancer recurrence in women who are diagnosed with Stage I or II hormone-responsive cancer that has not spread to the surrounding lymph nodes. In this setting, the abundance of multiple different transcripts in breast tumor tissue is determined by reverse transcriptase polymerase chain reaction. Tumor markers that exist as mutated or disrupted genes can be analyzed by several methods. Chromosomes can be inspected microscopically to confirm changes in genomic DNA. For example, abnormal amplification of MYCB (also known as N-myc) in neuroblastoma can be visualized as a homogenous staining region on chromosome 2p. 1192
Salem Health: Cancer Other tumor risk markers, such as mutated APC, can be detected through DNA sequencing or single-strand conformational polymorphism. Tumor markers that exist as small organic compounds such as 5-hydroxyindoleacetic acid (carcinoid tumors) are measured with chemical techniques such as high-performance liquid chromatography. Results: Numerical results (concentrations) for single tumor markers can be interpreted only with knowledge of the marker’s normal concentration range and its sensitivity, specificity, and positive and negative predictive value for the tumor type in question. Also essential are knowledge of the tumor’s prevalence and the patient’s clinical history. Serial tumor-marker determinations offer additional information by demonstrating the rate of the tumor marker’s increase or decrease. In the case of PSA, a short time to doubling may prompt more concern than higher levels that remain steady. No single tumor marker reaches the ideal standards of 100 percent sensitivity and specificity. Many proposed tumor markers are ultimately rejected by practitioners because of unacceptably low sensitivity or specificity. Results from multiplexed assays consist of patterns of individual data points that can yield more biologically relevant and clinically useful information than single markers. Analysis requires sophisticated and sometimes proprietary pattern-matching algorithms. Protein chips coupled with SELDI/TOF-MS, for example, have identified tumormarker patterns that correctly classified individuals with and without early-stage ovarian cancer with high sensitivity and specificity. Gene expression chips (oligonucleotide microarrays) have also shown remarkable accuracy in identifying the primary sites of poorly differentiated metastatic lesions. Test results are highly reproducible and provide information to aid the physician and patient in making treatment decisions. John B. Welsh, M.D., Ph.D. u
For Further Information Bigbee W., and R. B. Herberman. “Tumor Markers and Immunodiagnosis.” In Cancer Medicine, edited by James F. Holland and Emil Frei. 6th ed. Hamilton, Ont.: BC Decker, 2003. Diamandis, E. P., et al., eds. Tumor Markers: Physiology, Pathobiology, Technology, and Clinical Applications. Washington, D.C.: AACC Press, 2002. Hartwell, L., et al. “Cancer Biomarkers: A Systems Approach.” Nature Biotechnology 24 (2006): 905-908. Nakamura, R. M., et al., eds. Cancer Diagnostics: Current and Future Trends. Totowa, N.J.: Humana Press, 2004.
Salem Health: Cancer Perkins, G. L., et al. “Serum Tumor Markers.” American Family Physician 68 (2003): 1075-1082. Petricoin, E. F., et al. “Use of Proteomic Patterns in Serum to Identify Ovarian Cancer.” Lancet 359 (2002): 572577. Taube, S. E., et al. “Cancer Diagnostics: Decision Criteria for Marker Utilization in the Clinic.” American Journal of Pharmacogenomics 5 (2005): 357-364. u
Other Resources
Lab Tests Online Tumor Markers http://www.labtestsonline.org/understanding/ analytes/tumor_markers/glance.html National Cancer Institute Tumor Markers: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/ Detection/tumor-markers See also Alpha-fetoprotein (AFP) levels; Bone cancers; CA 15-3 test; CA 19-9 test; CA 27-29 test; CA 125 test; Carcinoembryonic antigen antibody (CEA) test; Carcinomas; Embryonal cell cancer; Endocrine cancers; Germcell tumors; Gynecologic oncology; Lactate dehydrogenase (LDH) test; Liver cancers; Malignant tumors; Neuroendocrine tumors; Placental alkaline phosphatase (PALP); Proteomics and cancer research; Testicular cancer; TNM staging.
u Tumor necrosis factor (TNF) Category: Chemotherapy and other drugs; cancer biology Also known as: Tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-beta (TNF-β, or lymphotoxin); the colloidal gold-bound form of TNF is also called Aurimmune Definition: TNF is a protein belonging to the class of cytokines (immunoregulatory proteins) that is made by the body’s white blood cells in response to an infection, or antigen. It can also be synthesized in the laboratory. Because it causes necrosis (cell death), it is being investigated as a possible immunotherapeutic drug to induce death of some types of tumor cells. Cancers treated: Breast, ovarian, colon, kidney, and liver cancers, as well as melanomas; tests carried out with a variety of other tumors
Tumor necrosis factor (TNF) Delivery routes: Tumor necrosis factor is generally delivered as an injection in a vein or muscle. Injection may also be under the skin. A colloidal form of TNF bound to small particles of gold has also been tested for improved specificity for cancer tissue, reducing the ability of the drug to bind normal tissue and possibly permitting systemic delivery. How this drug works: The term TNF actually refers to a family of trimeric proteins produced by certain types of white blood cells that can attack blood vessels in tumors, thereby destroying certain types of cancer cells. The most common forms are TNF-α and TNF-β. TNF-α is the form used for cancer therapy. Its existence was discovered fortuitously in the early twentieth century when physicians observed that certain types of tumors would spontaneously regress in the presence of bacterial infections. It was subsequently discovered that TNF production is a part of the immune response and is induced in the presence of bacterial endotoxin (lipopolysaccharide). The response to TNF is dose-dependent and can result either in inflammation, augmenting the immune response, or in binding to a cell surface, inducing the destruction of that cell. The induction of apoptosis, or “cell suicide,” appears to be the primary mechanism by which TNF may cause tumor regression. Depending upon the state of the particular cell, either tumor cells or the cells of the blood vessels that feed those tumors may express receptors on their respective surfaces for the drug. Binding of TNF sets in motion a series of intracellular signals that results in the death of the cell. Testing has also been carried out using a human recombinant form of TNF (rTNF), as well as treatments utilizing a combination of chemotherapies in conjunction with TNF. Side effects: Like other forms of chemotherapy, TNF has the potential to interact with other medications. Since TNF may interact with other cells of the immune system, vaccinations should be avoided during the course of treatment. Specific side effects of TNF may include a mild fever, chills or sweating, fatigue, and vomiting. Since most cells in the body have surface receptors to which TNF may bind, the drug is potentially toxic if given systemically. Richard Adler, Ph.D. See also Biological therapy; Cancer biology; Chemotherapy; Crohn disease; Cytokines; Gene therapy; Histiocytosis X; Hyperthermic perfusion; Immune response to cancer; Immunotherapy; Liver cancers. 1193
Tumor-suppressor genes
u Tumor-suppressor genes Category: Cancer biology Definition: Tumor-suppressor genes are genes found in normal cells that function to control cell division, repair damage to deoxyribonucleic acid (DNA), and tell cells when to die. Mutated tumor-suppressor genes can cause a loss of growth control and can lead to cancer. What they do: Tumor-suppressor genes regulate cell division and growth through many biochemical mechanisms. The quality the mechanisms have in common is that the loss of each increases the likelihood that a cell will undergo transformation from a normal cell to a cancerous one. Tumor-suppressor genes code for proteins that inhibit the division of cells if proper conditions for growth are not met. Conditions that could inhibit division include DNA damage, a lack of growth factors, or a malfunction of the cell’s division machinery. Scientists have identified about thirty tumor-suppressor genes. Types of tumor-suppressor genes: There are several types of tumor-suppressor genes. Some control cell division and growth. The retinoblastoma (RB1) gene is an example of this type. A second type is involved in repairing errors in DNA. The process of DNA replication leads to occasional mistakes, and cells have a set of proteins that function to repair these mistakes. A third type is responsible for inducing a cell to undergo programmed cell death, or apoptosis, if its DNA is damaged beyond repair or if the cell division process malfunctions. In this way the cell’s well-being is monitored, protecting the organism from the effects of runaway replication of wayward cells by activating the apoptotic pathway in such cells. The TP53 (also known as p53) gene is an example of this type of tumorsuppressor gene. Because the presence of tumor-suppressor genes contributes to normal cell division and function, both copies of a tumor-suppressor gene must be inactivated to result in a maximum increased risk of cancer development. An increased risk of developing a specific type of cancer in some families is often the result of the presence of one defective copy of a tumor-suppressor gene. Although there is a low likelihood that the good copy of the tumor-suppressor gene will be mutated in any given cell, there is a much higher likelihood that the necessary second mutation will occur somewhere in the vast number of cells in a human body. Many of the identified tumor-suppressor genes have been shown to be implicated in familial cancers. Inheritance of a defective copy of one of these genes carries a greatly increased risk of developing one or more specific 1194
Salem Health: Cancer types of cancer, often types that are otherwise rare. In some cases, mutant copies of these genes are linked to susceptibility to multiple cancer types, as is the case with the retinoblastoma (RB1) gene. The two most important tumor-suppressor genes code for the TP53 protein and the retinoblastoma protein (RB1 or pRB). TP53 gene: The TP53 gene has been found to be involved in numerous cellular processes and is considered to be one of the most important cancer-related genes. The TP53 protein belongs to a class of proteins containing covalently bound phosphate groups, called phosphoproteins. It is located in the nucleus of the cell and interacts directly with the cell’s DNA to function as a transcription factor by binding to a specific DNA sequence in the control regions of the genes it controls. The number of bound phosphate groups modulates the activity of TP53. Normal TP53 function results in a global transcriptional response that can negatively regulate cell division, or induce apoptosis. TP53 function is activated in response to various kinds of cell stress that increase the cell’s need for DNA repair and surveillance of the cell’s physiological status, including irradiation, lack of oxygen, oncogene activation, and DNA damage. The TP53 gene is the single most frequently inactivated gene in human cancers. More than 90 percent of small-cell lung cancers and more than 50 percent of breast and colon cancers have been shown to be associated with mutant forms of TP53. Retinoblastoma (RB1) gene: The RB1 gene encodes another phosphoprotein located in the nucleus of the cell. The RB1 protein acts as a negative regulator of cell division by binding to other transcription factors to alter their function. The action of these other transcription factors in turn regulates the level of expression of a number of other genes. The number of phosphate groups bound to the RB1 protein controls its ability to bind to other transcription factors and varies in a regular controlled manner during a normal cell cycle. The RB1 protein is responsible for a major “checkpoint,” or regulatory step, in the cell cycle, in which cells must make a decision whether to undergo another round of cell division. Normal RB1 protein function results in a coordinated progression of the cell through the division process. Loss of the RB1 protein leads to unregulated and increased cell division, characteristic of cancer cells. The RB1 gene is mutated in many types of cancer, including retinoblastoma (a cancer of the eye from which the gene got its name), as well as bone, lung, breast, and bladder cancers. Jill Ferguson, Ph.D.
Salem Health: Cancer
Turcot syndrome
u For Further Information Hanahan, D., and R. A. Weinberg. “The Hallmarks of Cancer.” Cell 100 (2000): 57-70. Sherr, C. J. “Principles of Tumor Suppression.” Cell 116 (2004): 235-246. Strano, S., et al. “Mutant p53: An Oncogenic Transcription Factor.” Oncogene 26 (2007): 2212-2219. Weinberg, R. A. The Biology of Cancer. New York: Garland Science, 2007.
be inherited in an autosomal recessive manner. Mutation or mismatch of the adenomatous polyposis coli (APC) gene in chromosome 5q is most likely involved in the disease. Mismatch repair genes, such as MLH1 or PMS2, were found in some families. The types of brain tumor differ, depending on the type of mutation; APC mutations are more commonly associated with medulloblastoma, while mismatch repair genes are associated with glioblastoma. The gene map locus is 7p22, 5q21-q22, or 3p21.3.
u
Etiology and the disease process: It has been debated whether Turcot syndrome is a variant of familial adenomatous polyposis or a separate disorder. The cause of Turcot syndrome is not known, but it has been characterized genetically. In this syndrome, there may be three types of polyposis coli in combination with central nervous system tumors. Type 1 is characterized by multiple colonic polyps numbering between twenty and one hundred; some of these may exceed 3 centimeters (cm) in diameter. These polyps frequently undergo malignant transformation in the second and third decades of life. In several of the type 1 cases, a familial cluster has been described. In type 2, the number of colonic polyps is usually less than ten, and the mode of inheritance is uncertain. In type 3, there are numerous small colonic polyps present, and the mode of inheritance may be autosomal dominant with respect to colonic lesions. Turcot syndrome may be divided into two distinct entities. The first entity includes patients who have gliomas and colorectal adenomas without polyposis. This type is associated with hereditary nonpolyposis colorectal cancer (HNPCC), which is characterized by germ-line mutations in the mismatch repair genes MLH1 and PMS2. The second entity includes patients who develop a central nervous sytem tumor (familiar adenomatous polyposis cases). These patients carry germ-line mutations in the APC gene, indicating a predisposition to brain tumors.
Other Resources
American Cancer Society Oncogenes and Tumor Suppressor Genes Http://www.cancer.org/docroot/ETO/content/ETO _1_4x_oncogenes_and_tumor_suppressor_genes.asp Emory University CancerQuest: Important Tumor Suppressors http://www.cancerquest.org/index.cfm?page=52 Tumor Suppressor Genes http://users.rcn.com/jkimball.ma.ultranet/ BiologyPages/T/TumorSuppressorGenes.html See also APC gene testing; BRCA1 and BRCA2 genes; Cancer biology; Cowden syndrome; Endocrine cancers; Gene therapy; Genetic testing; Genetics of cancer; Mutagenesis and cancer; Oncogenes; Oncogenic viruses; RB1 gene; RhoGD12 gene; TP53 protein.
u Turcot syndrome Category: Diseases, symptoms, and conditions Also known as: Brain tumor-polyposis syndrome, glioma-polyposis syndrome Related conditions: Malignant tumors of the central nervous system (CNS), familial polyposis of the colon, familial adenomatous polyposis (FAP), Gardner syndrome, hereditary nonpolyposis colorectal cancer (HNPCC) Definition: Turcot syndrome is a rare genetic disorder clinically characterized by the concurrence of a primary brain tumor and multiple colorectal adenomas. This syndrome is characterized by adenomatous polyps (benign growths) in the mucous lining of the gastrointestinal tract and tumors of the central nervous system, including medulloblastoma and malignant glioma. It was first reported by Canadian surgeon Jacques Turcot in 1959. Risk factors: Turcot syndrome has been linked to various mutations in a number of genes. Turcot syndrome seems to
Incidence: The normal onset of Turcot syndrome occurs between the ages of fifty and eighty. Turcot syndrome is strongly associated with an underlying genetic cause. The most common brain tumors associated with Turcot syndrome are medulloblastoma (79 percent) and glioblastoma multiforme. The glioblastomas and colorectal tumors often have replication errors characteristic of hereditary nonpolyposis colorectal cancer. Symptoms: The symptoms of Turcot syndrome are associated with polyp formation, and they include diarrhea, bleeding from the rectum, fatigue, abdominal pain, and weight loss. Because of the development of brain tumors, 1195
Tyrosine kinase inhibitors patients with this disease may also experience neurological symptoms, depending on the type, size, and location of the tumors. Patients with Turcot syndrome commonly complain of skin abnormalities, including café-au-lait spots, multiple lipomas (fatty tumors), and multiple scalp basal cell carcinomas (skin cancers of the scalp). Turcot syndrome polyps are somewhat fewer in number than in familial adenomatous polyposis, but they tend to be larger in size (greater than 3 cm in diameter). Many patients with Turcot syndrome have APC gene mutations, pigmented ocular fundus lesions, epidermal inclusion cysts, or osteosclerotic jaw lesions consistent with Gardner syndrome. Screening and diagnosis: Patients with Turcot syndrome often have multiple adenomatous colon polyps or colorectal cancer along with glioblastoma or medulloblastoma. Generally, blood tests can confirm mutation in the APC gene or in the MLH1 gene. Testing for mutations in PMS2 is still in development. If a specific gene mutation is found, family members are also tested for Turcot syndrome. Treatment and therapy: Typically tumors, such as adenomatous sigmoid polyps, are removed. Brain tumors, depending on their location, are more difficult to remove surgically. Colectomy and gastrectomy are also common treatments for patients with Turcot syndrome. Prognosis, prevention, and outcomes: In most cases, a complete resection of the brain tumors is difficult and the colonic polyps are malignant at the time of diagnosis, resulting in poor prognosis. Better prognosis can be expected with early diagnosis. Anita Nagypál, Ph.D. u
For Further Information De Vos, M., et al. “Novel PMS2 Pseudogenes Can Conceal Recessive Mutations Causing a Distinctive Childhood Cancer Syndrome.” American Journal of Human Genetics 74 (2004): 954-964. Dupuis, M. J. M., and C. Verellen-Dumoulin. “Gastrointestinal Polyposis and Nonpolyposis Syndromes.” New England Journal of Medicine 332 (1995): 1518. Hamilton, S. R., et al. “The Molecular Basis of Turcot’s Syndrome.” New England Journal of Medicine 332 (1995): 839-847. Lionel, J., N. Bathurst, D. Mohan, and D. Beckly. “Turcot’s Syndrome.” Diseases of the Colon and Rectum 31 (1998): 11. Van Meir, E. G. “Turcot’s Syndrome: Phenotype of Brain Tumors, Survival, and Mode of Inheritance.” International Journal of Cancer 75 (1998): 162-164. 1196
Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org American Society of Clinical Oncology http://opl.asco.org National Cancer Institute http://www.cancer.gov National Organization for Rare Disorders Turcot Syndrome http://www.rarediseases.org/search/ rdbdetail_abstract.html?disname= Turcot%20Syndrome See also Adenomatous polyps; Astrocytomas; Brain and central nervous system cancers; Colon polyps; Colorectal cancer; Gardner syndrome; Gliomas; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Neuroectodermal tumors; Rectal cancer.
u Tyrosine kinase inhibitors Category: Chemotherapy and other drugs ATC code: 101XE Definition: Tyrosine kinase inhibitors are a class of antitumor drugs that act by specifically targeting tyrosine kinase enzymes. Tyrosine kinase inhibitors are particularly effective in slowing tumor growth and killing tumor cells because of the importance of these enzymes in determining cellular fate, including survival and proliferation. Cancers treated: Chronic myeloid leukemia, gastrointestinal stromal tumors, non-small-cell lung cancer, pancreatic cancer, renal cell carcinoma, breast cancer, colorectal cancer Subclasses of this group: Small molecule inhibitors, biologic antibody inhibitors Delivery routes: The small molecule tyrosine kinase inhibitors are orally active and administered in a tablet form. Biologic antibody tyrosine kinase inhibitors are administered by a slow intravenous (IV) infusion, usually over the course of a few hours. How these drugs work: Through basic scientific research, several proteins critical for cellular growth, survival, and proliferation have been identified. One of the largest classes of these proteins is known as tyrosine kin-
Salem Health: Cancer
Tyrosine kinase inhibitors
Common Tyrosine Kinase Inhibitors Delivery Mode Cancers Treated
Drug
Brands
Subclass
Cetuximab
Erbitux
Biologic antibody therapy IV
Metastatic colorectal cancer, head and neck cancer
Dasatinib
Sprycel
Small molecule inhibitor
Oral
Chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia
Erlotinib
Tarceva
Small molecule inhibitor
Oral
Advanced non-small-cell lung cancer, advanced pancreatic cancer
Gefitinib
Iressa
Small molecule inhibitor
Oral
Advanced or metastatic non-small-cell lung cancer
Imatinib
Gleevec
Small molecule inhibitor
Oral
Philadelphia chromosome-positive chronic myeloid leukemia, gastrointestinal stromal tumor
Lapatinib
Tykerb
Small molecule inhibitor
Oral
Advanced or metastatic HER2-positive breast cancer
Sorafenib
Nexavar
Small molecule inhibitor
Oral
Advanced renal cell carcinoma
Sunitinib
Sutent
Small molecule inhibitor
Oral
Advanced renal cell carcinoma, gastrointestinal stromal tumor
Trastuzumab Herceptin Biologic antibody therapy IV
ases. Kinases are enzymes, proteins that can perform a specific activity or function. Kinases act by transferring a phosphate group onto a substrate protein, a process called phosphorylation. In particular, tyrosine kinases add a phosphate group onto specific tyrosine amino acid residues in the substrate protein. Phosphorylation can perform many different functions, including activating the substrate protein through an “on-off” mechanism, inducing proteinprotein interaction, and changing protein localization. The functional changes induced in the substrate protein are used in many different signaling pathways, including those important to relay growth and proliferation signals in cells. Cells can react to many external stimuli, including circulating growth factors and hormones, through binding of these ligands to cell surface receptors. Many of these receptors are actually tyrosine kinases themselves, or signal directly to downstream tyrosine kinases after being activated. Therefore, the activity of tyrosine kinases is a critical part of the signaling required to transmit information from the outside of the cell to the cellular interior, affecting the fate of the cell. Tumor cells often hijack the normal essential function of tyrosine kinases, mutating these proteins so that they remain in a constitutive “on” state. Because the kinase activity is then unable to be halted, the signaling pathways are continuously activated, and uncontrolled cell growth and proliferation ensue. Because of their importance in determining cellular fate, especially whether a cell will live or die, tyrosine kinases are a very attractive target for anticancer chemother-
HER2-positive breast cancer
apy. There are two major categories of tyrosine kinase inhibitors, small molecule inhibitors and targeted biological therapy. The major mechanism of action of small molecule inhibitors is to inhibit the binding of adenosine triphosphate (ATP) to the kinase. Because tyrosine kinases use ATP as a source of phosphate groups to perform phosphorylation, the enzyme cannot phosphorylate substrate proteins, thereby reducing the activation of the downstream signaling pathways. The second major class of tyrosine kinase inhibitors is targeted therapy, using antibodies that are generated against the tyrosine kinase receptors that reside on the cellular surface. These antibodies mainly work by blocking the ligand-binding sites on these receptors, inhibiting the binding and thus the activation of these receptors. One of the main benefits of using tyrosine kinase inhibitors as an anticancer chemotherapy is that they can selectively target tumor cells compared to normal cells because tumor cells often develop a dependence on overactivated and overexpressed tyrosine kinases. Side effects: The most common side effects of the oral small molecule inhibitors are nausea and vomiting, fatigue, muscle pain, fluid retention (swelling), and rash. In most cases, these symptoms can be effectively managed with medication, so that treatment can continue. The side effects caused by biologic antibody therapies are mainly induced by the actual administration of the drug. Many patients (approximately 40 percent) experience flulike symptoms, including fever, chills, muscle aches, and nau1197
Tyrosine kinase inhibitors sea. These side effects are generally lessened with the administration of drugs such as acetaminophen. Lisa M. Cockrell, B.S. u For Further Information Fabbro, Doriano, and Frank McCormick, eds. Protein Tyrosine Kinases: From Inhibitors to Useful Drugs. Totowa, N.J.: Humana Press, 2006. Kantarjian, Hagop M., et al. The M. D. Anderson Manual of Medical Oncology. New York: McGraw-Hill, 2006. Kufe, Donald W., et al., eds. Holland Frei Cancer Medicine 7. 7th ed. Hamilton, Ont.: BC Decker, 2006. Pratt, William B., et al. The Anticancer Drugs. 2d ed. New York: Oxford University Press, 1994. Skeel, Roland T. Handbook of Cancer Chemotherapy. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007.
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Salem Health: Cancer u
Other Resources
American Cancer Society http://www.cancer.org National Cancer Institute Drug Information Summaries http://www.cancer.gov/cancertopics/druginfo/ alphalist See also Biological therapy; Breast cancers; Bronchial adenomas; Carcinomas; Chemotherapy; Chronic myeloid leukemia (CML); Gastrointestinal complications of cancer treatment; Gastrointestinal stromal tumors (GISTs); Infusion therapies; Leukemias; Lung cancers; Medical oncology; Nausea and vomiting; Oncology; Pancreatic cancers; Rectal cancer.
Salem Health: Cancer
Ultrasound tests
u Ultrasound tests Category: Procedures Also known as: Sonogram, echogram Definition: An ultrasound test is a type of radiologic study that utilizes sound waves to detect an abnormality in an organ of the body under evaluation using a principle similar to sonar used in ship navigation. Ultrasound waves are mechanical pressure waves that occur at a higher frequency compared to audible sound waves, hence the name ultrasound. These high-frequency sound waves reflect off body surfaces and structures. Different tissues in the body have different acoustic velocities or speeds of sound propagating through them. The time that it takes for a pulsed sound wave to travel from a transducer to a reflector and back again can be measured and then, along with the known acoustic velocity of a tissue, can be used to calculate their separation and thus the depth from the skin surface of the organ or organ part under study. Bone, for example, has a higher acoustic velocity than soft tissue. One would expect higher-amplitude echoes from soft tissue-bone interfaces and lower-amplitude reflection or echoes from soft tissuesoft tissue interfaces because of the almost matched acoustic velocities among the latter. The ultrasound transducer converts the amplitude of the mechanical energy received from the organ under study into an electrical signal and vice versa. The emitting and receiving element of an ultrasound transducer is a piezoelectric crystal. The electrical signals from the transducer are fed into a computer, and an image is produced that can be stored on compact disc (CD), printed on film, or viewed on a computer monitor by the sonographer and the radiologist, who is ultimately responsible for the quality and interpretation of the study.
nign and malignant, as well as secondary cancers (also known as metastases). It is also used to diagnose ailments depending on the patient’s symptoms, including but not limited to the following: right-upper-quadrant abdominal pain caused by acute and chronic cholecystitis (both calculus and acalculus) and postoperative leaks following cholecystectomy (gallbladder and right-upper-quadrant ultrasound); goiter, Hashimoto’s thyroiditis, and ectopic parathyroid (thyroid ultrasound); mastitis and Paget disease of the breast (breast ultrasound); pain in the right lower quadrant of the abdomen caused by appendicitis (ultrasound of the appendix); scrotal pain caused by testicular torsion, testicular trauma, orchitis, epididymitis, and hydrocele, as well as undescended testes (testicular ultrasound); pain in the back caused by kidney stones, kidney obstruction, or infection (renal ultrasound); pain and swelling in the legs caused by deep venous thrombosis (DVT study); pain in the epigastric area caused by pancreatitis (abdominal ultrasound); pain in the left upper abdomen caused by splenic infarct or splenic trauma (abdominal ultrasound); pain in the right upper quadrant caused by liver trauma, liver infection, or liver cysts and evaluation for the presence of ascites (abdominal ultrasound); valvular heart disease (cardiac ultrasound or echocardiography); atherosclerosis of the lower-extremity arteries, abdominal aortic aneurysm, and carotid artery atherosclerosis (vascular or arterial Doppler ultrasound); and polycystic ovarian syndrome or pelvic pain and/or bleeding caused by ovarian torsion, uterine polyps, uterine fibroids, and retained products of conception (pelvic and transvaginal ultrasound).
Cancers diagnosed: Breast, thyroid, testicular, uterine, ovarian, prostate, renal (kidney), bladder, gallbladder, liver, spleen, and pancreatic cancers; cancers associated with pregnancy, such as gestational trophoblastic disease; unsuspected adenopathy often detected as an incidental finding during ultrasound examination, especially during examination of the thyroid, breast, and abdomen Why performed: Ultrasound is used to diagnose primary cancers, both be-
A sonogram showing prostate cancer. (James Cavallini/Photo Researchers, Inc.)
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Ultraviolet radiation and related exposures In addition, pregnancy in all three trimesters is evaluated by ultrasound. Ultrasound is also useful in guiding amniocentesis for evaluation of possible fetal anomalies such as Down syndrome (trisomy 21) involving sampling of fluid surrounding the fetus; sampling and removal of fluid from various body cavities in the adult, such as the lung (pleural effusion tap) and abdominal cavity (ascites); and guiding biopsy of various organs in the adult, such as liver, breast, thyroid, and kidney. Patient preparation: Patients are asked to fast at least four to eight hours prior to gallbladder ultrasound, as food causes the gallbladder to contract and minimizes the area visible for the ultrasound evaluation. Patients are asked to drink at least four glasses of water at least one half hour prior to pelvic ultrasound in order to distend the bladder, which acts as an acoustic window for the study (sound travels well through water). This enables the sonographer, usually a technologist, to evaluate the baby and the womb during pregnancy and to evaluate the state of the uterus, cervix, and ovaries in both the pregnant and the nonpregnant state. Steps of the procedure: The patient is placed on the back on a table, and the technologist and/or the radiologist applies a clear, water-based conducting gel to the skin over the organ or body part of interest. The gel helps in the transmission of sound waves and may feel wet and cold. The sonographer then rubs a handheld probe or transducer across the surface of the organ of interest. There will be some discomfort from pressure on a full bladder, but the ultrasound waves themselves are painless. Some transducers are designed to be inserted inside a body cavity, such as a transvaginal probe or transrectal probe, which may feel uncomfortable. After the procedure: The scan is generated by the computer attached to the ultrasound probe and read by the radiologist the same day. The patient will need to contact his or her doctor or health care provider for the radiology report and for follow-up therapy.
Salem Health: Cancer are ordered by a health care provider when an abnormality is suspected. Debra B. Kessler, M.D., Ph.D. u
For Further Information Bushong, Stewart C. Diagnostic Ultrasound. New York: McGraw-Hill, 1999. Curry, Thomas S., III, James E. Dowdey, and Robert C. Murry, Jr. Christensen’s Physics of Diagnostic Radiology. 4th ed. Philadelphia: Lea & Febiger, 1990. Rumak, Carole M., S. R. Wilson, and J. W. Charboneau. Diagnostic Ultrasound. St. Louis: Mosby-Year Book, 1991.
See also Breast ultrasound; Endorectal ultrasound; Pregnancy and cancer; Screening for cancer; Transrectal ultrasound; Transvaginal ultrasound.
u Ultraviolet radiation and
related exposures Category: Carcinogens and suspected carcinogens RoC status: Solar radiation and exposure to sunlamps or sun beds, known carcinogens since 2000; broadspectrum ultraviolet radiation (UVR), known carcinogen since 2002; ultraviolet A, B, and C (UVA, UVB, and UVC), reasonably anticipated carcinogens since 2002 Also known as: UV, ultraviolet light, black light, UVR, UVA, UVB, UVC Related cancers: Melanoma and nonmelanocytic skin cancers Definition: Ultraviolet light is electromagnetic radiation that lies between X rays and visible light in the spectrum, with wavelengths between 100 and 400 nanometers (nm). UV is divided into long-wave UVA (315-400 nn), UVB (280-315 nm), and short-wave UVC (100-280 nm). Exposure route: Through skin
Risks: The study is painless and relatively harmless, as no radiation is involved; transvaginal ultrasound is generally done early in a pregnancy to determine fetal age or to detect a suspected ectopic pregnancy. Use of the transvaginal probe late in pregnancy is a decision made by the health care provider, not the sonographer or radiologist. Results: The results are dependent on the type of scan performed and the reason for the study. Some ultrasound tests are screening tests and may be normal, while others 1200
Where found: Sunlight, tanning beds At risk: Individuals chronically exposed to sunlight or occupationally exposed to ultraviolet (UV) light sources, especially those with fair skin Etiology and symptoms of associated cancers: The damage caused by exposure to UV radiation depends on the intensity and wavelengths of the radiation, the duration of exposure, and many other highly individual factors.
Salem Health: Cancer Cancers caused by UV radiation are based on damage to cellular deoxyribonucleic acid (DNA) and suppression of the immune system. Since UV radiation is absorbed efficiently by the skin, this is the primary carcinogenic target, and UV radiation-caused skin cancers occur mostly on sun-exposed areas. The interaction of UV radiation with DNA results in abnormal dimerization of adjacent pyrimidine bases, damage to individual bases, strand breakage, and cross-linkages between DNA and adjacent proteins. Such DNA damage contributes to cancer formation through the release of cytokines, induction of latent viruses, or mutations that cause functional changes in encoded protein molecules. Skin cancers are typically noted and diagnosed by inspection before producing systemic illness. History: Hippocrates, a physician in ancient Greece, recognized that depression was more common in the winter months and recommended sunbathing to treat both medical and psychological maladies. Ultraviolet light as a component of sunlight and its interactions with matter were first demonstrated in the early 1800’s. Ultraviolet radiation’s ability to injure the eyes was noted in 1843 in welders, and papers from 1889 confirmed that ultraviolet rays cause skin burns. An epidemiologic study published in 1907 first associated sun exposure and skin cancer. A causal relationship was demonstrated in a 1928 publication that described induction of skin cancer in mice by exposure to UV radiation. The peak carcinogenic response of UVB at 310 nm was identified in 1975. Reduction of UVB in favor of UVA rays is a current strategy to reduce the carcinogenicity of tanning beds. Liberal use of sunscreens is a current recommendation to reduce the incidence of melanoma. John B. Welsh, M.D., Ph.D. See also Basal cell carcinomas; Carcinogens, known; Electromagnetic radiation; Melanomas; Merkel cell carcinomas (MCC); Moles; Occupational exposures and cancer; Premalignancies; Skin cancers; Squamous cell carcinomas; Sunlamps; Sunscreens.
u Umbilical cord blood
Umbilical cord blood transplantation row has been eradicated by chemotherapy with or without radiation. These healthy stem cells move into the bone and reconstitute the bone marrow, producing new, healthy blood cells. Cancers treated: Leukemia, lymphoma, myeloma, and neuroblastoma; other disorders treated include immunodeficiency, hemaglobinopathies, and metabolic disorders Why performed: In patients with various cancers and diseases, a cure can be achieved when the patient’s affected bone marrow is obliterated and replaced with healthy stem cells. Umbilical cord blood is discarded after birth. Donated umbilical cord blood is an accepted source of hematopoietic stem cells for marrow reconstitution. Two transplant-dependent variables affect long-term recipient survival: donor-recipient human leukocyte antigen (HLA) match grade and the dose of stem cells. HLA is a genetic fingerprint on white blood cells and platelets, composed of proteins that play a critical role in activating the body’s immune system to respond to foreign agents. There are six HLA factors. The more of these factors that match between the donor and the recipient, the more likely the transplant is to be successful and complications to be prevented. Patient preparation: A repeat HLA tissue typing is done to confirm donor-recipient match. Then the recipient’s bone marrow is destroyed by chemotherapy with and without radiation. This process kills diseased bone marrow. The patient must be protected to prevent infection, since his or her own immune system has been obliterated. Steps of the procedure: An intravenous (IV) device is placed in the recipient’s vein, and a solution containing the donor stem cells is infused. After the procedure: The patient will be monitored for engraftment, the process in which stem cells enter the bone marrow and begin to produce blood cells. The patient will remain in an environment free from infectious agents until the new stem cells engraft and produce disease-fighting white blood cells. The patient will be monitored for relapse (return) of the original disease.
Category: Procedures Also known as: Cord blood transplantation
Risks: The risks of this procedure are infection, graft failure (the absence of or inadequate production of blood cells), and graft-versus-host disease (GVHD), in which the donor stem cells attack the recipient’s body. GVHD can be either acute or chronic.
Definition: Umbilical cord blood transplantation is the administration of healthy stem cells obtained from umbilical cord blood into an individual after his own bone mar-
Results: Umbilical cord blood stem cells produce less GVHD than other forms of stem cell transplants. Umbilical cord blood transplant is limited in adults because of the
transplantation
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Upper gastrointestinal (GI) endoscopy relatively limited number of stem cells that can be harvested from one placenta and umbilical cord. Wanda Todd Bradshaw, R.N.C., M.S.N. See also Acute lymphocytic leukemia (ALL); Bone marrow aspiration and biopsy; Bone marrow transplantation (BMT); Chemotherapy; Chronic lymphocytic leukemia (CLL); Chronic myeloid leukemia (CML); Graft-versushost disease (GVHD); Leukemias; Lymphomas; Myeloma; Stem cell transplantation.
u Upper gastrointestinal (GI)
endoscopy Category: Procedures Also known as: Esophagogastroduodenoscopy (EGD) Definition: An upper gastrointestinal (GI) endoscopy is a diagnostic procedure in which a thin tube with a light and camera is inserted into the throat to evaluate the inside of the esophagus, stomach, and first part of the small intestine (duodenum).
Salem Health: Cancer the patient is awake but relaxed and able to respond to the physician’s instructions during the procedure. A painrelieving medication is infused in the IV, and a local anesthetic is applied via a spray at the back of the patient’s throat to numb it and reduce the natural gag reflex. A mouthpiece is placed in the patient’s mouth through which the endoscope is passed. The physician may ask the patient to swallow several times to help pass the endoscope down the throat to the stomach. An endoscope is a long, thin, lighted flexible instrument with a camera on the end that transmits images of the esophagus, stomach, and duodenum onto a video monitor to guide the physician during the procedure. The procedure lasts from twenty to thirty minutes. If an abnormality such as a polyp or lesion is found during the procedure, then instruments can be inserted through the endoscope to remove it. Tissue samples (biopsy) can be removed through the endoscope. If bleeding is found during the procedure, then a sclerosing agent can
Cancers treated: Esophageal cancer, gastric (stomach) cancer, duodenal cancer Why performed: An upper endoscopy helps identify the cause of unexplained abdominal or chest pain, nausea and vomiting, heartburn, bleeding, and swallowing disorders. It can evaluate tumors, ulcers, and areas of inflammation. Patient preparation: Patients who have heart valve disease, rheumatic heart disease, and some other cardiovascular conditions may need to take an antibiotic before the procedure to reduce the risk of infection. Patients must not eat solid foods for eight hours before the procedure, but clear liquids may be allowed until a few hours before the procedure, depending on the specific guidelines of the testing center. Before the procedure, an assessment of the patient’s health history is conducted, and the potential risks of the procedure will be discussed. Steps of the procedure: The patient will change into a hospital gown. An intravenous (IV) line is inserted into a vein in the patient’s arm to deliver medications. A blood pressure cuff is placed on the patient’s arm to monitor blood pressure, a small clip placed on the patient’s finger is attached to an oximeter monitor to check the patient’s blood oxygen level, and the patient’s pulse is monitored during the procedure. The patient lies on the left side during the procedure. A sedative is given (conscious or moderate sedation), so 1202
A physician performs an upper gastrointestinal endoscopy. (Will & Deni McIntyre/Photo Researchers, Inc.)
Salem Health: Cancer be injected or another instrument can be inserted through the endoscope to stop the bleeding. After the procedure: The patient is observed in a recovery room for one to two hours as he or she recovers from the effects of the sedation. The patient will receive homegoing instructions from the nurse, including diet restrictions and medication and activity guidelines. The patient should not drive or operate machinery for eight hours after the procedure and should avoid vigorous physical activity after the procedure, as directed by the physician. The patient may have temporary throat soreness for a few days after the procedure, which can be relieved with throat lozenges. If a polyp or tissue sample was removed, then the patient may need to avoid aspirin and products containing aspirin, ibuprofen, and anticoagulants for one week. The physician will provide specific guidelines. Within seventy-two hours after the procedure, the patient should call the physician if he or she experiences severe abdominal pain, black or bloody stools, a continuous cough, fever, chills, chest pain, nausea, or vomiting. Risks: Complications associated with an upper endoscopy procedure are rare but may include bleeding and puncture of the stomach lining. The risk of complications associated with the sedation given during the procedure is also rare, occurring in less than 1 in every 10,000 people, according to the American College of Gastroenterology. In general, most patients experience only a mild sore throat after the procedure. Results: If the results of the test indicate that prompt treatment is needed, then the physician will discuss the treatment options with the patient and his or her family and the necessary arrangements will be made. The abnormal tissue or biopsy sample is sent for analysis in the laboratory to determine if there is a malignancy. If bleeding in the stomach lining or duodenum is found, then a peptic or duodenal ulcer may be diagnosed and a proton pump inhibitor or H2 antagonist medication may be prescribed. Barrett esophagus (a condition that increases the risk of esophageal cancer) is revealed by upper endoscopy in up to 5 percent of high-risk patients with gastroesophageal reflux disease (GERD), according to the American College of Gastroenterology. When the laboratory results are available within two to three days, the physician will notify the patient with the results. If another physician referred the patient for the procedure, then he or she will also receive a copy of the results. Angela M. Costello, B.S.
Upper gastrointestinal (GI) series u
For Further Information Cohen, J., et al. “Quality Indicators for Esophagogastroduodenoscopy.” American Journal of Gastroenterology 101 (2006): 886-891. Faigel, D. O., et al. “Quality Indicators for Gastrointestinal Endoscopic Procedures: An Introduction.” American Journal of Gastroenterology 101 (2006): 866-872.
u
Other Resources
American College of Gastroenterology http://www.acg.gi.org American Gastroenterological Association http://gastro.org American Society for Gastrointestinal Endoscopy http://www.askasge.org International Foundation for Functional Gastrointestinal Disorders http://www.iffgd.org National Digestive Diseases Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases http://digestive.niddk.nih.gov/index.htm See also Barrett esophagus; Duodenal carcinomas; Endoscopy; Esophageal cancer; Gastrointestinal complications of cancer treatment; Gastrointestinal oncology; Helicobacter pylori; Infection and sepsis; Nausea and vomiting; Small intestine cancer.
u Upper gastrointestinal (GI)
series Category: Procedures Also known as: Barium swallow, upper GI and small bowel series Definition: An upper gastrointestinal (GI) series is a radiographic examination of the upper digestive tract, including the esophagus, stomach, and small intestine. Moving X-ray images of the digestive tract are produced with a fluoroscopy machine. Cancers diagnosed: Esophageal, gastric, duodenal, and laryngeal cancers Why performed: An upper GI series helps identify structural or functional abnormalities of the upper digestive tract, including a tumor in these organs, hiatal hernia, nar1203
Upper gastrointestinal (GI) series
Salem Health: Cancer they might be pregnant; this test is not advised for pregnant women, so another test may be recommended.
An upper GI series reveals a large cancerous ulceration on the anterior stomach wall. (©ISM/Phototake—All rights reserved)
rowing of the esophagus, esophageal muscle disorders, esophageal varices (enlarged veins), gastroesophageal reflux disease (GERD), achalasia, ulcers, strictures, polyps, diverticula, some causes of intestinal inflammation, and certain swallowing disorders. It also may be performed to determine the cause of frequent heartburn or unexplained abdominal pain. Patient preparation: Specific dietary restrictions may be given to be followed for a few days before the procedure. A laxative may need to be taken the day before the procedure to clear the digestive tract. Patients must not eat or drink anything or smoke after midnight the night before the procedure. In most cases, the patient can continue taking regularly scheduled medications, but they must be taken with small sips of water. Patients with diabetes should ask how to adjust their meal plans, insulin, or other diabetes medications in preparation for the test. Patients should tell the physician if they are allergic or sensitive to contrast dyes, certain medications, iodine, shellfish, or latex. Female patients should tell the physician if they are pregnant or think 1204
Steps of the procedure: The patient will change into a hospital gown. The X-ray technician will first take a regular X ray of the stomach and abdomen. A medication may be injected into a vein in the patient’s arm to temporarily slow bowel movement. The patient is asked to drink 16 to 20 ounces of a barium solution that coats the lining of the esophagus, stomach, and duodenum to allow these organs to be seen on the X rays. Using a fluoroscope, a radiologist passes a continuous X-ray beam through the part of the digestive system being examined, and detailed pictures of the organ and its motion are transmitted on a monitor as the barium moves through the digestive system. The patient will be asked to hold his or her breath as each picture is taken so that the movement of breathing does not interfere with the images. The patient may be lying on a table or standing during the test and will be asked to turn in different positions as the barium moves through the digestive system. In some cases, the table may move to tilt the patient in different positions. The patient may be asked to swallow a “fizzy” tablet that produces air bubbles in the stomach. After the fluoroscopy part of the test, another regular X ray is taken of the stomach and abdomen. The procedure lasts about one to two hours, including the barium preparation time. After the procedure: The patient will receive homegoing instructions from the nurse, including diet restrictions and medication and activity guidelines. The patient can go home right after the procedure and resume regular activities and diet, unless otherwise instructed by the physician. The patient should increase the intake of fluids and highfiber foods to help flush the barium. The patient will pass what remains of the barium during the next few days after the procedure, and the stool may be light-colored or white. If constipation occurs after the procedure, then the patient should ask his or her doctor about taking a laxative. The patient should call the physician if he or she experiences abdominal pain within twenty-four hours after the procedure or constipation for more than two days after the procedure. Risks: There are no significant risks of the upper GI series. There is a low exposure of radiation during the test, but the amount of radiation is minimal and not likely to cause any health problems. The patient may find the taste of the barium solution unpleasant and may experience constipation after the procedure. Results: Normal values indicate that there are no structural abnormalities found on the upper GI examination.
Salem Health: Cancer The physician will notify the patient within two to three days about the test results after the radiologist has reviewed the fluoroscopy films. If a structural or functional problem was identified during the procedure, then the physician will discuss the appropriate treatment options with the patient. If another physician referred the patient for the procedure, then he or she will receive a copy of the test results. Angela M. Costello, B.S. u For Further Information Allen, J. I., et al. “Best Practices: Community-Based Gastroenterology Practices.” Clinical Gastroenterology and Hepatology 4 (2006): 292-295. McPhee, Stephen J., Maxine A. Papadakis, and Lawrence M. Tierney, eds. Current Medical Diagnosis and Treatment, 2008. New York: McGraw-Hill Medical, 2007. u
Other Resources
American College of Gastroenterology http://www.acg.gi.org American Gastroenterological Association http://gastro.org American Society for Gastrointestinal Endoscopy http://www.askasge.org International Foundation for Functional Gastrointestinal Disorders http://www.iffgd.org National Digestive Diseases Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases http://digestive.niddk.nih.gov/index.htm See also Barium swallow; Cobalt 60 radiation; Colon polyps; Duodenal carcinomas; Endoscopy; Fiber; Gastrointestinal oncology; Imaging tests; Laryngeal cancer; Laryngeal nerve palsy; Laxatives; Polyps; Pregnancy and cancer; Risks for cancer; Small intestine cancer; X-ray tests.
u Urethral cancer Category: Diseases, symptoms, and conditions Also known as: Urethral neoplasm, urethral carcinoma Related conditions: Squamous cell carcinoma of the urethra, transitional cell carcinoma of the urethra, adenocarcinoma of the urethra
Urethral cancer Definition: Urethral cancer is a cancer of the urethra, the tube that carries urine from the bladder to outside the body. In women, the tube is about 3 centimeters (cm) in length, whereas in men it is about 20 cm in length. Risk factors: Patients with the disease may have a history of bladder cancer, frequent urinary tract infection, chronic irritation of the urethra, or chronic inflammation of the urethra caused by a sexually transmitted infection. Additional risk factors include a history of cigarette smoking and age older than sixty years. Approximately 37 to 44 percent of individuals with urethral cancer have had a sexually transmitted infection, and some researchers believe the human papillomavirus is associated with urethral cancer. Etiology and the disease process: The urethral mucosal tissue consists of transitional epithelial cells near the bladder and squamous epithelial cells near the urethral opening. These cell types thus classify urethral cancer either as squamous cell carcinoma (the most common type of this cancer), transitional cell carcinoma (the second most common), or adenocarcinoma (in which transitional cells undergo metaplasia). Incidence: Urethral cancer is exceedingly rare; only about 700 cases are diagnosed in the world each year. In the United States, it is diagnosed more often in whites than in blacks and more often in women than in men. It has been reported in Americans between the ages of thirteen and ninety. Most patients are in their sixties when they are diagnosed. Symptoms: Because chronic irritation, inflammation, and infection tend to interfere with the natural reproductive mechanisms of the urethral mucosal cells, these processes usually precede urethral cancer. Patients with urethral cancer may be entirely asymptomatic for up to three years. Symptoms may include voiding problems such as frequency, diminished stream and straining to void, increased nighttime urination, itching, painful urination, bladder opening obstruction, overflow incontinence, blood in the urine or semen, and malodorous or watery discharge as well as perineal, pelvic, or penile pain. Screening and diagnosis: Urethral cancer is difficult to diagnose, in part because it is so rare and patients generally do not seek early treatment. Like most cancers, however, early detection leads to a greater chance of cure. Once urethral cancer develops, it often invades nearby structures (such as the bladder), and thus becomes difficult to treat with traditional surgical and radiation techniques. Ure1205
Urethral cancer
Salem Health: Cancer
Relative Survival Rates for Urethral Cancer (Papillary Transitional Cell), 1988-2001 Years
Survival Rate (%)
1 3 5 10
83.5 63.4 55.9 49.6
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
thral cancer might be suspected if a urethral fistula (an unusual drainage of urine) or an abscess occurs or tissue necrosis is present. Most patients are in an advanced stage of the disease when it is diagnosed. Screening may consist of a chest X ray; a computed tomography (CT) scan of the pelvis and abdomen; magnetic resonance imaging (MRI) of the urethra, nearby lymph nodes, and other soft tissue; blood chemistry studies; and a complete blood count. Urethral cancer is staged on the basis of what part of the urethra is affected and how widespread the cancer is. Anterior urethral cancer means the cancer affects parts of the urethra closest to the outside of the body, whereas posterior urethral cancer occurs in deeper parts of the body, near the bladder. In men, this often means the prostate is affected as well. Most clinicians categorize urethral cancer using the following criteria: • Stage 0: The urethral lining contains abnormal cells that may become cancerous and spread to nearby normal tissue. • Stage A: Cancer is present and has spread into the tissue adjacent to the lining of the urethra. • Stage B: Cancer is present in the muscle surrounding the urethra. In men, nearby tissues in the penis may be affected. • Stage C: Cancer has spread beyond the tissue surrounding the urethra. In women, cancer may be present in the vagina, the vaginal labia, and nearby muscle; in men, cancer may be present in the penis or in nearby muscle. • Stage D1: Cancer has spread to the nearby lymph nodes in the pelvis and groin. • Stage D2: Cancer has spread to distant lymph nodes and other organs in the body.
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Treatment and therapy: Treatment options depend on a patient’s general health, the stage and location of the cancer, when the diagnosis is made, and whether the cancer has recurred. The most common treatment is surgery; several different types of surgery may be pursued depending on the stage and severity of cancer. Some patients may receive radiation therapy or chemotherapy to kill any remaining cancer cells. Prognosis, prevention, and outcomes: Prognosis depends on a patient’s general health, the stage and size of the cancer, where in the urethra the cancer first developed, when the diagnosis was made, and whether the cancer has recurred. In most patients, the cancer is locally advanced when a diagnosis is made, and the prognosis is generally poor. Invasive urethral cancer treated with surgery, radiation, and chemotherapy combined occurs in about 50 percent of patients. The five-year survival rate for patients with noninvasive urethral cancer receiving surgical or radiation therapy is 60 percent. Terry A. Anderson, B.S. u
For Further Information Parisi, S., et al. “Role of External Radiation Therapy in Urinary Cancers.” Annals of Oncology 18 (2007): vi157-vi161. Swartz, M. A., et al. “Incidence of Primary Urethral Carcinoma in the United States.” Urology 68, no. 6 (2006): 1164.
u
Other Resources
American Urological Association http://www.urologyhealth.org National Cancer Institute Urethral Cancer http://www.cancer.gov/cancertopics/types/urethral See also Anal cancer; Benign prostatic hyperplasia (BPH); Bladder cancer; Cigarettes and cigars; Cystoscopy; Dilation and curettage (D&C); Enterostomal therapy; Exenteration; Gynecologic cancers; Gynecologic oncology; Human papillomavirus (HPV); Hysteroscopy; Kidney cancer; Laparoscopy and laparoscopic surgery; Penile cancer; Prostate cancer; Renal pelvis tumors; Urinalysis; Urinary system cancers; Urography; Urologic oncology; Vulvar cancer.
Salem Health: Cancer
Urinalysis
u Urinalysis
includes a description of the color (pale yellow, yellow, red orange, or brown), appearance or transparency (clear to cloudy to opaque), odor if abnormal, and specific gravity. The chemical evaluation includes the pH, protein, glucose, occult blood, ketones, leukocyte esterase, nitrite, bilirubin, and urobilinogen. These chemistry detection systems are each impregnated on a series of reagent pads on a dipstick that are activated when dipped into the urine and can be read manually or with an instrument. The microscopic examination of the urine sediment looks for bacteria, cells, and other formed elements such as casts, squamous epithelial cells, and crystals.
Category: Procedures Also known as: UA, routine urinalysis, complete urinalysis Definition: A routine complete urinalysis is the physical, chemical, and microscopic examination of the urine and a comprehensive overview of kidney function. Cancers diagnosed: While urinalysis is the most cost effective and least invasive evaluation of kidney and urinary tract function, it is not a screening method for the detection of cancer. Suspicious cells may be seen, however, upon microscopic review of the urine sediment and forwarded for cytological examination and further pathology review to rule out cancer of the bladder or kidney. Why performed: Urinalysis is the single most important evaluation of kidney function. It may detect urinary tract infections, systemic diseases such as diabetes mellitus, glomerulonephritis, and malignancy. Patient preparation: First morning voided urine of a minimum of 10 milliliters is the preferred specimen for a urinalysis. A random urine sample taken at any time during the day is acceptable. The patient collects the urine sample at midstream while urinating. The source of the urine sample may also be through the catherization of the bladder through the urethra or, rarely, through a suprapubic transabdominal needle aspirate of the bladder. If the physician suspects a urinary tract infection, then the urine must be a clean-catch sample in which contaminating bacteria are absent. For more detailed studies, a twenty-four-hour urine specimen may be required. A sample contaminated by vaginal discharge or hemorrhage will be rejected for analysis. Steps of the procedure: After the patient voids the urine sample into a cup or other container, it is labeled and sent to the clinical laboratory. A sample might have to be collected again if the transport to the clinical laboratory has been delayed, the quantity is insufficient, or there is bacterial overgrowth. The clinical laboratory completes three evaluations of the urine. The physical characterization of the urine
After the procedure: The urine sample is analyzed as soon as possible after voiding, ideally in less than two hours after collection. The results are sent to the physician who ordered the test. Risks: There are no risks to collecting a routine urine sample other than inconvenience. Results: Fresh normal urine is sterile, pale to dark yellow or amber in color, clear, and faintly aromatic, with a specific gravity between 1.003 and 1.035 grams per milliliter and a pH of 4.5 to 8.0. The dipstick chemistries are negative, and the microscopic observation is absent of cells or other elements. The normal twenty-four-hour urine volume is 750 to 2,000 milliliters. Urine from a healthy individual is yellow to amber in color. A pale urine may suggest diabetes insipidus. A
Urinalysis is invaluable for evaluating kidney function. (PhotoDisc)
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Urinalysis milky urine may be caused by fat globules or by white cells in a urinary tract infection. A red urine may be the result of red blood cells, medications, or certain foods. A greenish urine suggests the presence of bile associated with jaundice. A brown/black urine suggests hemorrhage or poisoning. Normal urine is clear, through which newsprint can be read. Cloudy to turbid urine may be the result of precipitation of mucin or calcium phosphates, neither of which merits pathological significance. Milky urine may suggest the pathological presence of fat globules. Turbid urine can point to a urinary tract infection. Normally urine presents a faintly acrid odor. A pleasantly sweet-smelling urine may suggest ketone production associated with diabetes mellitus. Strong acrid odors may be the result of medications or ingestion of certain foods, such as an acrid odor associated with asparagus. The urinary specific gravity is a reliable indicator of a person’s hydration status. The body maintains a narrow acid-to-base ratio (pH) in order to sustain life. The kidney monitors metabolic activity, and excess acid or base ions are excreted in the urine to maintain that balance. In healthy persons, protein is not present in urine in detectable amounts. Proteinuria is the excretion of more that 150 milligrams per day or 10 to 20 milligrams per deciliter of protein in the urine and is a classic symptom of renal disease. The proteinuria may be transient or persistent. If the proteinuria is persistent, then additional studies will determine if the cause is glomerular, tubular, or the result of overflow in which low-molecular-weight proteins overwhelm the ability of the system to reabsorb filtered proteins. In healthy persons, glucose is filtered by the glomerulus and reabsorbed in the proximal tubule. Glucose appears in the urine when the amount of glucose overwhelms the ability of the tubule to reabsorb it. Further evaluation determines the source of the glycosuria: diabetes mellitus, Cushing syndrome, liver and pancreatic diseases, or Fanconi syndrome. Apositive test for occult blood indicates the presence of hemoglobin or myoglobin. A finding of blood in the urine chemistry and the presence of red blood cells in the microscopic examination of urinary sediment (hematuria) requires the clinician to determine the source of the bleeding. The hematuria may be caused by an infection; glomerular, tubular, renovascular, or metabolic disorders; tumors; or calculi (stones). The hematuria may be induced by exercise, such as long-distance running. Ketones are the end products of the body’s fat metabolism and are not usually detected in the urine. The clinician determines the cause of the presence of ketones 1208
Salem Health: Cancer (ketonuria): carbohydrate-free dieting, uncontrolled diabetes, or starvation. Normally, fresh voided urine is sterile. In the case of urinary tract infections and subsequent pyuria, the white blood cells produce leukocyte esterase, which is detected on the dipstick reagent strip. A healthy person does not have nitrites in the urine. In the case of a urinary tract infection, gram-negative and some gram-positive microorganisms reduce the nitrates in the urine to nitrites, which can be detected. Normally, unconjugated bilirubin is water insoluble and cannot pass through the glomerulus. Conjugated bilirubin is water soluble, however, and appears in the urine, suggesting liver disease or biliary obstruction. The urine is also tested for urobilinogen, a colorless derivative of bilirubin formed by the action of intestinal bacteria. Urinalysis also checks for microscopic formed elements. Except for an occasional epithelial, white, or red cell, the microscopic examination of normal healthy urine sediment is without comment. Any of the following may or may not suggest pathology and require clinical interpretation in context of patient history: white blood cells (leukocytes), red blood cells (erythrocytes), casts, crystals, and bacteria. Casts are cylindrical bodies with a protein matrix, formed in the lumen of the renal tubules. They may demonstrate a homogenous or cellular matix and include any of the following types: hyaline, waxy, erythrocyte, leukocyte, epithelia, bacteria, granular, fatty, or broad. Crystals result from the precipitation of urinary solute out of the urine. They are not normally present in fresh voided urine, and many are not clinically significant. Examples include calcium oxalate, uric acid, triple phosphate (struvite), and cystine. Five bacterial organisms per high-power field from a clean-catch urine sample is the classic diagnostic criteria for bacteriuria and a diagnosis of a urinary tract infection. Typically five organisms per high-power field represents 100,000 colony-forming units when the urine is cultured. Jane Adrian, M.P.H., Ed.M., M.T. (ASCP) u
For Further Information Brunzel, Nancy A. Fundamentals of Urine and Body Fluid Analysis. 2d ed. Philadelphia: W. B. Saunders, 2004. Ringsrud, Karen Munson, and Jean Jorgenson Linne. Urinalysis and Body Fluids: A Colortext and Atlas. Philadelphia: Elsevier, 1994. Simerville, Jeff A., William C. Maxted, and John J. Pahira. “Urinalysis: A Comprehensive Review.” American Family Physician, March 15, 2005, 1153.
Salem Health: Cancer Strasinger, Susan King, and Marjorie Schaub Di Lorenzo. Urinalysis and Body Fluids. 5th ed. Philadelphia: F. A. Davis, 2008. u
Other Resources
American Urological Association http://www.auanet.org Lab Tests Online http://www.labtestsonline.org Onco Link http://www.oncolink.com See also Calcium; Cushing syndrome and cancer; Exercise and cancer; Fanconi anemia; Hematuria; Pathology; Risks for cancer; Tubular carcinomas; Urethral cancer.
u Urinary system cancers Category: Diseases, symptoms, and conditions Also known as: Bladder cancer, kidney and renal pelvic cancer, renal cell carcinoma, cancer of the urothelium, transitional cell cancer of the renal pelvis and ureter, urethral cancer, urethral neoplasms, squamous cell carcinoma of the urethra Related conditions: Birt-Hogg-Dubé syndrome, von Hippel-Lindau disease, hereditary leiomyomatosis Definition: Urinary system cancers are malignancies occurring anywhere in the organs that make up the urinary tract, including the kidney, ureter, bladder, and urethra. The kidney removes wastes and water from the blood, creating urine, which collects in the renal pelvis in the kidney. A tube called a ureter carries the urine to the bladder, which stores urine. Typically the bladder is flat when empty and balloons when full with urine, triggering the urge to urinate. The urethra, another tube, carries urine from the bladder to the outside of the body. Nine out of ten kidney cancers are renal cell carcinomas. Cancers that form in the renal pelvis and ureters develop from transitional cells. Some 98 percent of bladder tumors occur in the transitional cells that line the bladder. Urethral cancers are most commonly squamous cell cancers, followed by transitional cell cancers. Risk factors: Risk factors vary by type of urinary tract cancer. Risk factors for kidney cancer include cigarette smoking (40 percent greater risk), obesity, high blood pressure, long-term dialysis, and occupational exposure to
Urinary system cancers carcinogens such as asbestos, benzene, cadmium, herbicides, and organic solvents. Several hereditary disorders also increase the risk of kidney cancer: von Hippel-Lindau (VHL) disease (about 25 percent of those afflicted develop the clear cell type of renal carcinoma), hereditary papillary renal cell carcinoma, Birt-Hogg-Dubé syndrome, hereditary leiomyomatosis, and hereditary renal oncocytoma. People with any of these hereditary conditions or a prior renal cell carcinoma should be evaluated frequently. Renal cancer affects more men than women, in part because men are more likely to smoke cigarettes and to be exposed to occupational carcinogens. Cigarette smokers have two to three times the risk of developing bladder cancer than do nonsmokers. Smokers account for 50 percent of bladder cancer cases. Other risk factors implicated in the development of bladder cancer are occupational exposure to benzene or benzidene (20 to 25 percent of cases), a high-fat diet, excessive use of drugs containing the pain reliever phenacetin, and infection from Schistosoma haematobium, a type of fluke endemic in Europe, North America, and regions of Northern Africa. There has also been an association found between chlorinated drinking water and incidence of bladder cancer. A history of bladder cancer and being the age of sixty or older are the major risk factors for urethral cancer. Some studies have implicated chronic urinary tract infections and irritation as causing urethral cancer cells to grow. A history of sexually transmitted infections, particularly the human papillomavirus (HPV), has also been associated with increased risk of urethral cancer. Etiology and the disease process: Exactly what causes urinary tract cancers is not known, although many cases are found in active or past cigarette smokers. Renal cell carcinomas are primarily of the clear cell type (80 percent), followed by papillary renal carcinoma (10 to 15 percent). The clear cell type has cells that look very pale under a microscope; the papillary type is characterized by fingerlike projections. The bladder wall is lined with transitional cells and squamous cells. More than 90 percent of bladder cancers begin in transitional cells and 8 percent in squamous cells. Cancer occurring only in cells that line the bladder is referred to as superficial bladder cancer (carcinoma in situ). Cancers that begin in the transitional cells may spread through the bladder’s lining and into the muscular wall of the bladder. In women, this type of bladder cancer may invade adjacent organs such as the vagina or uterus. In men, it may invade the prostate gland. In either gender, it may spread to the wall of the abdomen. When the cancer spreads outside the bladder, nearby lymph nodes are often 1209
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involved. Distant disease may develop when a primary bladder cancer spreads to another part of the body. Most urethral cancers invade locally, but they tend to be aggressive, metastasizing to nearby tissue. Often they are locally advanced by the time a diagnosis is made. However, the majority of urethral cancers do not spread distally. Cancer of the urethra manifests differently in men and women, differing in the type of cancer cells involved (squamous cell, transitional cell, or adenocarcinoma).
The Anatomy of the Urinary System
Adrenal glands
Aorta
Renal arteries
Kidneys
Ureters
Common iliac arteries
Urinary bladder Prostate (male only) Urethra
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Incidence: The median age of diagnosis for cancer of the kidney and renal pelvis is sixty-five years. Renal cell carcinoma accounts for approximately 70 percent of kidney cancers and renal pelvis cancers for about 15 percent. The incidence rate for kidney cancer adjusted for age is 12.8 per 100,000 men and women per year. The incidence rate is approximately twofold in men versus women across ethnic groups, with the highest incidence in black men, a rate of 20.4 cases per 100,000 population. Bladder cancer is the most common type of malignancy affecting the urinary system. About 50,000 cases of bladder cancer are diagnosed each year, making it the fourth most common cancer in men and the eighth most common cancer in women. The incidence is higher in men than women, with 40.5 cases per 100,000 population for white men. Bladder cancer occurs twice as often in whites as in blacks and Hispanics. The age-adjusted incidence for both men and women for bladder cancer is 21.1 cases per 100,000 people per year. Two-thirds of cases of bladder cancer occur in individuals over the age of sixty-five. Urethral cancer usually develops in the squamous cells that line the urethra. Most urethral cancer in women occurs in the labia, vagina, or bladder neck, while in men it occurs in the vascular spaces of the corpora and periurethal tissue, deep tissue in the perineum, urogenital diaphragm, prostate, or penial and scrotal skin. Urethral cancer is a very rare condition occurring in less than 1 percent of all cancer cases. It is the only genitourinary system cancer that has greater incidence in women than in men. Although most urethral cancers are squamous cell cancers (78 percent of cases in men), the second most common type for both genders is transitional cell cancer. Adenocarcinoma occurs in the glands near the urethra in both men and women. Symptoms: People with urinary tract cancer often experience hematuria, or blood in the urine, which in most cases is visible to the naked eye or upon inspection under a microscope. A thorough diagnostic evaluation following a finding of hematuria is essential to eliminate other conditions such as kidney stones or a urinary tract infection. Patients with renal cell carcinoma may complain of hematuria, pain in the side, an abdominal lump, anemia, loss of appetite, and unexplained weight loss. Symptoms of transitional cell cancer of the renal pelvis and ureters include hematuria, back pain, fatigue, unexplained weight loss, frequent urination, or pain on urination. Common symptoms of bladder cancer include hematuria, lower back pain, frequent urination, and pain during urination. Patients with urethral cancer may have no symptoms early on or may experience hematuria, trouble with urinary flow (such as interrupted flow), a discharge, a lump or thickness
Salem Health: Cancer
Urinary system cancers
Lifetime Risk of Developing Common Urinary System Cancers, Based on Rates from 2003-2005 Cancer Type
Lifetime Risk: %
Lifetime Risk: No.
Probability of Developing Cancer
Urinary bladder cancer
2.38% of people born today will be diagnosed with bladder cancer in their lifetime
1 in 42 people will be diagnosed with bladder cancer in his or her lifetime
1.22% of men and 0.35% of women will develop bladder cancer between their 50th and 70th birthdays
Kidney and renal pelvis cancer
1.38% of people born today will be diagnosed with kidney or renal pelvis cancer in their lifetime
1 in 72 people will be diagnosed with kidney or renal pelvis cancer in his or her lifetime
0.85% of men and 0.43% of women will develop kidney or renal pelvis cancer between their 50th and 70th birthdays
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008
in the penis or perineum, and enlarged lymph nodes in the groin area. Screening and diagnosis: There are no standard screening tests for cancers of the urinary tract. Often kidney cancer is detected during a physical examination conducted for another purpose. When a person complains of symptoms consistent with a urinary system cancer, the physician will perform a complete physical exam, feeling the abdomen for any masses or abnormalities, and take a medical history, asking about risk factors such as cigarette smoking and occupational exposure to environmental carcinogens. If the patient complains of hematuria, blood and urine tests will be ordered. A urine cytology test reveals markers in the urine associated with cancer cells or cancer cells coming from the lining of the bladder. A cystoscopy, in which a cystoscope (lighted tube) is inserted into the bladder through the urethra, checks for abnormal areas that can then be biopsied. (If the scope is extended into the ureter and renal pelvis, the test is called a ureteroscopy.) Another tool is an intravenous pyelogram (IVP), in which a contrast dye is injected into a vein and a series of X rays is taken to look for blockages in the kidney, ureter, and bladder. If cancer is detected, imaging studies such as computed tomography (CT) scans, magnetic resonance imaging (MRI), or ultrasound may be used to assess tumor growth and spread and to stage the cancer. Urinary system cancers follow various staging systems. Most systems divide cancers into stages according to the size of the tumor and its extent of spread (localized, regional, or distant areas of the body). Many systems also grade the tumor, depending on how aggressively the cancer is growing.
Treatment and therapy: Surgery, radiation therapy, chemotherapy, and biological therapy are typical treatment options for urinary system cancers. In renal cell carcinoma, surgery is the common option. A partial nephrectomy removes the tumor in the kidney and some tissue with it; a simple nephrectomy removes only the kidney; and a radical nephrectomy removes the kidney, surrounding tissue, adrenal gland, and lymph nodes. A radical nephrectomy may be more likely to cure the cancer in individuals with Stage II or Stage III tumors. Patients sometimes receive radiation therapy or chemotherapy after surgery to remove any remaining cancerous cells. Minimally invasive surgeries such as laparoscopy can be used for partial or radical nephrectomies. These techniques are gaining acceptance, since the use of laparoscopy reduces blood loss during surgery, requires less use of narcotics for pain, and shortens hospital stays and recovery time. Surgery is not undertaken for Stage IV renal cell cancers since the cancer cannot be cured. In these cases, a technique called arterial embolization is used. Gelatin sponges are used to block the flow of blood to the kidney and kill the cancerous cells. Newer targeted chemotherapies such as sorafenib, sunitinib, and temsirolimus seem to be helpful. Patients at this stage in otherwise good health may be able to tolerate the side effects associated with interleukin 2 (IL-2) or cytokine therapy. The patient’s physician may recommend that the kidney be removed before starting this therapy to enhance the response to treatment. For transitional cell cancer of the renal pelvis and ureter, standard surgical options include removing part of the ureter (in superficial cases) or a nephroureterectomy, which removes the kidney, ureter, and the tissue that connects the ureter to the bladder. 1211
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For bladder cancer, standard treatment includes surgery, radiation therapy, chemotherapy, and biological therapy. Surgical options include transurethral resection (TUR) with fulguration, in which high-energy electricity is used to burn away cancerous areas during a cytoscopy; a segmental cystectomy, in which part of the bladder is removed; and a radical cystectomy, in which the bladder, lymph nodes, and nearby organs (prostate and seminal vesicles in men; uterus, ovaries, and part of the vagina in women) are removed. If the bladder is removed, the surgeon creates another outlet in which urine is stored and leaves the body, referred to as a urinary diversion. Chemotherapy or radiation therapy may be performed following surgery to eliminate any remaining cancer cells or retard their growth. In cases of bladder cancer, radiation therapy is used externally and internally through radioactive seeds placed in the body near the cancer. Chemotherapy is delivered orally or by injection, placed directly in an affected area or delivered through a tube inserted into the bladder. Biological therapy may be used to bolster an affected individual’s immune system to fight the cancer. The standard treatments for urethral cancer are surgery, radiation therapy, and watchful waiting. Surgery may remove the cancer by excision, burning with high-energy electricity (electroresection with fulguration), or laser surgery. Depending on the cancer’s spread, other surgeries performed include lymph node dissection (removal of lymph nodes in groin and pelvis), cystourethrectomy (removal of bladder and urethra), cystoprostatectomy (removal of bladder and prostate), anterior exenteration (removal of urethra, bladder, and vagina), partial penectomy (removal of part of penis near urethra), and radical penectomy (removal of entire penis). External and internal radiation therapy are also used for urethral cancer. Some patients are simply monitored for signs that the cancer has developed to the point where further treatment is necessary. Patients should consult with their physician regarding treatment options, including those in clinical trials. Decisions should be based on the stage and grade of cancer, the patient’s age and overall health, and the expected quality of life following treatment.
The overall five-year relative survival rate for those with renal cell cancer is about 50 percent, and for those with renal pelvic or ureter cancers, it is about 65 percent. The overall five-year relative survival rate for bladder cancer is 79.8 percent. The five-year relative survival rate rises to 92 percent if bladder cancer is diagnosed while still localized, falling to 45 percent when diagnosed when regional and 6 percent when the cancer has spread to distant areas. Urethral cancer, if noninvasive and treated surgically or with radiation, has five-year survival rates of about 60 percent. Susan H. Peterman, M.P.H.
Prognosis, prevention, and outcomes: Outcomes experienced by those with urinary system cancers depend on many factors, including the stage of their cancers, whether they are superficial or invasive, the degree of metastasis, and patients’ overall health and age. It is estimated that one-third of renal cell cancers and more than half of renal pelvic and ureter cancers could be eliminated if people stopped smoking cigarettes.
Urologychannel: Your Urology Community http://www.urologychannel.com
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For Further Information Campbell, Steven C., et al. One Hundred Questions and Answers About Kidney Cancer. Sudbury, Mass.: Jones and Bartlett, 2009. Eble, John N., Guido Sauter, Jonathan Epstein, and Isabell Sesterhenn, eds. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Vol. 7 in World Health Organization Classification of Tumours. Lyon, England: International Agency for Research on Cancer Press, 2003. Ellsworth, Pamela, and Brett Carswell. One Hundred Questions and Answers About Bladder Cancer. Sudbury, Mass.: Jones and Bartlett, 2006. Schrier, Robert W., ed. Diseases of the Kidney and Urinary Tract. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2007. Tekes, Aylin, et al. “Dynamic MRI of Bladder Cancer: Evaluation of Staging Accuracy.” American Journal of Roentgenology 184, no. 1 (January, 2005): 121-127.
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Other Resources
American Cancer Society http://www.cancer.org American Urological Association http://www.aunet.org National Cancer Institute http://www.cancer.gov
See also Bladder cancer; Coke oven emissions; Cystography; Epidermoid cancers of mucous membranes; Exenteration; Kidney cancer; Nephrostomy; Renal pelvis tumors; Transitional cell carcinomas; Urethral cancer; Urography; Urologic oncology; X-ray tests.
Salem Health: Cancer
u Urography Category: Procedures Also known as: Intravenous pyelography (IVP), oral urography, retrograde urography, magnetic resonance urography, computed tomography urography Definition: Urography allows an assessment of the health and functioning of the urinary system by injecting a contrast material (dye) into the bloodstream. When this contrast material reaches the urinary tract, its soft-tissue structures become visible on imaging scans, so that abnormalities can be detected. Cancers diagnosed: Cancers of the kidney (renal cell carcinoma), ureters, and bladder
Urography inserted into the urethra. In computed tomography (CT) urography, contrast material is injected into the bloodstream, but instead of using conventional X rays to visualize the kidneys, ureters, and bladder, a CT scanner takes multiple cross-sectional images of the body and uses a computer to compile a three-dimensional image. In magnetic resonance imaging (MRI) urography, contrast material is injected, and then the individual is placed in a special tube while a three-dimensional picture is obtained through MRI. This type of urography is used most often to locate bladder cancer that has spread into the pelvic region. Patient preparation: For nonemergency urography, the physician will review the patient’s medications to make sure that they do not interact with the contrast material. Patients should tell their physicians if they are allergic to seafood or iodine, as this increases the likelihood that they may have an allergic reaction to the contrast dye. Women who are or think they might be pregnant should not have urographic tests that expose them to X rays. The night before the test, the patient takes a laxative to empty the bowel and should not eat or drink on the day of the test. During the test, the patient will wear a hospital gown.
Why performed: The urinary system is composed of the kidneys, ureters, bladder, and urethra. The kidneys are two bean-shaped organs located in the lower back below the rib cage. Their function is to filter blood, remove waste products, and help maintain the proper balance of fluid in the body. The ureters carry excess water and waste materials from the kidney to the bladder, where these waste materials are stored. The urethra removes this urine from the Steps of the procedure: The contrast material is injected body. Urography allows these structures to be examined into a vein (most commonly), injected into the urethra, or for cancer and other abnormalities in a noninvasive way. given by mouth. The patient may briefly feel a warm, tinMost often, urography is done for reasons unrelated to gling sensation. In rare cases, the patient can develop cancer. Kidney stones, for example, can cause obstruction breathing problems or experiences swelling in the throat in the urinary system accompanied by extreme pain. In this case, urography is done on an emergency basis to locate the obstruction. Cancer tumors can also cause obstruction or blood in the urine. Urography to detect cancer is done on a nonemergency basis in a radiology center or other outpatient setting. Urography can be done in several different ways using various imaging techniques. Sometimes it is necessary to use more than one method in order to acquire precise information about the location of tumors. In intravenous pyelography (IVP), a dye containing iodine is injected into a vein in the hand or arm. When the dye reaches the urinary tract, the tissues become visible on conventional X rays. The only difference between oral urography and IVP is that the individual drinks the dye instead of having it injected. Retrograde pyelography is similar to an IVP, only the dye is placed directly in the uriAn intravenous urogram showing a polyploid cancer of the bladder. (©ISM/ nary tract by way of a catheter (thin tube) Phototake—All rights reserved) 1213
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Salem Health: Cancer
or elsewhere. This is a sign of an allergic reaction, and the physician should be notified immediately. The patient is placed on the X-ray table, and a series of X rays are taken at timed intervals, usually at zero, five, ten, twenty, and sometimes forty minutes. While each X ray is being taken, the patient must remain still. Between X rays, the patient may move. For the final X ray, the patient is asked to urinate, and an X ray is taken of the bladder. CT and MRI urography are very similar. MRI urography takes about one hour and requires the patient to remain still during that time.
u Urologic oncology
After the procedure: After the procedure, the patient may eat, drink, and resume normal activities. The patient may have a mild headache or slight nausea from the contrast material. Urine will appear normal; the contrast material does not change its color.
Cancers treated: Urologic oncologists treat bladder, kidney, penile, and testicular cancer in men and bladder and kidney cancer in women.
Risks: This is a minimally invasive procedure with few risks. Rarely does a patient have a serious allergic reaction to the contrast material. Although X rays are very safe, pregnant women should not have them because of potential damage to the developing fetus. These women can have MRI or CT urography, neither of which uses X rays. Results: In a healthy kidney, the dye will show up on the X rays soon after it is injected. In people with kidney damage, the dye takes longer to appear in the X rays. Martiscia Davidson, A.M. u
For Further Information Anderson, E. M., et al. “Multidetector Computed Tomography Urography (MDCTU) for Diagnosing Urothelial Malignancy.” Clinical Radiology 62, no. 4 (April, 2007): 324-332. Guermazi, A., ed. Imaging of Kidney Cancer. New York: Springer, 2006. Strum, Stephen, and Donna L. Pogliano. A Primer on Prostate Cancer: The Empowered Patient’s Guide. Hollywood, Fla.: Life Extension Media, 2002. u
Other Resources
eMedicinehealth.com Intravenous Pyelogram http://www.emedicinehealth.com/ intravenous_pyelogram/article_em.htm See also Bladder cancer; Gastrointestinal complications of cancer treatment; Hematuria; Imaging tests; Kidney cancer; Nephrostomy; Prostate cancer; Urethral cancer; Urinary system cancers; X-ray tests. 1214
Category: Medical specialties Also known as: Genitourinary oncology Definition: Urology is the study of the male and female urinary systems and the male reproductive system. Oncology is the study of the development, diagnosis, treatment, and prevention of cancer. Urologic oncology is the diagnosis, treatment, and prevention of cancers involving the urinary and male reproductive system.
Training and certification: Urologic oncologists are doctors who are board certified in urology. In the hierarchy of medicine, urology is classified as a surgical subspecialty. This means the doctor has specialized training in surgery. Doctors who are fellows of the American College of Surgeons (FACS) have achieved more advanced qualifications in surgery. To become board certified in urology in the United States, the doctor must have graduated from an approved medical school and have completed an accredited urology residency program that involved at least five years of training. In the course of the residency training program, there must be one year of training in general surgery, three years in clinical urology, and at least six months in general surgery, urology, or another specialty relevant to urology. The doctor must be a senior or chief resident in urology during the last year of the program. Within five years of completing the education program, the doctor must complete a qualifying examination followed by a certifying examination to become board certified. The qualifying examination consists of a one-day written exam to assess the doctor’s knowledge of the entire field of urology and related subjects. The certification examination is designed to assess clinical competence. During the two-day certification process, the doctor is evaluated to ensure the existence of an approved practice log and a favorable professional reputation among peers. Additionally, the urologist is tested on knowledge in the areas of immunology, molecular biology, hypertension, transplantation, sexual dysfunction, urologic imaging, pathology, and problems with urination, such as benign prostatic hyperplasia (BPH) and incontinence. There are also questions that pertain to infections, inflammatory diseases, fertility problems, obstructive diseases, cancer, anatomy, fluid imbalances, and pediatric urology. The practicing urologist needs to have obtained a high level of expertise
Salem Health: Cancer in all these areas to become board certified. Doctors who were certified after January 1, 1985, must undergo a recertification process every ten years. There is no recognized board-certified subspecialty of urologic oncology. Doctors who choose to practice medicine in urologic oncology can receive additional training in this area of expertise through fellowship programs, attending conferences and other training programs, and membership in organizations such as the Society of Urologic Oncology. Services and procedures performed: Urologic oncologists are surgeons who specialize in the management and treatment of cancer. This includes evaluation, diagnosis, and treatment of cancer or suspected cancer in the prostate, bladder, kidney, and testicles. Additionally, conditions such as urinary retention and blood in the urine are treated. Typically, the doctor asks a series of questions on the first visit to assess the problem. After the patient’s initial examination, a series of tests may be recommended to determine the type and extent of disease. Some of these diagnostic tests may include a blood test, urine test, cystoscopy (insertion of a small scope to view the inside of the bladder and ureter), digital rectal exam, biopsy, cystourethrogram (an X ray taken of the bladder and urethra while urinating), ultrasound, or other imaging studies. Depending on the test results, the doctor devises a treatment plan, which may be aggressive to rid the body of disease or simply palliative to alleviate symptoms associated with the cancer. When the cancer is localized, meaning limited to an organ or specific area, aggressive treatment is often undertaken to get rid of disease. When the cancer has spread to other areas of the body, called metastasis, treatment often involves minimizing symptoms and discomfort instead of trying to cure the body of disease. Some of the procedures performed by urologic oncologists include laparotomy (incision in the abdominal wall to view inside the abdomen), transurethral resection (to diagnose and remove cancer of the bladder or prostate), cystectomy (partial or complete removal of the bladder), and prostatectomy (partial or complete removal of the prostate gland). In addition to surgery, treatment may include the use of hormone therapy, radiation, chemotherapy, or combinations of these therapies. When other treatment options are considered, a urologic oncologist may include other members on the team who specialize in these different types of cancer treatments. Related specialties and subspecialties: Many urologic oncologists work with specialists in oncology fields such as radiation, chemotherapy, and immunotherapy. Pathologists are also intimately involved in the diagnostic process.
Urologic oncology A pathologist is a doctor who specializes in identifying diseases by examining tissues and cells under a microscope to determine if cancer cells are present and, if they are, how aggressive the disease may be. The pathologist’s report is critical in setting the stage for treatment of the disease. A radiation oncologist uses radiotherapy, which is highenergy waves or particles, to destroy or damage cancer cells. It can be done using electron beam therapy, X-ray therapy radiation treatment, or cobalt therapy. This type of treatment is primarily used to treat localized cancer, though in some instances it is used for total body irradiation in preparation for a bone marrow transplant. A medical oncologist specializes in using chemotherapy, hormone therapy, and biological therapy for the treatment of cancer. Chemotherapy is often used when the cancer has metastasized or spread throughout the body. This can be delivered intravenously, by injection, or with a pill. Hormone therapy, commonly used in the treatment of prostate cancer, involves administering hormones to suppress the production of testosterone in the body. This helps stop the production of cancer cells. Immunotherapy, sometimes called biological therapy or biotherapy, uses treatments to stimulate the body’s immune system to fight disease. This can be done by administering a drug or by stimulating the body’s own immune system to work harder to fight disease. This type of treatment is often used in conjunction with other therapies to enhance the effect. When cancer is not contained within the urinary or male reproductive systems, assistance may be required from doctors who specialize in treating other areas of the body, such as gynecologists. It is not uncommon to have a treatment team consisting of specialists in urologic oncology, pathology, radiation therapy, chemotherapy, immunotherapy, and other areas who all work together to fight the disease. Vonne Sieve, M.A. u
For Further Information Ellsworth, Pamela, and Anthony Caldamone. The Little Black Book of Urology. Sudbury, Mass.: Jones and Bartlett, 2007. Society of Urologic Oncology. “Advances in the Treatment of Genitourinary Cancer: Highlights from the Third Annual Meeting of the Society of Urologic Oncology, December 13-14, 2002, Washington, D.C.” Reviews in Urology 5, no. 4 (Fall, 2003): 232-234. _______. “Report from the Society of Urologic Oncology: Highlights from the Fourth Annual Meeting of the Society of Urologic Oncology, December 5-6, 2003, Bethesda, Md.” Reviews in Urology 6, no. 4 (Fall, 2004): 193-199. 1215
Urostomy u
Organizations and Professional Societies
American Association of Clinical Urologists http://www.aacuweb.org Two Woodfield Lake 1100 E. Woodfield Road, Suite 520 Schaumburg, IL 60173 American Association of Genitourinary Surgeons http://www.aagus.org University of Michigan Department of Urology 3875 Taubman Center SPC 5330 1500 East Medical Center Drive Ann Arbor, MI 48109-5330 American Board of Urology http://www.abu.org 2216 Ivy Road, Suite 210 Charlottesville, VA 22903 American Urological Association http://www.auanet.org 1000 Corporate Boulevard Linthicum, MD 21090 National Cancer Institute, Center for Cancer Research: Urologic Oncology Branch http://ccr.cancer.gov/labs/lab.asp?labid=92 10 Center Drive, MSC 1501 10/2B47 Bethesda, MD 20892 Society of University Urologists http://www.suunet.org 1100 E. Woodfield Road, Suite 520 Schaumburg, IL 60173 Society of Urologic Oncology http://www.societyofurologiconcology.org 1100 E. Woodfield Road, Suite 520 Schaumburg, IL 60173 u
Other Resources
American Urology Association http://www.urologyhealth.org Journal of Urology http://www.jurology.com See also Benign prostatic hyperplasia (BPH); Chemotherapy; Digital rectal exam (DRE); Fertility drugs and cancer; Fertility issues; Imaging tests; Kidney cancer; Nephrostomy; Prostate cancer; Testicular cancer; Urethral cancer; Urinary system cancers; Urography; Urostomy; X-ray tests. 1216
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u Urostomy Category: Procedures Also known as: Urinary diversion Definition: A urostomy is a surgical opening (stoma) through the abdominal wall that allows urine to drain from the diseased bladder into an artificial pouch, to be emptied intermittently, when long-term drainage from the bladder is not possible. A urostomy can be conventional or standard, with an ileal conduit, or feature a continent urinary reservoir. Cancers treated: Bladder cancer Why performed: When a bladder is diseased, the body must have a way to excrete urine, liquid human waste. A surgeon creates a urostomy to drain urine from the kidney. Patient preparation: The surgeon discusses the risks and benefits of the urostomy with the patient and examines the patient’s abdomen to locate the best place for the stoma. Some patients try flat pouches at the predetermined place to see if the location allows maximum comfort and minimal interference in activities of daily living. Patients should tell the surgeon if their work or hobbies need special consideration. Steps of the procedure: The steps of the procedure depend on the type of surgery performed. In a conventional urostomy, a small pouch or urine reservoir is created surgically from a small bowel segment. A passage is created from the kidney and ureters to the ileal segment that bypasses the bladder (which may or may not be removed). The far end of the ileal segment is brought through the abdominal wall to make a stoma. After the procedure: Education regarding how to care for a pouch after surgery is provided by an ostomy specialist. After surgery, the stoma may swell but will decrease in size over six to eight weeks. Most health care facilities have ostomy visitors who have experienced a urostomy and understand concerns about body image. They can answer questions that the patient may have after surgery. Support groups are also useful. Risks: Typical risks include urinary crystals, infection, and skin irritation. A pouch that fits well along with adequate fluid intake and appropriate skin care with a protectant barrier can minimize problems. The patient should notify the health care provider if bleeding occurs from the stoma, if ulcers form on the skin around the stoma, or if fever or a strong odor in the urine (a sign of a kidney infection) occurs.
Salem Health: Cancer Results: The urostomy can improve quality of life for the bladder cancer patient, who can return to most normal activities. Managing the urostomy will become routine with practice. Marylane Wade Koch, M.S.N., R.N. See also Bladder cancer; Enterostomal therapy; Exenteration; Nephrostomy; Self-image and body image.
u Uterine cancer Category: Diseases, symptoms, and conditions Also known as: Endometrial carcinoma, cancer of the uterus, adenocarcinoma of the uterus, carcinosarcoma of the uterus, clear cell endometrial carcinoma, papillary serous carcinoma of the uterus, adenosquamous carcinoma of the uterus, endolymphatic stromal myosis, heterologous uterine sarcoma, homologous uterine sarcoma, leiomyosarcoma of the uterus, malignant mixed Mullerian tumor of the uterus, serous endometrial carcinoma, endometrial stromal sarcoma, rhabdosarcoma of the uterus, osteosarcoma of the uterus, chondrosarcoma of the uterus Related conditions: Cancer of the cervix, cancer of the Fallopian tube, bladder cancer, rectal cancer, vaginal cancer, cancer of the ovary Definition: The uterus has a body (also called the corpus), which is located within the lower portion of the abdominal cavity between the bladder and the rectum, and a vaginal portion, referred to as the cervix. Although the uterus and cervix are continuous, they are considered as separate structures with respect to cancer. Further, the uterus has a covering (the serosa), a layer of muscle (the myometrium), and a layer of cells (the endometrium) lining the uterine cavity (the uterine cavity is the site for fetal growth during pregnancy). Cancer of the uterus most often involves the endometrium, with the myometrium the less fequent site of cancer. The Fallopian tubes are connected to the top of the uterus on either side but are not considered part of the uterus. Cancer of the uterus is thus defined as cancer of the body of the uterus (the endometrium or myometrium), as opposed to cancer arising from the cervix or metastatic from an adjacent structure (such as the vagina, Fallopian tube, ovary, bladder, or rectum). Risk factors: There are factors that increase a woman’s risk of developing cancer of the uterus and those that decrease it. Factors that increase the risk are the use of estrogen-containing medications without the addition of
Uterine cancer progesterone (called the unopposed estrogen effect; progesterone neutralizes the stimulatory effect of estrogen on the endometrium of the uterus), late menopause (after reaching the age of fifty-two), obesity, not having given birth to a child (also known as nulliparity), diabetes, estrogen-secreting ovarian tumors, polycystic ovarian syndrome, high blood pressure, increased dietary fat intake, radiation therapy to the pelvis for other reasons, and the use for more than two years of the medication tamoxifen in the treatment of breast cancer. The factors known to decrease a woman’s risk of cancer of the uterus include interrupted ovulation (during and shortly after pregnancy or while using oral contraceptives, which prevent ovulation), use of progesterone, menopause before the age of forty-nine, normal weight, and having given birth to more than one child (also known as multiparity). In fact, use of oral contraceptives has been shown to reduce a woman’s risk of cancer of the uterus by approximately 50 percent, the benefit emerging after one year of use and lasting for up to fifteen years after discontinued use. Etiology and the disease process: Cancer of the uterus most often occurs in women in the menopause or those approaching the menopause (that is, perimenopause), with a peak occurrence between the ages of fifty and sixty-five. In women who have long-term unopposed estrogen stimulation, the endometrium undergoes hyperplastic changes that are benign but precede the development of cancer. In most cases, hyperplastic changes can be reversed with the discontinuation of estrogen or the addition of progester-
Age at Diagnosis of Uterine Cancer, 2001-2005 Age Group
Cases Diagnosed (%)
Under 20 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
0.0 1.5 6.4 18.9 28.8 22.8 16.5 5.1
Source: Data from National Cancer Institute, Surveillance Epidemiology and End Results, Cancer Stat Fact Sheets, 2008 Note: The median age of diagnosis from 2001 to 2005 was sixty-two, with an age-adjusted incidence rate of 23.4 per 100,000 women per year.
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Salem Health: Cancer abnormal and should be evaluated by a gynecologist.
Screening and diagnosis: Unlike cancer of the cervix or breast cancer, which have well-accepted and effective screening tests (Pap smears and mammography, respectively), no such screening test exists for cancer of the uterus. Nevertheless, two screening tests are available for anyone at high risk: endometrial sampling and measurement of the endometrial thickness (or lining). Endometrial sampling is an office-based procedure in which a small, flexible, plastic catheter is inserted into the uterus, and the cells lining the uterus (endometrial cells) are aspirated (sucked) into the catheter. Endometrial sampling is a relatively painless procedure, although some women experience mild uterA number of possible uterine pathologies, including uterine cancer (white). (LifeART© ine cramping. The aspirated cells are 2008 Wolters Kluwer Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.) sent to a laboratory for microscopic evaluation, similar to a Pap smear. one. The risk of hyperplasia progressing to cancer is age Endometrial sampling can also serve as the diagnostic test dependent: 11 percent for women less than the age of for endometrial cancer. In some cases, if the diagnosis of thirty-five, 12 percent for women between the ages of uterine cancer is in question based on endometrial samthirty-six and fifty-four, and 28 percent for women over pling, a dilation and curettage (D&C) can be performed as the age of fifty-five. an outpatient procedure in which more extensive sampling of the uterine cavity can be undertaken without causing Incidence: Cancer of the uterus is the most frequent candiscomfort to the patient. In rare cases, the diagnosis of cer involving the female reproductive tract in the United uterine cancer is made at the time of a hysterectomy being States and the fourth most frequent cancer affecting women, performed for other indications. behind breast, lung, and colorectal cancer. There are apMeasurement of the endometrial thickness is also an proximately 41,000 new cases of uterine cancer each year office-based procedure but in some cases is done by a radiwith about 7,300 deaths. An individual woman’s lifetime ologist. An ultrasound probe is inserted through the varisk of cancer of the uterus is about 1 in 50 (compared with gina (transvaginal ultrasound) to messure the thickness of 1 in 8 for breast cancer). the lining of the uterus. The procedure is painless and takes only a few minutes to perform. Measurement of the Symptoms: Abnormal bleeding through the vagina is the endometrial thickness is most appropriate for menopausal most common symptom associated with cancer of the women. An endometrial thickness less than 4 millimeters uterus, occurring in about 90 percent of cases. Such bleed(mm) is rarely associated with a uterine malignancy in a ing may arise from the vagina, bladder, or rectum and must woman not taking hormones, or less than 8 mm in a be thoroughly evaluated. Fortunately, abnormal bleedwoman on hormones. ing is a sign of uterine cancer in only 10 to 20 percent of Staging of uterine cancer is according to the Internaall cases. For premenopausal women, the bleeding may tional Federation of Gynecology and Obstetrics (FIGO) as take the form of breakthrough, prolonged, or heavy bleedfollows: ing, all of which generally reflect an underlying hormonal imbalance and can be treated as such. For post• Stage I: Cancer limited to the endometrium or myomenopausal women, any bleeding should be considered metrium 1218
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• Stage II: Cancer extending from the body of the uterus to the cervix • Stage III: Cancer protruding through the serosa or metastases to the vagina, pelvis, or lymph nodes adjacent to the aorta • Stage IV: Metastases to the bladder, bowel, or organs outside the pelvis in the abdomen Treatment and therapy: Surgery, typically a hysterectomy with removal of the Fallopian tubes and ovaries and sampling of the local lymph nodes, is the mainstay of treatment. Radiation therapy is reserved for patients who are poor surgical candidates (such as patients with severe heart or respiratory diseases) or have unresectable disease. Chemotherapy is usually of limited value, being used primarily for women with metastatic disease. The blood test for cancer antigen 125 (CA 125) is not diagnostic of cancer of the uterus but can be used to monitor a patient for recurrence. Prognosis, prevention, and outcomes: Prognostic factors for uterine cancer include age at the time of diagnosis, race (whites have a better prognosis than blacks), tumor stage, tumor grade, type of tumor (adenocarcinoma, clear cell adenocarcinoma, papillary serous adenocarcinoma, sarcoma, and so on), size of the uterus at the time of diagnosis, depth of invasion of the tumor into the layer of uterine muscle, presence of tumor in the blood vessels supplying the uterus, and spread of the tumor outside the uterus to other organs or lymph nodes. It is important to remember that cancer of the uterus is diagnosed more often than other cancers of the female reproductive tract and that fewer women die of cancer of the uterus than cancers of the cer-
Uterine cancer vix and ovary combined. The overall five-year survival rates for cancer of the uterus by stage at diagnosis are 87 percent for Stage I, 72 percent for Stage II, 51 percent for Stage III, and 9 percent for Stage IV. D. Scott Cunningham, M.D., Ph.D. u
For Further Information Creasman, W. T., F. Odicino, and P. Maigonnueve. “FIGO Annual Report on the Results of Treatment in Gynecological Cancer: Carcinoma of the Corpus Uteri.” Journal of Epidemiology and Biostatistics 23 (1998): 35-61. Parazzini, F., C. La Vecchia, L. Bocciolone, and S. Franceschi. “The Epidemiology of Endometrial Cancer.” Gynecologic Oncology 41 (1991): 1-16.
u
Other Resources
American Cancer Society Overview: Endometrial Cancer http://www.cancer.org/docroot/CRI/ CRI_2_1x.asp?rnav=criov&dt=11 National Cancer Institute Cancer of the Uterus http://www.cancer.gov/cancertopics/wyntk/uterus See also Adenocarcinomas; Adenomatoid tumors; Bladder cancer; Carcinosarcomas; Endometrial cancer; Fallopian tube cancer; Fertility drugs and cancer; Gynecologic cancers; Gynecologic oncology; Hormonal therapies; Hysterectomy; Ovarian cancers; Ovarian cysts; Rectal cancer; Vaginal cancer.
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Salem Health: Cancer
u Vaccines, preventive Category: Chemotherapy and other drugs ATC code: J07BC01, J07BM01, J07BM02 Definition: Vaccines are biological drugs used to induce immunity against a germ (virus or bacterium) without causing disease. After vaccination, the body’s immune system develops antibodies that then kill or neutralize the germ if exposed to it. These antibodies circulate in the bloodstream. The immune response induced by a vaccine may decrease or wane over time, requiring a booster dose—some vaccines require three or more doses to provide full protection against the germ. Vaccines may contain live germs that have been weakened so that they cannot cause disease; killed or inactivated viruses that cannot cause an infection but can stimulate antibody production; toxoids (harmless bacterial toxins) that do not cause illness but stimulate production of antibody; and parts or components of bacteria or viruses, which cannot cause disease but generate an immune response. Cancers treated: Liver cancer, cervical cancer Subclasses of this group: Recombinant DNA hepatitis B vaccine, plasma-derived hepatitis B vaccine, quadrivalent human papillomavirus (HPV) vaccine Delivery routes: The hepatitis B vaccine is administered by intramuscular injection in the anterolateral thigh of infants twenty-four months of age and younger and in the deltoid muscle (shoulder) of older children, adolescents, and adults. Most people should receive three doses of the vaccine. The HPV vaccine is also administered by intramuscular injection of 0.5 milliliter in three doses. The second and third doses should be administered two and six months after the first dose.
How these drugs work: Hepatitis B vaccine prevents hepatitis B disease and its serious consequences, such as hepatocellular carcinoma (liver cancer). The recombinant hepatitis B vaccine is made by copying the genetic sequence of a protein contained in the hepatitis B virus into a yeast cell, which is then cultured and purified. The immunization series with hepatitis B vaccines is 95 percent effective at inducing immunity. Plasma-derived hepatitis B vaccines are made by harvesting particles of the hepatitis B surface antigen (HBsAg) from plasma of people with chronic hepatitis B infection. HBsAg is a component of the hepatitis B virus that appears in the blood before symptoms of the disease. The HBsAg particles are purified and inactivated with heat or chemicals to produce the vaccine. Available HPV vaccines protect against two types of the virus that cause about 70 percent of cervical cancer cases—types 16 and 18. The vaccine is produced by assembling the L1 protein of HPV types 16 and 18 into viruslike-particles (VLPs). VLPs look like the virus to the immune system but do not contain deoxyribonucleic acid (DNA), so they cannot replicate and cause disease. The HPV vaccine will only protect women who have not previously been infected with HPV. The other two types included in the quadrivalent version of the vaccine—HPV 6 and HPV 11—are intended to protect against genital warts, not cancer. The quadrivalent HPV vaccine has been tested in thousands of women sixteen to twenty-six years of age. Clinical trials showed the vaccine to be 100 percent effective in preventing cervical precancers caused by types 16 and 18 in women who had not been previously exposed to these HPV types. Also, the vaccine was almost 100 percent effective in preventing vulvar and vaginal precancers and genital warts caused by the HPV types in the vaccine. People vaccinated against hepatitis B or HPV can still develop liver cancer or cervical cancer. Chronic hepatitis B infection is only one of many risk factors for liver
Licensed Anticancer Vaccines Drugs
Brands
Subclasses
Delivery Mode
Cancers Treated
Hepatitis B vaccine
Engerix-B, Recombivax HB, Comvax, Twinrix, Pediarix
Recombinant DNA hepatitis B vaccine, plasma-derived hepatitis B vaccine
Injection
Liver cancer
Human papillomavirus (HPV) vaccine
Gardasil, Cervarix
Quadrivalent human papillomavirus (HPV) vaccine
Injection
Cervical cancer, anogenital cancers
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Salem Health: Cancer cancer, and 30 percent of cervical cancer cases are caused by HPV types not included in the current HPV vaccines. Side effects: Of those who receive the hepatitis B vaccine, 65 percent do not experience any side effects. Only 3 percent of recipients will develop pain and tenderness where the injection has been given, and between 1 and 6 percent of recipients will have a low-grade fever. Serious allergic reactions occur in less than 1 out of 10,000 vaccines given, or about 0.001 percent. Serious allergic reactions include anaphylaxis, a rapid life-threatening allergic response affecting more than one part of the body—it may also affect the whole body, causing the airway to swell, close off, and prevent the intake of oxygen. Studies of more than 11,000 women between nine and twenty-six years of age around the world have shown that the quadrivalent HPV vaccine causes no serious side effects, but 84 percent of vaccine recipients experienced pain at the injection site. Other mild-to-moderate side effects were swelling and redness at the injection site. Diego Pineda, M.S. u
For Further Information Offit, Paul A. Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases. New York: Collins, 2007. Offit, Paul A., and Louis M. Bell. Vaccines: What You Should Know. New York: Wiley, 2003. Plotkin, Stanley A., Walter A. Orenstein, and Paul A. Offit, eds. Vaccines. 5th ed. Philadelphia: Saunders/ Elsevier, 2008. u
Other Resources
Liver Cancer Network http://www.livercancer.com National Cancer Institute Human Papillomaviruses and Cancer: Questions and Answers http://www.cancer.gov/cancertopics/factsheet/Risk/ HPV National Network for Immunization Information http://www.immunizationinfo.org See also Biological therapy; Complementary and alternative therapies; Immune response to cancer; Immunotherapy; Infectious cancers; Prevent Cancer Foundation; Prevention; Vaccines, therapeutic; Virus-related cancers.
Vaccines, therapeutic
u Vaccines, therapeutic Category: Chemotherapy and other drugs Also known as: Biological therapy, immunotherapy Definition: Therapeutic vaccines treat cancer by stimulating the body’s natural immune system. Therapeutic vaccines contain the whole cancer cell, parts of cells, or components of the body’s immune system. Cancers treated: The Food and Drug Administration (FDA) does not currently license any therapeutic vaccines. Advanced phase III clinical trials are now in progress to evaluate vaccines against a variety of cancers. Subclasses of this group: Whole cell vaccines, heat shock proteins, antigen/adjuvant vaccines, dendritic cell vaccines, anti-idiotype vaccines, DNA vaccines Delivery routes: Cancer vaccines may be delivered by scarification (scratch), subcutaneous or intramuscular injection, or intranasally. The delivery route depends on the type of vaccine and cancer. How these drugs work: The immune system is very complex and interconnected. It consists of various types of white blood cells (lymphocytes) and cytokines. The immune system is stimulated when it identifies foreign molecules known as antigens. The immune response can be either humoral (body fluids) or cellular. In the cellular process, phagocytes (macrophages and dendritic cells) engulf and digest cells and particles. The resultant fragments are attached to a molecule known as the major histocompatibility complex (MHC) and are presented on the cell surface. They are therefore known as antigen presenting cells (APCs). If helper T cells recognize the fragments as antigens, then they can either activate B cells to produce antibodies or activate cytotoxic T cells to kill the foreign invader or cancer cell directly. Another process involves natural killer (NK) cells. These cells are activated to destroy cancer cells when they recognize abnormalities on the surfaces of cells. Cytokines are soluble proteins secreted by activated immune cells. They facilitate communication and function among immune system components and enhance the immune response. Therapeutic vaccines are used to treat existing cancers, in contrast to the traditional role of vaccines to prevent infectious diseases. The immune response is very specific, so cancer vaccines have been developed to selectively destroy cancer cells without harming normal cells. Unfortunately, the field has been fraught with disappointments over the last century. A basic problem lies with the fact that cancer cells are derived from normal cells. Success de1221
Vaccines, therapeutic
Salem Health: Cancer
A mouse with cancer is being injected with a therapeutic vaccine developed by the Pasteur Institute. (©Vo Trung Dung/Corbis Sygma)
pends on the immune system recognizing very small molecular differences between normal and cancer cells. Although the immune system does respond naturally to the presence of cancer cells, this response is often weak and the cancer may be tolerated. Cancer cells develop many methods to evade the immune system. They can hide their identity by repressing display of their antigens. They can alter their metabolism to become resistant to attacks by the immune system. They can secrete cytokines that kill lymphocytes. Cancer cells can actively suppress the activation and function of dendritic cells and T cells. A variety of therapeutic vaccines have been developed. A key goal of the vaccines is to enhance the immune system’s response to cancer antigens. Preparations include whole cell vaccines, heat shock proteins, antigen/adjuvant vaccines, dendritic cell vaccines, anti-idiotype vaccines, and DNA vaccines. Whole cell vaccines are prepared from the patient’s whole cancer cells. Whole cell vaccines do not require the identification of antigens but presumably contain the full array of cancer antigens. Unfortunately, early whole 1222
cell vaccines were not very effective. Researchers discovered that T cells are activated only when a second costimulatory molecule is present. Current whole cell vaccines are genetically modified to secrete cytokines or express co-stimulatory molecules. Heat shock proteins are found in most cells and serve to repair protein structure. They are often found in excess in cancer cells. Vaccines are prepared by purifying heat shock proteins from tumor tissue removed from the patient and linking these to tumor antigen. Administration of the vaccine results in uptake and processing by APCs and a strong T-cell response. Antigen/adjuvant vaccines are prepared by combining a known cancer antigen with a chemical known as an adjuvant, which enhances the effect of the antigen. Dendritic cell vaccines have been found very effective. To prepare the vaccines, dendritic cells are removed from the patient, exposed to the patient’s own cancer antigens in the laboratory, and grown in culture. When the resultant vaccine is injected into the patient, the T cells in the immune system are stimulated to attack the tumor cells. Anti-idiotype vaccines have been developed for use
Salem Health: Cancer against cancers that poorly present antigens. Antibodies that are produced in response to an antigen have unique antigen regions called idiotypes. The body can produce antibodies to these idiotypes that are called anti-idiotypes. Anti-idiotype vaccines can be prepared in the laboratory, often using synthetic monoclonal antibodies. Since these anti-idiotype vaccines appear to be like the tumor antigen, they stimulate a stronger immune response. DNA vaccines are based on genes that code for antigen proteins. When these vaccines are administered, they are taken up by APCs. The vaccines are delivered to the APCs by means of vectors, such as modified viruses, bacteria, or synthetic polymers. Within the APCs, antigen protein is produced and presented to the T cells. This method provides a continuous supply of antigen to maintain the immune response. Side effects: The primary concern with therapeutic vaccines is the development of autoimmune responses, although this seldom occurs. Some patients may experience a skin reaction or mild flulike symptoms. David A. Olle, M.S. u For Further Information Finn, Olivera J. “Cancer Vaccines: Between the Idea and the Reality.” Nature Reviews Immunology 3, no. 8 (August, 2003): 630-641. Greten, Tim F., and Elizabeth M. Jaffe. “Cancer Vaccines.” Journal of Clinical Oncology 17, no. 3 (March, 1999): 1047-1060. Orentas, Rimas, James W. Hodge, and Bryon D. Johnson, eds. Cancer Vaccines and Tumor Immunity. Hoboken, N.J.: Wiley-Interscience, 2008. Weinberg, Robert A. The Biology of Cancer. New York: Garland Science, Taylor & Francis, 2007. u
Other Resources
Vaginal cancer
u Vaginal cancer Category: Diseases, symptoms, and conditions Also known as: Squamous cell carcinoma of the vagina, clear cell adenocarcinoma, malignant melanoma of the vagina, leiomyosarcoma of the vagina, endodermal sinus tumor, yolk-sac tumor, sarcoma botryoides, embryonal rhabdomyosarcoma, pseudosarcoma botryoides Related conditions: Cancers of the vulva, cervix, uterus, ovary, colon and rectum Definition: The vagina is a muscular, tubelike structure that extends from the vulva, or the visible external genitalia, to the uterus. Cancer of the vagina involves a tumor that arises within the vagina rather than as an extension, metastasis, or recurrence from the cervix or vulva. Risk factors: Risk factors for vaginal cancer include age, human papillomavirus (HPV) infection, exposure to diethylstilbestrol (DES, banned in the United States in 1971), a history of cervical cancer, vaginal adenosis, uterine prolapse, cigarette smoking, chronic vaginal irritation, low socioeconomic status, hysterectomy at an early age, and vaginal trauma. Etiology and the disease process: Precancerous changes involving the vagina are much less common than precancerous changes affecting the cervix or vulva. Although not proven, it is thought that the lack of glands in the vagina is the basis for the rarity. Most vaginal cancers are metastatic, originating from cancers of the cervix or vulva with spread to the vagina, although metastases have been reported to occur from the uterus, ovaries, colon, rectum, breast, and even the kidney. Metastasis to the vagina occurs by spread from the lymphatics or blood.
American Cancer Society Cancer Vaccines http://www.cancer.org/docroot/ETO/content/ ETO_1_4X_Cancer_Vaccines_Active_Specific_ Immunotherapies.asp?sitearea=ETO
Incidence: There are approximately 2,000 new cases of vaginal cancer in the United States each year. The actual incidence of vaginal cancer is 0.42 case per 100,000 women. Vaginal cancer accounts for 1 to 2 percent of malignancies involving the female reproductive tract.
National Cancer Institute Cancer Vaccine Fact Sheet http://www.cancer.gov/cancertopics/factsheet/ cancervaccine
Symptoms: The most common symptoms associated with cancers of the vagina are abnormal bleeding or an excessive, nonodorous, watery discharge; less frequent symptoms include pelvic pain, an increased frequency of urination or pain with urination, and constipation.
See also Bacillus Calmette Guérin (BCG); Biological therapy; Chemoprevention; Complementary and alternative therapies; Cytokines; Duke Comprehensive Cancer Center; Immune response to cancer; Immunotherapy; Vaccines, preventive.
Screening and diagnosis: Screening for vaginal cancer should be performed in the context of a woman’s annual physical examination, sometimes called a well-woman examination. During the examination, the gynecologist in1223
Vaginal cancer
Salem Health: Cancer
Age at Diagnosis of Vaginal Cancer, 1988-2001 Age Group 20-34 35-44 45-54 55-64 65-74 75-84 85 and older
Cases Diagnosed (%) 1.0 4.1 10.4 15.1 20.2 25.1 24.2
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
spects the vaginal walls for lesions, areas of discoloration, or abnormal discharge. Proper inspection of the vagina requires rotation of the speculum during the examination so that all areas of the vaginal wall are visualized, with continued inspection during removal of the speculum. A diagnosis of vaginal cancer is made, based on a tissue biopsy, after an abnormality is seen on physical examination. Because symptoms of vaginal cancer are often absent or nonspecific, its diagnosis is often missed or delayed. Although useful in determining the extent of disease, computed tomography (CT) and magnetic resonance imaging (MRI) are not used to make the initial diagnosis of cancer of the vagina. The most common types of vaginal cancer include squamous cell carcinoma, adenocarcinoma (including a rare variant, known as clear cell adenocarcinoma), and melanoma. Squamous cell carcinomas are by far the most common, accounting for 90 percent of all cases, and usually occur in women in their fifties. Squamous cell carcinomas usually occur high in the vagina and have the appearance of ulcerating masses that look like large warts or fleshy lesions. Unlike cancer of the cervix, in which infection with HPV has been clearly linked to the development of cancer, HPV is causal in the majority of true cancers of the vagina in adults in only 50 percent of the cases. Adenocarcinomas of the vagina have peak occurrences in women younger than thirty and then again in women older than seventy. It appears that women with late-onset adenocarcinoma have a genetic predisposition, but the precipitating factor has not been identified. The subtype of adenocarcinoma known as clear cell adenocarcinoma occurs in women with known exposure to DES as a fetus (in 1224
utero exposure) by maternal use to counteract the risk of pregnancy loss. It is known that DES exposure does not affect all such women; in fact, only 1 in 1,000 women exposed to DES in utero will develop clear cell adenocarcinoma. Nevertheless, women so exposed should undergo more frequent screening at the discretion of the physician and patient. It is generally recommended that women with exposure to DES as a fetus should undergo their initial gynecologic examination at the time of menarche (onset of menstrual activity) and have increased lifelong surveillance at the discretion of their physician. Vaginal melanomas are rare and usually affect women older than sixty. Infants and children are also affected by tumors of the vagina, usually of the three following types: endodermal sinus tumor (yolk sac tumor), sarcoma botryoides (embryonal rhabdomyosarcoma), and pseudosarcoma botryoides. Endodermal sinus tumors are rare tumors of the ovary that originate in the vagina, usually in infants less than two years old. Girls younger than eight years are those most often diagnosed with the rare sarcoma botryoides. This tumor usually manifests as a mass protruding from the vaginal opening. Pseudosarcoma botryoides is a rare, benign tumor that resembles sarcoma botryoides. Cancer of the vagina is staged according to the International Federation of Gynecology and Obstetrics (FIGO). • Stage 0: Carcinoma in situ; the cancer is localized without apparent spread. • Stage I: Cancer is limited to the vaginal wall. • Stage II: Cancer has extended to the subvaginal tissues but not to the pelvic wall. • Stage III: Cancer involves the pelvic wall. • Stage IV: Cancer has spread beyond the pelvis or has extended to the bladder or rectum. At the time of diagnosis, between 18 and 23 percent of women are found to have Stage I vaginal cancer, while 46 to 58 percent of women are found to have Stage II. Treatment and therapy: Although surgery and radiation therapy have been used to treat squamous cell carcinomas of the vagina, radiation therapy is preferred. Initially, external radiation is used to shrink the tumor mass; this is followed by internal radiation therapy to maximize the toxic effect. Surgical treatment of squamous cell carcinoma can range from local procedures (such as destruction of lesions with laser treatment or surgical excision of the lesions) to more radical procedures (such as removal of part or all of the vagina or vaginectomy; hysterectomy; or pelvic exenteration, a hysterectomy with removal of the bladder, bowel, or both). Because most patients with clear cell adenocarcinoma are young, removal of the uterus (hysterectomy) and par-
Salem Health: Cancer tial or complete removal of the vagina (vaginectomy), followed by creation of a new vagina (neovagina) with skin grafts, is the standard treatment. Vaginal melanomas are best treated with complete excision and dissection of the lymph nodes. Because of the depth of invasion, vaginal melanomas do not respond well to radiation or chemotherapy, and the goal is complete excision with clear surgical margins (in other words, the excised specimen has a central tumor with normal tissue completely surrounding the tumor). Endodermal sinus tumors are generally treated with surgery and radiation, but most affected children have died. Sarcoma botryoides is a very aggressive tumor and has been treated with radical surgery and multiagent chemotherapy. Pseudosarcoma botryoides can be successfully treated with local excision. Recurrent vaginal cancers are best treated with chemotherapy Prognosis, prevention, and outcomes: The prognosis for vaginal cancer is directly related to the stage at the time of diagnosis. The overall five-year survival rate for squamous cell carcinoma of the vagina is about 45 percent. By stage, five-year survival rates are 69 percent for Stage I, 45 percent for Stage II, 21.8 percent for Stage III, and 5 percent for Stage IV. With respect to clear cell adenocarcinoma of the vagina, patients older than nineteen have a better prognosis than patients less than fifteen years of age. Five-year survival rates for clear cell adenocarcinoma have been reported to be 91 percent for Stage I, 82 for Stage II, 37 percent for Stage III, and 0 percent for Stage IV. Vaginal melanomas frequently recur, and the five-year survival rate is about 20 percent. D. Scott Cunningham, M.D., Ph.D. u
For Further Information Creasman, W. T., J. L. Phillips, and H. R. Menck. “The National Cancer Data Base Report on Cancer of the Vagina.” Cancer 83 (1998): 1033-1040. Peters, W. A., N. B. Kuman, and G. W. Morley. “Carcinoma of the Vagina: Factors Influencing Treatment Outcome.” Cancer 55 (1985): 892-897. u
Other Resources
Detailed Guide: Vaginal Cancer http://www.cancer.org/docroot/CRI/content/ CRI_2_4_1X_What_is_vaginal_cancer_55.asp National Cancer Institute Vaginal Cancer http://www.cancer.gov/cancertopics/types/vaginal
Vascular access tubes See also Adenocarcinomas; Brachytherapy; Cervical cancer; Computed tomography (CT) scan; Endoscopy; Gynecologic cancers; Hysterectomy; Ovarian cancers; Ovarian cysts; Ovarian epithelial cancer; Pelvic examination; Pregnancy and cancer; Uterine cancer; Vulvar cancer.
u Vascular access tubes Category: Procedures Also known as: Peripherally inserted central catheters (PICC), subcutaneous ports, Hickman catheters, Groshong catheters, Broviac catheters Definition: A vascular access tube is a catheter inserted into the veins of the arm, neck, or just beneath the collarbone for long-term intravenous access (greater than seven to ten days). The catheter can also be used to draw blood for lab tests. Patients receiving long-term chemotherapy, pain medications, nutrition, or antibiotics will have vascular access. Cancers treated: All requiring long-term therapy Why performed: Many patients have poor veins or are unable to receive treatment without access. Patient preparation: Vascular access lines can be placed at the bedside, in the operating room (OR), or in vascular radiology. Procedures at the bedside have no preprocedure preparation. Patients going to the OR or vascular radiology are not allowed to eat or drink for at least eight hours before line placement as a result of the anesthesia. Steps of the procedure: All lines are placed using sterile technique. For peripherally inserted central catheters (PICC), a catheter is inserted through the antecube to be threaded up the arm and to end in the superior vena cava. PICC lines are flushed at least once a day and their dressings are changed once a week. For ports, a small titanium or plastic reservoir is inserted and stitched into place in the upper chest. The catheter is attached to the reservoir and inserted into the vein and then threaded into the superior vena cava. The reservoir is accessed through the patient’s chest wall with special needles. Ports must have a needle inserted and flushed at least once a month to prevent clotting. This line can be placed in the OR or vascular radiology. Hickman, Broviac, or Groshong catheters are also placed in the upper chest wall. The line is inserted through a small incision and into the vein and follows until the end rests in the superior vena cava. It is held into place by a small cuff located under the skin; typically stitches are not 1225
Vasectomy and cancer used. The patient or caregiver will be responsible for flushing the access and changing the dressing every seven days. After the procedure: Line placement is verified by a chest X ray. Once the line has been verified, it can be used to infuse therapy or for lab sampling. The patient or caregiver is responsible for home care, including flushing the access and changing the dressing. Risks: The risks associated with vascular access lines are pneumothorax (collapsed lung), bleeding, and infection. Results: The result of this procedure is reliable venous access to receive therapy and for blood draws. Katrina Green, R.N., B.S.N., O.C.N. See also Caregivers and caregiving; Chemotherapy; Infection and sepsis; Nutrition and cancer treatment; Pain management medications; Superior vena cava syndrome.
Salem Health: Cancer sible to show a correlation. There were too many other factors that introduced bias into the ability to draw the conclusion. Similarly, it has been impossible to identify a correlation between vasectomy and testicular cancer. Testicular cancer is a cancer of young men (ages fifteen to thirty-four), while prostate cancer is seen in older men. A 2002 study looked at vasectomy and the risk of prostate cancer and concluded that the association was small and could be explained by bias. This means that there were too many factors that interfered with the ability to scientifically make an association. The researchers concluded that studies should continue because of the popularity of vasectomy. Men should discuss any cancer concerns with their physician prior to having a vasectomy, but there is no evidence to show that a man should not have a vasectomy because of concerns about cancer. Janet R. Green, M.S.P.H. See also Birth control pills and cancer; Fertility issues; Pregnancy and cancer; Prostate cancer; Relationships; Sterility; Testicular cancer.
u Vasectomy and cancer Category: Procedures Also known as: Sterilization, permanent birth control Related cancers: None Definition: Vasectomy, a form of permanent birth control for men, is a commonly performed procedure that results in sterilization and is more than 99 percent effective in preventing pregnancy. No link has been established between having this procedure and developing cancer. Vasectomy facts: More than 13 million vasectomies have been performed in the United States. Of the men who had vasectomies, 91 percent were married or cohabiting, 87 percent were white, and 81 percent were educated beyond high school. Although vasectomy is effective at preventing pregnancy, it does not prevent or protect from sexually transmitted diseases. History: In 2004, prostate cancer was the most commonly identified new cancer in American men and the second highest cause of cancer mortality in men. Some questions were raised about a possible association between vasectomy and cancer, with the greatest concern being an association with prostate cancer. The cause of prostate cancer is unknown, and therefore there was concern that an association might be found between cancer and vasectomy. Several studies have been conducted in an effort to determine if there is a causal relationship between the two. The major studies done in 1993 found that it was not pos1226
u Veterinary oncology Category: Medical specialties Also known as: Animal cancer management, companion animal cancer management, domestic animal cancer management Definition: Veterinary oncology is officially defined as the study of tumors in animals, excluding humans. The most common usage of the term currently refers to the study and management of cancer in domestic and, more typically, companion animals. Most veterinary oncologists are trained primarily in the care of cancer in dogs and cats. However, many also become involved in diagnosing and treating or directing the management (in cooperation with the attending small, large, or exotic animal veterinarian) of cancer in other companion species such as birds, rodents, rabbits, horses, pet ruminants, aquatic animals, and exotic animals. Veterinary oncology is informative for the study and treatment of cancer in people because some animals can serve as models of human neoplasia. These cancers can either occur naturally in these animals or be experimentally induced. One example of naturally occurring cancer in animals possibly informing the treatment of humans involves the use of dogs as models of osteosarcoma in children, since the tumors show very similar behavior in dogs and children (growing most often on the metaphysis and
Salem Health: Cancer acting aggressively) and are associated with rapid bone growth (which occurs in large-breed dogs), trauma (such as bone fractures), and gender (male canines and humans are both more susceptible), among other correspondences. Another example is the recent development of the canine melanoma vaccine at the University of Wisconsin School of Veterinary Medicine. Animals also serve as models of experimentally induced neoplasia or metastasis, such as nude mice that receive implants of cancerous human cells to test pharmaceutical interventions and study tumor biology. Subspecialties: Veterinary oncology is divided into two specialties: veterinary medical oncology and veterinary radiation oncology. Medical oncologists are diplomates of the American College of Veterinary Internal Medicine. Radiation oncologists are diplomates of the American College of Veterinary Radiology. An unofficial specialty is surgical oncology. There is no diplomate status in this field, but these veterinarians are trained in special surgical procedures and techniques to remove cancerous tissue from animals (mostly dogs and cats). Cancers treated: The increase in life expectancy in companion animals due to vaccines, antiparasitic medications, and general improvements in health care has resulted in increased cancer incidence associated with advanced age. Some cancers are more prevalent in certain species and more responsive to treatment than in others. One of the most common blood cancers in all domestic animals is lymphoma (lymphosarcoma), which is comparable to non-Hodgkin lymphoma in people. In dogs, the incidence rate is about 30 cases per 100,000, and it is the most common blood cancer in this species, with a higher incidence recorded in boxers and golden retrievers, among others. This disease can generally be managed for a few years, if caught early, but not cured. Cats have an even higher prevalence of lymphoma than dogs or people but the use of the feline leukemia virus (FeLV) vaccine in cats beginning in the late 1990’s has lowered the incidence of certain forms of lymphoma in cats. However, feline lymphoma is generally less responsive to treatment than the canine variety. Another blood cell cancer, mast cell tumor, is the most common skin malignancy in dogs. Certain breeds, such as boxers, bull dogs, and Boston terriers, have shown increased incidence of this disease, which is amenable to treatment if caught early. An internal form of this disease in dogs and cats is less responsive to treatment. Other veterinary cancers treated include hemangiosarcoma, which is a very aggressive tumor of mesenchymal origin affecting the blood vessels and seen most commonly in dogs (about 2 percent of all canine cancers), with higher prevalence noted in German shepherds, golden re-
Veterinary oncology trievers, and poodles, among others. This condition generally has a very poor prognosis, despite treatment. Another cancer with a very poor prognosis is vaccineassociated sarcoma in cats. This is an unusually aggressive, but relatively rare, sarcoma that is believed to be promoted by inflammation accompanying the administration of certain vaccines and possibly other injected medications in cats. It has proven to be unresponsive to most treatment modalities, including surgery, and the location of the growth is a key prognostic factor. Vaccination guidelines, stating that certain vaccines (FeLV, rabies) be inoculated subcutaneously on the distal leg instead of in the interscapular region, have decreased the likelihood that an inoperable growth will develop on the trunk. If an aggressive sarcoma develops on the leg, the limb can be amputated, increasing the chance of a cure. Another aggressive cancer, osteosarcoma, occurs primarily in large-breed dogs and is also most successfully treated with surgery (generally amputation of the affected limb) but difficult to catch before it metastasizes—usually to the lungs. Mammary cell tumors are the most common neoplasia in female dogs and are third after skin tumors and lymphoma in cats. About 40 to 50 percent of canine mammary tumors are benign, while about 80 to 90 percent of feline mammary tumors are malignant. The best treatment for dogs is actually prevention, since spaying before the first heat virtually eliminates the risk of development of this tumor. Treating cats with progestin drugs increases their risk of developing mammary cancer. Complete surgical resection offers the best chance of a cure in dogs, while in cats the disease has usually metastasized to the lungs by the time of its diagnosis. Other cancers commonly treated by veterinary oncologists are bladder cancers (transitional cell carcinoma most commonly), prostate cancer (dogs are the only nonhuman species with a significant occurrence of this neoplasia), melanomas, oral and cutaneous squamous cell carcinoma (common in cats), transmissible venereal tumors, and various other sarcomas, carcinomas, and roundcell tumors in cats, dogs, and other species. Training and certification: For medical oncology, candidates for certification and diplomate status must apply for membership in the American College of Veterinary Internal Medicine (ACVIM). The college requires these candidates to be graduates of an accredited or approved veterinary school, licensed to practice veterinary medicine in a state, province, or other country; to be in satisfactory moral and ethical standing; and to pass both the general medicine and oncology certification examinations. 1227
Veterinary oncology The general exam for medical oncology consists of two parts: comprehensive, which tests knowledge of general medicine common to all species, and a more specialized section oriented toward the individual’s field of interest— that is, small animals (mostly dogs and cats) or large animals (mostly horses and ruminant species). To take the general exam, qualified veterinarians must have completed an approved one-year internship (or equivalent) in either small- or large-animal medicine and surgery and a two-year residency in veterinary oncology under the direct supervision of a diplomate of the ACVIM. To take the certification exam in veterinary medical oncology, veterinarians must additionally submit a letter from the supervisor of their oncology training program, other letters of recommendation, a case log, and publications. For radiation oncology, a candidate for certification must be a graduate of an accredited or approved veterinary school, maintain proper ethical and moral standing, be licensed to practice veterinary medicine and surgery in one or more states, and have completed a one-year internship in either small- or large-animal medicine and surgery. The candidate must also have successfully completed a pro-
Salem Health: Cancer gram in veterinary radiation oncology approved by the executive council of the American College of Veterinary Radiology (ACVR). Additionally, the candidate must have completed a two-year residency training program in veterinary oncology, submit references, and pass the written and oral exams in general and radiation oncology. The written exam tests the candidate’s knowledge of general veterinary oncology, radiation physics and dose calculations, radiation biology, and clinical aspects of radiation oncology. Surgical oncologists are diplomates of the American College of Veterinary Surgeons (ACVS). The unofficial designation of “surgical oncologist” follows successful completion of a fellowship in surgical excision of tumors and cancerous tissue from animals. Services and procedures performed: Veterinary oncologists diagnose, stage, and plan treatment strategies for their animal patients. Most of the time, they are not expecting or planning a cure for the malignant or metastatic conditions. Rather, they are looking to effect a remission or control the tumor’s growth to provide a good quality of life
Lacey, a six-year-old boxer, receives chemotherapy to treat her lymphoma. (AP/Wide World Photos)
1228
Salem Health: Cancer for the animal. Generally, extremely toxic treatment modalities are avoided in animals because of their shorter life spans, high costs, inconvenience to owners (traveling to distant treatment centers, caring for a sick pet, and so on), and the fact that animals primarily live in the moment (and cannot rationalize discomfort). For diagnosis and staging, veterinary oncologists examine blood work (complete blood count, blood chemistries); employ various imaging modalities, depending on need, availability, and cost (X rays, magnetic resonance imaging, computed tomography); and analyze the results of biopsies, cytologies, and bone marrow aspirates. For some conditions, such as mast cell tumors, the cancer cells are graded by a histopathologist. Not all tests are conducted in all animals. Staging is an extremely important part of planning the treatment process and forming a prognosis. Once this is completed, the veterinary oncologist will often work with a surgeon if the tumor is resectable. If spread to distant lymph nodes or metastases are found, most medical oncologists will plan adjunctive chemotherapy. Chemotherapy is also prescribed for diffuse cancers, such as lymphoma, that are not amenable to surgical intervention. Growths that cannot be resected or can be only partially resected are often treated with local radiation therapy directed by a radiation oncologist. Some veterinary referral or academic centers offer their own orthovoltage or megavoltage (linear accelerator, cobalt, or cesium) units. However, others outsource these therapies to human cancer treatment clinics that work directly with the veterinary oncologist. Other forms of radiotherapy, such as brachytherapy or systemic radiotherapy (offered for thyroid tumors in cats) are also offered to veterinary patients. Animal oncology employs just about every chemotherapeutic agent used for human chemotherapy, and specially trained veterinary nurses often administer the drugs under the direct supervision of the oncologist. The veterinary oncologist can also offer therapy for pain and the side effects of treatment, such as nausea and vomiting following chemotherapy, or oral mucositis following radiation therapy. The oncologist follows the animal’s progress over the course of treatment and modifies the protocol in the event of complications such as severe bone marrow suppression. The veterinary oncologist should ultimately provide a good idea of the animal’s prognosis and help the client make informed decisions about treatment options while considering costs and quality of life for the animal and owner. Related specialties and subspecialties: Veterinary oncologists and clients work closely with practitioners in the fields of veterinary pathology, veterinary clinical pathol-
Veterinary oncology ogy, veterinary dermatology, veterinary emergency and critical care, veterinary small-animal internal medicine, veterinary large-animal internal medicine, and veterinary surgery for the treatment and diagnosis of neoplastic conditions. Lisa J. Shientag, V.M.D. u
For Further Information Birchard, Stephen J., and Robert G. Sherding. Saunders’ Manual of Small Animal Practice. 3d ed. Philadelphia: Elsevier, 2006. Downing, Robin. Pets Living with Cancer: A Pet Owner’s Resource. Lakewood, Colo.: AAHA, 2000. Eldredge, Debra M., and Margaret H. Bonham. Cancer and Your Pet: The Complete Guide to the Latest Research, Treatments, and Options. Sterling, Va.: Capital Books, 2005. Ettinger, Stephen J., and Edward C. Feldman. “Section X: Cancer.” In Textbook of Veterinary Internal Medicine. 6th ed. Philadelphia: Elsevier, 2005. Meuten, Donald J., ed. Tumors in Domestic Animals. 4th ed. Malden, Mass.: Blackwell, 2002.
u
Organizations and Professional Societies
American College of Veterinary Internal Medicine http://www.acvim.org 1997 Wadsworth, Suite A Lakewood, CO 80214-5293 American College of Veterinary Radiology http://www.acvr.org 777 East Park Drive P.O. Box 8820 Harrisburg, PA 17105-8820 American College of Veterinary Surgeons http://www.acvs.org 19785 Crystal Rock Dr., Suite 305 Germantown, MD 20874 Veterinary Cancer Society http://www.vetcancersociety.org P.O. Box 1763 Spring Valley, CA 91979 u
Other Resources
Morris Animal Foundation: Canine Cancer Campaign http://www.curecaninecancer.org NetVet Veterinary Resources http://netvet.wustl.edu/vet.htm 1229
Vinyl chloride Oncolink Vet Types of Cancer http://www.oncolink.com/types/ section.cfm?c=22&s=69 ThePetCenter.com Cancer in Dogs and Cats http://www.thepetcenter.com/gen/can.html Vaccine-Associated Feline Sarcoma Task Force http://www.avma.org/vafstf/contact.asp See also Amputation; Arsenic compounds; Carcinomas; Chemotherapy; Imaging tests; Leukemias; Living with cancer; Medical oncology; Oncology; Pathology; Staging of cancer; Vaccines, preventive.
u Vinyl chloride Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 1980 Also known as: Chloroethene, chloroethylene, ethylene monochloride Related cancers: Liver cancer, possibly brain and lung cancers Definition: Vinyl chloride is a toxic, colorless, combustible gas that has a sweet odor. Exposure routes: For the general public, exposure to vinyl chloride occurs through inhalation of contaminated air, ingestion of contaminated foods and drinking water, or skin contact with consumer products containing vinyl chloride. Occupational exposure occurs by inhalation or skin contact during the production or use of vinyl chloride. Where found: More than 95 percent of all vinyl chloride is used to manufacture polyvinyl chloride (PVC) and copolymers. The rest is used in organic synthesis and miscellaneous applications. PVC, a plastic resin, is used in myriad applications, including pipes, automotive parts, furniture, electrical insulation, videodiscs, flooring, windows, toys, wrapping plastic, medical supplies, credit cards, and storage containers. At risk: People who work where vinyl chloride is produced; where plastics, rubber, resins, PVC, furniture, or automotive parts are manufactured; or around railroad cars that carry vinyl chloride have a high risk for vinyl chloride contamination. People who live near industries that manufacture or use vinyl chloride in their products or who live near hazardous waste sites or landfills also risk 1230
Salem Health: Cancer exposure to vinyl chloride. Between 1958 and 1974, hair sprays contained vinyl chloride, causing beauty salon workers and hair spray users to be exposed. Etiology and symptoms of associated cancers: Breathing high levels of vinyl chloride for short periods of time can cause dizziness, sleepiness, and unconsciousness. Extremely high levels over short periods of time can result in death. Breathing vinyl chloride over long periods of time can decrease blood flow to the hands, making hand bones brittle, and can produce permanent liver damage, nerve damage, immune reactions, and liver cancer. Exposure of the skin to vinyl chloride can produce numbness, redness, and blisters. Dioxins produced as by-products of vinyl chloride production and from burning waste PVC can suppress the immune system, cause a variety of cancers, and produce endometriosis. History: Vinyl chloride has been in existence since at least the early part of the nineteenth century. It was first produced commercially in the 1920’s. In the late 1960’s vinyl chloride was definitely linked to liver cancer. It has become one of the highest-volume chemicals produced in the United States. Approximately 15 billion pounds of vinyl chloride were manufactured annually in the United States during the mid-1990’s. Alvin K. Benson, Ph.D. See also Bisphenol A(BPA); Brain and central nervous system cancers; Bronchial adenomas; Carcinogens, known; Carcinogens, reasonably anticipated; Di(2-ethylhexyl) phthalate (DEHP); Dioxins; Endotheliomas; Fibrosarcomas, softtissue; Gliomas; Hemangiosarcomas; Liver cancers; Lung cancers; Occupational exposures and cancer; Organochlorines (OCs); Plasticizers; Sarcomas, soft-tissue.
u Viral oncology Category: Medical specialties Definition: Viral oncology is the study of cancers caused by viruses and other such infectious agents. Cancers treated: Cancers known to be associated with viral agents, including cervical carcinoma, hepatocarcinoma, nasopharyngeal carcinoma, and several forms of lymphoma Subspecialities: Retrovirology Training and certification: Viral oncology represents a discipline within the general area of medical oncology, the study of cancer. Although a small proportion of cancers
Salem Health: Cancer
Viral oncology
may be directly caused by infectious agents, particularly viruses, most oncologists associated with medical aspects of the disease are involved with the diagnosis and treatment of cancer rather than the study of the molecular basis of the disease. Certainly this is true for most physicians specializing in branches of oncology. Those physicians who both practice medical oncology and carry out research in the field of viral oncology are generally associated with medical schools that allow for research and study of the disease as well as diagnosis and treatment. These individuals divide their time between seeing patients and directing a laboratory that includes techTumor viruses. (Biophoto Associates/Photo Researchers, Inc.) nicians and postdoctoral trainees. Viral oncology primarily involves entity to one that progressively evolves into a malignant research into the molecular changes produced by viral incell. They also develop therapeutic strategies to control the fections that transform normal cells into malignant ones. disease or prevent the transformation of normal cells into Training may involve either medical school, the outcome of malignant ones. Viral oncologists may study samples obwhich is a medical degree, or a research, which may result tained from cancerous tissue to determine the presence of in a doctoral degree. Although postdoctoral training is not or possible role played by the virus. Generally, however, required, most people with doctorates in the sciences and they are not involved in the actual treatment of the disease. an interest in cancer research, viral or otherwise, generally The work carried out by viral oncologists depends on the pursue additional training after receiving their degrees. interests of the individual. Some viruses leave “footprints” A number of universities and medical schools, supin the cell following infection: the presence of viral genetic ported by a variety of federal grants and fellowships, material as well as the products—protein or ribonucleic provide specialized training in the field of viral oncoloacid (RNA)—encoded by the virus. The researcher may use gy. Generally these programs are postdoctoral, requiring either biopsy material or other cancerous tissue samples for either a medical or a doctoral degree. In these two- to analysis of viral information or evidence of viral expresthree-year programs, the individual studies and carries out sion. The results of such analysis may provide clues as to the research with highly regarded individuals in the field. mechanism of malignant transformation. Clues into the Training may be in any of a wide range of specialties, incause of the disease may provide ideas for research into cluding the study of tumor viruses, pathogenesis following treatment. infection by these viruses, and the regulation of cell proTreatment of virus-induced cancers may also involve cesses affected by such viruses. Those who complete such clinical trials, in which pharmaceuticals may be studied programs frequently move on to jobs at universities or to determine their efficacies. Most such studies involve medical schools, specializing in aspects of medical oncooperation between hospitals and pharmaceutical comcology. panies. Services and procedures performed: The primary concerns of physicians who deal with cancer are identifying Related specialties and subspecialties: Viral oncologists the form, staging, treatment, and prognosis of cancer. Apspecialize in the specific forms of cancers that may follow proximately 15 to 20 percent of cancers are associated certain viral infections. Human papillomaviruses (HPV), with infections by viruses and other agents. Viral oncolassociated in the mind of many with warts, have also been ogists study cancers caused by viruses to understand the shown to be the etiological agents behind development of underlying molecular mechanisms that result in the initial cervical carcinomas. The study of these deoxyribonucleic transformation of a cell from a normal, properly regulated acid (DNA)-containing viruses and the mechanism by 1231
Virus-related cancers which they initiate cancer represent a field of active investigation among some virologists. Retroviruses are a subclass of viruses that contain a genome consisting of RNA. These are relatively simple viruses that encode a relatively small number of genes, often as few as four to five, one of which is considered an oncogene, a gene that when unregulated may convert a normal cell into a malignant one. These viruses also encode an enzyme called an RNA-directed DNA polymerase, more commonly called a reverse transcriptase, which copies the RNA genome into DNA. The DNA copy then integrates into the host genome. Such viruses are frequently called RNA tumor viruses. Retrovirologists are viral oncologists who study such viruses, their genome makeup, and the mechanisms by which their encoded oncogene may disrupt cell regulation. Like most viral oncologists, retrovirologists are primarily concerned with the mechanism of malignant transformation rather than the treatment of patients. A subclass of retroviruses includes agents such as hepatitis B virus (HBV), associated with certain forms of viral hepatitis, but which may also serve as the etiological agent for hepatocarcinoma, cancer of the liver. HBV is a DNA virus but one that replicates through an RNA intermediary. HBV also is the subject of extensive study by retrovirologists interested in this unusual form of replication. Some universities and medical schools provide specialized programs in this area. For example, because hepatitis B infection often results in a lifelong chronic infection, viral oncologists may specialize not only in the study of the disease but also in the maintenence of quality care for the patient and education of the patient’s family. Some forms of lymphomas and leukemias also appear to be the result of viral infections, including T-lymphocyte leukemia. Evidence suggests Hodgkin disease may be the result of viral infection. Certain non-Hodgkin lymphomas are known to be associated with infection. For example, both Burkitt lymphoma and nasopharyngeal carcinoma are the result of infection by a type of herpesvirus called the Epstein-Barr virus, which is most commonly associated with infectious mononucleosis. Subspecialties in the field of viral oncology exist for the study of these diseases as well. Richard Adler, Ph.D. u
For Further Information Boshoff, Chris, and Robin Weiss. Kaposi Sarcoma Herpesvirus: New Perspectives. New York: SpringerVerlag, 2006. Pitot, Henry. Fundamentals of Oncology. 4th ed. New York: Marcel Dekker, 2002. 1232
Salem Health: Cancer Strauss, James, and Ellen Strauss. Viruses and Human Disease. 2d ed. Burlington, Mass.: Elsevier Academic Press, 2008. Tannock, Ian, et al. The Basic Science of Oncology. Columbus, Ohio: McGraw-Hill, 2005. u
Organizations and Professional Societies
American Society for Microbiology http://www.asm.org 1752 N Street, NW Washington, D.C. 20036 American Society for Virology http://www.asv.org University of Toledo College of Medicine 3000 Arlington Avenue, Mail Stop 1021 Toledo, OH 43614 u
Other Resources
Fred Hutchinson Cancer Research Center Virology Laboratory Core http://www.fhcrc.org/science/clinical/id/research/ vlc.html National Cancer Institute Center of Excellence in HIV/AIDS and Cancer Virology, CCR http://ccr.cancer.gov/initiatives/CEHIV See also Antiviral therapies; Burkitt lymphoma; Carcinomas; Cervical cancer; Epstein-Barr virus; Hepatitis B virus (HBV); Hepatitis C virus (HCV); HIV/AIDS-related cancers; Hodgkin disease; Human papillomavirus (HPV); Infection and sepsis; Kaposi sarcoma; Leukemias; Lymphomas; Non-Hodgkin lymphoma; Oncogenes; Oncogenic viruses; Oncology; Proto-oncogenes and carcinogenesis; Virus-related cancers.
u Virus-related cancers Category: Diseases, symptoms, and conditions Related conditions: Cervical cancer, hepatocarcinoma, Kaposi sarcoma, T-cell lymphomas, B-cell lymphomas Definition: Cancer is a malignant disease characterized by uncontrolled growth of anaplastic cells that invade or spread into sites beyond their origin. While most human cancers are the product of genetic mutations, some cancers are the result of infection by viruses.
Salem Health: Cancer
Virus-related cancers
to the disease, the most important of which is known as E7. The E7 gene A virus consists of nucleic acid, either ribonucleic acid (RNA) or deoxyribonuproduct inhibits tumor-suppressor procleic acid (DNA), inside a protein coat, or capsid, which is enclosed in an outer teins such as the retinoblastoma (Rb) membrane. On its own, a virus cannot replicate itself. molecule, a protein that regulates the To infect a person, a virus must first find a way into the individual. Usually, steps necessary for cell replication. Inthis is not through the skin but rather the mouth, lungs, penis, vagina, gastroinfection of cervical cells by these strains testinal tract, or breaks in the skin (wounds, sores). The virus attaches to its host of the virus may eventually result in uncell and injects genetic material. The cell begins to make viral DNA or RNA controlled growth and a malignancy. and produces viral proteins instead of its usual products. The host cell creates Hepatocellular carcinoma (liver cannew viruses, which are released, destroying the host cell. The new viruses find cer) is among the most common cancers other cells and begin the process anew. worldwide and has been shown to result Retroviruses, like the human immunodeficiency virus (HIV), have RNA in a protein capsid with a lipid envelope that contains receptor-binding proteins from infection with the hepatitis B virus used to attach to the host cell. The retrovirus injects RNA plus the enzyme re(HBV) and less commonly the hepatitis verse transcriptase (Rtase) into the cell. This allows the cell to make viral C virus (HCV). Both HBV and HCV are DNA, then a complementary strand of DNA. The double-strand copies of associated with potentially severe forms DNA become part of the host cell’s chromosome. of liver disease, and a person with a chronic hepatitis infection or a longterm carrier may eventually develop liver cancer. Little is understood as to Risk factors: Viruses associated with cancer—human imhow infection results in cancer, as no viral protein having munodeficiency virus (HIV) and hepatitis B and C viruses oncogenic ability has been described. However, one pro(HBV, HCV)—are most commonly spread through sexual tein encoded by HBV, the X gene product, appears to bind relations or contamination of intravenous fluids. The poolthe p53 protein, a tumor-suppressor molecule that reguing of blood fluids for isolation of the clotting factor VIII lates activation of genes associated with cell division. The during the early years of the acquired immunodeficiency core protein of HCV has also been shown to bind p53, sugsyndrome (AIDS) epidemic was the primary factor in the gesting tumor induction in a similar manner. infection of hemophiliacs with HIV. Unprotected sexual Kaposi sarcoma is believed to be caused by human relations with infected partners and intravenous drug use, herpesvirus 8 (HHV-8), which produces gene products in which infected users shared needles, also transmitted that induce cell replication. Classic Kaposi sarcoma, a rare HIV and the hepatitis viruses. The human papillomavirus form of the disease not associated with HIV infection, ap(HPV), the etiological agent for cervical carcinoma, is pears to involve both viral and genetic factors. The populacommonly transmitted by infected sexual partners. tion at risk for this form of Kaposi sarcoma appears to be limited to men from the Mediterranean region, indicating a possible genetic link, but HHV-8 infection may also play Etiology and the disease process: Most human cancers a role. are not infectious in that they are not the direct result of miA variety of B-cell and T-cell lymphomas are also assocrobial infection. However, certain groups of viruses have ciated with viral infections. The human T-cell lympholong been known to be associated with malignancies in antropic virus (HTLV) has been shown to be the etiological imals, and several members of these groups have been agent for certain forms of T-cell disease. T-cell lymphoshown to cause certain human cancers. Viruses can cause mas resulting from HTLV infection are most commonly genetic changes in oncogenes—genes that directly regufound in southern Japan, Africa, and portions of the Cariblate cell division such as growth factors and their recepbean. About 5 percent of persons infected by HTLV detors, signal mechanisms, and tumor suppressors—and disvelop cancer. The mechanism by which cancer is induced rupt regulation of cell growth. However, people can be is unclear but appears to involve a disruption of the cell’s infected with these viruses and not develop cancer, so how signaling mechanism, which regulates cell replication. they become activated is unknown. There are numerous non-Hodgkin lymphomas (NHLs), More than one hundred types of human papillomasome of which are associated with viral infection. The viruses have been identified, of which about half are capaEpstein-Barr virus (EBV), a member of the herpesvirus ble of causing cervical cancer. Some 75 percent of cervical family, is the etiological agent behind Burkitt lymphoma, cancer cases are associated with three serotypes of HPV. an illness in which malaria is a cofactor, and nasopharynThree genes encoded by these viruses appear to be linked
A Primer on Viruses
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Virus-related cancers geal carcinoma, an illness found among those whose ancestry can be traced to southern China. The precise mechanism by which EBV infection results in cancer is unclear but appears to involve a translocation event with the cell chromosome, activating a cellular oncogene. Incidence: Incidence rates for virus-related cancers vary widely by virus and affected site. Incidence rates for cancers that have viral and nonviral causes are generally not broken down by cause. Approximately 500,000 cases of cervical cancer are reported annually worldwide. In the United States, cervical cancer accounts for some 5,000 deaths each year. Incidence rates in the United States are about 7 per 100,000 women per year. Liver cancer is estimated to result in 500,000 deaths worldwide each year. Liver cancers account for one-quarter of all cancers in developing countries. In Africa and Southeast Asia, the incidence rate is 20 per 100,000 people, while in the United States, it is about 5 per 100,000 people. Most of these cases result from infection by HBV, though HCV has been shown to be increasingly associated with cases of liver cancer. A precise number is unavailable, since the extent of HCV in the population is unknown; however, studies from Japan have found HCV in 75 percent of cases of liver cancer. Most cases of liver cancer in the United States are found in immigrant populations from areas in which the disease is endemic. An increasing number of cases of Kaposi sarcoma began to appear in the late 1980’s as a result of the AIDS epidemic. Incidence rates grew to 9.5 per 100,000 men in 1989 and fell to 1.3 in 2005. In the United States, non-Hodgkin lymphomas (all types) are the fifth most common forms of cancer, with an incidence rate of about 20 per 100,000 people per year. Symptoms: Symptoms of virus-related cancers vary depending on the site affected. For cervical cancer, the early stages are generally asymptomatic, and as the disease progresses, women experience unusual vaginal bleeding or pain. For liver cancer, the symptoms include abdominal pain, unexplained weight loss, and a sudden onset of jaundice. A physician performing a physical examination will usually find an enlarged and tender liver and can hear turbulent bloodflow through the liver because it has an extensive vascular system. Blood tests may reveal elevation of certain liver proteins such as alpha-fetoprotein. The first symptoms of Kaposi sarcoma are generally purplish lesions or nodules on or under the skin or mucous membranes. Symptoms of lymphomas are general, usually mani1234
Salem Health: Cancer festing as swollen lymph nodes, fever, or unexplained weight loss. Screening and diagnosis: A standard screening test exists for cervical cancer, but the other virus-related cancers do not have routine screening procedures. Early diagnosis of cervical cancer results from the observation of abnormal cervical cells following a Pap test. Although not all abnormal-appearing cells are cancerous, their presence may indicate a precancerous state. A colposcopy, the visual observation of the cervix, may help the physician in deciding whether to perform a biopsy. As with most cancers, the extent of the disease is the basis for staging. If a patient’s symptoms suggest liver cancer, the physician will investigate further, using a variety of imaging scans. Ultrasound is generally the first choice because it is noninvasive and easily performed. This may be followed up with a computed tomography (CT) scan or magnetic resonance imaging (MRI). Ultimately, a biopsy is necessary to confirm the cancer. Staging of liver cancer is based on the size of the tumor and the extent of spread. Kaposi sarcoma is diagnosed by taking the patient’s history and examining the skin for the lesions typical of the disease. Biopsies are performed to confirm the disease, and imaging tests are used to find lesions in the stomach or lungs. Because Kaposi sarcoma is AIDS related, its staging is based on the extent of the tumor, the state of the immune system, and the amount of systemic illness. Non-Hodgkin lymphoma is commonly diagnosed by biopsy of an enlarged lymph node that does not respond to antibiotic treatment. If cancer is found in the sample, imaging tests such as X ray, CT scans, MRI, and positron emission tomography (PET) scans can help determine how much the cancer has spread. Staging for non-Hodgkin lymphoma uses the Ann Arbor system, which is based on the degree of spread. In addition, two prognostic systems, one for slow-growing and one for fast-growing lymphomas, have been developed. These systems attempt to describe a patient’s risk of dying and help physicians select appropriate courses of treatment. Treatment and therapy: Treatment for virus-related cancers varies depending on the site but generally involves surgery, radiation therapy, chemotherapy, or a combination of therapies. Treatment of cervical cancer generally starts with surgery to remove as much cancerous tissue as safely possible. Additional treatments depend on the stage of the disease. Radiation therapy may be external or internal using a radioactive implant. Chemotherapy, usually intravenous, is recommended if metastasis has occurred.
Salem Health: Cancer A small liver tumor can be removed surgically. Historically, a liver transplant had been recommended for most forms of liver cancer, though later it was determined that such a radical approach might not be necessary in the absence of extensive involvement. Extensive liver cancer may require chemotherapy, though other approaches have also been shown to be useful. Transarterial chemoembolization (TACE), the embolization of tumor blood vessels using a gel or coil; radiofrequency ablation (RFA), the insertion of an electrical probe directly into the tumor, followed by ablation of the tissue; and proton beam therapy have all been shown to be useful in reducing the size of localized tumors. Treatment of Kaposi sarcoma depends on the extent of the tumor and can involve either surgical removal or radiation therapy and chemotherapy. Non-Hodgkin lymphoma in HIV-infected patients is complicated by the patients’ low blood cell counts, although the use of highly active antiretroviral therapy has made it easier for patients to endure chemotherapy.
Von Hippel-Lindau (VHL) disease The prognosis for those with HIV-related Kaposi sarcoma is improving because of better treatments for AIDS patients. If detected early, the five-year survival rate can reach 90 percent; however, if the disease has reached the lungs, the survival rate drops to 30 percent. Similarly, the outlook for HIV-infected patients with lymphoma depends largely on how well their AIDS is controlled. Richard Adler, Ph.D. u
For Further Information Fields, Bruce, ed. Fields Virology. Philadelphia: Lippincott-Raven, 1996. Grand, J. A., ed. Viruses, Cell Transformation, and Cancer. New York: Elsevier, 2001. Pelengaris, Stella, and Michael Khan, eds. The Molecular Biology of Cancer. Malden, Mass.: Blackwell, 2006. Strauss, James, and Ellen Strauss. Viruses and Human Disease. New York: Academic Press, 2002. Tabor, Edward, ed. Viruses and Liver Cancer. New York: Elsevier, 2006.
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Prognosis, prevention, and outcomes: Prognosis and prevention of virus-related cancers varies depending on the specific cancer and virus. Prevention generally involves attempting to avoid the spread of viruses that cause cancers. The screening of donated blood has reduced the risk of viral infection through transfusion. Safe-sex practices (such as condom use) help prevent the spread of sexually transmitted viruses such as HPV, HIV, HBV, and HCV. Efforts have been made to educate intravenous drug users about the dangers of sharing needles and thereby spreading viruses. Vaccines have been developed for HBV and HPV. The HBV vaccine can prevent most infections by this virus. Since 80 percent of cases of liver cancer are associated with this virus, immunization should reduce the incidence rate. In 2006, a vaccine for HPV, Gardasil, was approved by the U.S. Food and Drug Administration. While the long-term results of vaccine use are unknown and questions as to its efficacy still exist, it is hoped that early immunization for HPV may serve to protect women against most forms of the virus. The prognosis for patients with cervical cancer depends on the stage of the disease and its response to therapy. Early diagnosis can result in the elimination of the disease, while once metastasis has taken place, the outcome becomes increasingly poor. Liver cancer is curable if caught early and the tumor removed. None of the techniques used to treat advanced cancer is effective long-term, and the prognosis for patients with advanced liver cancer remains poor, with death generally resulting within a year of diagnosis.
Other Resources
American Cancer Society http://cancer.org The Leukemia and Lymphoma Organization http://www.leukemia-lymphoma.org National Cancer Institute http://www.cancer.gov See also Antiviral therapies; Burkitt lymphoma; Carcinomas; Cervical cancer; Epstein-Barr virus; Hepatitis B virus (HBV); Hepatitis C virus (HCV); HIV/AIDS-related cancers; Human papillomavirus (HPV); Infection and sepsis; Kaposi sarcoma; Leukemias; Liver cancers; Lymphomas; Retinoblastomas; Vaccines, preventive; Viral oncology.
u Von Hippel-Lindau (VHL)
disease Category: Diseases, symptoms, and conditions Also known as: Von Hippel-Lindau syndrome, angiomatosis retinae Related conditions: Renal cysts; clear cell form of renal cell carcinoma; hemangioblastomas of the brain, spinal cord, and retina; pheochromocytoma; endolymphatic sac tumors Definition: A hereditary cancer syndrome, von HippelLindau (VHL) disease is associated with renal cell carci1235
Von Hippel-Lindau (VHL) disease noma (kidney cancer); pheochromocytoma (an adrenal gland tumor that releases stress hormones); catecholaminesecreting paraganglioma (a tumor that releases stress hormones like a pheochromocytoma but is located outside the adrenal gland); hemangioblastomas (blood vessel tumors) of the brain, spinal cord, and retina; neuroendocrine tumors (nerve-cell tumors that may produce hormones) of the pancreas; and endolymphatic sac tumors (inner ear tumors). Approximately 40 percent of individuals with VHL develop renal cell carcinoma, which is the leading cause of VHL-associated death. Several distinct clinical presentations of VHL have been described based on the risk for pheochromocytoma and renal cell carcinoma. The types of tumors and the severity of the disease vary within and between families. Risk factors: Because von Hippel-Lindau disease is hereditary, the main risk factor is having a family history of this syndrome. Each child of a person with von HippelLindau disease has a 50 percent chance of inheriting the disease. Etiology and the disease process: The underlying genetic cause of von Hippel-Lindau disease is a mutation, or a genetic change, in the VHL gene. Normally, the protein made by the VHL gene acts as a tumor suppressor, which means that it helps stop uncontrolled cell growth and proliferation. Mutations in the VHL gene either prevent the protein from being made or cause the protein to be made incorrectly, which leads to the multistep process of tumorigenesis (formation or production of tumors). Usually, each person has two normal copies of the VHL gene. A mutation in one copy of the gene is sufficient to cause von Hippel-Lindau disease, which is why this condition is referred to as autosomal dominant (autosomal means the VHL gene is located on one of the twenty-two pairs of autosomes, which are the non-sex chromosomes). A person with von Hippel-Lindau disease has a VHL gene mutation from the time of conception in the womb; however, symptoms of the disease may not manifest until later in life. Symptoms can occur before the age of five, and nearly all people with a VHL gene mutation have symptoms of the disease by the age of sixty-five. Different types of mutations in the VHL gene lead to different clinical presentations. Therefore, a person with von Hippel-Lindau disease may be more likely to have pheochromocytoma, renal cell carcinoma, or both. Incidence: Approximately 1 in 36,000 people has von Hippel-Lindau disease. Some 80 percent of people with von Hippel-Lindau disease inherit the disease from a parent, but 20 percent of people with the disease have a new 1236
Salem Health: Cancer gene mutation, meaning the mutation occurs for the first time in that individual. Symptoms: Symptoms depend on where the tumors are located. Hemangioblastomas of the brain or spinal cord can cause headaches, vomiting, coordination problems, and walking difficulties. Retinal (eye) hemangioblastomas can lead to vision problems. Pheochromocytomas and catecholamine-secreting paragangliomas release catecholamines (stress hormones) that can cause dangerously high blood-pressure levels. Neuroendocrine tumors of the pancreas usually do not produce hormones and may have no associated symptoms. Tumors of the endolymphatic sac can result in deafness, which may occur suddenly and be severe to profound. Screening and diagnosis: Von Hippel-Lindau disease is clinically diagnosed in a person who has two or more tumors associated with this condition. However, if a person has a family history of the disease, just one of the characteristic findings is needed to make a diagnosis. Tools used to check for disease include computed tomography (CT) or magnetic resonance imaging (MRI) to look for pheochromocytomas, endolymphatic sac tumors, or tumors of the brain and spinal cord. Ultrasound or CT may be used to examine the kidneys and pancreas, and urine testing may be done to check for catecholamines and metanephrines released by pheochromocytomas or paragangliomas. Ophthalmologic examination (an eye exam) is performed to check for retinal hemangioblastomas. Because von Hippel-Lindau disease is caused by mutations in the VHL gene, genetic testing is a valuable tool to confirm a suspected diagnosis or to test a family member who is at risk for the disease but has no symptoms. Genetic testing detects nearly 100 percent of VHL gene mutations. Treatment and therapy: The main focus of treatment for von Hippel-Lindau disease is surgery to remove tumors. Early surgery offers the best outcome for most of the tumors associated with von Hippel-Lindau disease, including renal cell carcinoma. Renal cell carcinoma may also be treated with chemotherapy, radiation therapy, ablation therapy (using probes to destroy the tumor with heat or cold), biological therapy (using the patient’s immune system to fight the cancer), and targeted therapy (using drugs that attack cancer cells without damaging normal cells). Prognosis, prevention, and outcomes: Because von Hippel-Lindau disease is a genetic condition, its manifestations cannot be prevented. However, monitoring of individuals who are at risk for the disease based on their family history or who are known to have a VHL gene mutation can detect problems early and lead to more effective treatment
Salem Health: Cancer and better outcomes. Such monitoring includes yearly ophthalmologic screening, yearly blood pressure checks, yearly urine testing for catecholamines and metanephrines, yearly abdominal ultrasounds, periodic MRI of the brain and spinal cord, and hearing evaluation if symptoms of hearing loss are present. The medical team caring for patients decides the age at which monitoring should start. Abbie L. Abboud, M.S., C.G.C. u For Further Information Linehan, W. M., B. Zbar, and D. R. Klausner. “Renal Carcinoma.” In The Metabolic and Molecular Bases of Inherited Disease, edited by Charles R. Scriver, Arthur L. Beaudet, David Valle, and William S. Sly. 8th ed. New York: McGraw-Hill, 2001. Molino, D., J. Sepe, P. Anastasio, and N. G. De Santo. “The History of Von Hippel-Lindau Disease.” Journal of Nephrology 10 (2006): S119-S123. Woodward, E. R., and E. R. Maher. “Von Hippel-Lindau Disease and Endocrine Tumour Susceptibility.” Endocrine Related Cancer 32 (2006): 415-425. u
Other Resources
Genetics Home Reference Von Hippel-Lindau Syndrome http://ghr.nlm.nih.gov/ condition=vonhippellindausyndrome Kidney Cancer Association http://www.kidneycancer.org VHL Family Alliance http://www.vhl.org See also Brain and central nervous system cancers; Hemangioblastomas; Hereditary leiomyomatosis and renal cell cancer (HLRCC); Hereditary non-VHL clear cell renal cell carcinomas; Islet cell tumors; Kidney cancer; Pheochromocytomas; Renal pelvis tumors; Spinal axis tumors; Urinary system cancers.
u Vulvar cancer Category: Diseases, symptoms, and conditions Also known as: Vulvar carcinoma Related conditions: Human papillomavirus (HPV), vaginal cancer, vaginal intraepithelial neoplasia (VAIN), vulvar intraepithelial neoplasia, malignant melanoma, squamous cell carcinoma, Paget disease, adenocarcinoma, verrucous carcinoma, basal cell carcinoma, Bowen disease
Vulvar cancer
Age at Diagnosis of Vulvar Cancer, 1988-2001 Age Group
Cases Diagnosed (%)
20-29 30-39 40-49 50-59 60-69 70-79 80 and older
1.2 5.2 11.9 12.4 16.5 26.9 25.8
Source: Data from L. A. G. Ries et al., eds., Cancer Survival Among Adults: U.S. SEER Program, 1988-2001—Patient and Tumor Characteristics, NIH Pub. No. 07-6215 (Bethesda, Md.: National Cancer Institute, 2007)
Definition: Vulvar cancer is the name for malignant growths that originate from the vulva, the visible part of the female external genitalia. The vulva is the collective term for the labia majora, labia minora, clitoris, and perineum. The parts of the vulva are similar in tissue type, which suggests the cancers that can arise from them. The most common tissue type is squamous cell, which makes up the lining of many organs such as the skin and mucous membranes of the vagina and mouth. This type accounts for about 90 percent of all types of vulvar cancer. Individual cells from this type of carcinoma appear flattened, immature, disordered, multilayered, and with dark-staining nuclei on light microscopy. The second most common type is melanoma, which is derived from the pigment cells of the skin (melanocytes). Other, less common types include Paget disease of the vulva, sometimes associated with adenocarcinoma and verrucous, Bartholin gland and basal cell carcinomas. Risk factors: The risk factors for acquiring vulvar cancer include older age, smoking, age of first sexual intercourse less than nineteen years, having more than two sexual partners, and low socioeconomic status. Abnormal Pap smears, long-standing vulvar dystrophy associated with diabetes, a compromised immune system, exposure to herpes simplex virus 2 (HSV2) and human papillomavirus (HPV) types 16 or 18 are also risk factors. Vulvar cancer has also been associated with a prior history of cervical or vaginal cancer. Precursor lesions such as lichen sclerosis and vulvar intraepithelial neoplasia grade III may also be risk factors. Etiology and the disease process: As with most cancers, the development of vulvar cancer is closely linked to dam1237
Vulvar cancer age to deoxyribonucleic acid (DNA) and the mechanisms that regulate cell division, particularly the TP53 tumorsuppressor gene. Multiple factors accumulate and contribute to the probability of inducing a cell to become cancerous. Toxic substances in cigarette smoke or replicating viral DNA that is spliced with cell DNA can cause damage to replicating or unwound DNA in tissue with high cell turnover and division (such as that in the skin and intestinal tract). Replication errors can also occur in aging cells.
Salem Health: Cancer nodes draining the vulvar area. Many clinical situations can preclude this, including more common etiologies of an infectious origin. Physical examination of the vulva may also be nominal in early-stage vulvar cancer. However, an irregularly shaped, changing and persistent ulcer or solid mass that may or may not be movable in the vulvar area, accompanied by a suggestive clinical history, increases the probability of cancer.
Screening and diagnosis: There is no screening test for vulvar cancer. However, if a lesion on the vulva does not respond to treatments for common etiologies, a wedge biopsy—removal of lesions less than 2 centimeters (cm) at greatest breadth with a margin of normal skin and underlying stroma—should be performed to confirm the diagnosis. Care must be taken to ensure groin lymph nodes are Symptoms: Persistent itching of the vulva in an elderly truly absent, as their presence can alter disease managewoman with involvement of the surrounding skin, with or ment. The margin of normal tissue is necessary to assess without the presence of a vulvar lesion, may be the first the microscopic extent of the cancer and correctly stage sign of vulvar cancer, as it is associated with increased the cancer. The diagnosis of vulvar cancer is confirmed proliferation of vulvar tissue. The itching may have been when microscopic examination of the cells and tissue arpreviously treated but unsuccessfully. The patient may chitecture shows changes characteristic of cancer cells. In have a wartlike lesion, lump, or an ulcer that has appeared addition, the gross specimen is evaluated in terms of depth and has been recalcitrant to treatment. A mass in or near of penetration of the lesion into the stroma and its widest the groin area that persists even after antibiotic treatment visible breadth. can be suggestive of cancer that has spread to the lymph Because of the possibility of microscopic spread to other organs, other diagnostic tests may include a cervical Pap smear, vaginal and cervical colposcopy to look for other lesions, pelvic computed tomography (CT) scan or magnetic resonance imagery (MRI) that includes the groin area to look for enlarged lymph nodes that were missed in the physical examination, a chest X ray, and blood tests before surgery. The International Federation of Gynecology and Obstetrics (FIGO) uses the following surgical staging system to classify the severity of vulvar cancer by tumor size, lymph node involvement, and the presence or absence of distal metastasis: • Stage 0: Carcinoma in situ or preinvasive carcinoma • Stage I: Vulvar cancer is confined to the vulva or vulva and perineum and measures 2 cm or less at greatest breadth. • Stage II: Vulvar cancer is confined to the vulva or both the vulva and perineum Treatment for genital warts on the vulva, probably caused by HPV. Some types of and measures greater than 2 cm at greatthis virus are suspected of causing cancer. (LifeART© 2008 Wolters Kluwer est breadth. Health, Inc.-Lippincott Williams &Wilkins. All rights reserved.) Incidence: Vulvar cancer occurs in about 1 percent of all women. However, the proportion of vulvar cancer occurring in women under the age of fifty has increased by almost a factor of ten over twenty years.
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Salem Health: Cancer
• Stage III: Invasive vulvar cancer has encroached into the lower urethra, vagina, or anus or has spread to corresponding right- or left-draining lymph nodes. • Stage IV: Invasive vulvar cancer has encroached into the bladder mucosa, rectal mucosa, or upper urethral mucosa or is fixed to underlying bone, involves bilateral lymph nodes, or has invaded other, distant organs starting from the pelvic lymph nodes. Surgical staging is not complete until the furthest extent of spread is evaluated, and it does not change afterward with treatment. Treatment and therapy: For cancer confined within the epithelium or precancerous lesions such as vulvar intraepithelial neoplasia located on the lateral aspect of the labia majora outward, local excision of vulvar epithelium with a 0.5 to 1.0 cm margin is warranted. Lesions of the labia minora inward may be amenable to local excision, with laser ablation as an alternative. For Stage IA lesions that are 2.0 cm or less in breadth and less than 1.0 millimeter (mm) in depth, wide local excision is recommended. There are essentially two procedures used in treatment of vulvar cancer beyond Stage IA: wide surgical excision of the lesion, surrounding vulvae, and perineal area; and dissection and biopsy of inguinal lymph nodes at the femoral region of the thigh. During the 1960’s, a conservatory approach to radical vulvectomy that involved preservation of as much normal tissue as possible and separate right and left inguinal incisions to dissect lymph nodes was adapted and became the standard approach. Bulky tumors that encroach into adjacent organs preclude conservation, where diseased areas are excised while preserving functionality where feasible. Postoperative radiation therapy may be warranted in Stage III and IV vulvar cancer if surgical intervention was insufficient to address spread into the vagina, bladder, urethra, rectum, or microscopic spread of tumor cells to neighboring lymph nodes. Prognosis, prevention, and outcomes: The overall fiveyear survival rate of women with vulvar cancer approaches 70 percent. Earlier diagnosis means a higher survival rate: Being in Stage I at diagnosis correlates with a survival rate of 96 percent; Stage II, 85 percent; Stage III, 74 percent;
Vulvar cancer and Stage IV, 31 percent. When lymph node status is considered, positive nodes have a 52.4 percent survival rate regardless of stage. Positive pelvic lymph nodes have an 11 percent survival rate. Preventive measures include modification of risk factors and early detection of disease. Smoking cessation, practice of safe sexual behaviors, and good hygiene are recommended. Yearly Pap smears, visual inspection of the vulvar area, and biopsy of suspicious lesions are also advised. Vaccination with the HPV vaccine has also been seen to deter the development of precancerous lesions. Aldo C. Dumlao, M.D. u
For Further Information Byers, Tim, Susan J. Curry, Maria Elizabeth Hewitt, and the National Cancer Policy Board. Fulfilling the Potential of Cancer Prevention and Early Detection. Washington, D.C.: National Academies Press, 2003. Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. Morra, Marion E., and Eve Potts. Choices. 4th ed. New York: HarperCollins, 2003.
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Other Resources
American Cancer Society Detailed Guide: Vulvar Cancer http://www.cancer.org/docroot/cri/content/ cri_2_4_3x_how_is_vulvar_cancer_diagnosed.asp American College of Obstetrics and Gynecologists http://www.acog.org National Cancer Institute Vulvar Cancer http://www.cancer.gov/cancertopics/types/vulvar See also Adenocarcinomas; Adenoid cystic carcinoma (ACC); Basal cell carcinomas; Bowen disease; Cervical cancer; Gynecologic cancers; Gynecologic oncology; Herpes simplex virus; Human papillomavirus (HPV); Infectious cancers; Pelvic examination; Sexuality and cancer; Vaccines, preventive; Vaginal cancer.
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Waldenström macroglobulinemia (WM)
u Waldenström
macroglobulinemia (WM) Category: Diseases, symptoms, and conditions Also known as: Lymphoplasmacytic lymphoma, Waldenström’s macroglobulinemia Related conditions: Multiple myeloma Definition: Waldenström macroglobulinemia (WM) is a slow-growing form of non-Hodgkin lymphoma distinguished by a significantly elevated level of immunoglobulin-M (IgM) in the blood, often leading to hyperviscosity (thickening) of the blood. The disease was named for Jan Gosta Waldenström, a Swedish physician who identified “monoclonal gammopathy” in patients experiencing a thickening of their serum (1944). In a 1961 report, he described two patients with bleeding from the gums and nose, high platelet count, low red blood cell count (anemia), high sedimentation rate, and swollen lymph nodes. He ruled out multiple myeloma based on bone marrow biopsy tests and a lack of bone pain. In the serum he found a large amount of a single, unknown globulin (protein) with an extremely high molecular weight (macroglobulin). This macroglobulin is now known as IgM. Risk factors: Researchers have found few risk factors for WM. At least some cases of WM (up to 20 percent) are familial, being passed from generation to generation. For others the cause is unknown. There is some evidence that infection with the hepatitis C virus may increase the incidence of WM in some individuals, as does prior diagnosis with monoclonal gammopathy of undetermined significance. Being older, white, and a man are known risk factors. None of these risk factors is controllable, so prevention remains elusive. Etiology and the disease process: B cells are an important part of the immune system of the human body. They are the antibody-secreting cells that are a principal part of the adaptive immune system (which creates immunity for specific invaders, such as bacteria, viruses, and so on). There are five types of antibody (immunoglobulin or Ig) secreted by B cells: IgA, IgD, IgE, IgG, and IgM. Of these, IgM is by far the largest (approximately 900,000 Daltons), hence the name “macroglobulin.” Some B cells circulate throughout the blood, while others reside in the lymph nodes of the body. Immature B cells are found in the bone marrow. The lymph nodes are small, pea-sized collections of immune system cells (B cells, T cells, and macrophages) found in recognizable locations throughout the body. The 1240
Salem Health: Cancer predominant nodes are in the underarm area, the groin, both sides of the neck, the chest, and the abdomen. Small amounts of lymphoid tissue are also found in the digestive tract and the respiratory system. For unknown reasons, early B cells, predominantly in the bone marrow, can multiply out of control. As they do this, they can crowd out the normal red blood cell production, leading to a low blood cell count. As they mature and circulate, these B cells secrete much larger amounts of IgM than normal. This leads to hyperviscosity (thickening of the serum) as more and more large protein is secreted and trapped in the bloodstream. Other symptoms, such as swelling of the lymph nodes and other parts of the immune system, are also related to the overpopulation of B cells and the overproduction of this macroglobulin. The cancerous cells found in individuals with WM are similar to those found in people suffering from multiple myeloma (cancer of plasma cells) and non-Hodgkin lymphomas (cancer of lymphocytes, including B cells). The cancer cells of WM are lymphoplasmacytoid, similar to both plasma cells and lymphocytes. These are the cells that secrete the large amounts of IgM and create the various symptoms of the disease. Incidence: Approximately 1,500 new cases are confirmed each year in the United States. The incidence is higher in whites than in blacks or Latinos, and higher in men than in women. The chance of developing this disease increases with age (mostly because of its slow nature), with the median age of diagnosis at sixty-three. It is very rare in people under the age of fifty but has been reported as early as age twenty-seven. Symptoms: Many patients are asymptomatic; in others the symptoms vary widely. The most common symptoms of WM are weakness, swollen lymph nodes, swollen liver or spleen, severe fatigue (often the result of severe anemia), low appetite and weight loss, and bleeding from the gums and nose (often the first signs of increased platelet activity). In addition, many patients experience visual problems (most likely due to bleeding of the small blood vessels inside the eyes) or neurological problems (dizziness, headache, vertigo), probably caused by slowed circulation of blood to the brain. Pain or numbness in the extremities may also be noted, a sign of early nerve damage. Heart problems often arise as a result of damage caused to the heart muscle by the high levels of IgM and because the heart has to work extra hard to pump the very thick blood through the body. Symptoms can vary widely depending on the severity of the disease and the amount of IgM being secreted. None of these symptoms by themselves are diagnostic of WM, since they
Salem Health: Cancer are also found in many other cancers and noncancerous diseases. Screening and diagnosis: There are no tests available that can screen for early WM. When signs and symptoms first appear, diagnosis can generally be made based on blood and urine tests along with a bone marrow biopsy or fine needle aspiration biopsy. Tests of blood viscosity are extremely important, as are measurements of the amount of IgM and other immunoglobulins in the serum. There is no standard staging system for WM (as there is for most other cancers). The amount of lymphoplasmacytoid cells in the bone marrow, the degree of anemia, the degree of viscosity, and age of the patient are all used to determine prognosis. Treatment and therapy: Although there is no cure for WM, there are several treatments that can help to control the symptoms. Since this is a slow-growing type of cancer, there is no rush to start treatment immediately upon diagnosis. Treatments are generally aimed at relieving symptoms, which vary tremendously from one individual to an-
Waldenström macroglobulinemia (WM) other. The decision about which treatment to use generally depends on the results of viscosity tests and bone marrow biopsies. Patients with high viscosity may undergo plasmapheresis. Blood from the patient is removed through a machine that separates the cellular part of the blood from the plasma (the liquid fraction containing the IgM). The cellular portion is returned to the patient along with a plasma substitute. Since this treatment removes only the IgM currently in the system and does not stop the body from producing more, it is only a temporary solution, but it does relieve symptoms, especially in newly diagnosed individuals. Most patients also undergo either chemotherapy (anticancer drugs) or biological therapy to destroy the IgMproducing cells and stimulate the immune system into attacking the cancer. The most often used regimen has been chlorambucil and prednisone in combination. Other anticancer drugs being used include cyclophosphamide, doxorubicin, fludarabine, and cladribine. Most treatments are given during outpatient therapy over a period of sev-
A spleen from a patient with Waldenström’s macroglobulinemia. (CNRI/Photo Researchers, Inc.)
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Watchful waiting eral days. Blood tests of IgM levels, physical examination of lymph nodes, and scans of lymph nodes are often used to determine whether a particular drug is working for the patient. All of these drugs have side effects that may include nausea, vomiting, loss of appetite, hair loss, lowered resistance to infection, and easy bruising. Careful monitoring is important. Biological therapies may include the use of interferon (a protein produced by lymphocytes to help fight infections) and monoclonal antibodies designed to attack lymphoma cells (rituximab). A few other treatments have been tried with a variety of successes. These include spleenectomy (removal of an enlarged spleen, where much IgM may be produced), and high-dose chemotherapy followed by stem cell transplantation (cells that will migrate to the bone marrow and replace those blood-forming and immune system cells destroyed by the chemotherapy). Additionally, drugs such as thalidomide and bortezomib, which have been used to treat multiple myeloma (a related type of cancer) have been tried in some patients. Researchers continue to look for new drugs, combinations of drugs, and new biological therapies. Prognosis, prevention, and outcomes: The prognosis for WM is extremely variable. Many textbooks describe a life span of five to seven years after diagnosis, but since the average age of diagnosis is sixty-three, there is a great likelihood of dying from other causes. According to the International Waldenström’s Macroglobulinemia Foundation, patients have been known to live for twenty-five or more years after diagnosis. Kerry L. Cheesman, Ph.D. u
For Further Information Bjorkholm, Magnus. “Lymphoplasmacytic Lymphoma/ Waldenström’s Macroglobulinemia.” In The Lymphomas, edited by George P. Canellos, T. Andrew Lister, and Bryan D. Young. Philadelphia: Elsevier/Saunders, 2006. Chen, C. I. “Treatment for Waldenström’s Macroglobulinemia.” Annals of Oncology 15 (2004): 550-558. Johnson, Stephen A. “Waldenström’s Macroglobulinemia.” Reviews in Clinical and Experimental Hematology 6, no. 4 (2002): 421-434. Rohatiner, Ama Z. S., Nancy L. Harris, Riccardo DallaFavera, and T. Andrew Lister. “Lymphoplasmacytic Lymphoma and Waldenström’s Macroglobulinemia.” In Non-Hodgkin’s Lymphomas, edited by Peter Mauch et al. Philadelphia: Lippincott Williams & Wilkins, 2004. 1242
Salem Health: Cancer u
Other Resources
American Cancer Society Detailed Guide: Waldenström’s Macroglobulinemia http://www.cancer.org/docroot/CRI/ CRI_2_3x.asp?dt=76 International Waldenström’s Macroglobulinemia Foundation http://www.iwmf.com See also Immunoelectrophoresis (IEP); Lymphomas; Myeloma; Non-Hodgkin lymphoma.
u Watchful waiting Category: Social and personal issues Also known as: Expectant management, active surveillance Definition: Watchful waiting is a conservative approach to disease management that delays treatment for slowgrowing, indolent cancers and those that are incurable. Watchful waiting is also referred to as expectant management and active surveillance. Usage: When watchful waiting is used with precancerous lesions, it requires frequent monitoring to ensure early intervention when signs of cancer appear. This management strategy is often an option for a variety of slow-growing cancers including prostate cancer and non-Hodgkin lymphoma. However, research and development of new targeted therapies for cancer treatment may reduce the need for this wait-and-see option in the future. Treatment criteria: The watchful waiting approach is for individuals who meet disease-specific criteria for delaying treatment. For example, in prostate cancer, the prostatespecific antigen (PSA), Gleason score, and PSA doubling time are used to determine when watchful waiting is appropriate. This approach is considered for low-grade cancers when the patient is asymptomatic and for older men who will more likely die of another cause. Guidelines for this form of treatment involve scheduled monitoring and an established plan that is instituted to document disease growth. Laboratory studies, diagnostic imaging, and other test findings are assessed at predetermined intervals. The most important consideration is that the patient is comfortable with the option to delay treatment and is educated about the signs and symptoms to watch for that may indicate progression.
Salem Health: Cancer Advantages: The major advantage is postponement of the toxic effects of therapy and cumulative doses of drugs until it is determined that the cancer is growing. The time gained can be used to evaluate treatments and make a choice before it is necessary to initiate treatment. Those with existing conditions that could make the side effects of cancer treatment worse may prefer this option to preserve quality of life. Watchful waiting does not preclude treating other symptoms, such as pain. Disadvantages: Delaying treatment is perceived as risky and irresponsible by some individuals. The anxiety and stress this choice would create for them make it unworkable. Also, it is possible that cancer growth could accelerate before it is detected, reducing the window of opportunity for early intervention. For others, however—especially those diagnosed very late in life—watchful waiting may be preferable to aggressive treatments that can compromise quality of life. The patient must be comfortable with the choice to derive the benefit of extending quality of life by avoiding the side effects of treatment. Linda August Vrooman, R.N., B.S.N., O.C.N. See also Adjuvant therapy; Elderly and cancer; Gleason grading system; Leiomyomas; Myeloproliferative disorders; Neuroblastomas; Overtreatment; Stress management.
u Weight loss Category: Diseases, symptoms, and conditions Also known as: Unintentional weight loss, anorexia (loss of appetite), cachexia (extreme weight loss) Related conditions: Fatigue, malnutrition, illness, infection, poor wound healing, reduced response to physiological and psychological stress, diminished physical and mental performance, inferior response to treatment, and shorter survival time are all complications of less than optimal weight in cancer patients. Definition: Weight loss is a reduction in body mass marked by a decrease in body fluid, fat, and muscle. Unintentional weight loss is involuntary weight loss. Risk factors: Medical research has identified more than 360 causes of weight loss, of which cancer is one. Weight loss is one of the most common symptoms of cancer and a common side effect of many cancer treatments. Cancer, then, is a risk factor for weight loss. Weight loss itself is not a risk factor for cancer. In fact, many physicians and nutritionists believe that normal, controlled weight loss to reach optimal weight for health may help in preventing
Weight loss some cancers. However, unintentional rapid weight loss is a sign of a serious health problem and reason to see a doctor. Etiology and the disease process: As body weight— along with fluids, fat, and muscle—decreases, normal physiological functions in cancer patients degenerate, contributing to a host of medical problems and even death. Being below optimal weight for health impedes treatment efforts. Metabolic changes brought about by cancer can lead to a condition known as malabsorption. Patients affected by malabsorption may seem to consume enough food, but they do not absorb enough of the nutrients from the food and are unable to produce enough energy to fuel the body. This leads to a loss of fat and muscle, a wasting syndrome known as cachexia, which accounts for the emaciated look of some cancer patients. Infection, fever, and hot flashes—common symptoms of cancer or side effects of treatment—increase body temperature. To cope with a rise in body temperature, the body needs increased energy, which is furnished by the calories in food. Patients need to increase their intake of calories by 10 to 13 percent for each degree above 98.6 degrees Fahrenheit (37 degrees Celsius). A cancerous tumor also places demands on the body for added energy, which comes from the intake of extra calories. One theory, not yet proven, suggests that the tumor benefits more than the patient does from the extra calories because the tumor is exceptionally efficient at using calories from food for its own growth. Moreover, a tumor can affect the appetite and the normal digestive process. Studies have shown that tumors produce chemicals that change the way the body makes efficient use of nutrients. Chemical changes in the body are common with cancer. One theory is that cancer produces chemicals that lead to anorexia, the loss of desire to eat. Anorexia is common among cancer patients, however, and is linked to a number of factors associated with cancer and cancer treatment: changes in smell or taste, dry mouth, mouth sores and infections, difficulty in swallowing, nausea, diarrhea, constipation, and the psychological and emotional impact of cancer, which can lead to anxiety or depression. Anxiety and depression, in turn, can lead to anorexia. To fully benefit from aggressive cancer treatments such as certain types of chemotherapy and radiation therapy, patients need stores of energy. Weight loss or less than optimal weight can diminish the effectiveness of treatment. To speed up normal tissue repair following aggressive cancer therapies, patients need sufficient calories and adequate amounts of the macronutrients: protein, carbohy1243
Weight loss
Salem Health: Cancer nosing weight loss in cancer patients is done through nutrition screening and assessment. Screening identifies patients who may be at risk of complications from weight loss. Assessment establishes the overall nutritional status of a patient and helps doctors and nutritionists determine if the patient needs nutrition therapy. Nutrition screening and assessment are done before cancer treatment begins. Finding and treating nutrition problems in the early stages of the disease can improve the patient’s response to treatment and chance of recovery. Nutrition screening is done by gathering information about the patient such as the following: • Changes in weight over the past six months • Changes in the amount and types of food the patient normally eats • Problems that affect eating such as dry mouth, mouth sores, diarrhea, constipation, and changes in taste and smell • The patient’s ability to reason, walk, and perform normal daily activities • The patient’s perceived quality of life Nutrition assessment also involves a complete physical exam. The examining physician checks for general health and signs of disease, along with fluid buildup in the body and the loss of fat or muscle. Nutrition assessment and monitoring, done by both doctors and nutritionists, continue throughout treatment of cancer.
Excessive weight loss in this patient with uterine cancer resulted in loose skin on her thighs. (Custom Medical Stock Photo)
drates, and fat. Poor nutrition weakens the body’s capability to tolerate certain treatments. For instance, a decrease in the dose of drugs or radiation to compensate for the patient’s low tolerance to a particular treatment could undermine the effectiveness of the treatment. Incidence: Virtually every cancer patient can expect to suffer weight loss sometime during the course of the disease. Unintentional rapid weight loss is a common symptom of cancer. Symptoms: Weight loss is a symptom of many possible diseases, including cancer. The primary symptom in relation to cancer is a rapid, unexplained, reduction of body mass. The cause of such weight loss will be identified by analysis of other symptons and test results. Screening and diagnosis: Because weight loss leads to nutrition problems such as malnutrition or anorexia, diag1244
Treatment and therapy: Preventing weight loss or encouraging weight gain is a major part of cancer treatment. Before actual treatment of the cancer, doctors treat any complications that may arise from weight loss. Drug therapy and medical nutrition therapy help patients gain or maintain a healthful weight, along with stores of energy, to better battle the cancer. Drugs are used to relieve both symptoms of weight loss and side effects of treatment. The drugs are meant to achieve the following: • Prevent nausea, vomiting, or diarrhea • Promote bowel movements (laxatives) • Relieve pain • Prevent infections • Heal sores in the mouth • Stimulate saliva • Encourage the action of pancreatic enzymes, proteins released by the pancreas that help break down food during digestion and create energy for the body • Battle anxiety or depression Medical nutrition therapy is a major component of cancer treatment. Depending on the condition of the patient and the stage of the cancer, medical nutrition therapy in-
Salem Health: Cancer volves one of three types of nutrition: oral, enteral, and parenteral. Oral nutrition is nutrition taken by mouth. This includes the normal intake of food, special diets prescribed by nutritionists, and nutritional supplements, including beverages and formulas, to build and maintain healthful nutrition levels. Enteral nutrition is providing nutrients through a tube placed in the nose, stomach, or small intestine. Tube feeding is for patients who do not meet their nutritional needs from food and beverages and who do not have problems with vomiting or diarrhea. Tube feeding can be used to supply supplements to a patient’s diet or as the only source of nutrition. Parenteral nutrition—also known as hyperalimentation or total parenteral nutrition (TPN)—delivers nutrients intravenously, through a blood vein, bypassing the digestive system. It is for patients who are unable to absorb nutrients through the gastrointestinal tract because of continual vomiting or severe diarrhea and for those undergoing high-dose chemotherapy or radiation and bone marrow transplantation. It is possible for patients to receive all the vitamins, minerals, protein, and calories they need through total parenteral nutrition. Prognosis, prevention, and outcomes: Studies have shown that maintaining nutritional health improves the chances of survival from cancer. However, maintaining a healthful weight is no guarantee that cancer can be prevented or successfully treated. Too many other factors are involved. Often the cancer eventually overwhelms the entire system. During the later stages of cancer, sometimes the best treatment for patients is to allow them to eat what they want and to preserve the more pleasant and social aspects of eating. Wendell Anderson, B.A. u
For Further Information Fearon, Kenneth C., Anne C. Voss, and Deborah S. Hustead. “Definition of Cancer Cachexia: Effect of Weight Loss, Reduced Food Intake, and Systemic Inflammation on Functional Status and Prognosis.” American Journal of Clinical Nutrition 83, no. 6 (June, 2006): 1345-1350. Ko, A., E. H. Rosenbaum, and M. Dollinger. Everyone’s Guide to Cancer Therapy: How Cancer Is Diagnosed, Treated, and Managed Day to Day. 5th ed. Kansas City, Mo.: Andrews McMeel, 2007. McIlwain, Harris H. The Fifty-Plus Wellness Program. Hoboken, N.J.: John Wiley and Sons, 1991.
Wilms’ tumor u
Other Resources
American Cancer Society Nutrition for the Person with Cancer http://www.cancer.org/docroot/MBC/ MBC_6.asp?sitearea=ETO National Cancer Institute Overview of Nutrition in Cancer Care http://www.cancer.gov/cancertopics/pdq/ supportivecare/nutrition/Patient See also Anorexia; Appetite loss; Artificial sweeteners; Cachexia; Carcinoma of unknown primary origin (CUP); Chemotherapy; Depression; Diarrhea; Dry mouth; Fatigue; Laxatives; Nausea and vomiting; Nutrition and cancer prevention; Nutrition and cancer treatment; Obesityassociated cancers; Psychosocial aspects of cancer; Side effects; Small intestine cancer; Stress management; Symptoms and cancer.
u Wilms’ tumor Category: Diseases, symptoms, and conditions Also known as: Nephroblastoma, renal (kidney) embryoma Related conditions: Clear cell carcinoma of the kidney, rhabdoid tumor of the kidney, neuroepithelial tumor of the kidney, cystic partially differentiated nephroblastoma, mesoblastic nephroma, renal carcinoma Definition: Wilms’ tumor is a solid tumor of the kidney that may spread to the lungs, liver, brain, bone, or lymph nodes. The majority of cases of Wilms’ tumor occur in children younger than five years old. Wilms’ tumors are categorized at the cellular level or histologically as tumors with either favorable histology or anaplastic histology. Wilms’ tumors with favorable histology are composed of the three types of cells normally found in the kidney and account for 90 percent of the Wilms’ tumor cases. The remaining 10 percent of Wilms’ tumor cases have cells that are anaplastic, which are primitive or undifferentiated cells that have large, distorted nuclei. The anaplastic cells can be focal, meaning located in a distinct area, or diffuse throughout the tumor. Risk factors: Wilms’ tumors usually occur in otherwise healthy children, although 10 percent of Wilms’ tumor cases occur in children with certain genetic and developmental abnormalities present at birth. These abnormalities are categorized as overgrowth or nonovergrowth syn1245
Wilms’ tumor
Salem Health: Cancer
dromes. Overgrowth syndromes include BeckwithWiedemann syndrome, hemihypertrophy, Perlman syndrome, Sotos’ syndrome, and Simpson-Golabi-Behemel syndrome. Nonovergrowth syndromes include aniridia, trisomy 18, WAGR syndrome, Blooms’ syndrome, and Denys-Drash syndrome. Wilms’ tumors in both kidneys, called bilateral Wilms’ tumor, are more common in children with associated developmental abnormalities. Children with diffuse hyperplastic perilobar nephroblastomatosis, characterized by abnormal tissue growth on the outer part of one or both kidneys, are also at higher risk for Wilms’ tumor. Etiology and the disease process: The exact cause of Wilms’ tumor is unknown, although the association of Wilms’ tumor with genetic and developmental abnormalities suggests that mutations in one or more genes may play a role. Researchers are studying the association of Wilms’ tumor with changes in the deoxyribonucleic acid (DNA) of the Wilms’ tumor 1 (WT1) gene, several genes that are either tumor-suppressor or tumor-progressive genes, and a chromosomal area identified as Wilms’ tumor 2 (WT2). Although genetic mutations are most likely involved with the development of Wilms’ tumor, only 1 to 2 percent of patients have a family member with Wilms’ tumor. Many Wilms’ tumors arise from nephrogenic rests, which are clusters of embryonic kidney precursor cells left over from development. These early building blocks of kidneys usually develop into the cells of a mature kidney, go dormant, or die off. Wilms’ tumor arises when the embryonic cells divide and grow out of control. Genetic
Prevalence of Wilms’ Tumors Among Total Renal Cancers in Children, 1975-1995 Age Group Under 5 5-9 10-14 13-19 Under 15 Under 20
Number of Cases
Percentage of Total Renal Cancers
880 260 39 21 1,149 1,200
96.2 95.9 66.1 35.0 94.7 92.0
Source: L. A. G. Ries et al., eds., Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program, 1975-1995, NIH Pub. No. 99-4649 (Bethesda, Md.: National Cancer Institute, SEER Program, 1999)
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mutations may cause nephrogenic rests to be abnormally retained. Incidence: Approximately 500 cases of Wilms’ tumor are diagnosed annually. A majority of patients are between the ages of one and five, with the average age of two to three years. Rates of Wilms’ tumor decrease as age increases. Adult Wilms’ tumor cases (sixteen years or older) are rare and associated with a poor prognosis. Bilateral Wilms’ tumors in both kidneys diagnosed at the same time or at different times make up approximately 4 to 5 percent of Wilms’ tumor cases. Wilms’ tumor accounts for the majority (95 percent) of childhood renal tumors diagnosed each year and for 6 to 7 percent of all childhood cancers. Symptoms: Wilms’ tumors are typically not detected until they become large enough to be felt as a mass in the abdomen; however, most are found before they metastasize. Additional symptoms may include blood in the urine, unexplained fever, high blood pressure, constipation, reduced appetite, abdominal pain, and weight loss. Screening and diagnosis: Unless a child is at risk for developing Wilms’ tumor, routine screenings are not typically done. Screening of a symptomatic child includes a physical exam; assessment of health history; blood tests to examine the number of blood cells, amount of hemoglobin, and the presence of certain substances improperly released by organs and tissues; urine tests to check for blood, bacteria, sugar, or proteins; liver function tests; renal function tests; and imaging tests to visualize the kidneys. The most common imaging test is an ultrasound, but computed tomography (CT), magnetic resonance imaging (MRI), and X rays may also be used. If a mass in the kidney is detected through imaging, diagnosis is established through surgery, rather than biopsy. Biopsies are avoided because they could rupture the tumor, causing the cancerous cells to spread outside of an otherwise contained area. If possible, the entire affected kidney is removed during surgery in a procedure called a nephrectomy. A pathologist examines the removed tissue to confirm the diagnosis of Wilms’ tumor and to assess the histology. The stage is determined by results of imaging studies, surgery, and the pathology report. Since stages are independent of histology type, they are reported together (for example, Stage I, favorable histology). The stages characterized by the Wilms’ Tumor Study Group are most commonly used: • Stage I: Cancer is found in only one kidney and was completely removed by surgery. The kidney and tumor
Salem Health: Cancer
Wilms’ tumor phrectomy and removal of nearby lymph nodes, followed by adjuvant chemotherapy. A dual chemotherapy regimen of vincristine and dactinomycin is typically used. Stages III and IV require a nephrectomy followed by combination chemotherapy (dactinomycin, vincristine, and doxorubicin, or dactinomycin and vincristine) with radiation. Depending on the size and location of the tumor, chemotherapy may be given before surgery to shrink the tumor. Stage V involves removal of the tumors in both kidneys while retaining kidney function (a partial nephrectomy). A biopsy in Stage V cases may be done preoperatively to determine the stage of the tumors in each kidney. Chemotherapy and radiation therapies are given based on the stages of the tumors in the kidneys. Wilms’ tumor is so rare that patients should be treated by specialists with experience (pediatric oncologists, pediatric surgeons, and pediatric radiation oncologists) and should be considered for a clinical trial.
The Wilms’ tumor is round when it attaches to a surface and then spreads out. (Science Source)
were intact before removal, and the tumor was not biopsied prior to surgery. There is no evidence that the cancer entered the blood vessels or the regions beyond where it was removed. The majority of patients are diagnosed at Stage I. • Stage II: The tumor is completely removed; however, before it was removed, the cancer spread to tissues and structures within and near the kidney. • Stage III: The cancer spread beyond the kidney to nearby lymph nodes and other structures in the abdomen. It could not be completely removed by surgery. The tumor may have broken open before or during surgery, was biopsied before surgery, or was removed in more than one piece. • Stage IV: Cancer spread to distant structures such as lungs, liver, brain, bone, or distant lymph nodes. • Stage V: The cancer is in both kidneys at the same time. Each kidney gets a separate stage rating. Treatment and therapy: Treatment depends on the stage and histology of the Wilms’ tumor. In general, tumors with anaplastic histology require more aggressive treatments and tend to be more resistant to chemotherapy than those with favorable histology. Stages I and II involve a ne-
Prognosis, prevention, and outcomes: Prognosis is related to the stage of disease at diagnosis, histological features, tumor size, patient age, whether Wilms’ tumor is diagnosed for the first time or is recurrent, the presence of abnormal chromosomes or genes, and access to experts with Wilms’ tumor experience. Some 90 percent of cases with a favorable histology respond to treatment, and four-year overall survival rates of Stages I through IV with favorable histology range from 98 to 90 percent. Anaplastic histology is associated with a less favorable prognosis, ranging from 82.6 to 44 percent four-year overall survival rates. Anaplastic histology is also associated with a higher rate of relapse. There are no known preventive measures in children who are otherwise healthy. Children with congenital abnormalities who have been treated for Wilms’ tumor, as well as those with other risk factors, should undergo ultrasound screening every three to six months until the age of eight. Children who have been exposed to high-intensity radiation or chemotherapy treatments are at risk for developing a second malignant neoplasm elsewhere in the body and congestive heart failure later in life. This is referred to the late effects of treatment for childhood cancer. Patients are candidates for a kidney transplant if they have been free of Wilms’ tumor for one to two years. Amanda McQuade, Ph.D. 1247
WAGR syndrome and cancer u For Further Information Janes-Hodder, Honna, and Nancy Keene. Childhood Cancer: A Parent’s Guide to Solid Tumor Cancers. 2d ed. Sebastopol, Calif.: O’Reilly, 1999. Steen, R. Grant, and Joseph Mirro, eds. Childhood Cancer: A Handbook from St. Jude Children’s Research Hospital. New York: Perseus, 2000. Woznick, Leigh A., and Carol D. Goodheart. Living with Childhood Cancer: A Practical Guide to Help Families Cope. Washington, D.C.: APA Life Tools, 2002. u
Other Resources
National Cancer Institute http://www.cancer.gov National Wilms’ Tumor Study http://www.nwtsg.org Pediatric Oncology Resource Center http://www.acor.org/ped-onc See also Beckwith-Wiedemann syndrome (BWS); Childhood cancers; Computed tomography (CT) scan; DenysDrash syndrome and cancer; Genetics of cancer; Kidney cancer; Malignant rhabdoid tumor of the kidney; Nephroblastomas; Pediatric oncology and hematology; Protooncogenes and carcinogenesis; Wilms’ tumor aniridiagenitourinary anomalies-mental retardation (WAGR) syndrome and cancer.
u Wilms’ tumor aniridia-
genitourinary anomaliesmental retardation (WAGR) syndrome and cancer Category: Diseases, symptoms, and conditions Also known as: Nephroblastoma Related condition: Wilms’ tumor in the absence of the associated abnormalities of WAGR syndrome Definition: Wilms’ tumor aniridia-genitourinary anomaliesmental retardation (WAGR) syndrome is a combination of abnormalities, which includes Wilms’ tumor, aniridia (loss of vision), genitourinary abnormalities, and mental retardation. Risk factors: The risk factor for WAGR syndrome is the combination of aniridia, genitourinary abnormalities, and 1248
Salem Health: Cancer mental retardation resulting from a defect or loss of genetic material from chromosome 11. Etiology and the disease process: The underlying cause of the syndrome is a genetic abnormality characterized by loss of a portion of the short arm of chromosome 11 (11p13 deletion). Genetic information in this region includes the WT1 gene, a transcription factor that functions in an unknown manner as a Wilms’ tumor-suppressor gene. Loss of function contributes to genitourinary malformations. A second gene, PAX6, is considered a master control for the regulation of eye and neural development of the central nervous system. Mutation or deletion of the gene may result in aniridia and mental retardation. The association of this gene with formation of the Wilms’ tumor is indirect, the result of a deletion of the region on chromosome 11. Incidence: The combination of abnormalities inherent in WAGR syndrome is uncommon and the incidence undetermined. However, children with the combination of aniridia, genitourinary abnormalities, and mental retardation have a greater than 30 percent chance of developing Wilms’ tumor. The incidence of Wilms’ tumor in the general population is 8 per 1 million, slightly higher among African Americans, and represents the most common form of kidney tumors in children. Most cases are not associated with known chromosomal mutations. Cases are most common before the age of five. Symptoms: The abnormalities of WAGR syndrome are generally observed immediately following birth, though diagnosis of mental retardation may not take place for months to years. Genitourinary abnormalities may include undescended testicles in male infants and abnormal development of the ovaries or uterus in female infants. Undescended testicles also pose a risk for development of testicular cancer. Children with aniridia may lack an iris, a condition apparent at birth, or have limited development of this region of the eye. The result is significant loss of visual acuity. Lack of an iris may also result in sensitivity to light, a problem that may be handled as the child grows through wearing of sunglasses. Symptoms of Wilms’ tumor include combinations of pain or swelling in the lower back, blood in the urine, and indistinct symptoms such as nausea or vomiting and loss of appetite. Any combination of such symptoms may be followed by more direct examination of the kidneys. Since blood pressure is regulated in part by the kidneys, elevated
Salem Health: Cancer
WAGR syndrome and cancer
blood pressure may also result from the presence of the tumor. Mental retardation, generally referred to as cognitive impairment, may not be apparent, since the mental capacity in many of these children does not deviate from that of the average child. Diagnosis often does not take place until testing following admittance to the educational system and often presents no significant difficulty for the child. Screening and diagnosis: Children known to have been born with the chromosomal deletion may be routinely screened for development of a tumor. Diagnosis of the syndrome otherwise results from recognition of the combination of abnormalities, particularly genitourinary malformations. Kidney function is assessed through several tests, including measurement of blood urea nitrogen (BUN), measurement of creatinine levels, and X-ray or computed tomography (CT) examination of the kidneys or abdominal region. If a mass is detected in the kidney, biopsy is performed. Staging is determined by the size and possible spread of the tumor: • Stage I: The tumor is confined to the kidney. • Stage II: The tumor extends into the capsule of the kidney. • Stage III: The tumor is confined to the region but has spread beyond the surface of the kidney. • Stage IV: Metastasis is taking place. • Stage V: The tumor is present on both kidneys. Treatment and therapy: Treatment is largely palliative. However, Wilms’ tumor can be removed surgically. Regional lymph nodes may be removed for determination of possible metastasis, as well as observation of other organs. If metastasis has occurred, radiation or chemotherapy may be included in the course of treatment. Prognosis, prevention, and outcomes: Aniridia, genitourinary abnormalities, and mental retardation present lifelong problems for patients but are not life-threatening. Prognosis of Wilms’ tumor depends on early diagnosis of the tumor. In general, prognosis is highly favorable, with more than 95 percent of patients with Stage I tumors showing no symptoms after five years. Even patients diagnosed at Stage IV have an 80 percent survival rate after five years. Once metastasis has occurred, the tumor may be found in most other organs, including bone, lungs, and brain. Such spread is problematic, and chances for recovery are reduced. If both kidneys are involved, reduced kidney function may result following removal of the tumor. Richard Adler, Ph.D.
Symptoms Sometimes Associated with WAGR Syndrome
• • • • • • • • • • • • • •
Autism Obsessive-compulsive disorder Attention deficit disorder Anxiety disorders Depression Polyphagia, hyperphagia (eating excessively) Obesity at an early age and high cholesterol levels Chronic renal failure after age twelve Breathing problems: asthma, sleep apnea, pneumonia Frequent childhood infections of the ear, nose, and throat Crowded or uneven teeth Problems with muscular strength and tone, particularly among infants and small children Epilepsy Inflammation of the pancreas
Source: National Human Genome Research Institute
u
For Further Information Pai, G. S., et al. Handbook of Chromosomal Syndromes. Hoboken, N.J.: John Wiley & Sons, 2003. Parker, James N., and Philip M. Parker, eds. The Official Parent’s Sourcebook on Wilms’ Tumor: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. Scott, Tamara. Wilms’ Tumor: A Handbook for Families. Glenview, Ill.: Association of Pediatric Oncology Nurses, 2002. Wright, Kenneth, et al. Handbook of Pediatric Eye and Systemic Disease. New York: Springer Science, 2006.
u
Other Resources
International WAGR Syndrome Association http://www.wagr.org/ National Organization for Rare Disorders WAGR Syndrome http://www.rarediseases.org/search/rdbdetail_abstract .html?disname=WAGR%20Syndrome See also Childhood cancers; Denys-Drash syndrome and cancer; Nephroblastomas; Pediatric oncology and hematology; Wilms’ tumor.
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Wine and cancer
u Wine and cancer Category: Lifestyle and prevention Definition: Red wine is a rich source of the natural antioxidants flavonoid and resveratrol. Antioxidants protect cells from the oxidative damage caused by free radicals, which have been implicated in cancer cell development. How red wine protects: Red wine is a rich source of active phytochemicals (plant chemicals) called polyphenols. Polyphenols are naturally found in the seeds and skins of grapes. Red wine contains more polyphenols than white wine because when white wine is made the skins are removed after the grapes are crushed. The polyphenols found in red wine are the naturally occurring antioxidants known as flavonoid and resveratrol. These antioxidants help clear cancer-causing free radicals from the body. Resveratrol also functions as an anti-inflammatory agent, inhibiting enzymes that promote tumor development and cancer cell proliferation. The flavonoid present in red wine may be especially effective against cancer during the initiation, promotion, and progression phases. Colorectal cancer and red wine: According to a report published by the American College of Gastroenterology, consuming three or more glasses of red wine per week may reduce a person’s risk of developing colorectal cancer. In a New York study that included 1,700 people who underwent routine colorectal cancer screening, 10 percent of those patients who did not drink alcohol had colorectal cancer, while only 3.4 percent of patients who routinely drank red wine had colorectal cancer. Prostate cancer and red wine: According to a study conducted by investigators at the Fred Hutchinson Cancer Research Center, men who drank four or more glasses of wine per week reduced the risk of prostate cancer by 50 percent. Moreover, there was a 60 percent lower incidence of aggressive types of prostate cancer. Resveratrol, according to the Fred Hutchinson Cancer Research Center, may reduce circulating testosterone levels. This is important because circulating testosterone can promote prostate cancer cell growth. Leukemia and red wine: Resveratrol has also been effective in causing apoptosis, cancer cell death, in patients with acute promyelocytic leukemia. Resveratrol works by inhibiting deoxyribonucleic acid (DNA) synthesis in the leukemia cells, which causes cell death. Collette Bishop Hendler, R.N., M.S. See also Alcohol, alcoholism, and cancer; Antioxidants; Beta-carotene; Bioflavonoids; Biopsy; Breast cancers; Cal1250
Salem Health: Cancer cifications of the breast; Calcium; Carotenoids; Coenzyme Q10; Complementary and alternative therapies; Curcumin; Dietary supplements; Free radicals; Herbs as antioxidants; Isoflavones; Mammography; Medical marijuana; Microcalcifications; Needle localization; Nutrition and cancer prevention; Prevention; Resveratrol; Ultrasound tests.
u Wire localization Category: Procedures Also known as: Needle localization Definition: Wire localization is the insertion of a fine wire under radiologic guidance to mark for biopsy areas of breast density or calcifications that can be seen on mammograms but are not detectable by touch. Cancers diagnosed: Breast cancers Why performed: Certain types of images seen on mammograms may indicate precancer or developing cancer. Some of these lesions cannot be seen with the naked eye or felt by touch. Wire localization enables the surgeon to accurately target areas for biopsy. A follow-up radiologic image after the biopsy assures that the suspect tissue was removed. Conditions of concern that require wire localization include microcalcifications and certain types of breast densities. Microcalcifications are tiny calcium deposits in the breast tissue, which show up on mammograms as white specks. Microcalcifications are generally only of concern when they appear in irregular patterns or are concentrated in one area of the breast. In these patterns or concentrations, they may indicate the rapid cell growth associated with precancer. Patient preparation: Patients usually get a local anesthetic to numb feeling in the area of the breast where the wire will be inserted. Steps of the procedure: To locate the area for biopsy, the surgeon uses radiologic images in which the wire site is marked. X ray is the preferred method used for wire localization. Ultrasound can also be used, but conditions requiring wire localization are often not visible by ultrasound. Guided by radiologic images of the breast, a radiologist locates the area in question, first inserts a thin, hollow needle into the area and then, through the needle, a fine wire with a hook. The hook keeps the wire in place in the breast and marks the specific area for biopsy. The wire in the breast provides a guide for where the incision is made. The wire is removed along with the breast tissue.
Salem Health: Cancer After the procedure: After the biopsy, the patient remains in the operating room until a repeat radiologic image confirms that the suspect area was removed. If the target area was missed, then another biopsy can be done immediately. Risks: The risks of wire localization are minimal and include minor pain, possible bruising, and limited radiation exposure. Results: Wire localization and follow-up radiologic images assure accurate targeting of the area for biopsy. Charlotte Crowder, M.P.H., ELS See also Biopsy; Breast cancers; Calcifications of the breast; Calcium; Mammography; Microcalcifications; Needle localization; Ultrasound tests.
u Wood dust Category: Carcinogens and suspected carcinogens RoC status: Known human carcinogen since 2002 Also known as: Sawdust, wood flour, sander dust Related cancers: Cancer of the nasal cavities and the sinuses Definition: Wood dust is composed of fine particles of the hard, fibrous substance that grows beneath the bark of trees in their trunks and branches. Woodworking tools release many lightweight specks of wood into the air. Electric and manual tools create wood dust when they chip, saw, turn, drill, sand, or carve wood. Outdoor compost piles also create visible clouds of wood dust when their layers of wood and leaves are agitated. Exposure routes: Inhalation Where found: Sawmills and other wood-processing mills, lumberyards, woodworking shops, furniture and cabinetmaking industry, carpentry industry, composting facilities At risk: Woodworkers in manufacturing industries; wood products press operators; workers who handle wood compost; wood carvers
Wood dust Etiology and symptoms of associated cancers: The carcinogenic actions of wood dust in the nose and sinuses are not clearly understood. Animal tests show that wood dust damages deoxyribonucleic acid (DNA) and breaks chromosomes. Human studies indicate that exposure to it is associated with nasal adenocarcinoma, sinus squamous cell carcinoma, and cancer of the nasopharynx. The active biological components of wood dust, cellulose and lignins (substances that make wood rigid), might cause these cancers. Organic chemical components, such as resin acids, terpenes, and tannins, might also be involved. Also, the particulate nature of wood dust most likely adds to its carcinogenicity. Symptoms of these cancers include spontaneous epistaxis (nosebleed) and chronic obstruction of the nasal or sinus passages. History: Studies in England in the 1960’s showed that rare nasal cancers occurred in woodworkers. During a 1970’s National Cancer Institute study, a high percentage of woodworkers died of these cancers. In 1995 the International Agency for Research on Cancer (IARC) classified wood dust as a Group 1 human carcinogen. In 2002 the National Toxicology Program of the Department of Health and Human Services declared wood dust to be a human carcinogen in the Tenth Report on Carcinogens (RoC). In 2005 the National Institutes of Health estimated that the occupations of 2 million people worldwide expose them to the carcinogenic effects of wood dust. The Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), the IARC, and the American Conference of Governmental Industrial Hygienists (ACGIH) have established exposure limits, and their recommendations include avoidance, use of dust masks, daily removal of wood dust, and ventilation. Susan E. Ullmann, M.T. (ASCP), M.A. See also Air pollution; Carcinogens, known; Carcinogens, reasonably anticipated; Carcinomas; Head and neck cancers; Occupational exposures and cancer; Prevention; Throat cancer.
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X-ray tests
u X-ray tests Category: Procedures Also known as: Radiology, medical imaging, radiologic procedures, radiographic imaging Definition: An X-ray test uses a machine to produce radiation that is passed through a particular body part. The size and density of the part show up as light and dark tones in the image on radiographic film, which helps the doctor diagnose the patient. Radiology encompasses many diagnostic types of imaging. Body parts, regions, and systems that can be seen by radiography include the chest, abdomen, skeletal system (skull, pelvis, spine, facial bones, extremities), brain, sinus, circulatory system (veins, arteries), lymphatic system, glands, muscles, urinary system, digestive system, reproductive system, cysts and tumors, and any soft tissues or organ in the body. Radiologic exams may include routine X rays; computed tomography (CT) scans, previously known as a computed axial tomography (CAT) scans; angiography to study the veins and arteries; intravenous urography (IVU), previously known as intravenous pyelogram (IVP), which uses tomography imaging to view the kidneys, ureters, and bladder; upper gastrointestinal (UGI) series, also known as barium swallow, to show the esophagus, stomach, and small intestines; colon imaging, also known as barium enema or lower GI, to demonstrate the large intestine, colon, rectum, and appendix; dental radiography and panoramic tomography, also known as Panorex imaging, to view the teeth, jaw, and tempromandibular joint; sinus radiography to view the paranasal sinus; bone densitometry scans to evaluate bone porosity; digital subtraction angiography (DSA) to illustrate the blood vessels; ER, also known as emergency room, portables, and trauma, to take radiographic images during emergency situations in surgery and in the emergency room; fluoroscopy, which shows an actively moving video image of the part being evaluated; mammography, which takes medical images of the breasts; single photon emission computerized tomography (SPECT) scans which shows an increase in blood flow; and nuclear medicine and positron emission tomography (PET) which use radioactive tracer materials or radiopharmaceuticals that are injected, inhaled, or swallowed by the patient to create images of the whole body and show areas of increased radioactive uptake according to the organ’s functioning ability. Other imaging technologies that fall outside the scope of X-ray technologies include magnetic resonance imaging (MRI), ultrasound, and endoscopy, which do not use radiation to produce an image. MRI uses a powerful mag1252
Salem Health: Cancer net to produce images on film, ultrasound uses sound waves to create its images, and an endoscope is a flexible viewing camera inserted orally or rectally to take internal pictures. Cancers diagnosed: Medical imaging using X rays is designed to help diagnose cancers, metastases, diseases, fractures, or abnormalities. These diagnostic tests are not to be confused with radiation therapy, which is used to destroy cancers. Most cancers can be seen with the use of radiographic imaging; however, all cancers vary widely in their visibility. Some cancers hide until late in the disease process and then metastasize (grow and spread) quickly. X-ray tests help diagnose bone cancers, bone marrow cancers, soft-tissue cancers, cancers of vital organs, bloodrelated cancers, lung cancers, lymph node and lymphoma cancers, spinal cord cancers, abdominal and pelvic cancers, head and neck cancers, liver and gallbladder cancers, reproductive organ cancers, breast cancers, leukemia, esophageal and colon cancers, Hodgkin and nonHodgkin diseases, advanced skin cancers, brain cancers, and metastases. Why performed: Diagnostic X rays are used to identify fractures, pneumonias, cancers, sinus infections, bowel obstructions, foreign objects, and anatomical abnormalities, or to confirm that there are no abnormalities. CT, MRI, nuclear medicine scans, and angiography are extremely helpful in locating diseases and cancers that are hard to find. Clinical observation and laboratory tests, combined with X-ray imaging, give the physician a more complete view of the extent of a particular disease. The combination of all tests and exams helps the doctor form a treatment plan for the patient. Any of these imaging devices may also be used to assist with guiding a biopsy, in needle placement, or to verify the location of wires and instruments during surgical procedures. Patient preparation: Because there is such a wide variety of exams and a vast range of reasons for a radiology exam, it is best for the patient to consult with the medical doctor or discuss the preparation with the technologist three days prior to the exam. Some of the tests are routine, involving no preparation. Others may require eating or drinking restrictions, an increase in the amount of fluids in the bladder, or ingestion of contrast preparations for enhanced viewing in certain areas. Steps of the procedure: The patient should tell the X-ray technician if there is any chance of pregnancy. If pregnancy is not a factor, then the patient is positioned between the X-ray tube and the radiographic film. Depending on the procedure and part being radiographed, the patient
Salem Health: Cancer
X-ray tests
may be sitting, standing, or lying on a table for the exam. A lead shield (radiation protection device) is placed on the area surrounding, but not on, the region to be radiographed. Technique is set according to the size and density of the part. The length of time for procedures varies from five minutes to two hours depending on the test. Often, several images using different angles are needed. Some X-ray exams require the use of a contrast medium (dye). It may be taken orally or injected into the patient prior to or during the imaging process. Contrast materials are used when specific parts need to be enhanced or defined on film. Contrast materials include barium sulfate (for upper GI and colon studies), iodine-based media (for IVP, CT, and angiography), gadolinium (for MRI), radioactive pharmaceutical materials and radioactive isotopes (for nuclear medicine scans), and xenon gas (for lung scans). After the procedure: A radiologist will view the X-ray images and document the findings. The report will be
given to the patient’s doctor. At a follow-up appointment, the results will be discussed. If the imaging used a contrast material, then it is often suggested that the patient drink plenty of fluids to flush the contrast from the body. Over the next several days, the contrast will be eliminated through the body’s waste products. Depending on the type of contrast and amount used, an unpleasant taste can linger in the mouth for a few weeks. Risks: The physician will evaluate the patient’s medical situation and determine if the diagnosis and treatment from the radiographic knowledge outweigh the potential risk from the X rays. If the patient is pregnant, then the procedure may be canceled or rescheduled or the patient may be double-shielded to protect the fetus. With the use of high-speed film, fast and accurate imaging equipment, collimation, and lead shielding, radiation is kept to a minimum for the patient. Diagnostic X-ray procedures carry no obvious short-term effects; however, any amount of radiation has the potential to harm cell structure. High doses of
Radiographic images help doctors detect and treat cancers. (Digital Stock)
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Xeroderma pigmentosa radiation that produce ill effects are seen in radiotherapy for cancer treatments. Long-term or high-dose effects of radiation can cause fetal or genetic defects, mutations or cancers, nausea, diarrhea, vomiting, or death. In addition to medical and dental X rays, the general population is exposed to background radiation that increases their total body exposure when they live in a brick house, walk by a brick building, fly in an airplane, smoke or breathe secondhand smoke, live at higher elevation levels, heat their home with natural gas, breathe air pollution, work with natural elements or radiation in their profession, watch television, and work or play on a computer. One can calculate the radiation dose from many potential sources at http://www.epa.gov/radiation/students/calculate.html. Other risks of X rays include claustrophobia in CT or MRI scanners and allergic reactions to contrast materials. Allergic reactions can include rash, itching, hives, nausea, vomiting, coma, or death. Results: The radiographic image is developed and viewed by the radiology technician, who gives the film to the physician or radiologist. Depending on the procedure, the patient may receive a preliminary diagnosis or may have to wait until the final report from the radiologist, which may be several days later. The patient’s current health status and extent of disease help determine a treatment plan. Suzette Buhr, R.T.R., C.D.A. u For Further Information Frank, Eugene D., Bruce W. Long, and Barbara J. Smith. Merrill’s Atlas of Radiographic Positions and Radiologic Procedures. 11th ed. St. Louis: Mosby/Elsevier, 2007. Goldmann, David R., and David A. Horowitz, eds. American College of Physicians Complete Home Medical Guide. New York: DK, 2003. Putman, Charles E., and Carl E. Ravin. Textbook of Diagnostic Imaging. 2d ed. Philadelphia: W. B. Saunders, 1994. u
Other Resources
American Cancer Society http://www.cancer.org University of Iowa Hospital and Clinics Radiation Exposure: The Facts vs. Fiction http://www.uihealthcare.com/topics/ medicaldepartments/cancercenter/prevention/ preventionradiation.html See also Barium enema; Barium swallow; Brain and central nervous system cancers; Breast cancers; Computed 1254
Salem Health: Cancer tomography (CT) scan; Endoscopy; Imaging tests; Lymphomas; Mammography; Radiation therapies; Upper gastrointestinal (GI) series; Urography.
u Xeroderma pigmentosa Category: Diseases, symptoms, and conditions Also known as: Xeroderma pigmentosum Related conditions: Skin cancer, eyelid tumors, telangiectasia, photophobia, mental retardation Definition: Xeroderma pigmentosa is an inherited genetic disease characterized by sensitivity to ultraviolet (UV) light. Patients with this disease have an extremely high risk of developing skin cancer and often die from skin cancer at an early age. Different classes of xeroderma pigmentosa have greater or lesser risks due to the severity of their disease. Dark skin color does not protect xeroderma pigmentosa patients from skin cancer. Risk factors: The main risk factor for xeroderma pigmentosa is having a family member with the disease. Etiology and the disease process: Xeroderma pigmentosa is caused by loss of function of genes responsible for repairing deoxyribonucleic acid (DNA) damage caused by ultraviolet light. The disease is classified as XPA, XPB, XPC, XPD, XPE, XPF, or XPG, depending on which of seven genes involved in nucleotide excision repair (DNA repair) are damaged. XP-variant (XPV) is a class for xeroderma pigmentosa patients who have a mutated DNA polymerase eta gene. Xeroderma pigmentosa is a recessive genetic trait. The disease is staged as follows: • Stage I: After six months of age, freckling, redness, and pigment changes appear on the skin. • Stage II: Patches of light and dark skin (poikiloderma) develop, and spider veins (telangiectasia) develop. • Stage III: Malignant skin cancers develop, including eyelid tumors. Incidence: In populations of European descent, xeroderma pigmentosa occurs in 1 in 250,000 people. In the Japanese population, xeroderma pigmentosa has been estimated at 1 in 40,000 people. Tunisia is noted to have a high proportion of xeroderma pigmentosa cases. Other parts of the world have not been systematically studied. Symptoms: Common symptoms in xeroderma pigmentosa are freckling, changes in skin pigmentation, and the eventual development of multiple, malignant skin cancers. Patients are sensitive to light, tend to suffer from conjunctival inflammation, and sunburn easily. Some pa-
Salem Health: Cancer tients exhibit immunosuppression and neurological problems, especially in XPA and XPD. The intensity of symptoms varies by xeroderma pigmentosa class and exposure to ultraviolet light. Screening and diagnosis: Clinical symptoms and family history are the first clues to xeroderma pigmentosa. Gene sequencing and other special tests are used to conclusively diagnose xeroderma pigmentosa. Treatment and therapy: Avoiding exposure to ultraviolet light, using sunscreen, and aggressive monitoring for skin cancer are necessary. Experimental gene therapy for xeroderma pigmentosa is in clinical trials.
Xeroderma pigmentosa Prognosis, prevention, and outcomes: Because xeroderma pigmentosa is an inherited genetic disease, genetic counseling is encouraged before having children. Extreme measures are needed to protect the xeroderma pigmentosa patient from ultraviolet light from the sun or fluorescent lamps. Death from skin cancer is typically the outcome at an early age, usually in childhood or young adulthood. Christopher Pung, B.S., C.L.Sp. (CG) See also Childhood cancers; Eyelid cancer; Family history and risk assessment; Gene therapy; Genetic counseling; Genetics of cancer; Risks for cancer; Skin cancers; Sunscreens; Young adult cancers.
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Yolk sac carcinomas
u Yolk sac carcinomas Category: Diseases, symptoms, and conditions Also known as: Endocervical sinus tumors, endodermal sinus tumors, orchidoblastomas Related conditions: Testicular carcinomas Definition: Yolk sac carcinomas are tumors that originate in the primitive germ tissue of humans, the cells of which resemble the yolk sac. The most common form of yolk sac carcinoma is testicular cancer in children, though the ovaries may also develop this form of disease. Yolk sac carcinomas are generally in a class known as nonseminomas, referring to the absence of sperm-producing cells. Risk factors: Most men who develop testicular carcinomas have no known risk factors. However, cryptorchidism, a lack of descent of one or both testicles, is associated with an increased risk, accounting for 14 percent of testicular cancers. Lack of descent is not rare, with the testicles remaining in the groin region in some 3 percent of male children. Most cases of testicular cancer that do occur develop in the undescended testicle. The molecular basis for the association is unknown, but scientists believe the two conditions are the result of a similar genetic factor rather than that the direct result of the lack of descent. The condition can be corrected through surgery. Etiology and the disease process: Most cancers that originate within the testicles are germ-cell tumors (GSTs), malignancies that develop in cells associated with sperm production. Most are seminomas, malignancies of spermproducing cells, with the remainder nonseminomas, malignancies of other embryonal cell types. Incidence: Malignant yolk sac tumors are rare in children and account for approximately 3 percent of childhood tumors. The incidence of malignant yolk sac carcinoma among the general population is less than 1 per 1 million. The actual chance of a man developing testicular cancer is low, with approximately 1 in 300 men at risk. Symptoms: Nonseminomas such as yolk sac carcinomas release alpha-fetoprotein (AFP), which can be measured in blood samples. Alpha-fetoprotein is synthesized by the yolk sac during fetal development, and elevated levels may suggest a malignancy. Screening and diagnosis: Diagnosis is based on biopsy of tissues, carried out in conjunction with the finding of elevated levels of alpha-fetoprotein. Treatment and therapy: Surgical removal of the testicle is the treatment of choice. Chemotherapy may also be war1256
Salem Health: Cancer ranted depending on the extent of the disease and may include combinations of vincristine, actinomycin D, and cyclophosphamide. Prognosis, prevention, and outcomes: Testicular carcinomas in children, when diagnosed early in their development, can usually be treated successfully. Similar malignancies developing in adults are more problematic, and prognosis depends on the stage of development and the types of cells associated with the tumor. Richard Adler, Ph.D. See also Alpha-fetoprotein (AFP) levels; Carcinomas; Cervical cancer; Childhood cancers; Cryptorchidism; Cyclophosphamide; Embryonal cell cancer; Germ-cell tumors; Teratocarcinomas; Testicular cancer.
u Young adult cancers Category: Diseases, symptoms, and conditions Also known as: Youth cancers, adolescent cancer, teen cancer Definition: Young adult cancers are malignancies that occur in youth from their mid-teens through their twenties (ages fifteen through twenty-nine). Some sources include people in their thirties in this grouping as well. Some common cancers diagnosed in young adults are as follows: • Lymphoma: cancer of the lymph glands that help fight disease • Melanoma: a malignant skin cancer • Thyroid cancer: cancer in the butterfly-shaped endocrine gland in the front of the neck below the voice box that produces hormones to regulate growth, metabolism, and level of energy • Leukemia: cancer of the blood and bone marrow • Soft-tissue sarcoma: cancer in supportive or connective tissue; forms in muscle, nerves, tendons, blood vessels, fat, joints, and lymph nodes • Germ-cell tumors: tumors of special cells that develop in an embryo that later become sexual organs, such as the male testes and female ovaries Less common cancers in young adults include brain tumors, breast cancer, and colorectal cancer. Risk factors: Researchers report no clear risk factors for cancer in young adults. Few studies have found any connection to environmental factors or inheritance. Most cases of young adult cancer appear sporadic and spontaneous with only 5 percent related to family history.
Salem Health: Cancer
Young adult cancers
Cancers that may be connected to environmental factors include melanoma, cervical cancer, Kaposi sarcoma, nonHodgkin lymphoma, Hodgkin disease, and Burkitt lymphoma. Having a cancer in childhood may increase the risk of developing a second cancer as a young adult. Etiology and the disease process: Because increased cancer occurrence is usually noted in older adults, cancer is often regarded as a disease of the elderly. However, cancer occurs in people of all ages. Historically, minimal research has been directed toward cancer in young adults, ages fifteen through twenty-nine, but that is changing. In 2006, the National Cancer Institute joined with the Lance Armstrong Foundation to identify barriers that face young adults with cancer and to develop approaches that can improve outcomes for this age group. Young adults with cancer face many challenges because of their age and developmental tasks. In the teenage years, young people try to achieve mature relationships with others of both sexes, establish gender role identities, learn to accept their bodies, achieve emotional independence from their parents, prepare for marriage, gain education for a career, acquire values that govern behaviors, and become socially responsible. In early adulthood, young adults select a mate, establish a home, start a family, struggle to establish their identity, complete their education and training to work and provide financial support, express independence, and become comfortable with their sexuality. These milestones may be difficult with a chronic disease process that threatens financial security and brings
Estimated Incidence of Invasive Cancer in the United States, 2000 Age Group Under 5 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44
Incidence per 1 Million People 217 113 129 216 365 662 983 1,462 2,156
Source: Data from A. Bleyer et al., eds., Cancer Epidemiology in Older Adolescents and Young Adults Fifteen to Twentynine Years of Age, Including SEER Incidence and Survival: 1975-2000 NIH Pub. No. 06-5767 (Bethesda, Md.: National Cancer Institute, 2006)
changes in body image, social relationships, and sexuality. The stresses of the young adult differ from those of children or older adults. Incidence: Young adult cancers account for only about 2 percent of all invasive cancers (excluding skin cancer) in the United States. However, each year about 70,000 young adults in the second or third decade of their lives learn they have some form of cancer. Young adults between the ages of fifteen and twenty-nine are 2.7 times as likely to develop cancer as they were before they turned fifteen. Young men between the ages of fifteen and twenty-nine have a higher incidence and a poorer prognosis than young women in this age group. The incidence of young adult cancers has experienced a steady increase. In 2000, nearly 21,400 young adults between the ages of fifteen and twenty-nine were diagnosed with invasive cancer. The United States Surveillance Epidemiology and End Results (SEER) report based on data from 1975 to 2000 provides the only treatise totally dedicated to young adults with cancer, ages fifteen through twenty-nine. SEER documented that the most common cancer in this age group is lymphoma, which accounts for 20 percent of young adult cancers; of these, 12 percent are Hodgkin disease. The next highest rate was skin cancer at 12 percent, with male genital system cancer equal to endocrine system cancer at 11 percent. Female genital cancers, primarily cervical and ovarian cancer, presented 9 percent of the cancer cases. Other young adult cancers were leukemia (6 percent); brain and spinal cord tumors (6 percent); breast cancer (5 percent); digestive tract cancers such as colon and liver (4 percent); soft-tissue sarcomas (3 percent); bone sarcomas such as Ewing sarcoma and osteosarcoma (3 percent); respiratory, oral, and urinary tract cancers (2 percent each); and germ-cell cancers (1 percent). The frequency of thyroid cancer is markedly higher in young women. Melanoma was fifth in frequency between the ages of fifteen and twenty-nine but moved up to first in the age group between twenty-five and twenty-nine. Symptoms: Symptoms of young adult cancers are specific to the type cancer they have developed. The following are some common young adult cancers and symptoms: Lymphoma symptoms include painless lumps in the neck, armpits, or groin; other possible signs are weight loss of up to 10 percent of total body weight, high infrequent fevers, loss of appetite, weakness and fatigue, generalized itchiness over the body, red irritated patches of skin, excessive sweating at night, and coughing or breathlessness with swelling of the face and neck. Melanomas present in moles that change in size (become bigger), shape (especially with an irregular edge), 1257
Young adult cancers
Salem Health: Cancer
color (get darker or multicolored), become itchy or painful, bleed or become crusty, or appear inflamed or irritated. Thyroid cancer symptoms are a lump or nodule on the neck; pain in the neck, jaw, and ear; difficulty swallowing; a tickle in the throat; or hoarseness. Leukemia symptoms vary by type but most are vague and nonspecific, such as fatigue or general weakness; malaise (general uncomfortable feeling throughout the body); abnormal bleeding and excessive bruising; reduced tolerance for exercise; an enlarged spleen, liver, or lymph nodes; joint or bone pain; increased infection and fever; and abdominal pain or fullness. A blood test will most likely show anemia, leukopenia (low white cell count), and thrombocytopenia The risk factors for young adult cancer are not clear, as most cases appear sporadic and (low blood-clotting cell count). spontaneous, with only 5 percent related to family history. (©Steve Nagy/Design Pics/ Corbis) Cervical cancer is a silent disease in its early stages, with later symptoms such as abnormal vaginal bleeding, their parents’ health insurance or have school health insurheavy vaginal discharge, pelvic pain, pain during urinaance with limited coverage; some may have no health intion, or bleeding after intercourse, between menses, or afsurance due to limited financial resources. They may delay ter douching. dealing with symptoms because of the costs associated Brain tumors may present with signs of increased intrawith health care providers, clinics, and testing. When they cranial pressure such as headaches, vomiting especially on do seek help, they may encounter a complicated health waking, mental changes such as drowsiness or sluggishcare system and become frustrated with the process. ness, seizures, and loss of coordination with clumsy movement. Depending on the tumor location, symptoms can also include buzzing or ringing in the ears, dizziness, Treatment and therapy: Cancer treatment for young blindness in one side, language disorders, loss of smell, or adults will be specific to the location, type, and stage of the impaired vision. cancer. If there is a malignant tumor or mass, surgery may Spinal cord tumors manifest with symptoms such as be the best option. With or without surgery, chemotherapy neck, arm, or leg pain; weakness; muscle wasting; spasms; (the use of drugs to kill cancer cells) may be used by the sensory changes; or decrease in bowel and bladder control. oncology physician to treat the cancer. Some cancers respond to radiation therapy, in which a high level of energy targets the cancer site to kill cancer cells. Immunotherapy Screening and diagnosis: Because young people are genmay be used to stimulate the immune system to fight the erally healthy, screening and diagnosis of cancer in young cancer. Hormone therapy might be employed in certain adults may be delayed. Young people may not recognize cancers. Targeted therapy may be a treatment for metastasymptoms or may ignore their body’s signs of illness. sis of the cancer. A stem cell transplant might be useful in They may think that symptoms are related to their lifestyle treatment. Joining a clinical trial directed to the young choices. Most screening procedures are recommended for adult’s specific cancer may prove beneficial. middle-age or older adults, not for young adults. Health Choosing a physician to provide cancer treatment and care providers may overlook cancer as a possibility because of the person’s youth and misdiagnose the disease. therapy is critical for young adults. The first consideration Young adults in school or college may be covered by is to contact an oncologist, a doctor that specializes in can1258
Salem Health: Cancer cer. Because cancer is less common in young adults, not all oncology physicians are familiar with this age-related specialty. They may not know about current treatment options and available support groups or resources for young adults. One example is that young adults with leukemia sometimes have better outcomes when treated with a regimen designed for children rather than the normal protocol for leukemia treatment in adults. Hence, young adults may need to consult specialists in pediatric oncology. However, practitioners who treat adults for cancers like breast, colon, or melanoma may provide the best treatment for young adults with these cancers. Prognosis, prevention, and outcomes: The prognosis for young adults varies with their specific cancer. While overall survival rates for adults and children with cancer have improved over the past few years, the same is not true for young adults. The SEER report states that survival of a young person diagnosed with cancer today is worse than in the past. The SEER report documents no improvement in survival for cancer patients between the ages of twentyfive and thirty-five. The least improvement in survival for young women was demonstrated between the ages of twenty-five and twenty-nine. One study showed that poor survival rates for young adults may reflect a lack of participation in clinical trials. Some research has documented improved survival when young adults participate in clinical trials, such as the survival rate for young adults with Kaposi sarcoma. Some studies suggest that young adult cancers can develop after previous childhood cancers. Research is currently examining lymphoma, leukemia, and testicular cancer, as these are diseases that affect children and young adults. Though no study has established why the second cancer occurs, some scientists believe that treatments such as chemotherapy and radiation therapy used to treat the first cancer may suppress the patient’s immune systems as well as damage normal cells. Key to decreasing second cancers is determining the factors that might contribute and minimizing exposure. One cancer on the rise among young adults is nonmelanoma skin cancers, which are preventable. Simple precautions can prevent skin cancer in young adults. The American Cancer Society has several recommendations to prevent skin cancer: • Avoid extended exposure to sunlight from 10 a.m. to 4 p.m. • Wear a hat, sunglasses, and clothes that cover the skin when in direct sunlight. • Use sunscreen with a sun protection factor (SPF) of at least 15.
Young adult cancers
• •
Avoid tanning booths. Check skin often for any unusual moles, spots, or blemishes. Note any change in size, shape, or color. • See a health care provider immediately if any suspicious spots or moles occur. Marylane Wade Koch, M.S.N., R.N. u
For Further Information Bleyer, A., M. O’Leary, R. Barr, and L. A. G. Ries, eds. Cancer Epidemiology in Older Adolescents and Young Adults Fifteen to Twenty-nine Years of Age, Including SEER Incidence and Survival: 1975-2000. Bethesda, Md.: National Cancer Institute, 2006. Eden, T. O. B., et al., eds. Cancer and the Adolescent. 2d ed. Malden, Mass.: Blackwell, 2005. Grinyer, Anne. Cancer in Young Adults: Through Parents’ Eyes. Philadelphia: Open University Press, 2002.
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Other Resources
Cancer Planet http://www.planetcancer.org/html/index.php CancerCare http://www.cancercare.org Cancer.Net Cancer in Young Adults http://www.cancer.net/portal/site/patient/ menuitem.724de8b96edd64acfd748f68ee37a01d/ ?vgnextoid=2ea803e8448d9010VgnVCM100000f27 30ad1RCRD LiveStrong Young Adult Alliance http://www.livestrong.org/site/c.jvKZLbMRIsG/ b.865471/k.B49/Young_Adult_Alliance.htm M. D. Anderson Cancer Center Adolescent and Young Adult Program http://www.mdanderson.org/children/ display.cfm?id=51555960-bbea-11d480fb00508b603a14&method=displayfull&pn= 38fff10f-474e-4506-9453cc8949d6732f Young Survival Coalition http://www.youngsurvival.org See also Aging and cancer; Astrocytomas; Breast cancer in children and adolescents; Childhood cancers; Choriocarcinomas; Dioxins; Family history and risk assessment; Fibroadenomas; Juvenile polyposis syndrome; Pediatric oncology and hematology; Self-image and body image; Sexuality and cancer; Stress management. 1259
Zollinger-Ellison syndrome
u Zollinger-Ellison syndrome Category: Diseases, symptoms, and conditions Also known as: Z-E syndrome, gastrinoma, ZES Related conditions: Gastroesophageal reflux disease (GERD), peptic ulcers, retained gastric antrum syndrome, antral G-cell syndrome Definition: Zollinger-Ellison syndrome is a rare condition in which tumors in the pancreas or small intestine produce abnormally high levels of the hormone gastrin. Gastrin overproduction induces excessive secretion of stomach acid, which erodes the inner linings of the stomach and upper small intestine. Risk factors: Some 25 percent of Zollinger-Ellison syndrome cases occur in people with multiple endocrine neoplasia type 1 (MEN 1), an autosomal dominant genetic condition characterized by pituitary and pancreatic endocrine tumors and overactivity of the parathyroid glands. Etiology and the disease process: The inner linings of the stomach and small intestine (mucous membranes) are composed of several different cell types that work together to digest food. One of these cell types, G cells, resides in the mucous membranes that line the stomach and upper small intestine (duodenum) and produces a protein hormone called gastrin that is released into the bloodstream. Gastrin directly stimulates another group of cells in the stomach mucosa called parietal cells to secrete hydrochloric acid. The production of acid by the parietal cells is the main reason for the highly acidic environment in the stomach. Gastrin also signals to a third group of cells in the lining of the stomach called enterochromaffin-like (ECL) cells, which produce histamine in response to gastrin. Histamine is a powerful parietal cell-signaling molecule that causes parietal cells to make even more hydrochloric acid, which helps purge the stomach of most microorganisms, denatures proteins in foodstuffs, and activates the stomach-specific enzyme pepsin, which is secreted by the chief cells, a fourth type of cell found in the stomach mucosa. Pepsin secretion by the chief cells is also stimulated by gastrin. Gastrin secretion is stimulated by the stretching of the stomach, activity of the vagus nerve, presence of digested proteins in the stomach, or high blood calcium levels. The presence of large amounts of stomach acid and hormones made by lower portions of the gastrointestinal tract inhibit gastrin release into the bloodstream. Patients with Zollinger-Ellison syndrome have one or more typically small tumors (gastrinomas) in the pancreas or duodenum that produce excessive quantities of gastrin. Because these tumors do not reside in the stomach, the 1260
Salem Health: Cancer usual mechanisms that down-regulate gastrin production are not available. Continuous production of high blood gastrin levels constantly stimulates the parietal cells to overproduce hydrochloric acid, which erodes the stomach and duodenal mucous membranes. Patients with multiple endocrine neoplasia type 1 (MEN 1) are at increased risk for Zollinger-Ellison syndrome. MEN 1 is also known as Wermer syndrome and is inherited as an autosomal dominant genetic condition that maps to chromosome 11. MEN 1 individuals also show a predisposition to develop pituitary, parathyroid, and pancreatic tumors. Incidence: The average international incidence is approximately 1 per 1 million patients. Symptoms: The most common symptoms are abdominal pain and diarrhea, usually experienced in combination, but not always. Other symptoms include heartburn, nausea, vomiting, gastrointestinal bleeding, and weight loss. People with MEN 1 also have a history of frequent kidney stones, excessive blood calcium (hypercalcemia), and pituitary disorders. Screening and diagnosis: A blood test called a fasting gastrin test examines blood gastrin levels and is usually performed in combination with a gastric acid secretory test, which examines basic acid output (BAO). High blood gastrin levels and basic acid output are usually diagnostic for Zollinger-Ellison syndrome. Provocative tests determine if gastrin production is subject to the normal control mechanisms. Typically blood gastrin levels are measured before and after the patient, who has fasted all night, is injected with secretin, an inhibitor of gastrin production. Large jumps in blood gastrin concentrations (above 200 nanograms per liter) are diagnostic for Zollinger-Ellison syndrome. Imaging studies serve to detect the actual tumor and determine its location, size, and whether it has undergone metastasis. The imaging method of choice is somatostatin receptor scintigraphy (SRS). Somatostatin binds to any gastrin-producing cell, and during SRS, a radioactively labeled somatostatin-like molecule is injected into the patient. This molecule homes to the tumor and labels it, allowing it to be viewed. Computed tomography (CT) and magnetic resonance imaging (MRI) scans are also used, as is endoscopic ultrasound, which is more effective for detecting pancreatic gastrinomas. Esophagogastroduodenoscopy (EGD) is effective for visualizing the ulcerations present in the stomach and duodenum. Treatment and therapy: Proton pump inhibitors are the drugs of choice to manage the excessive acid production.
Salem Health: Cancer
Zollinger-Ellison syndrome
These include omeprazole (Prilosec), pantoprazole (Protonix), esomeprazole (Nexium), and rabeprazole (Aciphex). Histamine-2 receptor antagonists (H2 blockers) such as cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac), or nizatidine (Azid) prevent reception of the histamine signal by the parietal cells and are much less effective for treating excessive acid production. In almost all cases, surgical removal of the tumors is highly recommended to prevent metastasis.
Parker, James N., and Philip M. Parker, eds. The Official Patient’s Sourcebook on Zollinger-Ellison Syndrome: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Icon Health, 2002. Piekin, Steven R. Gastrointestinal Health: The Proven Nutritional Program to Prevent, Cure, or Alleviate Irritable Bowel Syndrome (IBS), Ulcers, Gas, Constipation, Heartburn, and Many Other Digestive Disorders. 3d ed. Chino Hills, Calif.: Collins, 2005.
Prognosis, prevention, and outcomes: In patients without metastasis of the gastrinomas, prognosis is excellent. MEN 1 patients have a high frequency of recurrence. In those patients whose tumors have metastasized, the prognosis is rather poor. Michael A. Buratovich, Ph.D.
u
u
For Further Information Fox, Stuart I. Human Physiology. 10th ed. New York: McGraw-Hill, 2007. Miskovitz, Paul A., and Marian Betancourt. The Doctor’s Guide to Gastrointestinal Health. Hoboken, N.J.: Wiley, 2005.
Other Resources
MayoClinic.com Zollinger-Ellison Syndrome http://www.mayoclinic.com/health/ zollinger-ellison-syndrome/DS00461 National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov/index.htm See also Gastrinomas; Histamine 2 antagonists; Islet cell tumors; Neuroendocrine tumors; Pancreatic cancers; Small intestine cancer; Stomach cancers.
1261
u
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
abarelix
none
prostate cancer
absorbable gelatin sponge
Gelfoam
homeostasis
5-AC
Mylosar; Vidaza
myelodysplastic syndrome
acetylsalicylic acid
Aspergum; Ecotrin; Empirin; Entericin; Extren; Measurin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
acitretin
Etretin; Soriatane
cutaneous T-cell lymphoma
acridinyl anisidide
Amsa P-D
leukemia
ACT-D
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
actinomycin A IV
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
actinomycin C1
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
actinomycin D
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
actinomycin I1
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
actinomycin IV
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
actinomycin X 1
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
1265
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
actinomycin-[thr-val-pro-sarmeval]
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
AD
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
adefovir dipivoxil
Hepsera
chronic hepatitis B
adipogenesis inhibitory factor
Neumega
chemotherapy-related thrombocytopenia
ADM
Adriamycin
leukemias; Wilms’ tumor; neuroblastoma; soft-tissue and bone sarcomas; small-cell carcinoma of the lung; lymphomas; multiple myeloma; mesotheliomas; germ-cell tumors of the ovary or testis
ADR
Adriamycin
leukemias; Wilms’ tumor; neuroblastoma; soft-tissue and bone sarcomas; small-cell carcinoma of the lung; lymphomas; multiple myeloma; mesotheliomas; germ-cell tumors of the ovary or testis
adria
Adriamycin
leukemias; Wilms’ tumor; neuroblastoma; soft-tissue and bone sarcomas; small-cell carcinoma of the lung; lymphomas; multiple myeloma; mesotheliomas; germ-cell tumors of the ovary or testis
alanine nitrogen mustard
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
albumin-stabilized nanoparticle paclitaxel
Taxol; Abraxane; Onxol
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; non-small-cell lung cancer; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
aldesleukin
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
alemtuzumab
Campath
B-cell chronic lymphocytic leukemia
alitretinoin
Panretin
topical treatment of cutaneous lesions in patients with AIDSrelated Kaposi sarcoma
all-trans retinoic acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
all-trans retinol
Aquasol A; Del-Vi-A; PediVit-A
diminishing malignant cell growth; enhancing the immune system
1266
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
all-trans vitamin A acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
allopurinol
Zyloprim
treats high levels of uric acid in the body caused by certain cancer medications, especially for patients with leukemia, lymphoma, and solid-tumor malignancies
alpha-phthalimidoglutarimide
Synovir; Thalomid
Kaposi sarcoma; multiple myeloma; primary brain tumors
alprostadil
Caverject; MUSE
erectile dysfunction; patent ductus arteriosus
altretamine
Hexalen; Hexamethylmelamine
ovarian cancer
alum adjuvant
none
allergy; diagnosis
aluminum hydroxide
none
allergy; diagnosis
aluminum sulfate
none
allergy; diagnosis
amifostine trihydrate
Ethyol
cisplatin-induced nephrotoxicity; radiation-induced mucositis and xerostomia
aminobenzoate potassium
none
diseases involving fibrosis and nonsuppurative inflammation
aminoglutethimide
Cytadren
breast cancer; prostate cancer; decreases the production of sex hormones (estrogen in women or testosterone in men) and suppresses the growth of tumors that need sex hormones to grow
aminolevulinic acid
Levulan
photodynamic therapy to treat a skin condition called actinic keratosis
aminopropylaminoethylthiophosphoric acid
Ethyol
cisplatin-induced nephrotoxicity; radiation-induced mucositis and xerostomia
amoxicillin-clavulanate potassium
Augmentin
various bacterial infections
amsacrine
Amsa P-D
leukemia
anagrelide
Agrylin
thrombocythemia secondary to myeloproliferative disorders; disrupts the postmitotic phase of megakaryocyte development
anastrozole
Arimidex
hormone receptor-positive early breast cancer
androfluorene
Android-F; Halodrin; Halotestin; Ora-Testryl; Ultandren; Androxy
certain types of breast cancer
androsterolo
Android-F; Halodrin; Halotestin; Ora-Testryl; Ultandren; Androxy
certain types of breast cancer
anidulafungin
Eraxis
candidemia
anti-B1; anti-B1 monoclonal antibody
Bexxar
CD20 positive follicular non-Hodgkin lymphoma refractory to rituximab
anti-CD20 antibody
Bexxar
CD20 positive follicular non-Hodgkin lymphoma refractory to rituximab
1267
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
anti-CD20 monoclonal antibody
Rituxan
diffuse large B-cell, CD20-positive, non-Hodgkin lymphoma
anti-CD52 monoclonal antibody
Campath
B-cell chronic lymphocytic leukemia
anti-c-erB-2; anti-c-erbB2 monoclonal antibody
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
anti-EGFR monoclonal antibody
Erbitux
advanced colorectal cancer; head and neck cancer
antiepidermal growth factor receptor monoclonal antibody
Erbitux
advanced colorectal cancer; head and neck cancer
anti-ERB-2; anti-erbB2 monoclonal antibody
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
anti-HER2/c-erbB2 monoclonal antibody
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
anti-infective vitamin
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
anti-p185-HER2
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
antithymocyte globulin
ATGAM; Thymoglobulin
heart and renal transplantation rejection; prophylaxis
anti-VEGF; anti-VEGF monoclonal antibody
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
anti-VEGF humanized monoclonal antibody
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
anti-VEGF RhuMAb
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
antixerophthalmic vitamin
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
aprepitant
Emend
antiemetic (prevents vomiting)
arabinofuranosylcytosine
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; myelodysplasic syndrome; non-Hodgkin lymphoma; ovarian cancer; retinoblastoma
arabinosylcytosine
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; myelodysplasic syndrome; non-Hodgkin lymphoma; ovarian cancer; retinoblastoma
aracytidine
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; myelodysplasic syndrome; non-Hodgkin lymphoma; ovarian cancer; retinoblastoma
1268
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
arsenic (III) oxide
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
arsenic sesquioxide
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
arsenic trioxide
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
arsenous acid
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
arsenous acid anhydride
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
arsenous oxide
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
ASNase
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
ASP-1
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
asparaginase; asparaginase II
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
asparaginase erwinia
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
aspirin
Aspergum; Ecotrin; Empirin; Entericin; Extren; Measurin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
aureolic acid
Mithracin
testicular cancer
axerophthol
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
axerophtholum
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
azacitidine
Mylosar; Vidaza
myelodysplastic syndrome
azacytidine
Mylosar; Vidaza
myelodysplastic syndrome
5-azacytidine
Mylosar; Vidaza
myelodysplastic syndrome
5-aza-dCyd
Dacogen
myelodysplastic syndrome
azaepothilone B
Ixempra
metastatic or locally advanced breast cancer
azathioprine sodium
Imuran; Imurel
converted in vivo to its active metabolite 6-mercaptopurine (6-MP), which substitutes for the normal nucleoside and mistakenly gets incorporated into DNA sequences. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes
azathiopurine
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
BAY 43-9006
Nexavar
advanced renal cell carcinoma; metastatic colorectal cancer
1269
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
BAY 43-9006 Tosylate Salt
Nexavar
advanced renal cell carcinoma; metastatic colorectal cancer
BCG
Immucyst
bladder cancer; malignant melanoma
bendamustine hydrochloride
Treanda
chronic lymphocytic leukemia
beta-carotene
Lumitene; Solatene
chemoprevention for cardiovascular disease and cancer
beta-cytosine arabinoside
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; myelodysplasic syndrome; non-Hodgkin lymphoma; ovarian cancer; retinoblastoma
beta-retinoic acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
bevacizumab
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
bexarotene
Targretin
oral or topical treatment of manifestations of cutaneous T-cell lymphoma
bicalutamide
Casodex
metastatic prostate cancer
biocarbazine
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
biosterol
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
bis(chloroethyl) nitrosourea
BiCNU; Becenum; Carmubris
cancerous brain tumors; colon cancer; lung cancer; Hodgkin disease; non-Hodgkin lymphomas; lymphomas; melanoma; multiple myeloma; mycosis fungoides
bis-chloronitrosourea
BiCNU; Becenum; Carmubris
cancerous brain tumors; colon cancer; lung cancer; Hodgkin disease; non-Hodgkin lymphomas; lymphomas; melanoma; multiple myeloma; mycosis fungoides
bleomycin
Blenoxane; bleomycin sulfate
skin cancer (squamous cell carcinoma) of the head, neck, penis, cervix, and vulva; lymphomas; testicular cancer; malignant pleural effusion
BMS-354825
Sprycel
chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia
bortezomib
Velcade
multiple myeloma; advanced thyroid cancer
BSF
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
bupropion hydrochloride
Wellbutrin; Zyban
depression; smoking cessation
buserelin
Suprecur
breast cancer; contraception, female; endometriosis; infertility; in vitro fertilization; polycystic ovary syndrome; prostate cancer; uterine leiomyoma
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Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
buspirone hydrochloride
Buspar
alcohol abuse; anxiety; depression; migraine prophylaxis; smoking cessation; panic disorder
bussulfam
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
busulfan; bunsulfanum
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
busulphan
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
C2B8 monoclonal antibody
Rituxan
diffuse large B-cell, CD20-positive, non-Hodgkin lymphoma
C225 monoclonal antibody
Erbitux
advanced colorectal cancer; head and neck cancer
cabergoline
Dostinex
pituitary tumors
CACP
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
Cain’s acridine
Amsa P-D
leukemia
calcitriol
Rocaltrol
hyperparathyroidism; hypocalcemia
calcium carbonate
none
calcium deficiency, prophylaxis; hyperacidity; hyperphosphatemia; osteoporosis; rickets
calcium citrate
Acicontral; Citracal
calcium supplement; hypocalcemia; osteoporosis; rickets; tetany
calcium folinate
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
calcium (6S)-folinate
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
calcium gluconate
Calglucon
hyperkalemia; hypocalcemic tetany; magnesium intoxication
calicheamicin-conjugated humanized anti-CD33 monoclonal antibody
Mylotarg
acute myeloid leukemia
campath-1H
Campath
B-cell chronic lymphocytic leukemia
camptothecin-11
Camptosar
stage IVB cervical cancer; colorectal cancer; esophageal cancer; gastric cancer; non-small-cell lung cancer; small-cell lung cancer
1271
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
cannabinol
Marinol
antinausea
capecitabine
Xeloda
breast cancer; colorectal cancer; Stage III colon cancer
captopril
Capoten
hypertension; heart failure; left ventricular dysfunction; diabetic nephropathy
carbamazepine
Epitol; Tegretol
epilepsy
carbon-11 acetate
none
diagnostic imaging
carboplatin; carboplatin hexal
Paraplatin; Paraplat
ovarian cancer
carboplatino
Paraplatin; Paraplat
ovarian cancer
carmustin; carmustine
BiCNU; Becenum; Carmubris
cancerous brain tumors; colon cancer; lung cancer; Hodgkin disease; non-Hodgkin lymphomas; lymphomas; melanoma; multiple myeloma; mycosis fungoides
CBL
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
CDC-501
Revlimid
transfusion-dependent anemia due to low- or intermediate-1 risk myelodysplastic syndrome; multiple myeloma
cefepime hydrochloride
Maxipime
upper respiratory tract and urinary tract infections; febrile neutropenic conditions
celecoxib
Celebrex
familial adenomatous polyposis (inherited colorectal cancer syndrome)
cell cycle inhibitor 779
Torisel
renal cell carcinoma; advanced renal cell carcinoma
cetuximab
Erbitux
advanced colorectal cancer; head and neck cancer
cevimeline hydrochloride
Evoxac
Sjögren syndrome
CFR
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
chimeric anti-EGFR monoclonal antibody
Erbitux
advanced colorectal cancer; head and neck cancer
chimeric monoclonal antibody C225
Erbitux
advanced colorectal cancer; head and neck cancer
chloditan; chlodithane
Lysodren
adrenal cortical carcinoma
chlorambucil; chlorambucilum
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
chloramin
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
chloraminophen
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
1272
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
chlorbutin; chlorbutine
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
chlorbutinum
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
chlorethamine HCl; chlorethamine hydrochloride
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
chlorethazine
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
chlorethazine hydrochloride
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
chlormethine
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
chlormethine hydrochloride
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
chloroambucil
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
chlorobutin; chlorobutine
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
2-chlorodeoxyadenosine
Leustatin
acute myeloid leukemia; chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia; Langerhans cell histiocytosis; non-Hodgkin lymphoma; Waldenstrom macroglobulinemia
2-chloro-2-deoxyadenosine
Leustatin
acute myeloid leukemia; chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia; Langerhans cell histiocytosis; non-Hodgkin lymphoma; Waldenström macroglobulinemia
chloromethine HCl
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
ciclofosfamida; ciclofosfamide
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cimetidine
Tagamet
gastrointestinal conditions; allergic reaction prevention; immune modulation
cinacalcet
Sensipar
treating an overactive parathyroid in dialysis patients with chronic kidney disease; also used to treat high blood calcium levels in patients with parathyroid cancer
ciprofloxacin
Cipro
inhaled anthrax, postexposure; susceptible infectious diseases
1273
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
cis-DDP
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cis-diamminedichloro platinum (II)
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cis-diamminedichloroplatinum
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cis-dichloroammine platinum (II)
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cis-platinous diamine dichloride
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cis-platinum; cis-platinum II
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cis-platinum II diamine dichloride
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cismaplat
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cisplatin; cisplatina
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
9-cis-retinoic acid
Panretin
topical treatment of cutaneous lesions in patients with AIDSrelated Kaposi sarcoma
citrovorum factor
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
cladribina; cladribine
Leustatin
acute myeloid leukemia; chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia; Langerhans cell histiocytosis; non-Hodgkin lymphoma; Waldenström macroglobulinemia
claphene
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
clarithromycin
Abbott-56268; Biaxin
H. pylori infection; various bacterial infections
clobetasol propionate
Olux-E
psoriasis, eczema
1274
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
clodronate disodium
Clasteon; Difosfonal; Loron; Mebonat; Ossiten
adjuvant usage in bone metastasis of breast cancer
clofarabine
Clolar
accelerated approval (clinical benefit not established) for the treatment of pediatric patients one to twenty-one years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens
clopidogrel bisulfate
Plavix
thromboembolic disorders
cloridrato de daunorubicina
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
co-codamol
Solpadol; Tylex; Kapake
painkiller
coenzyme Q10
Ubidecarenone; Ubiquinone 10
chronic heart failure; mitochondrial cytopathies
colaspase
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
compound 112531
Eldisine
acute leukemia; lung cancer; carcinoma of the breast; squamous cell carcinoma of the esophagus, head, and neck; Hodgkin disease and non-Hodgkin lymphomas
conjugated estrogens
Femest; Premarin
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative
cordycepin
Kordicepin
TdT-positive acute lymphocytic leukemia
co-vidarabine
Nipent
chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia
CP monohydrate
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
CPDD
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
CPM
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cyclophospham
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cyclophosphamid monohydrate
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cyclophosphamide
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cyclophosphamidum
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
1275
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
cyclophosphan; cyclophosphanum
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cyclosporine
Neoral; Sandimmun; SangCya
allogenic transplants; prophylaxis of organ rejection in bone marrow; kidney; liver and heart transplants; psoriasis; rheumatoid arthritis; various diseases that involve autoimmune response
cyproheptadine hydrochloride
Periactin
hypersensitivity reactions
cyproterone acetate
Cyprostat
prostate cancer
cysplatyna
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
cytarabine
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; lymphomatous meningitis; myelodysplasic syndrome; nonHodgkin lymphoma; ovarian cancer; retinoblastoma
cytarabine hydrochloride
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; lymphomatous meningitis; myelodysplasic syndrome; nonHodgkin lymphoma; ovarian cancer; retinoblastoma
cytarabinum
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; lymphomatous meningitis; myelodysplasic syndrome; nonHodgkin lymphoma; ovarian cancer; retinoblastoma
cytophosphane
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
cytosine arabinoside
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; lymphomatous meningitis; myelodysplasic syndrome; nonHodgkin lymphoma; ovarian cancer; retinoblastoma
cytosine arabinosine hydrochloride
Cytosar-U; Tarabine PFS
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; lymphomatous meningitis; myelodysplasic syndrome; nonHodgkin lymphoma; ovarian cancer; retinoblastoma
6-D-tryptophan-LH-RH
Decapeptyl
prostate carcinoma, palliative treatment
6-D-tryptophanluteinizing hormone-releasing factor
Decapeptyl
prostate carcinoma, palliative treatment
DAB389-IL2
Ontak
cutaneous T-cell lymphoma
DAB389 interleukin-2
Ontak
cutaneous T-cell lymphoma
1276
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
DAB389 interleukin-2 immunotoxin
Ontak
cutaneous T-cell lymphoma
dacarbazina
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
dacarbazina almirall
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
Dacarbazine; dacarbazine-DTIC
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
daclizumab
Zenapax
kidney transplant rejection, prevention
dactinomycin; dactinomycine
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
dakarbazin
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
dalteparin
Fragmin
deep vein thrombosis, prophylaxis; ischemic complications in unstable angina and non-Q wave myocardial infarction, prophylaxis
dantrolene
Dantrium
treating episodes of severe high body temperature; also used to prevent or reduce the risk of severe high body temperature in certain patients before or after surgery or anesthesia
darbepoetin alfa
Aranesp
chemotherapy-induced anemia; chronic renal failure/insufficiency
dasatinib
Sprycel
chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia
daunomycin
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
daunomycin-HCL
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
daunorubicin
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
daunorubicin hydrochloride
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
daunorubicin liposomal
DaunoXome
acute nonlymphocytic leukemia; acute lymphocytic leukemia; advanced HIV-associated Kaposi sarcoma
dauno-rubidomycine
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
DDP
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
deacetyl vinblastine carboxamide
Eldisine
acute leukemia; lung cancer; carcinoma of the breast; squamous cell carcinoma of the esophagus, head, and neck; Hodgkin disease and non-Hodgkin lymphomas
decitabine
Dacogen
myelodysplastic syndrome
defibrotide
none
thrombotic thrombocytopenic purpura
delta 9-tetrahydrocannabinol
Marinol
antinausea
1277
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
deltacortisone
Delta-Dome; Deltasone; Liquid Pred; Lisacort; Meticorten; Orasone; Prednicen-M; Sk-Prednisone; Sterapred
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
delta(1)-cortisone
Delta-Dome; Deltasone; Liquid Pred; Lisacort; Meticorten; Orasone; Prednicen-M; Sk-Prednisone; Sterapred
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
deltadehydrocortisone
Delta-Dome; Deltasone; Liquid Pred; Lisacort; Meticorten; Orasone; Prednicen-M; Sk-Prednisone; Sterapred
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
4-demethoxydaunomycin
Idamycin
acute myeloid leukemia (AML); acute nonlymphocytic leukemia
4-demethoxydaunorubicin
Idamycin
acute myeloid leukemia (AML); acute nonlymphocytic leukemia
demethyl epipodophyllotoxin ethylidine glucoside
VePesid; Lastet; Etopophos; Toposar
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
denileukin diftitox
Ontak
cutaneous T-cell lymphoma
deoxyazacytidine
Dacogen
myelodysplastic syndrome
deoxycoformycin
Nipent
chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia
2′-deoxycoformycin
Nipent
chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia
desacetylvinblastine amide
Eldisine
acute leukemia; lung cancer; carcinoma of the breast; squamous cell carcinoma of the esophagus, head, and neck; Hodgkin disease and non-Hodgkin lymphomas
desamethasone
Aeroseb-Dex; Alba-Dex; Decaderm; Decadrol; Decadron; Decasone R.p.; Decaspray; Deenar; Deronil; Dex-4; Dexace; Dexameth; Dezone; Gammacorten; Hexadrol; Maxidex; Sk-Dexamethasone
antiemetic (prevents vomiting)
deslorelin
Ovuplant
central precocious puberty
detryptoreline
Decapeptyl
prostate carcinoma, palliative treatment
1278
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
dexamethasone; dexamethasonum
Aeroseb-Dex; Alba-Dex; Decaderm; Decadrol; Decadron; Decasone R.p.; Decaspray; Deenar; Deronil; Dex-4; Dexace; Dexameth; Dezone; Gammacorten; Hexadrol; Maxidex; Sk-Dexamethasone
antiemetic (prevents vomiting)
dexrazoxane hydrochloride
Totect; Zinecard
severe side effects caused by certain types of chemotherapy including extravasation; cardiac side effects by doxorubicin
dextroamphetamineamphetamine
Adderall
attention deficit/hyperactivity disorder (ADHD); narcolepsy
dezocitidine
Dacogen
myelodysplastic syndrome
diaminocyclohexane oxalatoplatinum
Eloxatin
metastatic colorectal cancer; ovarian cancer
diazoxide
Proglycem
malignant hypertension
diethylstilbenediol
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
diethylstilbesterol
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
diethylstilbestrol dipropionate
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
1279
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
diethylstilbestrolum
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
diethylstilboestrol
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
difluorodeoxycytidine
Gemzar
bladder cancer; breast cancer; carcinoma of unknown primary origin; lung cancer; ovarian cancer; pancreatic cancer; renal cell carcinoma
dihematoporphyrin ether
Photofrin
photosensitizer; bladder, esophageal, gastric, lung, and rectal cancers
dihydroxyanthracenedione
Novantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
dihydroxyanthracenedione dihydrochloride
Novantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
dimesna
Mesna Disulfide; Tavocept
ifosfamide-induced hemorrhagic cystitis, prophylaxis
dimethyl triazeno imidazol carboxamide; dimethyl (triazeno) imidazolecarboxamide
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
disodium pamidronate
Aredia
myeloma, secondary breast cancer
DMDR
Idamycin
acute myeloid leukemia (AML); acute nonlymphocytic leukemia
docetaxel
Taxotere
breast cancer; esophageal cancer; gastric cancer; head/neck cancers; locally advanced or metastatic non-small-cell lung cancer; ovarian cancer; metastatic prostate cancer
dolasetron mesylate
Anzemet
nausea and vomiting prophylaxis, chemotherapy-induced and postoperative
donepezil hydrochloride
Aricept
Alzheimer’s disease and opioid-induced sedation
doxercalciferol
Hectorol
secondary hyperparathyroidism in end-stage renal disease in patients on hemodialysis
1280
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
doxorubicin hydrochloride
Adriamycin
leukemias; Wilms’ tumor; neuroblastoma; soft-tissue and bone sarcomas; small cell carcinoma of the lung; lymphomas; multiple myeloma; mesotheliomas; germ-cell tumors of the ovary or testis
doxorubicin hydrochloride liposome
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
dronabinol
Marinol
antinausea
D-TRP-6-LHRH
Decapeptyl
prostate carcinoma, palliative treatment
DXM
Aeroseb-Dex; Alba-Dex; Decaderm; Decadrol; Decadron; Decasone R.p.; Decaspray; Deenar; Deronil; Dex-4; Dexace; Dexameth; Dezone; Gammacorten; Hexadrol; Maxidex; Sk-Dexamethasone
antiemetic (prevents vomiting)
eculizumab
Alexion; Soliris
paroxysmal nocturnal hemoglobinuria
elcoril
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
Elliotts B solution
Elliotts B Solution
diluent for the intrathecal administration of methotrexate sodium and cytarabine for the prevention or treatment of meningeal leukemia or lymphocytic lymphoma
encapsulated cytarabine
DepoCyt; DepoFoam
lymphomatous meningitis
epi-ADR
Ellence
breast cancer; adjuvant in breast cancer therapy
4′-epiadriamycin
Ellence
breast cancer; adjuvant in breast cancer therapy
epidoxorubicin
Ellence
breast cancer; adjuvant in breast cancer therapy
4′-epidoxorubicin
Ellence
breast cancer; adjuvant in breast cancer therapy
4′-epi-doxorubicin HCl
Ellence
breast cancer; adjuvant in breast cancer therapy
epipodophyllotoxin
VePesid; Lastet; Etopophos; Toposar
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
epirubicin
Ellence
breast cancer; adjuvant in breast cancer therapy
epoetin alfa
Epogen; Procrit
anemias associated with chronic renal failure, zidovudine (AZT) therapy, and cancer chemotherapy of nonmyeloid malignancies
epoetin beta
NeoRecormon
anemia associated with end-stage renal disease
epothilone-B BMS 247550
Ixempra
metastatic or locally advanced breast cancer
1281
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
epothilone B lactam
Ixempra
metastatic or locally advanced breast cancer
epratuzumab
LymphoCide; hLL2
systemic lupus erythematosus
erlotinib
Tarceva
malignant glioma; locally advanced or metastic non-small-cell lung carcinoma; locally advanced, unresectable or metastatic pancreatic carcinoma
erlotinib hydrochloride
Tarceva
malignant glioma; locally advanced or metastic non-small-cell lung carcinoma; locally advanced, unresectable or metastatic pancreatic carcinoma
erwinia asparaginase
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
erythropoietin
Epogen; Procrit
anemias associated with chronic renal failure, zidovudine (AZT) therapy, and cancer chemotherapy of nonmyeloid malignancies
esterified estrogens
Menest; Estratab
breast cancer
estradiol
Clinagen LA 40; Dep Gynogen; Estrace; Estradiol Patch; Estragyn LA 5; Estro-Cyp; Estrogen Patches; Fempatch; Gynodiol, Gynogen LA 20; Menaval-20
breast cancer, palliative
estramustine phosphate
Emcyt
prostate neoplasm
estramustine phosphate sodium
Emcyt
prostate neoplasm
etanercept
Enbrel
juvenile arthritis; psoriatic arthritis; rheumatoid arthritis
ethinyl estradiol
Estinyl; Ethinoral; Eticylol; Feminone; Inestra; Lynoral; Orestralyn
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
ethiodized oil
Ethiodol; Lipiodol
diagnostic imaging, hysterosalpingography and lymphography
ethiofos
Ethyol
cisplatin-induced nephrotoxicity; radiation-induced mucositis and xerostomia
etidronate
Didronel
treating adults with Paget disease; preventing and treating abnormal bone growth following hip replacement surgery or spinal cord injury
etoposide
VePesid; Lastet; Etopophos; Toposar
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
1282
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
etoposide phosphate
Etopophos
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
exemestane
Aromasin
estrogen receptor-positive early breast cancer
exisulind
Aptosyn; FGN-1; Sulindac sulfone
colonic adenomatous polyps in the inherited disease adenomatous polyposis coli, control and suppression
FdUrD
FUDF
gastrointestinal adenocarcinoma metastatic to the liver
fentanyl citrate
Actiq; Oralet; Sublimaze; Fentora
breakthrough pain in cancer patients
fibrin sealant
Beriplast P; TISSEEL
cardiovascular surgery; colostomy closure; congenital heart defects; coronary artery bypass grafting; mediastinal bleeding; microvascular bleeding; splenic trauma
filgrastim
Neupogen
bone marrow transplantation; cancer patients receiving myelosuppressive chemotherapy; neutropenia
filgrastim SD-01
Neulasta
chemotherapy-induced neutropenia
floxuridin
FUDF
gastrointestinal adenocarcinoma metastatic to the liver
floxuridine
FUDF
gastrointestinal adenocarcinoma metastatic to the liver
flucinom
Eulexin
prostate carcinoma; hirsutism
fluconazole
Diflucan
antifungal, prophylaxis in allogeneic bone marrow transplantation; candidiasis; cryptococcal meningitis
fludarabine phosphate
Fludara; Fludara Oral
chronic lymphocytic leukemia (CLL)
fludeoxyglucose F 18
FDG
radiopharmaceutical, cancer diagnostic
fludestrin
Teslac
advanced breast cancer in women, palliative
fludrocortisone
Florinef
breast cancer; adrenal cortical cancer
flugerel
Eulexin
prostate carcinoma; hirsutism
fluoro uracil
Adrucil; Efudex; Fluoroplex
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
fluorodeoxyuridine
FUDF
gastrointestinal adenocarcinoma metastatic to the liver
fluorouracil
Adrucil; Efudex; Fluoroplex
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
5-fluorouracil
Adrucil; Efudex; Fluoroplex
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
1283
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
fluorouridine deoxyribose
FUDF
gastrointestinal adenocarcinoma metastatic to the liver
fluouracil
Adrucil; Efudex; Fluoroplex
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
5-fluoracil
Adrucil; Efudex; Fluoroplex
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
fluoxymesterone
Android-F; Halodrin; Halotestin; Ora-Testryl; Ultandren; Androxy
certain types of breast cancer
flutamide
Eulexin
prostate carcinoma; hirsutism
folinate calcium
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
folinic acid
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
folinic acid calcium salt pentahydrate
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
FU
Adrucil; Efudex; Fluoroplex
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
fulvestrant
Faslodex
hormone receptor-positive metastatic breast cancer
gabapentin
Neurontin
management of epilepsy; pain; mania; depression and anxiety disorders
gadopentetate dimeglumine
Gd-DTPA; Magnevist; MultiHance
angiography for leptomeningeal metastases and multiple sclerosis and magnetic resonance imaging for spine and brain
gammaphos
Ethyol
cisplatin-induced nephrotoxicity; radiation-induced mucositis and xerostomia
ganciclovir
Cymevan; DHPG; Nordeoxyguanosine; Virgan
cytomegalovirus (CMV) infections in immunocompromised patients
gefitinib
Iressa
non-small-cell lung carcinoma
1284
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
gemcitabine
Gemzar
bladder cancer; breast cancer; carcinoma of unknown primary origin; lung cancer; ovarian cancer; pancreatic cancer; renal cell carcinoma
gemcitabine hydrochloride
Gemzar
bladder cancer; breast cancer; carcinoma of unknown primary origin; lung cancer; ovarian cancer; pancreatic cancer; renal cell carcinoma
gemtuzumab ozogamicin
Mylotarg
acute myeloid leukemia
glutamine
Glutacerebro; Glutaven; L-Glutamine; Memoril; Nutrestore; Q. Levoglutamide
short bowel syndrome
glyzophrol
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
goserelin
Zoladex
breast cancer, palliative; prostate cancer
granisetron hydrochloride
Kytril
antinausea
granulocyte colonystimulating factor
Neupogen
bone marrow transplantation; cancer patients receiving myelosuppressive chemotherapy; neutropenia
granulocyte macrophage colony-stimulating factor
Leukine; Prokine
melanoma; chemotherapy-induced neutropenia
haemophilus influenzae B vaccine
Hib TITER vaccine; HibTITER; PedvaxHIB
haemophilus influenzae B prophylaxis
halofuginone hydrobromide
Halofuginone IV (intravenous); RU 19110; Tempostatin
scleroderma and antiprotozoal; coccidiosis (vet)
hemel
Hexalen; Hexamethylmelamine
ovarian cancer
hexadecadrol
Aeroseb-Dex; Alba-Dex; Decaderm; Decadrol; Decadron; Decasone R.p.; Decaspray; Deenar; Deronil; Dex-4; Dexace; Dexameth; Dezone; Gammacorten; Hexadrol; Maxidex; Sk-Dexamethasone
antiemetic (prevents vomiting)
hexaloids
Hexalen; Hexamethylmelamine
ovarian cancer
histrelin acetate
Histrelin implant
palliative treatment of advanced prostate cancer
hP67.6-Calicheamicin
Mylotarg
acute myeloid leukemia
hycamptamine
Hycamtin
small cell lung carcinoma; cervical cancer
HYD
Hydrea, Droxia
chronic myelogenous leukemia; head and neck cancer; malignant melanoma; ovarian carcinoma; sickle cell anemia; adjuvant in retroviral therapy
1285
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
hydroxycarbamide
Hydrea, Droxia
chronic myelogenous leukemia; head and neck cancer; malignant melanoma; ovarian carcinoma; sickle cell anemia; adjuvant in retroviral therapy
hydroxychloroquine
none
malaria; rheumatoid arthritis
hydroxyurea
Hydrea, Droxia
chronic myelogenous leukemia; head and neck cancer; malignant melanoma; ovarian carcinoma; sickle cell anemia; adjuvant in retroviral therapy
hydurea
Hydrea, Droxia
chronic myelogenous leukemia; head and neck cancer; malignant melanoma; ovarian carcinoma; sickle cell anemia; adjuvant in retroviral therapy
hyperbaric oxygen
none
various diseases or injuries associated with hypoxia
131-I-anti-B1 antibody; 131-I-anti-B1 monoclonal antibody
Bexxar
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma
ibandronate sodium
Bondronate; Boniva
osteoporosis, treatment and prevention
ibenzmethyzin
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
ibenzmethyzin hydrochloride; ibenzmethyzine hydrochloride
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
ibritumomab (In2B8/Y2B8 radiolabeling kit)
Zevalin
non-Hodgkin lymphoma
ibritumomab tiuxetan
Zevalin
accelerated approval (clinical benefit not established) treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin lymphoma, including patients with rituximab refractory follicular non-Hodgkin lymphoma
ibuprofen
none
painkiller
idarubicin
idamycin
acute myeloid leukemia (AML); acute nonlymphocytic leukemia
IDEC-C2B8 monoclonal antibody
Rituxan
diffuse large B-cell, CD20-positive, non-Hodgkin lymphoma
IDEC-Y2B8 monoclonal antibody
Zevalin
non-Hodgkin lymphoma
ifomide
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
ifosfamide
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
IFX
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
IL-11
Neumega
chemotherapy-related thrombocytopenia
1286
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
imatinib mesylate
Gleevec
Philadelphia chromosome-positive chronic myeloid leukemia (CML); acute lymphocytic leukemia; gastrointestinal stromal tumor; hypereosinophillic syndrome; dermatofibrosarcoma protuberans; mutated-PDGFR myelodysplastic/myeloproliferative diseases
IMiD-1
Revlimid
transfusion-dependent anemia due to low- or intermediate-1 risk myelodysplastic syndrome; multiple myeloma
imidazole carboxamide
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
imidazole carboxamide dimethyltriazeno
DTIC-Dome
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
imiquimod
Aldara
condyloma; superficial basal cell carcinoma; actinic keratosis
immunoglobulin G1
Erbitux
advanced colorectal cancer; head and neck cancer
immunoglobulin G1, anti(human epidermal growth factor receptor) (humanmouse monoclonal C225 gamma1-chain), disulfide with human-mouse monoclonal C225 kappa-chain, dimer
Erbitux
advanced colorectal cancer; head and neck cancer
in 111 ibritumomab tiuxetan
IDEC In2B8
non-Hodgkin lymphoma
indomethacin
Indocin
dysmenorrhea; inflammatory disorders; pain
infliximab
Avakine; Remicade
ankylosis spondylitis; Crohn disease; plaque psoriasis; rheumatoid arthritis; sarcoidosis
interferon alfa-2a
Roferon-A
treating chronic hepatitis C and certain types of leukemia
interferon alfa-2b
Intron-A
certain types of leukemia, lymphoma, and hepatitis; certain AIDSrelated illnesses (Kaposi sarcoma); and genital warts (condylomata acuminata); also used in addition to surgery to treat a certain type of skin cancer (malignant melanoma)
interferon beta-1b
Betaseron
treating relapsing forms of multiple sclerosis (MS) to reduce the number of flare-ups and slow down the development of physical disability associated with MS
interleukin; interleukin II
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
interleukin-11
Neumega
chemotherapy-related thrombocytopenia
interleukin-2 fusion protein
Ontak
cutaneous T-cell lymphoma
interleukin-2 fusion toxin
Ontak
cutaneous T-cell lymphoma
iodine-131 anti-B1 antibody
Bexxar
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma
iodine-131 anti-CD20 monoclonal antibody
Bexxar
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma
iodine I 125
I-125
prostate cancer
1287
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
iodine I 131
I-131; Iodotope
hyperthyroidism
iodine I 131 metaiodobenzylguanidine
131 I-MIBG
diagnostic imaging
iodine I 131 MOAB anti-B1
Bexxar
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma
iodine I 131 monoclonal antibody anti-B1
Bexxar
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma
iodine I 131 tositumomab
Bexxar
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma
iphosphamid; iphosphamide
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
IPP
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
irinotecan
Camptosar
stage IVB cervical cancer; colorectal cancer; esophageal cancer; gastric cancer; non-small-cell lung cancer; small-cell lung cancer
irinotecan HCl; irinotecan hydrochloride
Camptosar
stage IVB cervical cancer; colorectal cancer; esophageal cancer; gastric cancer; non-small-cell lung cancer; small-cell lung cancer
iron sucrose injection
Venofer
treatment of iron deficiency for both dialysis and nondialysis patients with kidney disease, with or without concurrent erythropoietin therapy
isoendoxan
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
isophosphamide
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
isosulfan blue
Lymphazurin
diagnostic imaging
isotretinoin
Accutane
cutaneous T-cell lymphoma; juvenile metastatic neuroblastoma and leukemia
itraconazole
Sporanox
fungal infections
ixabepilone
Ixempra
metastatic or locally advanced breast cancer
juven
none
wasting syndrome, nutritional supplement
ketoconazole
Fungarest; Fungoral; Ketoderm; Ketoisdin; Nizoral; Orifungal M; Panfungol; R-41400; Xolegel
seborrheic dermatitis; prostate cancer
khloditan
Lysodren
adrenal cortical carcinoma
L-ASP
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
1288
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
L-asparaginase
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
L-asparaginase with polyethylene glycol
Oncaspar
acute lymphoblastic leukemia
L-asparagine amidohydrolase
Elspar; Cristanaspase; L-Asnase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
L-phenylalanine mustard
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
L-sarcolysin phenylalanine mustard
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
L-sarcolysine
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
ladakamycin
Mylosar; Vidaza
myelodysplastic syndrome
lamivudine
Epivir
chronic hepatitis B; HIV infection
lamotrigine
Lamictal
epilepsy
lanreotide
Somatuline
acromegaly
lapatinib
Tykerb
advanced or metastatic breast cancer
lapatinib ditosylate
Tykerb
advanced or metastatic breast cancer
lard-factor
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
LCR
Oncovin; Vincasar PFS
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
lenalidomide
Revlimid
transfusion-dependent anemia due to low- or intermediate-1 risk myelodysplastic syndrome; multiple myeloma
lenograstim
Granocyte; Neutrogin
chemotherapy-induced neutropenia
letrozole
Femara
hormone receptor-positive early breast cancer; adjuvant in breast cancer therapy; endometrial cancer
leucovorin
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
1289
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
leucovorin calcium
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
leukersan
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
leukoran
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
leuprolide acetate
Lupron; Lupron Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Viadur
prostate cancer; uterine fibroid tumors
leuprorelin
Lupron; Lupron Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Viadur
prostate cancer; uterine fibroid tumors
leuprorelin acetate
Lupron; Lupron Depot; Lupron Depot-3 Month; Lupron Depot-4 Month; Lupron Depot-Ped; Viadur
prostate cancer; uterine fibroid tumors
leupurin
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
leurocristine
Oncovin; Vincasar PFS
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
leurocristine sulfate
Oncovin; Vincasar PFS
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
levamisole
Ergamisol
colon cancer; nephrotic syndrome
levocarnitine
Carnitor
carnitine deficiency; end-stage renal disease
linfolizin
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
liposomal adriamycin
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
1290
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
liposomal cytarabine
DepoCyt; DepoFoam
lymphomatous meningitis
liposomal daunorubicin
DaunoXome
acute nonlymphocytic leukemia; acute lymphocytic leukemia; advanced HIV-associated Kaposi sarcoma
liposomal daunorubicin citrate
DaunoXome
acute nonlymphocytic leukemia; acute lymphocytic leukemia; advanced HIV-associated Kaposi sarcoma
liposomal doxorubicin
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
liposomal doxorubicin hydrochloride
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
liposome-encapsulated doxorubicin
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
lomustine; lomustinum
CeeNU; CCNU
brain tumors; Hodgkin disease
lovastatin
Mevacor; Mevinolin; Monacolin K
atherosclerosis; coronary heart disease, prevention; hypercholesterolemia
LV
Wellcovorin
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
lymphocyte mitogenic factor
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
lymphokine-activated killer cells
none
adoptive immunotherapy
lympholysin
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
mechlorethamine
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
mechlorethamine HCl; mechlorethamine hydrochloride
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
medroxyprogesterone
Curretab; Depo-Provera; Provera; Provera Dosepak
breast carcinoma; endometrial carcinoma; renal cell carcinoma
medroxyprogesterone acetate
Curretab; Depo-Provera; Provera; Provera Dosepak
breast carcinoma; endometrial carcinoma; renal cell carcinoma
megestrol acetate
Megace; Megace ES; Ovaban; Pallace
appetite enhancement, AIDS patients; breast cancer, palliative; endometrial carcinoma, palliative treatment
1291
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
melphalan
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
meractinomycin
Cosmegen; Lyovac Cosmegen
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
mercaptoethane sulfonate
Mesnex
helps protect the kidneys and bladder from the toxic effects of anticancer drugs such as ifosfamide and cyclophosphamide
mercaptopurine
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
6-mercaptopurine
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
6-mercaptopurine monohydrate
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
mercapurin
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
mern
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
mesna
Mesnex
helps protect the kidneys and bladder from the toxic effects of anticancer drugs such as ifosfamide and cyclophosphamide
mesnum
Mesnex
helps protect the kidneys and bladder from the toxic effects of anticancer drugs such as ifosfamide and cyclophosphamide
metacortandracin
Delta-Dome; Deltasone; Liquid Pred; Lisacort; Meticorten; Orasone; Prednicen-M; Sk-Prednisone; Sterapred
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
methanesulfonic acid tetramethylene ester
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
methionine C 11
none
PET radiopharmaceutical
methotrexate
Rheumatrex; Abitrexate; Folex; Folex PFS; Methotrexate LPF; Mexate; Mexate-AQ
bladder cancer; breast cancer; carcinomatous meningitis; chorioadenoma destruens; esophageal cancer; gestational choriocarcinoma; head/neck cancer; meningeal leukemia; lymphomas; Burkitt lymphoma; lung cancer; mycosis fungoides; osteosarcoma; Wegener granulomatosis
methoxsalen
Ammoidin; Oxsoralen; Oxsoralen-Ultra; Uvadex; Xanthotoxin
cutaneous T-cell lymphoma
1292
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
methoxy polyethylene glycolbeta
Mircera
anemia associated with chronic renal failure
methoxypsoralen
Ammoidin; Oxsoralen; Oxsoralen-Ultra; Uvadex; Xanthotoxin
cutaneous T-cell lymphoma
8-methoxypsoralen
Ammoidin; Oxsoralen; Oxsoralen-Ultra; Uvadex; Xanthotoxin
cutaneous T-cell lymphoma
3-methyl TTNEB
Targretin
oral or topical treatment of cutaneous manifestations of cutaneous T-cell lymphoma
methylchlorethamine
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
methylene blue
CI Basic Blue 9; Collubleu; Desmoidpillen; Methylthioninium chloride; Schultz No. 1038; Tetramethylthionine Chloride Trihydrate; Urolene Blue; Vitableu
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
methylfluorprednisolone
Aeroseb-Dex; Alba-Dex; Decaderm; Decadrol; Decadron; Decasone R.p.; Decaspray; Deenar; Deronil; Dex-4; Dexace; Dexameth; Dezone; Gammacorten; Hexadrol; Maxidex; Sk-Dexamethasone
antiemetic (prevents vomiting)
methylphenidate hydrochloride
Concerta; Ritalin
attention deficit/hyperactivity disorder (ADHD); narcolepsy
methylprednisolone
Prednilen; Wyacort
adrenocortical insufficiency; conditions requiring immunosuppression; inflammatory conditions; multiple sclerosis; nephrotic syndrome
methyltestosterone
Android, Testred, Virilon
breast cancer, palliative
metoclopramide
Reglan; Octamide
antinausea
MIH
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
MIH hydrochloride
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
miltefosine
Miltex
skin metastasis of breast cancer
MITC
Mutamycin; Mitozytrex
gastric carcinoma; pancreatic adenocarcinoma
mithramycin
Mithracin
testicular cancer
mitocin-C
Mutamycin; Mitozytrex
gastric carcinoma; pancreatic adenocarcinoma
mitogenic factor
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
1293
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
mitomycin C
Mutamycin; Mitozytrex
gastric carcinoma; pancreatic adenocarcinoma
mitotane
Lysodren
adrenal cortical carcinoma
mitoxan
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
mitoxantrone dihydrochloride
Novantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
mitoxantrone HCl; mitoxantrone hydrochloride
Novantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
mitoxantroni hydrochloridum
Novantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
mitozantrone
Novantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
modafinil
Provigil
narcolepsy
monobenzone
Benoquin
vitiligo
monoclonal antibody ABX-EGF
Vectibix
advanced stage colorectal cancer
monoclonal antibody C225
Erbitux
advanced colorectal cancer; head and neck cancer
monoclonal antibody campath-1H
Campath
B-cell chronic lymphocytic leukemia
monoclonal antibody CD52
Campath
B-cell chronic lymphocytic leukemia
monoclonal antibody c-erb-2
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
monoclonal antibody HER2
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
morphine
none
painkiller
moxifloxacin hydrochloride
Avelox; Viagmox
various bacterial infections
MTC
Mutamycin; Mitozytrex
gastric carcinoma; pancreatic adenocarcinoma
multitargeted antifolate
Alimta
malignant pleural mesothelioma; non-small-cell lung cancer
multivitamin
Geritol
vitamin supplement
muromonab-CD3
Orthoclone OKT3
allograft rejection
mustard
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
mustargen HCl; mustargen hydrochloride
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
mustine
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
1294
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
mycophenolate mofetil
Cellcept
heart transplantation; kidney transplantation; liver transplantation; lupus nephritis
myeleukon
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
myeloleukon
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
myelosan
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
mylecytan
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
mytotan
Lysodren
adrenal cortical carcinoma
N-lost
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
N-phthaloylglutamimide
Synovir; Thalomid
Kaposi sarcoma; multiple myeloma; primary brain tumors
N-phthalylglutamic acid imide
Synovir; Thalomid
Kaposi sarcoma; multiple myeloma; primary brain tumors
nab-paclitaxel
Taxol; Abraxane; Onxol
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; non-small-cell lung cancer; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
nandrolone decanoate
Deca-Durabolin
anemia of renal insufficiency; metastatic breast cancer
nanoparticle paclitaxel
Taxol; Abraxane; Onxol
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; non-small-cell lung cancer; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
navelbine ditartrate
Biovelbin; Eunades
non-small-cell lung cancer; metastatic breast cancer; uterine and cervical cancer; desmoid tumors; advanced Kaposi sarcoma
naxamide
Ifex; Cyfos; Ifosfamidum
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
NDC-zoledronate
Zometa; Reclast
hypercalcemia of malignancy; multiple myeloma and metastatic bone lesions from solid tumors; Paget disease
nelarabine
Arranon
T-cell acute lymphoblastic leukemia; T-cell lymphoblastic lymphoma
NH-2
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
1295
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
niacinamide
Nicamid; Nicosedine
pellagra, treatment and prophylaxis; various dermatologic conditions
nicotine
none
smoking cessation
niftolid
Eulexin
prostate carcinoma; hirsutism
nilotinib
Tasigna
chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia
nilutamide
Nilandron
prostate cancer
nimotuzumab
Theraloc
glioma
nitrogen mustard
Mustargen
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
nolatrexed dihydrochloride
Thymitaq
hepatocellular carcinoma
norgestrel
Neogest; Ovrette; Microlut
oral contraception
noscapine hydrochloride
none
cough
novaldex
Nolvadex; Soltamox
breast cancer, palliative; adjuvant in breast cancer therapy; endometrial cancer; gynecomastia; melanoma; ovarian cancer
novel erythropoiesis stimulating protein
Aranesp
chemotherapy-induced anemia; chronic renal failure/insufficiency
novo-levamisole
Ergamisol
colon cancer; nephrotic syndrome
octreotide acetate
Sandostatin; Longastatina; Samilstin
acromegaly; diarrhea
6-[O-(1,1-dimethylethyl)-Dserine]-10-deglycinamide luteinizing hormonereleasing factor (pig) 2-(aminocarbonyl)hydrazide
Zoladex
breast cancer, palliative; prostate cancer
ofloxacin
none
various bacterial infections
oleovitamin A
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
ondansetron
Zofran
nausea and vomiting prophylaxis, chemotherapy-induced and postoperative
o,p′-DDD
Lysodren
adrenal cortical carcinoma
ophthalamin
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
oprelvekin
Neumega
prevention of severe thrombocytopenia following myelosuppressive chemotherapy
oregovomab
OvaRex
epithelial ovarian cancer
ortho,para-DDD
Lysodren
adrenal cortical carcinoma
oxalatoplatin; oxalatoplatinum
Eloxatin
metastatic colorectal cancer; ovarian cancer
oxaliplatin
Eloxatin
metastatic colorectal cancer; ovarian cancer
1296
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
oxandrolone
Oxandrin
bone pain; Duchenne and Becker muscular dystrophy; HIVassociated muscle weakness; HIV-related wasting syndrome
paclitaxel
Taxol; Abraxane; Onxol
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; lung cancer; non-small cell; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
paclitaxel protein-bound
Taxol; Abraxane; Onxol
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; lung cancer; non-small cell; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
palifermin
Kepivance
decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoetic stem cell support
palladium 103
none
early stage prostate cancer; localized tumors of the head, neck, lung, pancreas, breast, and uterus
palonosetron hydrochloride
Aloxi
antinausea; antiemetic (prevents vomiting)
pamidronate disodium
Aredia
hypercalcemia of malignancy; osteolytic bone lesions of multiple myeloma; osteolytic bone metastases of breast cancer; Paget disease
panitumumab
Vectibix
advanced stage colorectal cancer
papaverine
Cerespan; Pavabid; Pavatym; Cerebid; Pavacap; Unicelles; Vasal
ischemia, cerebral and peripheral
paracetamol
Panadol; Disprol
painkiller
paricalcitol
Zemplar
secondary hyperparathyroidism, prevention and treatment
paroxetine hydrochloride
Paxil
depression
PCB hydrochloride
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
PCZ
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
PDD
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
PEG-asparaginase
Oncaspar
acute lymphoblastic leukemia
PEG-interferon alfa-2a
PEGASYS
chronic hepatitis C; renal cell carcinoma; advanced melanoma; chronic myelogenous leukemia
PEG-interferon alfa-2b
PEG-Intron
chronic hepatitis C; renal cell carcinoma
PEG-L-asparaginase
Oncaspar
acute lymphoblastic leukemia
PEG-L-asparaginase(K-H)
Oncaspar
acute lymphoblastic leukemia
pegademase
Adagen
enzyme replacement therapy for patients with severe combined immunodeficiency as a result of adenosine deaminase deficiency
pegaspargase
Oncaspar
acute lymphoblastic leukemia
1297
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
pegfilgrastim
Neulasta
chemotherapy-induced neutropenia
pegylated doxorubicin HCl liposome
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
pegylated interferon alfa
PEG-interferon alfa
hepatitis C
pegylated liposomal doxorubicin
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
pegylated liposomal doxorubicin hydrochloride
DOXIL; Dox-SL; Evacet; LipoDox; CAELYX; Doxilen
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
pemetrexed disodium
Alimta
malignant pleural mesothelioma; non-small-cell lung cancer
penicillamine
Cuprenil; Cuprimine; Depen; Perdolat; Sufortan; Atamir; Cupripen; Distamine; Kelatin; Mercaptyl; Metalcaptase; Pendramine; Trolovol
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
pentostatin
Nipent
chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia
Peyrone’s chloride
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
Peyrone’s salt
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
phenobarbital
none
epilepsy
phentolamine mesylate
Regitine; Vasomax
dermal necrosis; hypertensive-associated episodes with pheochromocytoma, prevention or control
phenylalanine mustard
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
phenylalanine nitrogen mustard
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
phenylbutyric acid nitrogen mustard
Ambochlorin; Amboclorin; Leukeran
chronic lymphocytic leukemia; malignant lymphomas
photofrin II
Photofrin
photosensitizer; bladder, esophageal, gastric, lung, and rectal cancers
PI-88
none
malignant melanoma
pidorubicin
Ellence
breast cancer; adjuvant in breast cancer therapy
pipobroman
Vercyte
leukemias
1298
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
platinoxan
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
platinum diamminodichloride
Platinol; Platinol-AQ
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
plenaxis
none
prostate cancer
plicamycin
Mithracin
testicular cancer
polifeprosan 20 with carmustine implant
Gliadel wafer
malignant glioma, adjuvant to surgery and radiation; recurrent glioblastoma multiforme, adjuvant to surgery
polyethylene glycol-Lasparaginase
Oncaspar
acute lymphoblastic leukemia
porfimer
Photofrin
photosensitizer; bladder, esophageal, gastric, lung, and rectal cancers
porfimer sodium
Photofrin
photosensitizer; bladder, esophageal, gastric, lung, and rectal cancers
posaconazole
Noxafil
fungal infection prevention for immunocompromised host
potaba
none
diseases involving fibrosis and nonsuppurative inflammation
potassium p-aminobenzoate
none
diseases involving fibrosis and nonsuppurative inflammation
potassium paraaminobenzoate
none
diseases involving fibrosis and nonsuppurative inflammation
PRD
Delta-Dome; Deltasone; Liquid Pred; Lisacort; Meticorten; Orasone; Prednicen-M; Sk-Prednisone; Sterapred
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
prednisolone
Cortalone; Delta-Cortef; Hydeltra; Hydeltrasol; Meti-derm; Prelone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
prednisone; prednisonum
Delta-Dome; Deltasone; Liquid Pred; Lisacort; Meticorten; Orasone; Prednicen-M; Sk-Prednisone; Sterapred
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
procarbazin
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
procarbazine hydrochloride
Matulane
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
prochlorperazine
Compazine
antinausea
purimethol
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
6-purinethiol
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
1299
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
raloxifene
Evista; Keoxifene
breast cancer; cardiovascular disease prophylaxis; osteoporosis
raltitrexed
Tomudex
advanced colorectal cancer
ranpirnase
Onconase
mesothelioma
rapamycin analog; rapamycin analog CCI-779
Torisel
renal cell carcinoma; advanced renal cell carcinoma
rasburicase
Elitek
chemotherapy-induced acute hyperuricemia, treatment and prophylaxis
recombinant adenovirus-p53
none
primary ovarian cancer
recombinant human interleukin-11
Neumega
chemotherapy-related thrombocytopenia
recombinant human papillomavirus 16 E6 peptide
none
cervical cancer vaccine (TA-HPV) component
recombinant humanized antiVEGF monoclonal antibody
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
recombinant humanized monoclonal antibody to vascular endothelial growth factor
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
recombinant interferon alfa
Alferon N; Intron A; Roferon-A
used as antiviral and antitumor agents
recombinant interferon alpha-2a
Alferon; Roferon-A; Laroferon; Roceron; Roceron-A
chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia; hairy cell leukemia; chronic hepatitis C; AIDS-related Kaposi sarcoma; bladder cancer; ovarian cancer; cervical cancer; non-Hodgkin lymphoma; renal cell carcinoma; melanoma
recombinant interferon beta
Betaseron; Rebif
multiple sclerosis
recombinant interferon gamma
Actimmune
chronic granulomatous disease; osteopetrosis
recombinant interleukin-2
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
recombinant interleukin-11
Neumega
chemotherapy-related thrombocytopenia
recombinant methionyl human granulocyte colony stimulating factor
Neupogen
bone marrow transplantation; cancer patients receiving myelosuppressive chemotherapy; neutropenia
recombinant urate oxidase
Elitek
chemotherapy-induced acute hyperuricemia, treatment and prophylaxis
retinoic acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
1300
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
retinoicacid-9-cis
Panretin
topical treatment of cutaneous lesions in patients with AIDSrelated Kaposi sarcoma
retinol
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
retinyl acetate
Retinol Acetate; vitamin A acetate
dietary supplement; vitamin A deficiency
r-HuEPO
Epogen; Procrit
anemias associated with chronic renal failure, zidovudine (AZT) therapy, and cancer chemotherapy of nonmyeloid malignancies
rhuMAb VEGF
Avastin
metastatic colorectal cancer, non-small-cell lung cancer
rifabutin
Mycobutin
prevention and treatment of Mycobacterium avium complex (MAC) and tuberculosis in patients with HIV infection
risedronate sodium
Actonel
osteoporosis, treatment and prevention; Paget disease
rituximab
Rituxan
diffuse large B-cell, CD20-positive, non-Hodgkin lymphoma
rofecoxib
Vioxx
pain; dysmenorrhea; osteoarthritis; rheumatoid arthritis
rosiglitazone maleate
Avandia
noninsulin-dependent diabetes mellitus and type II diabetes mellitus; type 2 diabetes
rubetican
Camptogen; Orathecin
AIDS, pediatric; HIV infection, pediatric
rubomycin C
Cerubidine; Rubidomycin
acute lymphoblastic leukemia
S-liposomal doxorubicin
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
samarium-153 EDTMP
Quadramet
pain due to bone cancer
samarium-153 ethylenediaminetetramethylenephosphonate
Quadramet
pain due to bone cancer
samarium-153 ethylenediaminetetramethylenephosphonic acid
Quadramet
pain due to bone cancer
samarium SM 153 lexidronam pentasodium
Quadramet
pain due to bone cancer
sarcoclorin
Alkeran
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
sargramostim
Leukine; Prokine
melanoma; chemotherapy-induced neutropenia
SD-01; SD-01 sustained duration G-CSF
Neulasta
chemotherapy-induced neutropenia
selenium
none
dandruff; psoriasis; seborrheic dermatitis; tinea capitis; tinea versicolor
sertraline hydrochloride
Zoloft
major depressive disorder; obsessive-compulsive disorder; panic disorder; posttraumatic stress disorder; premenstrual dysphoric disorder; social phobia
1301
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
sildenafil citrate
Viagra
erectile dysfunction
silymarin
none
nutritional supplement for liver damage induced by chemicals or toxins
sinestrol
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
siplizumab
none
T-cell lymphoma
sirolimus
Rapamune
kidney transplant rejection, prevention
sm-153 EDTMP
Quadramet
pain due to bone cancer
sodium clodronate
Bonefos, Loron
myeloma, secondary breast cancer
sodium iodide I 131
Iodotope
thyroid cancer
sodium phosphate P32
Sodium Phosphate P32 Solution
polycythemia vera; chronic myelocytic leukemia and chronic lymphocytic leukemia; multiple areas of skeletal metastases, palliative treatment
sodium salicylate
Disalcid
fever; inflammatory conditions; pain
sorafenib tosylate
Nexavar
advanced renal cell carcinoma; metastatic colorectal cancer
soy protein isolate
Revival
heart disease prevention; hyperlipidemia; menopausal symptoms
stealth liposomal doxorubicin
Doxil; Dox-SL; Evacet; LipoDox
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
stilboestrol dipropionate
Acnestrol; Cyren A; Deladumone; Diastyl; Domestrol; Estrobene; Estrosyn; Fonatol; Makarol; Milestrol; Neo-Oestronol I; Oestrogenine; Oestromenin; Oestromon; Palestrol; Stilbestrol; Stilbetin; Stilboestroform; Stilboestrol; Synestrin; Synthoestrin; Vagestrol
breast cancer; prostate cancer
streptozocin
Zanosar
carcinoid tumor and syndrome; colorectal cancer, palliative; Hodgkin disease; metastatic islet cell carcinoma of the pancreas
streptozotocin
Zanosar
carcinoid tumor and syndrome; colorectal cancer, palliative; Hodgkin disease; metastatic islet cell carcinoma of the pancreas
strontium chloride Sr 89
Metastron
palliation of pain in bone metastases
1302
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
suberoylanilide hydroxamic acid
Zolinza
cutaneous T-cell lymphoma
sulfabutin
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
sulindac
Aflodac; Clinoril
arthritis; inflammatory conditions
sunitinib
Sutent
gastrointestinal stromal tumor; advanced metastatic renal cell carcinoma
sunitinib malate
Sutent
gastrointestinal stromal tumor; advanced metastatic renal cell carcinoma
suramin
309 F; Bayer 205; Fourneau 309; Germanin; Moranyl; Naganin; Naganine
trypanosomiasis; hormone-refractory prostate cancer
syklofosfamid
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
SZN
Zanosar
carcinoid tumor and syndrome; colorectal cancer, palliative; Hodgkin disease; metastatic islet cell carcinoma of the pancreas
T-cell growth factor
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
tacrolimus
none
atopic dermatitis; kidney transplant rejection, prophylaxis; liver transplant rejection, prophylaxis
talc
Sclerosol Intrapleural Aerosol; Sterile Talc Powder; Steritalc
malignant pleural effusion; pneumothorax
tamoxifen
Nolvadex; Soltamox
breast cancer, palliative; adjuvant in breast cancer therapy; endometrial cancer; gynecomastia; melanoma; ovarian cancer
tamoxifen citrate
Nolvadex; Soltamox
breast cancer, palliative; adjuvant in breast cancer therapy; endometrial cancer; gynecomastia; melanoma; ovarian cancer
tamoxifeni citras
Nolvadex; Soltamox
breast cancer, palliative; adjuvant in breast cancer therapy; endometrial cancer; gynecomastia; melanoma; ovarian cancer
tamsulosin hydrochloride
Flomax
benign prostatic hyperplasia
tanespimycin
KOS-953
chronic myelogenous leukemia
tazarotene
Avage; Tazorac; Retisol-A; Stieva-A; Stieva-A Forte; Vitinoin
topical treatment of facial acne vulgaris; stable plaque psoriasis; mitigation (palliation) of facial fine wrinkling; facial mottled hyper- and hypopigmentation; benign facial lentigines
Tc 99m sulfur colloid
none
diagnostic imaging
TCGF
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
technetium Tc 99m sulfur colloid
none
diagnostic imaging
1303
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
tegafur with uracil
Uftoral
bowel cancer
temozolomide
Methazolastone; Temodar
malignant glioma (anaplastic astrocytoma; anaplastic oligodendrogliomas; anaplastic oligoastrocytomas; glioblastoma multiforme); metastatic melanoma
temsirolimus
Torisel
renal cell carcinoma; advanced renal cell carcinoma
teniposide
Vumon
childhood acute lymphocytic leukemia
testolactone
Teslac
advanced breast cancer in women, palliative
testosterone
Andro LA 200; Andro-Cyp 100; Delatestryl; Delatest; Depandro 100; Depo-Testosterone; Testro; Testro AQ; Virilon IM; Depotest; Duratest; Durathate 200; Everone; FIRST-Testosterone; FIRST-Testosterone MC; Histerone; Meditest; Testamone-100; Testoderm; Testolin; Testopel; Testosterone Enanthate; Testostroval; Testostroval-PA; Testro AQ
breast cancer in women; delayed puberty in men; hypogonadism; metastatic mammary cancer
testosterone enanthate
Delatestryl; Testoderm; Testolin; Testostroval; Testostroval-PA; Testro AQ
delayed puberty, male; hypogonadism; metastatic mammary cancer
tetanus toxoid
none
tetanus prophylaxis
tetrahydrocannabinol
Marinol
antinausea
tetramethylene bis(methanesulfonate)
Busulfex; Mitosan; Myleran
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
thalidomide
Synovir; Thalomid
Kaposi sarcoma; multiple myeloma; primary brain tumors
thenvlidene-lignan-P; thenylidene-lignan-P
Vumon
childhood acute lymphocytic leukemia
therapeutic dehydroepiandrosterone
Fidelin
adrenal insufficiency, replacement; systemic lupus erythematosus, treatment and steroid treatment reduction
therapeutic interleukin-11
Neumega
chemotherapy-related thrombocytopenia
therapeutic melatonin
Circadin
sleep disorders in blind people with no light perception
therapeutic progesterone
Colprosterone; Gesterol 100; Lipo-Lutin; Luteohormone; Progestin
amenorrhea; functional uterine bleeding; infertility; maintenance of pregnancy
therapeutic testolactone
Teslac
advanced breast cancer in women, palliative
therapeutic testosterone
Delatestryl; Testoderm; Testolin; Testostroval; Testostroval-PA; Testro AQ
delayed puberty, male; hypogonadism; metastatic mammary cancer
1304
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
thioguanine
Tabloid; Tabloid brand thioguanine; Tioguanine; Lanvis
acute nonlymphocytic leukemia
6 thiohypoxanthine
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
thiophosphamide
Girostan; STEPA; TESPA; Thiofozil; Thioplex; Tifosyl
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
thiophosphoramide
Girostan; STEPA; TESPA; Thiofozil; Thioplex; Tifosyl
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin disease
6-thiopurine
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
6-thioxopurine
Mercaptopurinum; Purinethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
thiotepa
Girostan; STEPA; TESPA; Thiofozil; Thioplex; Tifosyl
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease non-Hodgkin lymphoma
thymocyte stimulating factor
Proleukin
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
thyrotropin alfa
Thyrogen
thyroid cancer
tinzaparin sodium
Innohep
treatment of acute symptomatic deep venous thrombosis (DVT) with or without a pulmonary embolism (PE), in conjunction with warfarin
TMQ
Neutrexin
head and neck cancer; metastatic colorectal adenocarcinoma; non-small-cell lung cancer; osteogenic sarcoma; pancreatic adenocarcinoma; pneumocystitis carinii pneumonia
topotecan hydrochloride
Hycamtin
small-cell lung carcinoma; cervical cancer
toremifene
Fareston
breast cancer; desmoid tumors
tositumomab
Bexxar
CD20 positive follicular non-Hodgkin lymphoma refractory to rituximab
TRA
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
trans retinoic acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
trans-testosterone
Delatestryl; Testoderm; Testolin; Testostroval; Testostroval-PA; Testro AQ
delayed puberty, male; hypogonadism; metastatic mammary cancer
1305
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
trans vitamin A acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
trastuzumab
Herceptin
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
treosulfan
none
ovarian cancer; leukemia
tretinoin; tretinoinum
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
triacetyluridine
none
mitochondrial disease
triethylene thiophosphoramide
Girostan; STEPA; TESPA; Thiofozil; Thioplex; Tifosyl
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
trimethoprimsulfamethoxazole
Bactrim; Cotrim; Septra
pneumocystis carinii pneumonia; various bacterial infections
trimethylmethoxyphenylretinoic acid
Etretin; Soriatane
cutaneous T-cell lymphoma
trimetrexate glucuronate
Neutrexin
head and neck cancer; metastatic colorectal adenocarcinoma; non-small-cell lung cancer; osteogenic sarcoma; pancreatic adenocarcinoma; pneumocystitis carinii pneumonia
triptorelin
Decapeptyl
prostate carcinoma, palliative treatment
trivalent influenza vaccine
FluMist; Flushield; Fluvirin; Fluzone
influenza prophylaxis
tropisetron
Navoban
chemotherapy-induced nausea and vomiting
uracil mustard
Uracil Mustard Capsules
lymphomaûûnon-Hodgkin
urate oxidase
Elitek
chemotherapy-induced acute hyperuricemia, treatment and prophylaxis
ursodiol
Actigall; URSO; Deursil
gallstone dissolution; primary biliary cirrhosis
valdecoxib
Bextra
osteoarthritis; rheumatoid arthritis; dysmenorrhea
valganciclovir
Valcyte
cytomegalovirus retinitis
valproic acid
Depakene; Alti-Valproic; Ergenyl; Novo-Valproic
epilepsy; mania; migraine
valrubicin
Valstar
bladder cancer
vandetanib
Zactima
thyroid cancer
venlafaxine
Effexor
anxiety; depression
verteporfin
Visudyne
photosensitizer; subfoveal choroidal neovascularization
1306
Salem Health: Cancer
Drugs by Generic Name
Generic Drug
Trade Name
Indicated For
vinblastine
Velban; Velsar
bladder cancer; breast cancer; choriocarcinoma; germ-cell tumors; idiopathic thrombocytopenic purpura; Kaposi sarcoma; LettererSiwe disease; various lymphomas; melanoma; mycosis fungoides; prostate cancer; testicular cancer
vincaleucoblastine
Velban; Velsar
bladder cancer; breast cancer; choriocarcinoma; germ-cell tumors; idiopathic thrombocytopenic purpura; Kaposi sarcoma; LettererSiwe disease; various lymphomas; melanoma; mycosis fungoides; prostate cancer; testicular cancer
vincasar
Oncovin; Vincasar PFS
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
vincristine; vincrystine
Oncovin; Vincasar PFS
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
vindesine
Eldisine
acute leukemia; lung cancer; carcinoma of the breast; squamous cell carcinoma of the esophagus, head, and neck; Hodgkin disease and non-Hodgkin lymphomas
vinorelbine ditartrate
Biovelbin; Eunades
non-small-cell lung cancer; metastatic breast cancer; uterine and cervical cancer; desmoid tumors; advanced Kaposi sarcoma
vinorelbine tartrate
Biovelbin; Eunades
non-small-cell lung cancer; metastatic breast cancer; uterine and cervical cancer; desmoid tumors; advanced Kaposi sarcoma
vitamin A
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
vitamin A acid
Aberel; Aknoten; Avita; Renova; Retin-A; Retin-A MICRO; Vesanoid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
vitamin A alcohol
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
vitamin A compound
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
vitamin A USP
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
vitamin A1
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
vitamin E compound
none
vitamin E deficiency; used in cancer prevention
1307
Drugs by Generic Name
Salem Health: Cancer
Generic Drug
Trade Name
Indicated For
vitaminum A
Aquasol A; Del-Vi-A; Pedi-Vit-A
diminishing malignant cell growth; enhancing the immune system
VM26
Vumon
childhood acute lymphocytic leukemia
voriconazole
none
aspergillosis, invasive; esophageal candidiasis; fungal infections, nonaspergillosis
vorinostat
Zolinza
cutaneous T-cell lymphoma
warfarin
Athrombin-K; Compound 42; Co-Rax; Coumadin; Panwarfin; Rodex; WARF Compound 42
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
white arsenic
Trisenox
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
90Y ibritumomab tiuxetan
Zevalin
non-Hodgkin lymphoma
Y90-labeled ibritumomab tiuxetan
Zevalin
non-Hodgkin lymphoma
Y90 zevalin
Zevalin
non-Hodgkin lymphoma
YM177
Celebrex
familial adenomatous polyposis (inherited colorectal cancer syndrome)
yttrium-90 ibritumomab tiuxetan
Zevalin
non-Hodgkin lymphoma
yttrium Y 90 glass microspheres
TheraSphere
hepatocellular carcinoma, transarterial internal radiation
yttrium Y 90 ibritumomab tiuxetan
Zevalin
non-Hodgkin lymphoma
zidovudine
Retrovir; Aztec
AIDS-related complex; HIV infection; HIV transmission, prevention
zileuton
Zyflo
prevention and chronic treatment of asthma
zinc sulfate
none
common cold, symptoms; wound healing; zinc supplement
zoledronate
Zometa; Reclast
hypercalcemia of malignancy; multiple myeloma and metastatic bone lesions from solid tumors; Paget disease
zoledronic acid
Zometa; Reclast
hypercalcemia of malignancy; multiple myeloma and metastatic bone lesions from solid tumors; Paget disease
zytoxan
Cytoxan; Clafen; Neosar
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
1308
u
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Abbott-56268
clarithromycin
H. pylori infection; various bacterial infections
Aberel
tretinoin; all-trans retinoic acid; all-trans vitamin A acid; betaretinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; vitamin A acid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
Abitrexate
methotrexate
bladder cancer; breast cancer; carcinomatous; meningitis; chorioadenoma destruens; esophageal cancer; gestational choriocarcinoma; head/neck cancer; meningeal leukemia; lymphomas; Burkitt lymphoma; lung cancer; mycosis fungoides; osteosarcoma; Wegener granulomatosis
Abraxane
paclitaxel; paclitaxel proteinbound; albumin-stabilized nanoparticle paclitaxel; nabpaclitaxel; nanoparticle paclitaxel
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; non-small-cell lung cancer; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
Accutane
isotretinoin
cutaneous T-cell lymphoma; juvenile metastatic neuroblastoma and leukemia
Acicontral
calcium citrate
calcium supplement; hypocalcemia; osteoporosis; rickets; tetany
Acnestrol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Actigall
ursodiol
gallstone dissolution; primary biliary cirrhosis
Actimmune
recombinant interferon gamma
chronic granulomatous disease; osteopetrosis
Actiq
fentanyl citrate
breakthrough pain in cancer patients
Actonel
risedronate sodium
osteoporosis, treatment and prevention; Paget disease
Adagen
pegademase
enzyme replacement therapy for patients with severe combined immunodeficiency as a result of adenosine deaminase deficiency
Adderall
dextroamphetamine-amphetamine
attention deficit/hyperactivity disorder (ADHD); narcolepsy
Adriamycin
doxorubicin hydrochloride; ADM; ADR; adria
leukemias; Wilms’ tumor; neuroblastoma; soft-tissue and bone sarcomas; small-cell carcinoma of the lung; lymphomas; multiple myeloma; mesotheliomas; germ-cell tumors of the ovary or testis
Adrucil
fluorouracil; 5-fluorouracil; 5-fluracil; fluoro uracil; fluouracil; FU
palliative treatment for colorectal, breast, and pancreatic cancers; topical treatment for superficial basal cell carcinoma that cannot be treated with surgery and actinic keratosis
Aeroseb-Dex
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
1309
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Aflodac
sulindac
arthritis; inflammatory conditions
Agrylin
anagrelide
thrombocythemia secondary to myeloproliferative disorders; disrupts the postmitotic phase of megakaryocyte development
Aknoten
tretinoin; all-trans retinoic acid; all-trans vitamin A acid; betaretinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; vitamin A acid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
Alba-Dex
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Aldara
imiquimod
condyloma; superficial basal cell carcinoma; actinic keratosis
Alexion
eculizumab
paroxysmal nocturnal hemoglobinuria
Alferon
recombinant interferon alpha-2a
chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia; hairy cell leukemia; chronic hepatitis C; AIDS-related Kaposi sarcoma; bladder cancer; ovarian cancer; cervical cancer; non-Hodgkin lymphoma; renal-cell carcinoma; melanoma
Alferon N
recombinant interferon alfa
used as antiviral and antitumor agents
Alimta
pemetrexed disodium; multitargeted antifolate
malignant pleural mesothelioma; non-small-cell lung cancer
Alkeran
melphalan; alanine nitrogen mustard; L-phenylalanine mustard; L-sarcolysin; L-sarcolysin phenylalanine mustard; L-sarcolysine; phenylalanine mustard; phenylalanine nitrogen mustard; sarcoclorin
breast cancer; neuroblastoma; palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; rhabdomyosarcoma
Aloxi
palonosetron hydrochloride
antinausea; antiemetic (prevents vomiting)
Alti-Valproic
valproic acid
epilepsy; mania; migraine
Ambochlorin
chlorambucil; CBL; chlorambucilum; chloraminophen; chlorbutin; chlorbutine; chlorbutinum; chloroambucil; chlorobutin; chlorobutine; elcoril; leukersan; leukoran; linfolizin; lympholysin; phenylbutyric acid nitrogen mustard
chronic lymphocytic leukemia; malignant lymphomas
Ammoidin
methoxsalen; 8-methoxypsoralen; methoxypsoralen
cutaneous T-cell lymphoma
Amsa P-D
amsacrine; acridinyl anisidide; Cain’s acridine
leukemia
1310
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Andro LA 200
testosterone
breast cancer in women, palliative
Andro-Cyp 100
testosterone
breast cancer in women, palliative
Android, Testred, Virilon
methyltestosterone
breast cancer, palliative
Android-F
fluoxymesterone; androfluorene; androsterolo
certain types of breast cancer
Androxy
fluoxymesterone; androfluorene; androsterolo
certain types of breast cancer
Anzemet
dolasetron mesylate
nausea and vomiting prophylaxis, chemotherapy-induced and postoperative
Aptosyn
exisulind
colonic adenomatous polyps in the inherited disease adenomatous polyposis coli, control and suppression
Aquasol A
vitamin A compound; all transretinol; anti-infective vitamin; antixerophthalmic vitamin; axerophthol; axerophtholum; biosterol; lard-factor; oleovitamin A; ophthalamin; retinol; vitamin A; vitamin A alcohol; vitamin A USP; vitamin A1; vitaminum A
diminishing malignant cell growth; enhancing the immune system
Aranesp
darbepoetin alfa; novel erythropoiesis stimulating protein
chemotherapy-induced anemia; chronic renal failure/insufficiency
Aredia
disodium pamidronate; pamidronate disodium
myeloma, secondary breast cancer; hypercalcemia of malignancy; osteolytic bone lesions of multiple myeloma; osteolytic bone metastases of breast cancer; Paget disease
Aricept
donepezil hydrochloride
Alzheimer’s disease and opioid-induced sedation
Arimidex
anastrozole
hormone receptor-positive early breast cancer
Aromasin
exemestane
estrogen receptor-positive early breast cancer
Arranon
nelarabine
T-cell acute lymphoblastic leukemia; T-cell lymphoblastic lymphoma
Aspergum
acetylsalicylic acid; aspirin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
Atamir
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
ATGAM
antithymocyte globulin
heart and renal transplantation rejection; prophylaxis
Athrombin-K
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Augmentin
amoxicillin-clavulanate potassium
various bacterial infections
Avage
tazarotene
topical treatment of facial acne vulgaris; stable plaque psoriasis; mitigation (palliation) of facial fine wrinkling; facial mottled hyper- and hypopigmentation; benign facial lentigines
1311
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Avakine
infliximab
ankylosis spondylitis; Crohn disease; plaque psoriasis; rheumatoid arthritis; sarcoidosis
Avandia
rosiglitazone maleate
noninsulin-dependent diabetes mellitus and type II diabetes mellitus; type 2 diabetes
Avastin
bevacizumab; anti-VEGF; antiVEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; anti-VEGF RhuMAb; recombinant humanized antiVEGF monoclonal antibody; recombinant humanized monoclonal antibody to vascular endothelial growth factor; rhuMAb VEGF
metastatic colorectal cancer, non-small-cell lung cancer
Avelox
moxifloxacin hydrochloride
various bacterial infections
Avita
tretinoin; all-trans retinoic acid; all-trans vitamin A acid; betaretinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; vitamin A acid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
Aztec
zidovudine
AIDS-related complex; HIV infection; HIV transmission, prevention
Bactrim
trimethoprim-sulfamethoxazole
Pneumocystis carinii pneumonia; various bacterial infections
Bayer 205
suramin
trypanosomiasis; hormone-refractory prostate cancer
Becenum
carmustine; bis(chloroethyl) nitrosourea; bischloronitrosourea; carmustin
cancerous brain tumors; colon cancer; lung cancer; Hodgkin disease; non-Hodgkin lymphomas; lymphomas; melanoma; multiple myeloma; mycosis fungoides
Benoquin
monobenzone
vitiligo
Beriplast P
fibrin sealant
cardiovascular surgery; colostomy closure; congenital heart defects; coronary artery bypass grafting; mediastinal bleeding; microvascular bleeding; splenic trauma
Betaseron
recombinant interferon beta; interferon beta-1b
multiple sclerosis (MS); treating relapsing forms of multiple sclerosis (MS) to reduce the number of flare-ups and slow down the development of physical disability associated with MS
Bextra
valdecoxib
osteoarthritis; rheumatoid arthritis; dysmenorrhea
Bexxar
iodine I 131 tositumomab; 131-Ianti-B1 antibody; 131-I-anti-B1 monoclonal antibody; iodine I 131 MOAB anti-B1; iodine I 131 monoclonal antibody anti-B1; iodine-131 anti-B1 antibody; iodine-131 anti-CD20 monoclonal antibody; tositumomab; anti-CD20 antibody
CD-20-antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin lymphoma; CD20 positive follicular non-Hodgkin lymphoma refractory to rituximab
1312
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Biaxin
clarithromycin
H. pylori infection; various bacterial infections
BiCNU
carmustine; bis(chloroethyl) nitrosourea; bischloronitrosourea; carmustin
cancerous brain tumors; colon cancer; lung cancer; Hodgkin disease; non-Hodgkin lymphomas; lymphomas; melanoma; multiple myeloma; mycosis fungoides
Biovelbin
vinorelbine ditartrate; navelbine ditartrate; vinorelbine tartrate
non-small-cell lung cancer; metastatic breast cancer; uterine and cervical cancer; desmoid tumors; advanced Kaposi sarcoma
Blenoxane
bleomycin
skin cancer (squamous cell carcinoma) of the head, neck, penis, cervix, and vulva; lymphomas; testicular cancer; malignant pleural effusion
Bondronate
ibandronate sodium
osteoporosis, treatment and prevention
Bonefos, Loron
sodium clodronate
myeloma, secondary breast cancer
Boniva
ibandronate sodium
osteoporosis, treatment and prevention
Buspar
buspirone hydrochloride
alcohol abuse; anxiety; depression; migraine prophylaxis; smoking cessation; panic disorder
Busulfex
busulfan; BSF; bussulfam; busulfanum; busulphan; glyzophrol; methanesulfonic acid tetramethylene ester; myeleukon; myeloleukon; myelosan; mylecytan; sulfabutin; tetramethylene bis(methanesulfonate)
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
CAELYX
pegylated liposomal doxorubicin hydrochloride
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
Calglucon
calcium gluconate
hyperkalemia; hypocalcemic tetany; magnesium intoxication
Campath
alemtuzumab; anti-CD52 monoclonal antibody; Campath-1H; monoclonal antibody Campath-1H; monoclonal antibody CD52
B-cell chronic lymphocytic leukemia
Camptogen
rubetican
AIDS, pediatric; HIV infection, pediatric
Camptosar
irinotecan hydrochloride; camptothecin-11; irinotecan; irinotecan HCI
Stage IVB cervical cancer; colorectal cancer; esophageal cancer; gastric cancer; non-small-cell lung cancer; small-cell lung cancer
Capoten
captopril
hypertension; heart failure; left ventricular dysfunction; diabetic nephropathy
Carmubris
carmustine; bis(chloroethyl) nitrosourea; bischloronitrosourea; carmustin
cancerous brain tumors; colon cancer; lung cancer; Hodgkin disease; non-Hodgkin lymphomas; lymphomas; melanoma; multiple myeloma; mycosis fungoides
Carnitor
levocarnitine
carnitine deficiency; end-stage renal disease
Casodex
bicalutamide
metastatic prostate cancer
Caverject
alprostadil
erectile dysfunction; patent ductus arteriosus
1313
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
CCNU
lomustine; lomustinum
brain tumors; Hodgkin disease
CeeNU
lomustine; lomustinum
brain tumors; Hodgkin disease
Celebrex
celecoxib; YM177
familial adenomatous polyposis (inherited colorectal cancer syndrome)
Cellcept
mycophenolate mofetil
heart transplantation; kidney transplantation; liver transplantation; lupus nephritis
Cerebid
papaverine
ischemia, cerebral and peripheral
Cerespan
papaverine
ischemia, cerebral and peripheral
Cerubidine
daunorubicin hydrochloride; cloridrato de daunorubicina; daunomycin; daunomycin-HCL; daunorubicin; daunorubidomycine; rubomycin C
acute lymphoblastic leukemia
CI Basic Blue 9
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Cipro
ciprofloxacin
inhaled anthrax, postexposure; susceptible infectious diseases
Circadin
therapeutic melatonin
sleep disorders in blind people with no light perception
Citracal
calcium citrate
calcium supplement; hypocalcemia; osteoporosis; rickets; tetany
Clafen
cyclophosphamide; ciclofosfamida; ciclofosfamide; claphene; CP monohydrate; CPM; cyclophospham; cyclophosphamid monohydrate; cyclophosphamidum; cyclophosphan; cyclophosphanum; cytophosphane; mitoxan; syklofosfamid; zytoxan
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
Clasteon
clodronate disodium
adjuvant usage in bone metastasis of breast cancer
Clinagen LA 40
estradiol
breast cancer, palliative
Clinoril
sulindac
arthritis; inflammatory conditions
Clolar
clofarabine
accelerated approval (clinical benefit not established) for the treatment of pediatric patients one to twenty-one years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens
Collubleu
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Colprosterone
therapeutic progesterone
amenorrhea; functional uterine bleeding; infertility; maintenance of pregnancy
Compazine
prochlorperazine
antinausea
1314
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Compound 42
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Concerta
methylphenidate hydrochloride
attention deficit/hyperactivity disorder (ADHD); narcolepsy
Co-Rax
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Cortalone
prednisolone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Cosmegen
dactinomycin; ACT-D; actinomycin A IV; actinomycin C1; actinomycin D; actinomycin I1; actinomycin IV; actinomycin X 1; actinomycin-[thr-val-prosar-meval]; AD; dactinomycine; meractinomycin
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
Cotrim
trimethoprim-sulfamethoxazole
Pneumocystis carinii pneumonia; various bacterial infections
Coumadin
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Cristanaspase
asparaginase; ASNase; ASP-1; asparaginase erwinia; asparaginase II; colaspase; erwinia asparaginase; L-ASP; L-asparaginase; L-asparagine amidohydrolase
some blood cancers; acute lymphocytic leukemia; (acute nonlymphocytic leukemia)
Cuprenil
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Cuprimine
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Cupripen
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Curretab
medroxyprogesterone; medroxyprogesterone acetate
breast carcinoma; endometrial carcinoma; renal cell carcinoma
Cyfos
ifosfamide; ifomide; IFX; iphosphamid; iphosphamide; IPP; isoendoxan; iso-endoxan; isophosphamide; naxamide
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
Cymevan
ganciclovir
cytomegalovirus (CMV) infections in immunocompromised patients
Cyprostat
cyproterone acetate
prostate cancer
1315
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Cyren A
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Cytadren
aminoglutethimide
breast cancer; prostate cancer; decreases the production of sex hormones (estrogen in women or testosterone in men) and suppresses the growth of tumors that need sex hormones to grow
Cytosar-U
cytarabine; arabinofuranosylcytosine; arabinosylcytosine; aracytidine; beta-cytosine arabinoside; cytarabine hydrochloride; cytarabinum; cytosine arabinoside; cytosine arabinosine hydrochloride
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; meningitis lymphomatous; myelodysplasic syndrome; non-Hodgkin lymphoma; ovarian cancer; retinoblastoma
Cytoxan
cyclophosphamide; ciclofosfamida; ciclofosfamide; claphene; CP monohydrate; CPM; cyclophospham; cyclophosphamid monohydrate; cyclophosphamidum; cyclophosphan; cyclophosphanum; cytophosphane; mitoxan; syklofosfamid; zytoxan
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
Dacogen
decitabine; 5-aza-dCyd; deoxyazacytidine; dezocitidine
myelodysplastic syndrome
Dantrium
dantrolene
treating episodes of severe high body temperature; also used to prevent or reduce the risk of severe high body temperature in certain patients before or after surgery or anesthesia
DaunoXome
liposomal daunorubicin citrate; daunorubicin liposomal; liposomal daunorubicin
acute nonlymphocytic leukemia; acute lymphocytic leukemia; advanced HIV-associated Kaposi sarcoma
Decaderm
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Decadrol
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Decadron
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Deca-Durabolin
nandrolone decanoate
anemia of renal insufficiency; metastatic breast cancer
1316
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Decapeptyl
triptorelin; 6-D-tryptophan-LHRH; 6-D-tryptophanluteinizing hormone-releasing factor; detryptoreline; D-TRP-6-LHRH
prostate carcinoma, palliative treatment
Decasone R.p.
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Decaspray
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Deenar
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Deladumone
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Delatest
testosterone
breast cancer in women, palliative
Delatestryl
therapeutic testosterone; testosterone; testosterone enanthate; trans-testosterone
delayed puberty, male; hypogonadism; metastatic mammary cancer; breast cancer in women, palliative
Delta-Cortef
prednisolone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Delta-Dome
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Deltasone
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Del-Vi-A
vitamin A compound; all trans retinol; anti-infective vitamin; antixerophthalmic vitamin; axerophthol; axerophtholum; biosterol; lard-factor; oleovitamin A; ophthalamin; retinol; vitamin A; vitamin A alcohol; vitamin A USP; vitamin A1; vitaminum A
diminishing malignant cell growth; enhancing the immune system
1317
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Dep Gynogen
estradiol
breast cancer, palliative
Depakene
valproic acid
epilepsy; mania; migraine
Depandro 100
testosterone
breast cancer in women, palliative
Depen
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
DepoCyt
liposomal cytarabine; encapsulated cytarabine
lymphomatous meningitis
DepoFoam
liposomal cytarabine; encapsulated cytarabine
lymphomatous meningitis
Depo-Provera
medroxyprogesterone; medroxyprogesterone acetate
breast carcinoma; endometrial carcinoma; renal cell carcinoma
Depotest; Depo-Testosterone
testosterone
breast cancer in women, palliative
Deronil
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Desmoidpillen
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Deursil
ursodiol
gallstone dissolution; primary biliary cirrhosis
Dex-4
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Dexace
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Dexameth
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Dezone
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
DHPG
ganciclovir
cytomegalovirus (CMV) infections in immunocompromised patients
1318
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Diastyl
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Didronel
etidronate
treating adults with Paget disease; preventing and treating abnormal bone growth following hip replacement surgery or spinal cord injury
Diflucan
fluconazole
antifungal, prophylaxis in allogeneic bone marrow transplantation; candidiasis; cryptococcal meningitis
Difosfonal
clodronate disodium
adjuvant usage in bone metastasis of breast cancer
Disalcid
sodium salicylate
fever; inflammatory conditions; pain
Disprol
paracetamol
painkiller
Distamine
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Domestrol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Dostinex
cabergoline
pituitary tumors
Doxil; DOXIL
doxorubicin hydrochloride liposome; doxorubicin hydrochloride liposome injection; liposomal adriamycin; liposomal doxorubicin; liposomal doxorubicin hydrochloride; liposome-encapsulated doxorubicin; pegylated doxorubicin HCl liposome; pegylated liposomal doxorubicin; pegylated liposomal doxorubicin hydrochloride; S-liposomal doxorubicin; stealth liposomal doxorubicin
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
Doxilen
pegylated liposomal doxorubicin hydrochloride
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
1319
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Dox-SL
doxorubicin hydrochloride liposome; doxorubicin hydrochloride liposome injection; liposomal adriamycin; liposomal doxorubicin; liposomal doxorubicin hydrochloride; liposome-encapsulated doxorubicin; pegylated doxorubicin HCl liposome; pegylated liposomal doxorubicin; pegylated liposomal doxorubicin hydrochloride; S-liposomal doxorubicin; stealth liposomal doxorubicin
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
DTIC-Dome
dacarbazine; biocarbazine; dacarbazina; dacarbazina almirall; dacarbazine-DTIC; dakarbazin; dimethyl (triazeno) imidazolecarboxamide; dimethyl triazeno imidazol carboxamide; dimethyl triazeno imidazole carboxamide; imidazole carboxamide; imidazole carboxamide dimethyltriazeno
carcinoid cancer; Hodgkin disease; islet cell carcinoma; melanoma; neuroblastoma; soft-tissue sarcoma
Duratest
testosterone
breast cancer in women, palliative
Durathate 200
testosterone
breast cancer in women, palliative
Ecotrin
acetylsalicylic acid; aspirin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
Effexor
venlafaxine
anxiety; depression
Efudex
fluorouracil; 5-fluorouracil; 5-fluracil; fluoro uracil; fluouracil; FU
palliative treatment: colorectal cancer, breast cancer, stomach cancer, pancreatic cancer; topical treatment for the following: superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
Eldisine
vindesine; compound 112531; deacetyl vinblastine carboxamide; desacetylvinblastine amide
acute leukemia; lung cancer; carcinoma of the breast; squamous cell carcinoma of the esophagus, head, and neck; Hodgkin disease and non-Hodgkin lymphomas
Elitek
rasburicase; recombinant urate oxidase; urate oxidase
chemotherapy-induced acute hyperuricemia, treatment and prophylaxis
Ellence
epirubicin; 4′-epiadriamycin; 4′-epidoxorubicin; 4′-epi-doxorubicin Hcl; epi-ADR; epidoxorubicin; pidorubicin
breast cancer; adjuvant in breast cancer therapy
Elliott B Solution
Elliott B solution
diluent for the intrathecal administration of methotrexate sodium and cytarabine for the prevention or treatment of meningeal leukemia or lymphocytic lymphoma
1320
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Eloxatin
oxaliplatin; diaminocyclohexane oxalatoplatinum; oxalatoplatin; oxalatoplatinum
metastatic colorectal cancer; ovarian cancer
Elspar
asparaginase; ASNase; ASP-1; asparaginase erwinia; asparaginase II; colaspase; erwinia asparaginase; L-ASP; L-asparaginase; L-asparagine amidohydrolase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
Emcyt
estramustine phosphate sodium; estramustine phosphate
prostate neoplasm
Emend
aprepitant
antiemetic (prevents vomiting)
Empirin
acetylsalicylic acid; aspirin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
Enbrel
etanercept
juvenile arthritis; psoriatic arthritis; rheumatoid arthritis
Entericin
acetylsalicylic acid; aspirin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
Epitol
carbamazepine
epilepsy
Epivir
lamivudine
chronic hepatitis B; HIV infection
Epogen
epoetin alfa; erythropoietin; r-HuEPO
anemias associated with chronic renal failure, zidovudine (AZT) therapy, and cancer chemotherapy of nonmyeloid malignancies
Eraxis
anidulafungin
candidemia
Erbitux
cetuximab; anti-EGFR monoclonal antibody; antiepidermal growth factor receptor monoclonal antibody; C225 monoclonal antibody; chimeric anti-EGFR monoclonal antibody; chimeric monoclonal antibody C225; immunoglobulin G1, anti-(human epidermal growth factor receptor) (humanmouse monoclonal C225 gamma1-chain), disulfide with human-mouse monoclonal C225 kappa-chain, dimer; monoclonal antibody C225
advanced colorectal cancer; head and neck cancer
Ergamisol
levamisole; novo-levamisole
colon cancer; nephrotic syndrome
Ergenyl
valproic acid
epilepsy; mania; migraine
Estinyl
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
Estrace
estradiol
breast cancer, palliative
Estradiol Patch
estradiol
breast cancer, palliative
1321
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Estragyn LA 5
estradiol
breast cancer, palliative
Estratab
esterified estrogens
breast cancer
Estrobene
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Estro-Cyp
estradiol
breast cancer, palliative
Estrogen Patches
estradiol
breast cancer, palliative
Estrosyn
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Ethinoral
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
Ethiodol
ethiodized oil
diagnostic imaging, hysterosalpingography and lymphography
Ethyol
amifostine trihydrate; aminopropylaminoethylthiophosphoric acid; ethiofos; gammaphos
cisplatin-induced nephrotoxicity; radiation-induced mucositis and xerostomia
Eticylol
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
Etopophos
etoposide phosphate; etoposide; demethyl epipodophyllotoxin ethylidine glucoside; epipodophyllotoxin
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
Etretin
acitretin; trimethylmethoxyphenyl-retinoic acid
cutaneous T-cell lymphoma
Eulexin
flutamide; flucinom; flugerel; niftolid
prostate carcinoma; hirsutism
Eunades
vinorelbine ditartrate; navelbine ditartrate; vinorelbine tartrate
non-small-cell lung cancer; metastatic breast cancer; uterine and cervical cancer; desmoid tumors; advanced Kaposi sarcoma
1322
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Evacet
doxorubicin hydrochloride liposome; doxorubicin hydrochloride liposome injection; liposomal adriamycin; liposomal doxorubicin; liposomal doxorubicin hydrochloride; liposome-encapsulated doxorubicin; pegylated doxorubicin HCl liposome; pegylated liposomal doxorubicin; pegylated liposomal doxorubicin hydrochloride; S-liposomal doxorubicin; stealth liposomal doxorubicin
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
Everone
testosterone
breast cancer in women, palliative
Evista
raloxifene
breast cancer; cardiovascular disease prophylaxis; osteoporosis
Evoxac
cevimeline hydrochloride
Sjögren syndrome
Extren
acetylsalicylic acid; aspirin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
Fareston
toremifene
breast cancer; desmoid tumors
Faslodex
fulvestrant
hormone receptor-positive metastatic breast cancer
FDG
fludeoxyglucose F 18
radiopharmaceutical, cancer diagnostic
Femara
letrozole
hormone receptor-positive early breast cancer; adjuvant in breast cancer therapy; endometrial cancer
Femest
conjugated estrogens
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative
Feminone
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
Fempatch
estradiol
breast cancer, palliative
Fentora
fentanyl citrate
breakthrough pain in cancer patients
FGN-1
exisulind
colonic adenomatous polyps in the inherited disease adenomatous polyposis coli, control and suppression
Fidelin
therapeutic dehydroepiandrosterone
adrenal insufficiency, replacement; systemic lupus erythematosus, treatment and steroid treatment reduction
FIRST-Testosterone; FIRST-Testosterone MC
testosterone
breast cancer in women, palliative
Flomax
tamsulosin hydrochloride
benign prostatic hyperplasia
Florinef
fludrocortisone
breast cancer; adrenal cortical cancer
Fludara; Fludara Oral
fludarabine phosphate
chronic lymphocytic leukemia (CLL)
FluMist
trivalent influenza vaccine
influenza prophylaxis
1323
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Fluoroplex
fluorouracil; 5-fluorouracil; 5-fluracil; fluoro uracil; fluouracil; FU
palliative treatment: colorectal cancer, breast cancer, stomach cancer, pancreatic cancer; topical treatment for the following: superficial basal cell carcinoma that cannot be treated with surgery, and actinic keratosis
Flushield
trivalent influenza vaccine
influenza prophylaxis
Fluvirin
trivalent influenza vaccine
influenza prophylaxis
Fluzone
trivalent influenza vaccine
influenza prophylaxis
Folex; Folex PFS
methotrexate
bladder cancer; breast cancer; carcinomatous meningitis; chorioadenoma destruens; esophageal cancer; gestational choriocarcinoma; head/neck cancer; meningeal leukemia; lymphomas; Burkitt lymphoma; lung cancer; mycosis fungoides; osteosarcoma; Wegener granulomatosis
Fonatol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Fourneau 309
suramin
trypanosomiasis; hormone-refractory prostate cancer
Fragmin
dalteparin
deep vein thrombosis, prophylaxis; ischemic complications in unstable angina and non-Q wave myocardial infarction, prophylaxis
FUDF
floxuridine; FdUrD; floxuridin; fluorodeoxyuridine; fluorouridine deoxyribose; fluoruridine deoxyribose
gastrointestinal adenocarcinoma metastatic to the liver
Fungarest
ketoconazole
seborrheic dermatitis; prostate cancer
Fungoral
ketoconazole
seborrheic dermatitis; prostate cancer
Gammacorten
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Gd-DTPA
gadopentetate dimeglumine
angiography for leptomeningeal metastases and multiple sclerosis and magnetic resonance imaging for spine and brain
Gelfoam
absorbable gelatin sponge
homeostasis
Gemzar
gemcitabine hydrochloride; difluorodeoxycytidine; gemcitabine
bladder cancer; breast cancer; carcinoma of unknown primary origin; lung cancer; ovarian cancer; pancreatic cancer; renal cell carcinoma
Geritol
multivitamin
vitamin supplement
Germanin
suramin
trypanosomiasis; hormone-refractory prostate cancer
Gesterol 100
therapeutic progesterone
amenorrhea; functional uterine bleeding; infertility; maintenance of pregnancy
1324
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Girostan
thiotepa; thiophosphamide; thiophosphoramide; triethylene thiophosphoramide
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
Gleevec
imatinib mesylate
Philadelphia chromosome-positive chronic myeloid leukemia (CML); acute lymphocytic leukemia; gastrointestinal stromal tumor; hypereosinophillic syndrome; dermatofibrosarcoma protuberans; mutated-PDGFR myelodysplastic/myeloproliferative diseases
Gliadel wafer
polifeprosan 20 with carmustine implant
malignant glioma, adjuvant to surgery and radiation; recurrent glioblastoma multiforme, adjuvant to surgery
Glutacerebro
glutamine
short bowel syndrome
Glutaven
glutamine
short bowel syndrome
Granocyte
lenograstim
chemotherapy-induced neutropenia
Gynodiol, Gynogen LA 20
estradiol
breast cancer, palliative
Halodrin
fluoxymesterone; androfluorene; androsterolo
certain types of breast cancer
Halofuginone IV (intravenous)
halofuginone hydrobromide
scleroderma and antiprotozoal; coccidiosis (vet)
Halotestin
fluoxymesterone; androfluorene; androsterolo
certain types of breast cancer
Hectorol
doxercalciferol
secondary hyperparathyroidism in end-stage renal disease in patients on hemodialysis
Hepsera
adefovir dipivoxil
chronic hepatitis B
Herceptin
trastuzumab; anti-c-erB-2; anti-c-erbB2 monoclonal antibody; anti-ERB-2; anti-erbB2 monoclonal antibody; anti-HER2/c-erbB2 monoclonal antibody; anti-p185-HER2; monoclonal antibody c-erb-2; monoclonal antibody HER2
breast cancer overexpressing HER2 protein; pancreatic cancer overexpressing p185HER2
Hexadrol
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Hexalen
altretamine; hemel; hexaloids
ovarian cancer
Hexamethylmelamine
altretamine; hemel; hexaloids
ovarian cancer
Hib TITER vaccine
haemophilus influenzae B vaccine
haemophilus influenzae B prophylaxis
Histerone
testosterone
breast cancer in women, palliative
Histrelin implant
histrelin acetate
palliative treatment of advanced prostate cancer
hLL2
epratuzumab
systemic lupus erythematosus
1325
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Hycamtin
topotecan hydrochloride; hycamptamine
small-cell lung carcinoma; cervical cancer
Hydeltra
prednisolone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Hydeltrasol
prednisolone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Hydrea, Droxia
hydroxyurea; HYD; hydroxycarbamide; hydurea
chronic myelogenous leukemia; head and neck cancer; malignant melanoma; ovarian carcinoma; sickle cell anemia; adjuvant in retroviral therapy
I-125
iodine I 125
prostate cancer
I-131
iodine I 131
hyperthyroidism
Idamycin
Idarubicin; 4-demethoxydaunomycin; 4-demethoxydaunorubicin; DMDR
acute myeloid leukemia (AML); acute nonlymphocytic leukemia
IDEC in2B8
in 111 ibritumomab tiuxetan
non-Hodgkin lymphoma
Ifex
ifosfamide; ifomide; IFX; iphosphamid; iphosphamide; IPP; isoendoxan; iso-endoxan; isophosphamide; naxamide
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
Ifosfamidum
ifosfamide; ifomide; IFX; iphosphamid; iphosphamide; IPP; isoendoxan; iso-endoxan; isophosphamide; naxamide
breast cancer; gastric carcinoma; lung cancer; lymphocytic leukemias; Hodgkin disease and non-Hodgkin lymphoma; ovarian cancer; pancreatic carcinoma; sarcomas; testicular cancer
131 I-MIBG
iodine I 131 metaiodobenzylguanidine
diagnostic imaging
Immucyst
BCG
bladder cancer; malignant melanoma
Imuran
azathioprine sodium
converted in vivo to its active metabolite 6-mercaptopurine (6MP), which substitutes for the normal nucleoside and mistakenly gets incorporated into DNA sequences. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes
Imurel
azathioprine sodium
converted in vivo to its active metabolite 6-mercaptopurine (6MP), which substitutes for the normal nucleoside and mistakenly gets incorporated into DNA sequences. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes
Indocin
indomethacin
dysmenorrhea; inflammatory disorders; pain
Inestra
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
1326
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Innohep
tinzaparin sodium
treatment of acute symptomatic deep venous thrombosis (DVT) with or without a pulmonary embolism (PE), in conjunction with warfarin
Intron-A
interferon alfa-2b; recombinant interferon alfa
certain types of leukemia, lymphoma, and hepatitis; certain AIDS-related illnesses (Kaposi sarcoma); and genital warts (condylomata acuminata); also used in addition to surgery to treat a certain type of skin cancer (malignant melanoma)
Iodotope
sodium iodide I 131; iodine I 131
thyroid cancer; hyperthyroidism
Iressa
gefitinib
non-small-cell lung carcinoma
Ixempra
ixabepilone; azaepothilone B; epothilone B lactam; epothilone-B BMS 247550
metastatic or locally advanced breast cancer
Kapake
co-codamol
painkiller
Kelatin
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Keoxifene
raloxifene
breast cancer; cardiovascular disease prophylaxis; osteoporosis
Kepivance
palifermin
decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoetic stem cell support
Ketoderm
ketoconazole
seborrheic dermatitis; prostate cancer
Ketoisdin
ketoconazole
seborrheic dermatitis; prostate cancer
Kordicepin
cordycepin
TdT-positive acute lymphocytic leukemia
KOS-953
tanespimycin
chronic myelogenous leukemia
Kytril
granisetron hydrochloride
antinausea
L-Asnase
asparaginase; ASNase; ASP-1; asparaginase erwinia; asparaginase II; colaspase; erwinia asparaginase; L-ASP; L-asparaginase; L-asparagine amidohydrolase
some blood cancers; acute lymphocytic leukemia; acute nonlymphocytic leukemia
Lamictal
lamotrigine
epilepsy
Lanvis
thioguanine
acute nonlymphocytic leukemia
Laroferon
recombinant interferon alfa
used as antiviral and antitumor agents
1327
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Lastet
etoposide; demethyl epipodophyllotoxin ethylidine glucoside; epipodophyllotoxin
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
Leukeran
chlorambucil; CBL; chlorambucilum; chloraminophen; chlorbutin; chlorbutine; chlorbutinum; chloroambucil; chlorobutin; chlorobutine; elcoril; leukersan; leukoran; linfolizin; lympholysin; phenylbutyric acid nitrogen mustard
chronic lymphocytic leukemia; malignant lymphomas
Leukine
sargramostim; granulocyte macrophage colony-stimulating factor
melanoma; chemotherapy-induced neutropenia
Leustatin
Cladribine; 2-chloro-2-deoxyadenosine; 2-chlorodeoxyadenosine; cladribina
acute myeloid leukemia; chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia; Langerhans cell histiocytosis; non-Hodgkin lymphoma; Waldenström macroglobulinemia
Levulan
aminolevulinic acid
photodynamic therapy to treat a skin condition called actinic keratosis
L-Glutamine
glutamine
short bowel syndrome
Lipiodol
ethiodized oil
diagnostic imaging, hysterosalpingography and lymphography
LipoDox
doxorubicin hydrochloride liposome; doxorubicin hydrochloride liposome injection; liposomal adriamycin; liposomal doxorubicin; liposomal doxorubicin hydrochloride; liposome-encapsulated doxorubicin; pegylated doxorubicin HCl liposome; pegylated liposomal doxorubicin; pegylated liposomal doxorubicin hydrochloride; S-liposomal doxorubicin; stealth liposomal doxorubicin
refractory metastatic carcinoma of the ovary; AIDS-related Kaposi sarcoma; breast cancer; relapsed/refractory multiple myeloma (with bortezomib)
Lipo-Lutin
therapeutic progesterone
amenorrhea; functional uterine bleeding; infertility; maintenance of pregnancy
1328
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Liquid Pred
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Lisacort
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Longastatina
octreotide acetate
acromegaly; diarrhea
Loron
clodronate disodium
adjuvant usage in bone metastasis of breast cancer
Lumitene
beta carotene
chemoprevention for cardiovascular disease and cancer
Lupron
leuprolide acetate; leuprorelin; leuprorelin acetate
prostate cancer; uterine fibroid tumors
Lupron Depot; Lupron Depot-3 Month; -4 Month
leuprolide acetate; leuprorelin; leuprorelin acetate
prostate cancer; uterine fibroid tumors
Lupron Depot-Ped
leuprolide acetate; leuprorelin; leuprorelin acetate
prostate cancer; uterine fibroid tumors
Luteohormone
therapeutic progesterone
amenorrhea; functional uterine bleeding; infertility; maintenance of pregnancy
Lymphazurin
isosulfan blue
diagnostic imaging
LymphoCide
epratuzumab
systemic lupus erythematosus
Lynoral
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
Lyovac Cosmegen
dactinomycin; ACT-D; actinomycin A IV; actinomycin C1; actinomycin D; actinomycin I1; actinomycin IV; actinomycin X 1; actinomycin[thr-val-pro-sar-meval]; AD; dactinomycine; meractinomycin
Wilms’ tumor; childhood rhabdomyosarcoma; Ewing sarcoma; testicular cancer; gestational trophoblastic neoplasia; choriocarcinoma; melanoma; neuroblastoma; retinoblastoma; uterine sarcomas; Kaposi sarcoma; sarcoma botryoides; soft-tissue sarcoma
Lysodren
mitotane; chloditan; chlodithane; khloditan; mytotan; o,p′-DDD; ortho,para-DDD
adrenal cortical carcinoma
Magnevist
gadopentetate dimeglumine
angiography for leptomeningeal metastases and multiple sclerosis and magnetic resonance imaging for spine and brain
Makarol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
1329
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Marinol
dronabinol; cannabinol; delta 9-tetrahydrocannabinol; tetrahydrocannabinol
antinausea
Matulane
procarbazine hydrochloride; ibenzmethyzin; ibenzmethyzin hydrochloride; ibenzmethyzine hydrochloride; MIH; MIH hydrochloride; PCB hydrochloride; PCZ; procarbazin
brain tumors; Hodgkin disease; non-Hodgkin lymphoma
Maxidex
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Maxipime
cefepime hydrochloride
upper respiratory tract and urinary tract infections; febrile neutropenic conditions
Measurin
acetylsalicylic acid; aspirin
mild to moderate pain; fever; prevention of arterial and venous thrombosis
Mebonat
clodronate disodium
adjuvant usage in bone metastasis of breast cancer
Meditest
testosterone
breast cancer in women, palliative
Megace; Megace ES
megestrol acetate
appetite enhancement, AIDS patients; breast cancer, palliative; endometrial carcinoma, palliative treatment
Memoril
glutamine
short bowel syndrome
Menaval-20
estradiol
breast cancer, palliative
Menest
esterified estrogens
breast cancer
Mercaptopurinum
Mercaptopurine; 6-thiohypoxanthine; 6-mercaptopurine; 6-mercaptopurine monohydrate; 6-purinethiol; 6-thiopurine; 6-thioxopurine; azathiopurine; leupurin; mercapurin; mern; purimethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
Mercaptyl
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Mesna Disulfide
dimesna
ifosfamide-induced hemorrhagic cystitis, prophylaxis
Mesnex
mesna; mercaptoethane sulfonate; mesnum
helps protect the kidneys and bladder from the toxic effects of anticancer drugs such as ifosfamide and cyclophosphamide
Metalcaptase
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Metastron
strontium chloride Sr 89
palliation of pain in bone metastases
1330
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Methazolastone
temozolomide
malignant glioma (anaplastic astrocytoma; anaplastic oligodendrogliomas; anaplastic oligoastrocytomas; glioblastoma multiforme); metastatic melanoma
Methotrexate LPF
methotrexate
bladder cancer; breast cancer; carcinomatous; meningitis; chorioadenoma destruens; esophageal cancer; gestational choriocarcinoma; head/neck cancer; meningeal leukemia; lymphomas; Burkitt lymphoma; lung cancer; mycosis fungoides; osteosarcoma; Wegener granulomatosis
Methylthioninium chloride
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Meticorten
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Meti-derm
prednisolone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Mevacor
lovastatin
atherosclerosis; coronary heart disease, prevention; hypercholesterolemia
Mevinolin
lovastatin
atherosclerosis; coronary heart disease, prevention; hypercholesterolemia
Mexate; Mexate-AQ
methotrexate
bladder cancer; breast cancer; carcinomatous; meningitis; chorioadenoma destruens; esophageal cancer; gestational choriocarcinoma; head/neck cancer; meningeal leukemia; lymphomas; Burkitt lymphoma; lung cancer; mycosis fungoides; osteosarcoma; Wegener granulomatosis
Microlut
norgestrel
oral contraception
Milestrol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Miltex
Miltefosine
skin metastasis of breast cancer
Mircera
methoxy polyethylene glycolbeta
anemia associated with chronic renal failure
Mithracin
plicamycin; aureolic acid; mithramycin
testicular cancer
1331
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Mitosan
busulfan; BSF; bussulfam; busulfanum; busulphan; glyzophrol; methanesulfonic acid tetramethylene ester; myeleukon; myeloleukon; myelosan; mylecytan; sulfabutin; tetramethylene bis(methanesulfonate)
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
Mitozytrex
mitomycin C; MITC; mitocin-C; MTC
gastric carcinoma; pancreatic adenocarcinoma
Monacolin K
lovastatin
atherosclerosis; coronary heart disease, prevention; hypercholesterolemia
Moranyl
suramin
trypanosomiasis; hormone-refractory prostate cancer
MultiHance
gadopentetate dimeglumine
angiography for leptomeningeal metastases and multiple sclerosis and magnetic resonance imaging for spine and brain
MUSE
alprostadil
erectile dysfunction; patent ductus arteriosus
Mustargen
mechlorethamine hydrochloride; chloramin; chlorethamine HCl; chlorethamine hydrochloride; chlorethazine; chlorethazine hydrochloride; chlormethine; chlormethine hydrochloride; chloromethine HCl; mechlorethamine; mechlorethamine HCl; methylchlorethamine; mustard; mustargen HCl; mustargen hydrochloride; mustine; NH-2; nitrogen mustard; N-lost
bronchogenic carcinoma; chronic lymphocytic and myelcytic leukemia; Hodgkin disease, palliative; lymphosarcoma; mycosis fungoides; polycythemia vera
Mutamycin
mitomycin C; MITC; mitocin-C; MTC
gastric carcinoma; pancreatic adenocarcinoma
Mycobutin
rifabutin
prevention and treatment of Mycobacterium avium complex (MAC) and tuberculosis in patients with HIV infection
Myleran
busulfan; BSF; bussulfam; busulfanum; busulphan; glyzophrol; methanesulfonic acid tetramethylene ester; myeleukon; myeloleukon; myelosan; mylecytan; sulfabutin; tetramethylene bis(methanesulfonate)
bone marrow disorders; chronic myelogenous leukemia; palliative; neoadjuvant to allogeneic hematopoietic progenitor cell transplantation; neoplastic meningitis; primary brain malignancies
Mylosar
azacitidine; 5-AC; 5-azacytidine; azacytidine; ladakamycin
myelodysplastic syndrome
1332
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Mylotarg
gemtuzumab ozogamicin; calicheamicin-conjugated humanized anti-CD33 monoclonal antibody; hP67.6-calicheamicin
acute myeloid leukemia
Naganin; Naganine
suramin
trypanosomiasis; hormone-refractory prostate cancer
Navoban
tropisetron
chemotherapy-induced nausea and vomiting
Neo-Oestronol I
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Neogest
norgestrel
oral contraception
Neoral
cyclosporine
allogenic transplants; prophylaxis of organ rejection in bone marrow; kidney; liver and heart transplants; psoriasis; rheumatoid arthritis; various diseases that involve autoimmune response
NeoRecormon
epoetin beta
anemia associated with end-stage renal disease
Neosar
cyclophosphamide; ciclofosfamida; ciclofosfamide; claphene; CP monohydrate; CPM; cyclophospham; cyclophosphamid monohydrate; cyclophosphamidum; cyclophosphan; cyclophosphanum; cytophosphane; mitoxan; syklofosfamid; zytoxan
breast cancer; leukemias; lupus nephritis; lymphoma; multiple myeloma; neuroblastoma; nephrotic syndrome; ovarian cancer; retinoblastoma
Neulasta
pegfilgrastim; filgrastim SD-01; SD-01; SD-01 sustained duration G-CSF
chemotherapy-induced neutropenia
Neumega
recombinant interleukin-11; adipogenesis inhibitory factor; IL-11; interleukin-11; oprelvekin; recombinant human interleukin-11; therapeutic interleukin-11
chemotherapy-related thrombocytopenia; prevention of severe thrombocytopenia following myelosuppressive chemotherapy
Neupogen
filgrastim; granulocyte colonystimulating factor; recombinant methionyl human granulocyte colony stimulating factor
bone marrow transplantation; cancer patients receiving myelosuppressive chemotherapy; neutropenia
Neurontin
gabapentin
management of epilepsy; pain; mania; depression and anxiety disorders
Neutrexin
trimetrexate glucuronate; TMQ
head and neck cancer; metastatic colorectal adenocarcinoma; non-small-cell lung cancer; osteogenic sarcoma; pancreatic adenocarcinoma; pneumocystitis carinii pneumonia
1333
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Neutrogin
lenograstim
chemotherapy-induced neutropenia
Nexavar
sorafenib tosylate; BAY 43-9006; BAY 43-9006 tosylate salt
advanced renal cell carcinoma; metastatic colorectal cancer
Nicamid
niacinamide
pellagra, treatment and prophylaxis; various dermatologic conditions
Nicosedine
niacinamide
pellagra, treatment and prophylaxis; various dermatologic conditions
Nilandron
nilutamide
prostate cancer
Nipent
pentostatin; 2′-deoxycoformycin; co-vidarabine; deoxycoformycin; pentostatine
chronic lymphocytic leukemia; cutaneous T-cell lymphoma; hairy cell leukemia
Nizoral
ketoconazole
seborrheic dermatitis; prostate cancer
Nolvadex
tamoxifen citrate; novaldex; tamoxifen; tamoxifeni citras
breast cancer, palliative; adjuvant in breast cancer therapy; endometrial cancer; gynecomastia; melanoma; ovarian cancer
Nordeoxyguanosine
ganciclovir
cytomegalovirus (CMV) infections in immunocompromised patients
Novantrone
mitoxantrone hydrochloride; dihydroxyanthracenedione; dihydroxyanthracenedione dihydrochloride; mitoxantrone dihydrochloride; mitoxantrone HCl; mitoxantroni hydrochloridum; mitozantrone
acute leukemia; breast cancer; prostate cancer; non-Hodgkin lymphoma; multiple sclerosis
Novo-Valproic
valproic acid
epilepsy; mania; migraine
Noxafil
posaconazole
fungal infection prevention for immunocompromised host
Nutrestore
glutamine
short bowel syndrome
Octamide
metoclopramide
antinausea
Oestrogenine
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Oestromenin
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Oestromon
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
1334
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Olux-E
clobetasol propionate
psoriasis, eczema
Oncaspar
pegaspargase; L-Asparaginase with polyethylene glycol; PEG-asparaginase; PEG-L-asparaginase; PEG-L-asparaginase(K-H); polyethylene glycolL-asparaginase
acute lymphoblastic leukemia
Onconase
ranpirnase
mesothelioma
Oncovin
vincristine; LCR; leurocristine; leurocristine sulfate; vincasar; vincrystine
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
Ontak
denileukin diftitox; DAB(389)-interleukin-2; DAB389 interleukin-2; DAB389 interleukin-2 immunotoxin; DAB389-IL2; interleukin-2 fusion protein; interleukin-2 fusion toxin
cutaneous T-cell lymphoma
Onxol
paclitaxel; paclitaxel proteinbound; albumin-stabilized nanoparticle paclitaxel; nab-paclitaxel; nanoparticle paclitaxel
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; non-small-cell lung cancer; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
Oralet
fentanyl citrate
breakthrough pain in cancer patients
Orasone
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Ora-Testryl
fluoxymesterone; androfluorene; androsterolo
certain types of breast cancer
Orathecin
rubetican
AIDS, pediatric; HIV infection, pediatric
Orestralyn
ethinyl estradiol
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative; estrogen replacement; menopausal symptoms; postmenopausal osteoporosis
Orifungal M
ketoconazole
seborrheic dermatitis; prostate cancer
Orthoclone OKT3
muromonab-CD3
allograft rejection
Ossiten
clodronate disodium
adjuvant usage in bone metastasis of breast cancer
Ovaban
megestrol acetate
appetite enhancement, AIDS patients; breast cancer, palliative; endometrial carcinoma, palliative treatment
1335
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
OvaRex
oregovomab
epithelial ovarian cancer
Ovrette
norgestrel
oral contraception
Ovuplant
deslorelin
central precocious puberty
Oxandrin
oxandrolone
bone pain; Duchenne and Becker muscular dystrophy; HIVassociated muscle weakness; HIV-related wasting syndrome
Oxsoralen; OxsoralenUltra
methoxsalen; 8-methoxypsoralen; methoxypsoralen
cutaneous T-cell lymphoma
Palestrol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Pallace
megestrol acetate
appetite enhancement, AIDS patients; breast cancer, palliative; endometrial carcinoma, palliative treatment
Panadol
paracetamol
painkiller
Panfungol
ketoconazole
seborrheic dermatitis; prostate cancer
Panretin
alitretinoin; 9-cis-retinoic acid; retinoicacid-9-cis
topical treatment of cutaneous lesions in patients with AIDSrelated Kaposi sarcoma
Panwarfin
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Paraplat
carboplatin; carboplatin hexal; carboplatino
ovarian cancer
Paraplatin
carboplatin; carboplatin hexal; carboplatino
ovarian cancer
Pavabid
papaverine
ischemia, cerebral and peripheral
Pavacap
papaverine
ischemia, cerebral and peripheral
Pavatym
papaverine
ischemia, cerebral and peripheral
Paxil
paroxetine hydrochloride
depression
Pedi-Vit-A
vitamin A compound; all trans retinol; anti-infective vitamin; antixerophthalmic vitamin; axerophthol; axerophtholum; biosterol; lard-factor; oleovitamin A; ophthalamin; retinol; vitamin A; vitamin A alcohol; vitamin A USP; vitamin A1; vitaminum A
diminishing malignant cell growth; enhancing the immune system
PedvaxHIB
haemophilus influenzae B vaccine
haemophilus influenzae B prophylaxis
PEGASYS
PEG-interferon alfa-2a
chronic hepatitis C; renal cell carcinoma; advanced melanoma; chronic myelogenous leukemia
1336
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
PEG-Interferon Alfa
pegylated interferon alfa
hepatitis C
PEG-Intron
PEG-interferon alfa-2b
chronic hepatitis C; renal cell carcinoma
Pendramine
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Perdolat
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Periactin
cyproheptadine hydrochloride
hypersensitivity reactions
Photofrin
porfimer sodium; dihematoporphyrin ether; photofrin II; porfimer
photosensitizer; bladder, esophageal, gastric, lung, and rectal cancers
Platinol; Platinol-AQ
cisplatin; CACP; cis-DDP; cisdiamminedichloro platinum (II); cis-diamminedichloroplatinum; cis-dichloroammine platinum (II); cismaplat; cisplatina; cis-platinous diamine dichloride; cis-platinum; cis-platinum II; cis-platinum II diamine dichloride; CPDD; cysplatyna; DDP; PDD; Peyrone’s chloride; Peyrone’s salt; platinoxan; platinum diamminodichloride
metastatic testicular cancer; ovarian cancer; head and neck cancer; breast cancer; Hodgkin disease and non-Hodgkin lymphoma; myeloma and melanoma; advanced bladder cancer
Plavix
clopidogrel bisulfate
thromboembolic disorders
Prednicen-M
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Prednilen
methylprednisolone
adrenocortical insufficiency; conditions requiring immunosuppression; inflammatory conditions; multiple sclerosis; nephrotic syndrome
Prelone
prednisolone
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Premarin
conjugated estrogens
advanced androgen-dependent prostate cancer, palliative; breast cancer, palliative
Procrit
epoetin alfa; erythropoietin; r-HuEPO
anemias associated with chronic renal failure, zidovudine (AZT) therapy, and cancer chemotherapy of nonmyeloid malignancies
Progestin
therapeutic progesterone
amenorrhea; functional uterine bleeding; infertility; maintenance of pregnancy
Proglycem
diazoxide
malignant hypertension
1337
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Prokine
sargramostim; granulocyte macrophage colony-stimulating factor
melanoma; chemotherapy-induced neutropenia
Proleukin
aldesleukin; interleukin II; interleukin-2; lymphocyte mitogenic factor; mitogenic factor; recombinant interleukin-2; T-cell growth factor; TCGF, interleukin; thymocyte stimulating factor
metastatic renal cell carcinoma; metastatic melanoma; stimulates the production of blood cells, especially platelets, during chemotherapy
Provera; Provera Dosepak
medroxyprogesterone; medroxyprogesterone acetate
breast carcinoma; endometrial carcinoma; renal cell carcinoma
Provigil
modafinil
narcolepsy
Purinethol
Mercaptopurine; 6 thiohypoxanthine; 6-mercaptopurine; 6-mercaptopurine monohydrate; 6-purinethiol; 6-thiopurine; 6-thioxopurine; azathiopurine; leupurin; mercapurin; mern; purimethol
acute lymphocytic leukemia; acute myelogenous leukemia; Crohn disease; Hodgkin disease in children; lymphoblastic lymphoma; ulcerative colitis
Q. Levoglutamide
glutamine
short bowel syndrome
Quadramet
samarium SM 153 lexidronam pentasodium; samarium-153 EDTMP; samarium-153 ethylenediaminetetramethyleneph osphonate; samarium-153 ethylenediaminetetramethyleneph osphonic acid; Sm-153 EDTMP
pain due to bone cancer
R-41400
ketoconazole
seborrheic dermatitis; prostate cancer
Rapamune
sirolimus
kidney transplant rejection, prevention
Rebif
interferon beta-1b
treating relapsing forms of multiple sclerosis (MS) to reduce the number of flare-ups and slow down the development of physical disability associated with MS
Reclast
zoledronic acid; NDC-zoledronate; zoledronate
hypercalcemia of malignancy; multiple myeloma and metastatic bone lesions from solid tumors; Paget disease
Regitine
phentolamine mesylate
dermal necrosis; hypertensive-associated episodes with pheochromocytoma, prevention or control
Reglan
metoclopramide
antinausea
Remicade
infliximab
ankylosis spondylitis; Crohn disease; plaque psoriasis; rheumatoid arthritis; sarcoidosis
1338
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Renova
tretinoin; all-trans retinoic acid; all-trans vitamin A acid; beta-retinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; vitamin A acid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
Retin-A; Retin-A MICRO
tretinoin; all-trans retinoic acid; all-trans vitamin A acid; beta-retinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; vitamin A acid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene; for patients refractory to or who have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
Retinol Acetate
retinyl acetate
dietary supplement; vitamin A deficiency
Retisol-A
tazarotene
topical treatment of facial acne vulgaris; stable plaque psoriasis; mitigation (palliation) of facial fine wrinkling; facial mottled hyper- and hypopigmentation; benign facial lentigines
Retrovir
zidovudine
AIDS-related complex; HIV infection; HIV transmission, prevention
Revival
soy protein isolate
heart disease prevention; hyperlipidemia; menopausal symptoms
Revlimid
lenalidomide; CDC-501; IMiD-1
transfusion-dependent anemia due to low- or intermediate-1 risk myelodysplastic syndrome; multiple myeloma
Rheumatrex
methotrexate
bladder cancer; breast cancer; carcinomatous; meningitis; chorioadenoma destruens; esophageal cancer; gestational choriocarcinoma; head/neck cancer; meningeal leukemia; lymphomas; Burkitt lymphoma; lung cancer; mycosis fungoides; osteosarcoma; Wegener granulomatosis
Ritalin
methylphenidate hydrochloride
attention deficit/hyperactivity disorder (ADHD); narcolepsy
Rituxan
rituximab; anti-CD20 monoclonal antibody; C2B8 monoclonal antibody; IDEC-C2B8 monoclonal antibody
diffuse large B-cell, CD20-positive, non-Hodgkin lymphoma
Rocaltrol
calcitriol
hyperparathyroidism; hypocalcemia
Roceron; Roceron-A
recombinant interferon alfa
used as antiviral and antitumor agents
Rodex
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Roferon-A
interferon alfa-2a; recombinant interferon alfa
treating chronic hepatitis C and certain types of leukemia; used as antiviral and antitumor agents
RU 19110
halofuginone hydrobromide
scleroderma and antiprotozoal; coccidiosis (vet)
Rubidomycin
daunorubicin hydrochloride; cloridrato de daunorubicina; daunomycin; daunomycin-HCL; daunorubicin; daunorubidomycine; rubomycin C
acute lymphoblastic leukemia
Samilstin
octreotide acetate
acromegaly; diarrhea
1339
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Sandimmun
cyclosporine
allogenic transplants; prophylaxis of organ rejection in bone marrow; kidney; liver and heart transplants; psoriasis; rheumatoid arthritis; various diseases that involve autoimmune response
Sandostatin
octreotide acetate
acromegaly; diarrhea
SangCya
cyclosporine
allogenic transplants; prophylaxis of organ rejection in bone marrow; kidney; liver and heart transplants; psoriasis; rheumatoid arthritis; various diseases that involve autoimmune response
Schultz No. 1038
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Sclerosol Intrapleural Aerosol
talc
malignant pleural effusion; pneumothorax
Sensipar
cinacalcet
treating an overactive parathyroid in dialysis patients with chronic kidney disease; also used to treat high blood calcium levels in patients with parathyroid cancer.
Septra
trimethoprim-sulfamethoxazole
Pneumocystis carinii pneumonia; various bacterial infections
Sk-Dexamethasone
dexamethasone; desamethasone; dexamethasonum; DXM; hexadecadrol; methylfluorprednisolone
antiemetic (prevents vomiting)
Sk-Prednisone
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Sodium Phosphate P32 Solution
sodium phosphate P32
polycythemia vera; chronic myelocytic leukemia and chronic lymphocytic leukemia; multiple areas of skeletal metastases, palliative treatment
Solatene
beta-carotene
chemoprevention for cardiovascular disease and cancer
Soliris
eculizumab
paroxysmal nocturnal hemoglobinuria
Solpadol
co-codamol
painkiller
Soltamox
tamoxifen citrate; novaldex; tamoxifen; tamoxifeni citras
breast cancer, palliative; adjuvant in breast cancer therapy; endometrial cancer; gynecomastia; melanoma; ovarian cancer
Somatuline
lanreotide
acromegaly
Soriatane
acitretin; trimethylmethoxyphenyl-retinoic acid
cutaneous T-cell lymphoma
Sporanox
itraconazole
fungal infections
Sprycel
dasatinib; BMS-354825
chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia
STEPA
thiotepa; thiophosphamide; thiophosphoramide; triethylene thiophosphoramide
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
1340
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Sterapred
prednisone; delta(1)-cortisone; deltacortisone; deltadehydrocortisone; metacortandracin; PRD; prednisonum
inflammatory conditions; allergic conditions; hematologic conditions; neoplastic conditions; autoimmune conditions; replacement therapy in adrenal insufficiency
Sterile Talc Powder
talc
malignant pleural effusion; pneumothorax
Steritalc
talc
malignant pleural effusion; pneumothorax
Stieva-A; Stieva-A Forte
tazarotene
topical treatment of facial acne vulgaris; stable plaque psoriasis; mitigation (palliation) of facial fine wrinkling; facial mottled hyper- and hypopigmentation; benign facial lentigines
Stilbestrol; Stilboestrol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Stilbetin
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Stilboestroform
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Sublimaze
fentanyl citrate
breakthrough pain in cancer patients
Sufortan
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Sulindac sulfone
exisulind
colonic adenomatous polyps in the inherited disease adenomatous polyposis coli, control and suppression
Suprecur
buserelin
breast cancer; contraception, female; endometriosis; infertility; in vitro fertilization; polycystic ovary syndrome; prostate cancer; uterine leiomyoma
Sutent
sunitinib malate; sunitinib
gastrointestinal stromal tumor; advanced metastatic renal cell carcinoma
Synestrin
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
1341
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Synovir
thalidomide; alphaphthalimidoglutarimide; N-phthaloylglutamimide; N-phthalylglutamic acid imide
Kaposi sarcoma; multiple myeloma; primary brain tumors
Synthoestrin
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Tabloid
thioguanine
acute nonlymphocytic leukemia
Tagamet
cimetidine
gastrointestinal conditions; allergic reaction prevention; immune modulation
Tarabine PFS
cytarabine; arabinofuranosylcytosine; arabinosylcytosine; aracytidine; beta-cytosine arabinoside; cytarabine hydrochloride; cytarabinum; cytosine arabinoside; cytosine arabinosine hydrochloride
acute nonlymphocytic leukemia; acute lymphocytic leukemia; chronic myelogenous leukemia; bone marrow transplantation; carcinomatous meningitis; Hodgkin disease; meningeal leukemia; meningitis lymphomatous; myelodysplasic syndrome; nonHodgkin lymphoma; ovarian cancer; retinoblastoma
Tarceva
erlotinib hydrochloride; erlotinib
malignant glioma; locally advanced or metastic non-small-cell lung carcinoma; locally advanced, unresectable or metastatic pancreatic carcinoma
Targretin
bexarotene; 3-methyl TTNEB
oral or topical treatment of manifestations of cutaneous T-cell lymphoma
Tasigna
nilotinib
chronic myeloid leukemia; Philadelphia chromosome-positive acute lymphoblastic leukemia
Tavocept
dimesna
ifosfamide-induced hemorrhagic cystitis, prophylaxis
Taxol
paclitaxel; paclitaxel proteinbound; albumin-stabilized nanoparticle paclitaxel; nab-paclitaxel; nanoparticle paclitaxel
bladder cancer; breast cancer; adjuvant in breast cancer therapy; cervical cancer; endometrial adenocarcinoma; esophageal cancer; head and neck cancer; non-small-cell lung cancer; lymphoma; ovarian cancer; prostate cancer; testicular cancer; AIDS-related Kaposi sarcoma
Taxotere
docetaxel
breast cancer; esophageal cancer; gastric cancer; head/neck cancers; locally advanced or metastatic non-small-cell lung cancer; ovarian cancer; metastatic prostate cancer
Tazorac
tazarotene
topical treatment of facial acne vulgaris; stable plaque psoriasis; mitigation (palliation) of facial fine wrinkling; facial mottled hyper- and hypopigmentation; benign facial lentigines
Tegretol
carbamazepine
epilepsy
Temodar
temozolomide
malignant glioma (anaplastic astrocytoma; anaplastic oligodendrogliomas; anaplastic oligoastrocytomas; glioblastoma multiforme); metastatic melanoma
Tempostatin
halofuginone hydrobromide
scleroderma and antiprotozoal; coccidiosis (vet)
1342
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Teslac
testolactone; fludestrin; therapeutic testolactone
advanced breast cancer in women, palliative
TESPA
thiotepa; thiophosphamide; thiophosphoramide; triethylene thiophosphoramide
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
Testamone-100
testosterone
breast cancer in women, palliative
Testoderm
therapeutic testosterone; testosterone; testosterone enanthate; trans-testosterone
delayed puberty, male; hypogonadism; metastatic mammary cancer; breast cancer in women, palliative
Testolin
therapeutic testosterone; testosterone; testosterone enanthate; trans-testosterone
delayed puberty, male; hypogonadism; metastatic mammary cancer; breast cancer in women, palliative
Testopel
testosterone
breast cancer in women, palliative
Testosterone Enanthate
testosterone
breast cancer in women, palliative
Testostroval; Testostroval-PA
therapeutic testosterone; testosterone; testosterone enanthate; Trans-Testosterone
delayed puberty, male; hypogonadism; metastatic mammary cancer
Testro; Testro AQ
therapeutic testosterone; testosterone; testosterone enanthate; Trans-Testosterone
delayed puberty, male; hypogonadism; metastatic mammary cancer; breast cancer in women, palliative
Tetramethylthionine Chloride Trihydrate
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Thalomid
thalidomide; alphaphthalimidoglutarimide; N-phthaloylglutamimide; N-phthalylglutamic acid imide
Kaposi sarcoma; multiple myeloma; primary brain tumors
Theraloc
nimotuzumab
glioma
TheraSphere
yttrium Y 90 glass microspheres
hepatocellular carcinoma, transarterial internal radiation
Thiofozil
thiotepa; thiophosphamide; thiophosphoramide; triethylene thiophosphoramide
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
Thioplex
thiotepa; thiophosphamide; thiophosphoramide; triethylene thiophosphoramide
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
309 F
suramin
trypanosomiasis; hormone-refractory prostate cancer
Thymitaq
nolatrexed dihydrochloride
hepatocellular carcinoma
Thymoglobulin
antithymocyte globulin
heart and renal transplantation rejection; prophylaxis
Thyrogen
thyrotropin alfa
thyroid cancer
Tifosyl
thiotepa; thiophosphamide; thiophosphoramide; triethylene thiophosphoramide
bladder cancer; breast cancer; ovarian cancer; Hodgkin disease; non-Hodgkin lymphoma
1343
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Tioguanine
thioguanine
acute nonlymphocytic leukemia
TISSEEL
fibrin sealant
cardiovascular surgery; colostomy closure; congenital heart defects; coronary artery bypass grafting; mediastinal bleeding; microvascular bleeding; splenic trauma
Tomudex
raltitrexed
advanced colorectal cancer
Toposar
etoposide; demethyl epipodophyllotoxin ethylidine glucoside; epipodophyllotoxin
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
Torisel
temsirolimus; cell cycle inhibitor 779; rapamycin analog; rapamycin analog CCI-779
renal cell carcinoma; advanced renal cell carcinoma
Totect
dexrazoxane hydrochloride
severe side effects caused by certain types of chemotherapy including extravasation; cardiac side effects by doxorubicin
Treanda
bendamustine hydrochloride
chronic lymphocytic leukemia
Trisenox
arsenic trioxide; arsenic (III) oxide; arsenic sesquioxide; arsenous acid; arsenous acid anhydride; arsenous oxide; white arsenic
myelodysplastic syndrome; multiple myeloma; chronic myeloid leukemia; acute myelocytic leukemia
Trolovol
penicillamine
Wilson disease; heavy metal intoxication; cystinuria; rheumatoid arthritis; primary biliary cirrhosis; Felty syndrome; rheumatoid vasculitis
Tykerb
lapatinib ditosylate; lapatinib
advanced or metastatic breast cancer
Tylex
co-codamol
painkiller
Ubidecarenone
coenzyme Q10
chronic heart failure; mitochondrial cytopathies
Ubiquinone 10
coenzyme Q10
chronic heart failure; mitochondrial cytopathies
Uftoral
tegafur with uracil
bowel cancer
Ultandren
fluoxymesterone; androfluorene; androsterolo
certain types of breast cancer
Unicelles
papaverine
ischemia, cerebral and peripheral
Uracil Mustard Capsules
uracil mustard
non-Hodgkin lymphoma
Urolene Blue
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
URSO
ursodiol
gallstone dissolution; primary biliary cirrhosis
1344
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Uvadex
methoxsalen; 8-methoxypsoralen; methoxypsoralen
cutaneous T-cell lymphoma
Vagestrol
diethylstilbesterol; diethylstilbenediol; diethylstilbestrol dipropionate; diethylstilbestrolum; diethylstilboestrol; sinestrol; stilboestrol dipropionate
breast cancer; prostate cancer
Valcyte
valganciclovir
cytomegalovirus retinitis
Valstar
valrubicin
bladder cancer
Vasal
papaverine
ischemia, cerebral and peripheral
Vasomax
phentolamine mesylate
dermal necrosis; hypertensive-associated episodes with pheochromocytoma, prevention or control
Vectibix
panitumumab; monoclonal antibody ABX-EGF
advanced stage colorectal cancer
Velban
vinblastine; vincaleucoblastine
bladder cancer; breast cancer; choriocarcinoma; germ-cell tumors; idiopathic thrombocytopenic purpura; Kaposi sarcoma; LettererSiwe disease; various lymphomas; melanoma; mycosis fungoides; prostate cancer; testicular cancer
Velcade
bortezomib
multiple myeloma; advanced thyroid cancer
Velsar
vinblastine; vincaleucoblastine
bladder cancer; breast cancer; choriocarcinoma; germ-cell tumors; idiopathic thrombocytopenic purpura; Kaposi sarcoma; LettererSiwe disease; various lymphomas; melanoma; mycosis fungoides; prostate cancer; testicular cancer
Venofer
iron sucrose injection
treatment of iron deficiency for both dialysis and nondialysis patients with kidney disease, with or without concurrent erythropoietin therapy
VePesid
etoposide; demethyl epipodophyllotoxin ethylidine glucoside; epipodophyllotoxin
acute leukemia; adrenal cortical cancer; brain cancer; chronic lymphocytic leukemia; choriocarcinoma; esophageal cancer; Ewing sarcoma; gastric cancer; germ-cell cancer; gestational trophoblastic neoplasms; hepatocellular cancer; Hodgkin disease; hypereosinophilic syndrome; Kaposi sarcoma; testicular cancer; thymoma; thyroid cancer; uterine cancer; Wilms’ tumor; Langerhans cell histiocytosis; mobilization of peripheral-blood progenitor cells; multiple myeloma; neuroblastoma; non-smallcell lung cancer; osteogenic sarcoma; ovarian cancer; retinoblastoma; small-cell lung cancer; soft-tissue sarcomas
Vercyte
pipobroman
leukemias
Vesanoid
tretinoin; all-trans retinoic acid; all-trans vitamin A acid; beta-retinoic acid; retinoic acid; TRA; trans retinoic acid; trans vitamin A acid; tretinoinum; vitamin A acid
(oral) acute promyelocytic leukemia (APL), characterized by the t(15;17) translocation or the PML/RARa gene refractory to or have relapsed from anthracycline chemotherapy, or for where anthracycline-based chemotherapy is contraindicated; (topical) acne vulgaris; other dermatologic conditions; some skin cancers
Viadur
leuprolide acetate; leuprorelin; leuprorelin acetate
prostate cancer; uterine fibroid tumors
1345
Drugs by Trade Name
Salem Health: Cancer
Trade Name
Generic Drug
Indicated For
Viagmox
moxifloxacin hydrochloride
various bacterial infections
Viagra
sildenafil citrate
erectile dysfunction
Vidaza
azacitidine; 5-AC; 5-azacytidine; azacytidine; ladakamycin
myelodysplastic syndrome
Vincasar PFS
vincristine; LCR; leurocristine; leurocristine sulfate; vincasar; vincrystine
acute leukemia; brain tumors; chronic lymphocytic leukemia; gestational trophoblastic neoplasms; head and neck squamous cell carcinoma; Kaposi sarcoma; liver cancer; Hodgkin disease and non-Hodgkin lymphoma; malignant thymoma; multiple myeloma; osteogenic sarcoma; ovarian cancer; pheochromocytoma; retinoblastoma; rhabdomyosarcoma; soft-tissue sarcoma; testicular cancer; Wilms’ tumor
Vioxx
rofecoxib
pain; dysmenorrhea; osteoarthritis; rheumatoid arthritis
Virgan
ganciclovir
cytomegalovirus (CMV) infections in immunocompromised patients
Virilon IM
testosterone
breast cancer in women, palliative
Visudyne
verteporfin
photosensitizer; subfoveal choroidal neovascularization
Vitableu
methylene blue
cyanide poisoning, antidote; diagnostic, indicator dye; genitourinary antiseptic; glutaricaciduria; methemoglobinemia; oxalate and phosphate urinary tract calculi, management
Vitinoin
tazarotene
topical treatment of facial acne vulgaris; stable plaque psoriasis; mitigation (palliation) of facial fine wrinkling; facial mottled hyper- and hypopigmentation; benign facial lentigines
Vumon
teniposide; thenvlidene-lignan-P; thenylidene-lignan-P; VM26
childhood acute lymphocytic leukemia
WARF Compound 42
warfarin
pulmonary embolism and thromboembolic disorders, treatment and prophylaxis; venous thrombosis, prophylaxis and treatment
Wellbutrin
bupropion hydrochloride
depression; smoking cessation
Wellcovorin
leucovorin calcium; calcium (6S)-folinate; calcium folinate; CFR; citrovorum factor; folinate calcium; folinic acid; folinic acid calcium salt pentahydrate; leucovorin; LV
used to protect normal cells from high doses of the anticancer drug methotrexate; also used to increase the antitumor effects of fluorouracil and tegafur-uracil; megaloblastic anemia due to folate deficiency; enhanced fluorouracil inhibition of thymidylate synthase; reverse dihydrofolate reductase inhibition by methotrexate; folic acid antagonist overdose; nitrous oxide toxicity
Wyacort
methylprednisolone
adrenocortical insufficiency; conditions requiring immunosuppression; inflammatory conditions; multiple sclerosis; nephrotic syndrome
Xanthotoxin
methoxsalen; 8-methoxypsoralen; methoxypsoralen
cutaneous T-cell lymphoma
Xeloda
capecitabine
breast cancer; colorectal cancer; Stage III colon cancer
Xolegel
ketoconazole
seborrheic dermatitis; prostate cancer
Zactima
vandetanib
thyroid cancer
1346
Salem Health: Cancer
Drugs by Trade Name
Trade Name
Generic Drug
Indicated For
Zanosar
streptozocin; streptozotocin; SZN
carcinoid tumor and syndrome; colorectal cancer, palliative; Hodgkin disease; metastatic islet cell carcinoma of the pancreas
Zemplar
paricalcitol
secondary hyperparathyroidism, prevention and treatment
Zenapax
daclizumab
kidney transplant rejection, prevention
Zevalin
yttrium Y 90 ibritumomab tiuxetan; 90Y ibritumomab tiuxetan; ibritumomab (In2B8/ Y2B8 radiolabeling kit); ibritumomab tiuxetan; IDECY2B8 monoclonal antibody; Y90 zevalin; Y90-labeled ibritumomab tiuxetan; yttrium-90 ibritumomab tiuxetan
accelerated approval (clinical benefit not established) treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin lymphoma, including patients with rituximab refractory follicular non-Hodgkin lymphoma
Zinecard
dexrazoxane hydrochloride
severe side effects caused by certain types of chemotherapy including extravasation; cardiac side effects by doxorubicin
Zofran
ondansetron
nausea and vomiting prophylaxis, chemotherapy-induced and postoperative
Zoladex
goserelin; 6-[O-(1,1dimethylethyl)-D-serine]-10deglycinamide luteinizing hormone-releasing factor (pig) 2-(aminocarbonyl)hydrazide
breast cancer, palliative; prostate cancer
Zolinza
vorinostat; suberoylanilide hydroxamic acid
cutaneous T-cell lymphoma
Zoloft
sertraline hydrochloride
major depressive disorder; obsessive-compulsive disorder; panic disorder; posttraumatic stress disorder; premenstrual dysphoric disorder; social phobia
Zometa
zoledronic acid; NDC-zoledronate; zoledronate
hypercalcemia of malignancy; multiple myeloma and metastatic bone lesions from solid tumors; Paget disease
Zyban
bupropion hydrochloride
depression; smoking cessation
Zyflo
zileuton
prevention and chronic treatment of asthma
Zyloprim
allopurinol
treats high levels of uric acid in the body caused by certain cancer medications, especially for patients with leukemia, lymphoma, and solid-tumor malignancies
1347
u
Associations and Agencies
American Association for Cancer Research http://www.aacr.org Provides programs and services that promote the exchange of knowledge and new ideas among cancer research scientists; provides training opportunities for upcoming cancer researchers and promotes public education about cancer. American Cancer Society http://www.cancer.org Nonprofit organization providing the largest private source of cancer research funds in the United States. Offers prevention and early detection information in addition to a wide variety of patient services programs. American Lung Association http://www.lungusa.org Provides educational materials on treatments and research related to lung cancer, as well as information on the dangers of smoking and secondhand smoke. Offers smoking-cessation support programs. American Society of Clinical Oncology (ASCO) http://www.asco.org; http://www.Cancer.Net A nonprofit organization consisting of more than twentyfive thousand oncology practitioners who conduct clinical cancer research and treat cancer patients. Primary Web site provides news releases, cancer research articles, and new drug information. ASCO also manages a Web site called Cancer.Net (formerly People Living with Cancer), which provides information on different types of cancer, discusses clinical trials, offers suggestions for managing side effects, and features an oncologist database. Association of American Cancer Institutes (AACI) http://www.aaci.org Comprises ninety-one U.S. cancer research centers; promotes cancer research, prevention, treatment, and patient care; provides research news and a list of member cancer centers. Blue Faery: The Adrienne Wilson Liver Cancer Association http://www.bluefaery.org Dedicated to increasing research, education, and advocacy for the prevention, treatment, and cure of primary liver cancer, specifically hepatocellular carcinoma. Web site provides liver cancer information and latest news updates. 1348
Breast Cancer Action http://www.bcaction.org Advocates for policy changes related to breast cancer issues and educates people about breast cancer and related topics. Provides a booklet for newly diagnosed breast cancer patients, monthly e-alerts with important breast cancer news, and a bimonthly newsletter called The Source. Web site offers recent breast cancer news and downloadable flyers and fact sheets. The Breast Cancer Fund http://www.breastcancerfund.org Identifies environmental and other preventable contributors to breast cancer and advocates for their elimination. Educates the public about cancer prevention. Web site offers a monthly e-newsletter and fact sheets. The Breast Cancer Research Foundation http://www.bcrfcure.org Raises funds for breast cancer research and increases awareness of good breast health. Provides a biannual newsletter. C3: Colorectal Cancer Coalition http://www.fightcolorectalcancer.org Advocates to promote colorectal cancer research, policy, and awareness in an effort to improve screening, diagnosis, and treatment of colorectal cancer. Provides a monthly e-newsletter and a quarterly print newsletter called Momentum. Offers information on treatment options and clinical trials. Canadian Cancer Society http://www.cancer.ca A Canadian, community-based organization of volunteers that provides information about cancer, prevention, research, support services, and publications. Web site provides information by province/territory in English and French. Centers for Disease Control and Prevention (CDC) http://www.cdc.gov Web site offers information on cancer, provides statistical information on cancer diagnosis in the United States, discusses smoking-cessation programs, and provides educational materials on cancer treatment and awareness. It also hosts a cancer survivorship issues page. Children’s Cause for Cancer Advocacy http://www.childrenscause.org Works with leading medical, scientific, and public policy experts to advance cancer research and treatment and to
Salem Health: Cancer provide services for childhood cancer patients, survivors, and families. Web site offers information on Rise to Action Survivors Program and the opportunity to sign up for their newsletter, The Next Step. CureSearch http://www.curesearch.org Unites Children’s Oncology Group and National Childhood Cancer Foundation in their efforts to cure and prevent pediatric cancer. Web site provides information about types of pediatric cancers, treatment options available, risks and benefits of different treatment methods, prevention of and preparation for side effects, and ways to maintain a healthy lifestyle after treatment. Esophageal Cancer Awareness Association (ECAA) http://www.ecaware.org Dedicated to helping patients, survivors, and caregivers deal more effectively with the uncertainties and consequences of esophageal cancer. Web site provides information about esophageal cancer and its diagnosis, staging, and treatments, as well as their newsletter, Swallow Tales, and contact information for members willing to offer support and advice. Food and Drug Administration (FDA) http://www.fda.gov Web site provides information on clinical trials, discusses clinical trial regulations, and provides consumer education information. The FDA’s Cancer Liaison Program provides answers to questions about therapies asked by cancer patients and patient advocates; its Drug Development Patient Consultant Program allows cancer patient advocates to participate in the FDA drug review regulatory process; and its Cancer Patient Representative Program recruits, assesses, and selects patient representatives to serve as members of advisory committees. Friends of Cancer Research http://www.focr.org Pioneers public-private partnerships in research and clinical trials, organizes public policy forums, educates public about prevention, detection, and treatment of cancers, and collaborates with media and the motion picture industry to promote cancer research and education. Web site offers news and events articles related to cancer and a monthly newsletter. Hurricane Voices http://www.hurricanevoices.org Organizes public awareness campaigns and educational programs and provides grants and sponsorships in sup-
Associations and Agencies port of breast cancer programs. Web site provides news articles about breast cancer and a list of books suggested for families affected by breast cancer. Inflammatory Breast Cancer Association http://www.ibchelp.org Educates people about inflammatory breast cancer (IBC). Web site provides information about signs and symptoms, screening methods, and treatments of IBC, news reports and videos about IBC, an IBC forum and registries, as well as survivors’ stories. Inflammatory Breast Cancer Research Foundation http://www.ibcresearch.org Educates people about inflammatory breast cancer. Advocates for advancement of research and raises awareness of the symptoms associated with the disease, to aid in early detection. Web site offers educational materials, e-mail discussion lists, and a newsletter. Institute of Medicine (IOM) http://www.iom.edu Consists of volunteer scientists and laypeople not employed by the U.S. government who provide analysis and guidance on important health issues. Web site provides reports on cancer research, survivorship, and palliative care. Intercultural Cancer Council http://iccnetwork.org Advocates for programs, policies, partnerships, and research aimed at eliminating cancer within racial and ethnic minorities and medically underserved populations in the United States. Sponsors biennial symposia. Web site provides cancer fact sheets and a quarterly newsletter called The Voice. International Agency for Research on Cancer (IARC) http://www.iarc.fr Part of the World Health Organization, IARC coordinates and conducts cancer research, including monitoring global cancer occurrence, identifying causes of cancer and the mechanisms of carcinogenesis, and developing scientific strategies for cancer control; also distributes scientific information through publications, meetings, courses, and fellowships. International Union Against Cancer http://www.uicc.org A global association of cancer-fighting organizations that educates people about cancer prevention and control worldwide. Offers fellowship and training opportunities for scientists. Publishes the International Journal 1349
Associations and Agencies of Cancer. Web site provides press releases, newsletters, publications, and a list of suggested books. Joan Scarangello Foundation to Conquer Lung Cancer http://www.joanslegacy.org Increases awareness about lung cancer and raises money to provide research grants. The Joanie Award recognizes journalists who focus on the problem of lung cancer. Web site offers information on lung cancer and a list of patient resources. Kidney Cancer Association http://kidneycancer.org Provides information on kidney cancer, treatment options, and clinical trials. Funds research, advocates on behalf of patients, and distributes the Kidney Cancer Journal. Web site provides links to a forum, calendar of events, online store, and the Fourth Angel Caregiver Mentoring Program. Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Provides information on blood cancers such as leukemia, lymphoma, Hodgkin disease, and myeloma. Funds blood cancer research, education, and patient services. Web site offers information on blood cancers, newsletters, a First Connection (peer-to-peer) program, education programs, calendar of events, and a call center. Multiple Myeloma Research Foundation (MMRF) http://www.multiplemyeloma.org Provides research grants and advocates for myeloma research. Web site offers information about the disease, treatment options, and clinical trials, in addition to news and events. National Asian Women’s Health Organization (NAWHO) http://www.nawho.org Raises awareness about the health issues facing Asian American women, including breast cancer and cervical cancer, and provides a list of Asian-language informational resources. National Breast Cancer Coalition (NBCC) http://www.natlbcc.org Promotes breast cancer research and works toward improving access for all women to high-quality breast cancer screening, diagnosis, treatment, and care; informs and trains breast cancer survivors and others in effective advocacy efforts aimed at eradicating breast cancer. Web site provides breast cancer information, latest news, and sign-up for their e-newsletter. 1350
Salem Health: Cancer National Cancer Institute (NCI) http://www.cancer.gov Part of the medical research agency of the U.S. government, NCI conducts and supports research, training, and information distribution regarding the cause, diagnosis, prevention and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients. Web site offers fact sheets, a dictionary of cancer terms, a dictionary of drug names, suggestions on coping with cancer, research news, and information on cancer prevention and screening, clinical trials, statistics, research funding, and complementary and alternative medicine. National Cancer Institute of Canada (NCIC) http://www.ncic.cancer.ca Provides support for cancer research and related programs undertaken at Canadian universities, hospitals, and other research institutions. Web site offers video of commonly asked questions about cancer, information about program project grants, and an e-newsletter for cancer researchers. National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) http://www.ctg.queensu.ca Conducts clinical trials related to cancer therapy and prevention. Web site provides a list of publications and descriptions of clinical trials. National Cervical Cancer Coalition (NCCC) http://www.nccc-online.org Educates people about cervical cancer and the importance of early detection, advocates for quality patient care, and provides support through its Phone Pals and E-Pals programs, which match women with cervical cancer survivors. Web site provides links to many resources related to cervical cancer, the NCCC Store, latest news, and its newsletter Extraordinary Moments. National Comprehensive Cancer Network (NCCN) http://www.nccn.org A not-for-profit alliance of leading cancer centers. Web site provides information on treatment guidelines and supportive care, clinical trials, and member centers for people looking for physicians, pediatric cancer treatment, and genetic testing or screening. National Institute of Environmental Health Sciences (NIEHS) http://www.niehs.nih.gov Part of the medical research agency of the U.S. government, the institute studies how environmental factors
Salem Health: Cancer affect a person’s chances of developing certain diseases, including cancers. Web site offers a library of resources, such as fact sheets, research reports, and a peer-reviewed journal called Environmental Health Perspectives. NIEHS performs a long-term study, called the Sister Study, of women whose sisters had breast cancer in an effort to learn how environment and genes affect a woman’s chances of developing breast cancer. National Library of Medicine http://www.nlm.nih.gov World’s largest medical library offering a link to PubMed, an online searchable database of biomedical journal literature, and a link to MedlinePlus, an online searchable database of health and drug information for patients and loved ones, as well as links to many NLM databases and electronic resources. National Ovarian Cancer Coalition (NOCC) http://www.ovarian.org Raises awareness and promotes education about ovarian cancer. Web site lists state chapters, support groups and services, and clinical trials, in addition to providing latest news, NOCC newsletter, and medical information about ovarian cancer. Ovarian Cancer National Alliance (OCNA) http://www.ovariancancer.org An alliance of seven ovarian cancer groups that advocate for ovarian cancer education, policy, and research issues with national policy makers and women’s health care leaders. Web site provides educational resources, support services, latest news, and clinical trials.
Associations and Agencies Prevent Cancer Foundation http://www.preventcancer.org Attempts to prevent cancer by funding research, educating people about prevention, and reaching out to communities through events and partnerships with other organizations. Sarcoma Foundation of America http://www.curesarcoma.org Advocates for increased sarcoma research, raises funds to provide research grants to sarcoma researchers, and works to raise awareness of the treatment needs of sarcoma patients. Skin Cancer Foundation http://www.skincancer.org Provides educational material about skin cancer prevention and detection. Web site provides information about different types of skin cancer, an Ask the Expert feature, a link to the SCF Store, and a Physician Finder database. WebMD http://www.webmd.com/cancer An online cancer health center that provides timely reports about medical research and other cancer issues. Web site includes links to top cancer news articles, information about common cancers and treatments, current clinical trials and research, blogs, message boards, Ask the Experts resource, drug information, a database for finding a doctor, WebMD video library, sign-up for WebMD newsletter, a symptom checker, and much more.
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Abramson Cancer Center of the University of Pennsylvania http://www.penncancer.org A National Cancer Insitute (NCI)-designated comprehensive cancer center in Philadelphia that is part of a network of hospitals throughout Pennsylvania and New Jersey dedicated to providing state-of-the-art cancer care, research, and education. Arizona Cancer Center at the University of Arizona http://www.azcc.arizona.edu An NCI-designated comprehensive cancer center in Tucson, Arizona. Offers specialized care to each patient through research, outreach, education, and information programs (including a patient education library), and support groups as well as social services and interpreters, and leading-edge clinical care. Barbara Ann Karmanos Cancer Institute/Meyer L. Prentis Comprehensive Cancer Center of Metropolitan Detroit http://www.karmanos.org An NCI-designated comprehensive cancer center based in Detroit, Michigan. Videoconferencing and physicianto-physician communication throughout the Karmanos affiliate network allows for leading-edge patient care, cancer research, clinical trials, and education statewide. Cancer Institute of New Jersey (CINJ) at Robert Wood Johnson Medical School http://www.cinj.org An NCI-designated comprehensive cancer center based in New Brunswick, New Jersey, consisting of a statewide network of sixteen hospitals. Provides cancer research, clinical trials, patient care, support groups, and education. Produces publications useful to patients and their families, including its quarterly newsletter Oncolyte. Cancer Treatment Centers of America (CTCA) http://www.cancercenter.com Uses aggressive research and innovative new techniques to provide personalized medical, nutritional, physical, psychological, and spiritual therapies to fight cancer. Several locations nationwide. Web site offers many survivor stories, CTCA news releases, media coverage, brochures, and treatment diagrams. Case Comprehensive Cancer Center http://cancer.case.edu An NCI-designated comprehensive cancer center based in 1352
Cleveland, Ohio, in partnership with University Hospitals of Cleveland and the Cleveland Clinic. Uses coordinated interdisciplinary clinical research to improve cancer diagnosis, treatment, prevention, and control. Chao Family Comprehensive Cancer Center at the University of California, Irvine http://www.ucihs.uci.edu/cancer An NCI-designated comprehensive cancer center located in Irvine, California, that integrates research, prevention, diagnostic, treatment, and rehabilitation programs to provide patient-centered care for patients and families coping with cancer. City of Hope http://www.cityofhope.org A biomedical research, treatment, and educational institution in Duarte, California, and an NCI-designated comprehensive cancer center dedicated to the prevention and cure of cancer and other life-threatening diseases. Mission follows a compassionate patient-centered philosophy. Supported by a national foundation of humanitarian philanthropy. Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Massachusetts General Hospital http://www.cancercare.harvard.edu Teaching affiliates of Harvard Medical School and founding members of Dana-Farber/Harvard Cancer Center, an NCI-designated comprehensive cancer center, in Boston. Develops and provides comprehensive, multidisciplinary care plans for cancer patients. A major leader in cancer research. Duke Comprehensive Cancer Center http://www.cancer.duke.edu An NCI-designated comprehensive cancer center in Durham, North Carolina, that strives to provide cuttingedge research and compassionate care. Web site provides a tumor registry detailing cancer incidence seen at Duke. Fox Chase Cancer Center http://www.fccc.edu An NCI-designated comprehensive cancer center in Philadelphia that provides basic, clinical, and prevention research in addition to programs for detection and treatment of cancer and community outreach services.
Salem Health: Cancer Fred Hutchinson Cancer Research Center (Seattle Cancer Care Alliance) http://www.fhcrc.org (http://www.seattlecca.org) An NCI-designated comprehensive cancer center in Seattle, Washington. Has pioneered new diagnostic and treatment techniques. Web site offers a Patient Guide to Clinical Trials and information on its Survivorship Program. H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida http://www.moffitt.org A nonprofit, NCI-designated comprehensive cancer center in Tampa, Florida, that provides rapid translation of scientific research discoveries to patient care, a blood and marrow transplant program, outpatient treatment programs, and a lifetime cancer screening program.
Cancer Centers and Hospitals John Wayne Cancer Institute at St. John’s Health Center http://www.jwci.org A cancer research institute in Santa Monica, California, that conducts multidisciplinary basic, clinical translational research, focusing mainly on melanoma, sarcoma, breast cancer, prostate cancer, and colon cancer. Jonsson Comprehensive Cancer Center http://www.cancer.mednet.ucla.edu An NCI-designated comprehensive cancer center at the University of California, Los Angeles, that provides interdisciplinary, team-oriented care for cancer patients. Provides information on research advances in the laboratory, clinical trials, Food and Drug Administrationapproved treatments, and psychosocial and supportive care for cancer patients and their families, including people at high risk of cancer due to family histories or inherited genetic mutations.
Herbert Irving Comprehensive Cancer Center at Columbia University http://www.ccc.columbia.edu An NCI-designated comprehensive cancer center in New York, in partnership with New York Presbyterian Hospital, that provides patient care, clinical trials, research, and education.
Kimmel Cancer Center at Thomas Jefferson University Hospital http://www.kimmelcancercenter.org An NCI-designated comprehensive cancer center in Philadelphia. Translates latest research discoveries and clinical trials into high-quality patient care, provides patient education and support programs, and maintains a cancer registry.
Holden Comprehensive Cancer Center at the University of Iowa http://www.uihealthcare.com/depts/cancercenter An NCI-designated comprehensive cancer center in Iowa City, Iowa, that provides cancer-related research, clinical trials, education, and patient care throughout many departments in the University of Iowa and its hospitals and clinics.
Lineberger Comprehensive Cancer Center at University of North Carolina http://cancer.med.unc.edu A comprehensive cancer center at Chapel Hill’s School of Medicine. A member of the Lance Armstrong Foundation Survivorship Network, the center provides multidisciplinary teams, patient and family support, research, clinical trials, survivor services, and an NC Cancer Hospital oncology newsletter.
Huntsman Cancer Institute at the University of Utah http://www.huntsmancancer.org An NCI-designated cancer center in Salt Lake City, Utah, that consists of scientists, physicians, and health educators working to prevent, diagnose, and treat cancers. Web site offers a link to the Huntsman Online Patient Education (HOPE) Guide. Indiana University Melvin and Bren Simon Cancer Center http://iucc.iu.edu An NCI-designated cancer center in Indianapolis, Indiana, that consists of a partnership between the Indiana University School of Medicine and Clarian Health. Provides quality patient care, research, clinical trials, and educational programs.
Lombardi Comprehensive Cancer Center, Georgetown University Medical Center http://lombardi.georgetown.edu An NCI-designated comprehensive cancer center in Washington, D.C., that provides comprehensive patient care, research, clinical trials, and community outreach. The center also provides the Lombardi Cancerline to answer questions confidentially. M. D. Anderson Cancer Center http://www.mdanderson.org In association with Children’s Cancer Hospital, a comprehensive cancer center in Houston, Texas, that provides integrated programs in cancer treatment, clinical trials, education programs and cancer prevention. 1353
Cancer Centers and Hospitals Mayo Clinic Cancer Center http://mayoresearch.mayo.edu/mayo/research/ cancercenter An NCI-designated comprehensive cancer center with three campuses nationwide. Offers research, clinical trials, patient care, and outreach programs, including Outreach to American Indians and Alaska Natives. Memorial Sloan-Kettering Cancer Center http://www.mskcc.org Close collaboration between scientists and physicians underlines this NCI-designated comprehensive cancer center’s commitment to exceptional patient care, research, and educational programs. Located in New York. Norris Cotton Cancer Center at DartmouthHitchcock Medical Center http://www.cancer.dartmouth.edu/index.shtml An NCI-designated comprehensive cancer center in Lebanon, New Hampshire. Multidisciplinary teams work to provide the best treatment, cure, and recovery environment possible for patients through research, clinical trials, support groups, and education. NYU Cancer Institute http://www.med.nyu.edu/nyuci Part of the New York University Medical Center in New York, it provides programs in patient care, research, prevention, and community outreach and education dealing with cancer. Ohio State University Comprehensive Cancer Center http://www.OSUCCC.osu.edu An NCI-designated comprehensive cancer center in Columbus, Ohio, that translates research into high-quality patient care by offering educational programs, individualized treatments and preventive strategies designed to meet unique personal health care needs. Rebecca and John Moores University of California, San Diego, Cancer Center http://cancer.ucsd.edu An NCI-designated comprehensive cancer center in San Diego, California, dedicated to translating research into promising new treatments and to providing community outreach to educate the public, especially underserved populations, about prevention studies and cancer information. Robert H. Lurie Comprehensive Cancer Center of Northwestern University http://www.cancer.northwestern.edu An NCI-designated comprehensive cancer center in Chicago that performs laboratory and clinical cancer re1354
Salem Health: Cancer search and offers innovative cancer treatments involving clinical trials, cancer prevention and control programs, training and education of health care professionals, cancer information services, and community outreach and education. Roswell Park Cancer Institute http://www.roswellpark.org America’s first cancer center, now an NCI-designated comprehensive cancer center in Buffalo, New York, includes a comprehensive diagnostic and treatment center and a medical research complex. St. Jude Children’s Research Hospital http://www.stjude.org A comprehensive pediatric cancer center in Memphis, Tennessee, St. Jude is America’s third-largest health care charity. Concentrates its efforts on researching and curing childhood cancers and diseases, becoming pioneers in unique procedures and cures. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins http://www.hopkinskimmelcancercenter.org An NCI-designated comprehensive cancer center in Baltimore, Maryland, dedicated to finding more effective cancer treatments through programs in clinical and laboratory research, education, community outreach, and prevention and control. Offers counseling, survivors and palliative care programs, and two residences for out-of-town patients. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine http://www.siteman.wustl.edu An NCI-designated comprehensive cancer center in St. Louis, Missouri, that provides expertise of research scientists and physicians, advanced diagnostic and treatment services, and an active outreach program of cancer screening and education. Stanford Cancer Center http://cancer.stanford.edu An NCI-designated cancer center in Stanford, California, that uses the latest detection, diagnosis, treatment, and prevention discoveries with comprehensive support services to provide the most advanced patient care available. UC Davis Cancer Center http://www.ucdmc.ucdavis.edu/cancer An NCI-designated cancer center in Sacramento, California, that provides multidisciplinary teams for patient care, clinical trials, and support groups and services, in-
Salem Health: Cancer cluding the Triumph Fitness Program and the Writing as Healing Program. Web site provides survivor stories, news releases, and a link to its biannual magazine called Synthesis. UCSF Helen Diller Family Comprehensive Cancer Center http://cancer.ucsf.edu An NCI-designated comprehensive cancer center in San Francisco that combines basic science, clinical research, population science, epidemiology/cancer control, and patient care. University of Alabama at Birmingham Comprehensive Cancer Center http://www3.ccc.uab.edu An NCI-designated comprehensive cancer center in Birmingham, Alabama, that includes a large patient resource library, a preventive care program for women’s cancers, many support groups, and its magazine called Crossroads. University of Colorado Cancer Center http://www.uccc.info An NCI-designated comprehensive cancer center in Aurora, Colorado, that provides a multidisciplinary team approach to patient care. Web site offers information on support groups, patient programs and classes, spiritual counseling, and palliative care.
Cancer Centers and Hospitals University of New Mexico Cancer Center http://cancer.unm.edu An NCI-designated cancer center in Albuquerque, New Mexico, integrates research, clinical trials, patient care, support services, and community outreach to serve its region’s multiethnic populations. University of Pittsburgh Cancer Institute http://www.upci.upmc.edu An NCI-designated comprehensive cancer center in Pittsburgh, Pennsylvania. Provides research, clinical trials, patient care, and education. Web site offers links to a variety of cancer-related publications. University of Tennessee Cancer Institute http://www.utcancer.com A partnership between the University of Tennessee Health Science Center and Boston Baskin Cancer Group in Memphis, this institute provides surgical oncology, radiation oncology, gynecologic oncology, genetic counseling, multidisciplinary clinics, and cancer prevention and supportive care programs. University of Virginia Health System Cancer Center http://www.healthsystem.virginia.edu/internet/cancer An NCI-designated cancer center in Charlottesville, Virginia, that provides cancer care teams, research, clinical trials, and support services.
University of Michigan Comprehensive Cancer Center http://www.mcancer.org An NCI-designated comprehensive cancer center in Ann Arbor, Michigan, that provides research, patient care, a patient education resource center, complementary therapies, nutrition counseling, child and family life services, art therapy, and social work services.
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center http://www.cancer.wisc.edu An NCI-designated comprehensive cancer center in Madison, Wisconsin, that provides research, clinical trials, patient care, and outreach. Web site provides information on news articles and outreach programs, including tobacco cessation and quality of life/pain and symptom management.
University of Minnesota Cancer Center http://www.cancer.umn.edu An NCI-designated comprehensive cancer center in Minneapolis that strives to enhance knowledge of the prevention, causes, detection, and treatment of cancer to improve quality of life for patients and survivors through research, clinical trials, and education. Web site offers access to cancer center stories, news, and publications.
USC/Norris Comprehensive Cancer Center http://ccnt.hsc.usc.edu An NCI-designated comprehensive cancer center in Los Angeles that provides inpatient and outpatient care in its affiliated hospitals and outpatient clinics, conducts research and clinical trials, and translates that research into new patient therapies.
University of Nebraska Medical Center Eppley Cancer Center http://www.unmc.edu:80/cancercenter A comprehensive cancer center in Omaha, Nebraska, that performs cancer research and provides patient care and educational programs.
Vanderbilt-Ingram Cancer Center http://www.vicc.org An NCI-designated comprehensive cancer center in Nashville, Tennessee, that performs research and clinical trials and uses an interdisciplinary team approach to patient care; also provides childhood cancer programs. 1355
Cancer Centers and Hospitals Vermont Cancer Center at the University of Vermont http://www.vermontcancer.org An NCI-designated comprehensive cancer center in Burlington, Vermont, that provides interdisciplinary approaches to cancer research, prevention, patient care, and community education. Web site provides cancer, information, news, and information about support groups and services. Wake Forest University Baptist Medical Center http://www1.wfubmc.edu/cancer An NCI-designated comprehensive cancer center in Winston-Salem, North Carolina, that provides patient care, clinical trials, research, pastoral care, support
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Salem Health: Cancer groups, and education. Web site provides drug interaction information, health encyclopedia, nutrition center, alternative and complementary medicine information, and a physician directory. Yale Cancer Center at Yale University School of Medicine http://yalecancercenter.org An NCI-designated comprehensive cancer center in New Haven, Connecticut, that provides specialized team care, customized treatment plans, many support services, and a weekly informative radio show called Yale Cancer Center Answers. Web site offers an alphabetical list of cancer information and information on clinical trials and research.
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Cancer Support Groups
Adenoid Cystic Carcinoma Organization International http://www.accoi.org Provides information about adenoid cystic carcinoma. Offers support services in several different languages. Web site provides information on treatment options, research, clinical trials, the ACC tumor registry, and financial resources. American Cancer Society http://www.cancer.org Educates the public about cancer, raises funds for cancer research, and runs support groups across the country. Web site provides links to a variety of support groups. Association of Cancer Online Resources http://www.acor.org Provides links to more than one hundred mailing lists and support resources. BC Cancer Agency http://www.bccancer.bc.ca Educates people of British Columbia and the Yukon about cancer, including prevention, screening, early detection, and treatment options, as well as alternative therapies. Offers one-on-one support services and support groups. The Brain Tumor Society http://www.tbts.org Provides educational material and support services, including a newsletter called Heads Up, a monthly e-newsletter called Head Lines, and a comprehensive resource guide called Color Me Hope. Its COPE (Connection of Personal Experiences) program provides sharing of mutual experiences via e-mail and telephone conversations. Breast Cancer Network of Strength http://www.networkofstrength.org Provides support services and resources for people affected by breast cancer and offers a twenty-four-hour breast cancer hotline with interpreters in 150 languages. Cancer Hope Network http://www.cancerhopenetwork.org Provides free, confidential one-on-one support to those affected by cancer by specially trained cancer survivor volunteers. CancerCare http://www.cancercare.org
Provides free counseling and support, online and by telephone, in English and Spanish, by trained oncology social workers. Also provides financial assistance to those in need and affected by cancer. The Carcinoid Cancer Foundation http://www.carcinoid.org Provides information on carcinoid cancer, treatment options, and clinical trials. Web site offers a list of doctors in the United States and Canada who specialize in treating carcinoid cancer, a list of carcinoid cancer support groups, resources for medical professionals, financial assistance resources, and archived articles. The Childhood Brain Tumor Foundation http://www.childhoodbraintumor.org Provides information about brain tumors and cancer research, especially that related to childhood brain tumors. Offers the Childhood Cancer Ombudsman Program, which helps families with health insurance analysis and applications and with employment and educational difficulties that may arise during or after treatment. Children’s Cancer Association http://www.childrenscancerassociation.org Provides many resources and support services to help children and their families cope with cancer, including the DreamCatcher Wish program, the CCA Caring Cabin, and the Kids’ Cancer Pages. Colon Cancer Alliance http://www.ccalliance.org Provides support and educational resources for newly diagnosed colon cancer patients. Web site lists organizations and programs that may help with the financial issues related to medical treatment. Colorectal Cancer Network http://clickonium.com/colorectal-cancer.net/html Provides a support network, including support groups, listserves, chat rooms, and a system of matching longterm survivors with newly diagnosed patients. Web site provides information about prevention and screening, treatment options, advocacy, and resources for newly diagnosed colon cancer patients. Corporate Angel Network http://www.corpangelnetwork.org Arranges free travel on corporate jets, using empty seats on routine business flights, for cancer patients, bone marrow donors, and bone marrow recipients who are traveling to cancer treatment centers. 1357
Cancer Support Groups Florida Prostate Cancer Network http://www.charityadvantage.com/www.floridaprostate-cancer.org/HomePage.asp Educates men of Florida about the risks of developing prostate cancer. Supports research and promotes legislation to increase health insurance coverage of prostate cancer screenings. Web site offers information about early detection, support organizations, clinical trials, and current treatment options. Gilda’s Club Worldwide http://www.gildasclub.org Provides lectures, workshops, and support groups for those people whose lives have been touched by cancer, including a support program called Noogieland for children and teens. Web site lists Gilda’s Clubhouse locations across the United States. The Gynecologic Cancer Foundation http://www.thegcf.org Provides brochures and educational materials about gynecologic cancer. Supports research and training related to gynecologic cancers and organizes annual ovarian cancer survivor’s courses. International Myeloma Foundation http://www.myeloma.org Provides comprehensive information on myeloma treatment options, disease management, and programs and services for patients, family members, and health care professionals. Resources are available in fourteen languages. Web site offers educational resources, webcasts, a newsletter, and a toll-free hotline. Lance Armstrong Foundation http://www.livestrong.org Provides survivorship education and resources, national advocacy initiatives, community programs, and scientific and clinical research grants. Web site provides information on LiveStrong SurvivorCare, a LiveStrong blog, a LiveStrong survivorship notebook, many cancer survivor brochures, sign-up for the LiveStrong Newsletter, and a link to the LiveStrong Store, where LiveStrong apparel and accessories can be purchased, the proceeds of which help support LiveStrong programs and services. Leukemia and Lymphoma Society http://www.leukemia-lymphoma.org Provides information on leukemia, lymphoma, myeloma, and other blood cancers and support services for newly diagnosed and long-term survivors. Also supports research on blood cancers and pursues advocacy aimed at 1358
Salem Health: Cancer governmental decision makers. Web site hosts several discussion boards and offers medical news, event listings, and treatment information. Informational booklets are published in English, Spanish, and French. Linda Creed Breast Cancer Foundation http://www.lindacreed.org Provides educational materials about the detection, treatment, and survivorship of breast cancer; offers access to detection and treatment resources; provides financial assistance to women in the Philadelphia area receiving breast cancer treatment; and advocates for critical cancer legislation and governmental funding for breast cancer research. Living Beyond Breast Cancer http://www.lbbc.org Provides educational programs and services to women affected by breast cancer, including a toll-free Survivors’ Helpline, a quarterly newsletter called Insight, publications for African American and Latina women, current information about treatment options, and networking programs for women of color and young survivors. Lung Cancer Alliance http://www.lungcanceralliance.org Provides support and advocacy for people at risk for and those living with lung cancer. Offers a peer-to-peer support network, toll-free information and referral services, and a quarterly newsletter called Spirit and Breath. Lustgarten Foundation for Pancreatic Cancer Research http://www.lustgarten.org/LUS/CDA/HomePage.jsp Provides research grants to support pancreatic cancer research, information on clinical trials, and patient and caregiver support services. Web site provides information on selecting a treatment provider, an Ask an Expert series, research news, and information on legal, insurance, and benefits assistance. Lymphoma Research Foundation http://www.lymphoma.org Raises funds for lymphoma research; provides educational materials on Hodgkin disease and non-Hodgkin lymphoma; provides information on diagnostic techniques, treatment options, and clinical trials; offers support for people living with lymphoma; sponsors lectures for scientists who conduct lymphoma research; and matches patients with peer support through its Lymphoma Support Network. Web site provides lymphoma news and features, fact sheets and booklets, and access to webcasts and podcasts.
Salem Health: Cancer Marti Nelson Cancer Foundation/ CancerActionNow.org http://www.canceractionnow.org Advocates for different options for cancer patients when standard treatments have not helped by providing information on nonstandard cancer treatment options, clinical trials, and experimental drugs. Mautner Project, the National Lesbian Health Organization http://www.mautnerproject.org Offers support, advocacy, and educational information for lesbian, bisexual, and transgender women and their families, especially those living with cancer. Melanoma International Foundation http://www.melanomainternational.org Provides melanoma facts, and tips on coping with a melanoma diagnosis. Web site provides an extensive list of melanoma treatment centers, forums, blogs, message boards, the latest news, and upcoming events. National Brain Tumor Foundation http://www.braintumor.org Provides information about types of brain tumors, treatments, treatment centers, financial assistance, support services, and upcoming events as well as survivor stories and the latest news. National Breast Cancer Coalition http://www.natlbcc.org Promotes breast cancer research and works toward improving access for all women to high-quality breast cancer screening, diagnosis, treatment, and care; informs and trains breast cancer survivors and others in effective advocacy efforts aimed at eradicating breast cancer. Web site provides breast cancer information, the latest news, and an e-newsletter. National Cervical Cancer Coalition http://www.nccc-online.org Educates people about cervical cancer and the importance of early detection, advocates for quality patient care, and provides support through its Phone Pals and E-Pals programs. Web site provides links to many resources related to cervical cancer, the NCCC Store, and sign-up for its newsletter Extraordinary Moments. National Coalition for Cancer Survivorship http://www.canceradvocacy.org Raises awareness about cancer survivorship issues, selfadvocacy, and public advocacy, and provides resources for cancer patients, including information on types of cancer, treatment issues, side effects, financial advice,
Cancer Support Groups and other cancer-related topics. Web site offers sign-up for online newsletter called InterAction and a Cancer Survival Toolbox. National Lymphedema Network http://www.lymphnet.org Provides information about lymphedema and news about medical and scientific developments, sponsors a national conference and a patient summit, supports research into causes and possible alternative treatments, and advocates to standardize quality treatment for lymphedema patients. Web site lists treatment centers, health care professionals, and support groups. National Ovarian Cancer Coalition http://www.ovarian.org Raises awareness and promotes education about ovarian cancer. Web site lists state chapters, support groups and services, and clinical trials, and provides the latest news, an NOCC newsletter, and medical information about ovarian cancer. Native American Cancer Research http://natamcancer.org Provides culturally sensitive information and support to Native Americans living with cancer. Web site provides information on clinical trials, treatment, the Native American Cancer Survivors Network, and printable handouts. Native People’s Circle of Hope http://www.nativepeoplescoh.org A coalition of Native American cancer support groups in which Native American cancer survivors offer culturally sensitive support and counseling for newly diagnosed Native American cancer patients. Oklahoma Brain Tumor Foundation http://www.okbtf.org Provides education, support groups, advocacy, and financial assistance for people in Oklahoma affected by primary brain or central nervous system tumors. Web site provides information about tumors, treatments, clinical trials, and area oncologists. Oncolink http://www.oncolink.com Online cancer resource Web site operated by the University of Pennsylvania with an Ask the Experts page. Includes links to OncoLife, which offers an individualized survivorship care plan created on the basis of answers provided in a questionnaire; OncoTip of the Day; OncoPilot, a guide for navigating the cancer journey; and OncoLink eNews, a monthly newsletter. 1359
Cancer Support Groups Ovarian Cancer Canada http://www.ovariancancercanada.ca Provides ovarian cancer education, support, a quarterly newsletter, and other resources to Canadian residents. All services are available in English and French. Ovarian Cancer Research Fund http://www.ocrf.org Promotes and raises funds for ovarian cancer research and its early diagnosis, and provides support and information to patients and loved ones, including an informational hotline mainly staffed by ovarian cancer survivor volunteers. Pediatric Brain Tumor Foundation http://www.pbtfus.org Offers educational materials and support to children with brain tumors and their parents, and raises money for pediatric brain tumor research, awareness, and detection. The Prostate Net http://www.prostate-online.org Provides information, support, and resources to simplify the treatment decision-making process. Research Advocacy Network http://www.researchadvocacy.org Provides education, support, and advocacy by working with all participants in the medical research process to improve patient care. Sarcoma Alliance http://www.sarcomaalliance.org Provides guidance, education, and support to those people whose lives have been affected by sarcoma. Web site provides information on services, programs, survivor and caregiver support groups, and an assistance fund developed to help sarcoma patients obtain second opinions from sarcoma specialists across the country.
Salem Health: Cancer Skin Cancer Foundation http://www.skincancer.org Provides educational material about skin cancer prevention and detection. Web site provides information about different types of skin cancer, an Ask the Expert feature, and a physician finder database. Support for People with Oral and Head and Neck Cancer http://www.spohnc.org Provides information and support groups for people living with oral cancer and cancers of the head and neck. Web site provides educational resources, information on clinical trials, and news releases. Susan G. Komen for the Cure http://www.komen.org Funds research grants; provides breast cancer education; gives information about screening, treatment options, and community support groups; and provides a national tollfree helpline, which is available in English and Spanish. ThyCa: Thyroid Cancer Survivors’ Association http://www.thyca.org Provides information and support services for people living with thyroid cancer and hosts survivor workshops and an annual conference. Web site provides access to a new-patient packet, resource list, low iodine cookbook, and an online newsletter. The Ulman Cancer Fund for Young Adults http://www.ulmanfund.org Provides educational programs and support groups for teens and young adults facing the challenges of cancer, and conducts community outreach programs as well as maintains a scholarship fund for young people who are facing or who have overcome cancer.
SHARE: Self-help for Women with Breast or Ovarian Cancer http://www.sharecancersupport.org Trained breast or ovarian cancer survivors staff nationwide hotlines and run support groups and educational programs for women with breast or ovarian cancer in the New York metropolitan area.
Us TOO International http://www.ustoo.com Provides prostate cancer education and a support network with hundreds of support groups across the United States, and advocates for increased funding for prostate cancer detection, diagnosis, treatment, and research. Web site provides a list of clinical trials, publications, informational newsletters, and a resource kit for newly diagnosed patients.
Sisters Network http://www.sistersnetworkinc.org A national African American breast cancer survivorship organization that provides African American women with educational materials about breast cancer risk, symptoms, and treatment, as well as support services.
The Wellness Community http://www.thewellnesscommunity.org Provides online support groups in English and Spanish, as well as an online resource guide with information about various types of cancer, clinical trials, and advice on managing treatment side effects.
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Salem Health: Cancer Wisconsin Multiple Myeloma Support Group http://www.madison.com/communities/ multiplemyeloma Hosts monthly support meetings and publishes a monthly newsletter that provides a resource list and notes on new research.
Cancer Support Groups Young Survival Coalition http://www.youngsurvival.org Provides educational and support services that are unique to young women and breast cancer. Web site provides information about research, clinical trials, and programs; informational brochures; a quarterly newsletter; and an online bulletin board.
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Carcinogens
The following list of carcinogens is based on the National Toxicology Program’s Report on Carcinogens (RoC, 11th ed.). Human carcinogens that are both “known” and “reasonably anticipated” are listed here, with a summary of each carcinogen along with its status (K for “known” or RA for “reasonably anticipated”) according to the ROC. The ROC can be fully accessed as a PDF file for more in-depth technical description from the home page of the National Toxicology Program, http://ntp.niehs.nih.gov. acetaldehyde: RA. Primarily used in the production of a variety of chemicals. Also found in tobacco, ripe fruit, wine, and other alcoholic beverages. Produced by plants as part of their normal life cycle. Main source of human exposure is through the metabolism of alcohol. Other sources include food, beverages, and, to a lesser extent, the air. Studies indicate an increased incidence of squamous cell carcinomas and adenocarcinomas in exposed laboratory animals; inadequate evidence to evaluate the carcinogenicity in humans. 2-acetylaminofluorene: RA. Used as a positive control by toxicologists. Potential human exposure includes inhalation and skin contact. Resulting cancers in laboratory animals include carcinomas of the urinary bladder and the liver and subcutaneous carcinomas on the face; no adequate data are available to evaluate the carcinogenicity in humans. acrylamide: RA. Used in treating municipal drinking water and wastewater. Also found in home appliances, building materials, automotive parts, cosmetics, soaps, and lotions. Can be absorbed through unbroken skin, mucous membranes, lungs, and the gastrointestinal tract. Resulting cancers in laboratory animals; no adequate data are available to evaluate the carcinogenicity in humans. acrylonitrile: RA. Used extensively in the manufacture of synthetic fibers, resins, plastics, elastomers, and rubber for consumer goods such as textiles, dinnerware, food containers, toys, luggage, automotive parts, small appliances, and telephones. A variety of cancers have developed in laboratory animals. Studies have indicated an increased risk of lung cancer in textile plant workers exposed to acrylonitrile. Adriamycin (doxorubicin hydrochloride): RA. An antibiotic used in antimitotic chemotherapy to treat various neoplastic diseases; human exposure routes include injection, skin contact, and inhalation. Cancers that developed in laboratory animals include mammary tumors, bladder papillomas, urinary bladder tumors, and local sarcomas near injection sites. Although no adequate data are available to evaluate the carcinogenicity in humans, in a study of cancer patients receiving Adriamycin in combination with alkylating agents and 1362
radiotherapy, patients developed leukemia and bone cancer. aflatoxins: K. Toxins produced by Aspergillus fungi that grow naturally on grains and other agricultural crops. Exposure occurs by eating contaminated foods or by inhalation of dust containing aflatoxins. Studies have confirmed carcinogenicity in humans resulting in liver cancer (hepatocellular carcinoma and primary livercell cancer). alcoholic beverage consumption: K. Known or suspected as human carcinogens, include acetaldehyde, nitrosamines, aflatoxins, ethyl carbamate (urethane), asbestos, and arsenic compounds. Studies have indicated an increased risk of cancers of the mouth, pharynx, larynx, and esophagus with increased alcoholic beverage consumption, especially when combined with smoking. 2-aminoanthraquinone: RA. Used in the production of anthraquinone dyes, which are used in automotive paints, high-quality paints and enamels, textile dyes, plastics, rubber, and printing inks. Hepatocellular carcinomas, neoplastic nodules, and lymphomas have resulted in laboratory animals that have ingested 2-aminoanthraquinone; however, potential human exposure is through skin contact, and no adequate data are available to evaluate the carcinogenicity in humans. o-aminoazotoluene: RA. Used in coloring oils, fats, waxes, and medicine, and in the production of the dyes Solvent Red 24 and Acid Red 115. Cancers of the liver, lungs, and urinary bladder have resulted in laboratory animals that have ingested o-aminoazotoluene; potential human exposure is through skin contact and inhalation and no adequate data are available to evaluate the carcinogenicity in humans. 4-aminobiphenyl: K. Previously used commercially as a rubber antioxidant, as a dye intermediate, and in the detection of sulfates; later used only in laboratory research because of sufficient evidence for carcinogenicity in humans. 1-amino-2,4-dibromoanthraquinone: RA. Used in the production of dyes, especially those used in textiles. Tumors in various sites have been reported in laboratory animals in which 1-amino-2,4-dibromoanthraquinone had been orally administered; however, no adequate
Salem Health: Cancer data are available to evaluate the carcinogenicity in humans. Human exposure is primarily through skin contact. 1-amino-2-methylanthraquinone: RA. Was used in the production of dyes for synthetic fibers, furs, and thermoplastic resins, specifically for the dyes Solvent Blue 13 and Acid Blue 47. No longer commercially produced in the United States. Liver and kidney cancer have occurred in exposed laboratory animals; no adequate data are available to evaluate the carcinogenicity in humans. Human exposure would be primarily through skin contact and inhalation. amitrole: RA. Widely used as an herbicide on annual and perennial broadleaf and grass-type weeds, on noncrop land prior to sowing, and as control of pondweeds. When administered in the diet of laboratory animals, increased incidence of tumors in the liver and thyroid occurred. No adequate data are available to evaluate the carcinogenicity in humans. Human exposure is through inhalation and skin contact or ingestion of contaminated food or drinking water. o-anisidine hydrochloride: RA. Used in the production of dyes and pharmaceuticals, as a corrosion inhibitor for steel, and as an antioxidant for polymercaptan resins. Tumors of the urinary bladder, the renal pelvis, and the thyroid occurred in laboratory animals. No adequate data are available to evaluate the carcinogenicity in humans. Human exposure is through inhalation and skin contact; the general population may be exposed to the chemical as an environmental pollutant or through cigarette smoke. arsenic compounds, inorganic: K. Used in a variety of substances ranging from pesticides to medicines; later more commonly used in pressure-treated wood. Effective December 31, 2003, a voluntary phaseout in wood for residential uses began. Also used in the production of lead alloys. Sufficient evidence confirms that humans exposed to arsenic compounds have increased risks of cancers of the skin, lung, digestive tract, liver, bladder, kidney, and lymphatic and hematopoietic systems. Occupational exposure includes inhalation and skin contact. For the general population, exposure is primarily through the ingestion of foods or by inhalation of contaminated air. asbestos: K. Has been used in roofing, flooring, thermal and electrical insulation, cement pipe and sheets, friction materials, gaskets, coatings, plastics, textiles, paper, and other products. Banned in general-use garments, but it may be used in firefighting garments. Human exposure is primarily through inhalation and ingestion. Although the potential for exposure is widespread be-
Carcinogens cause of its previous extensive use, the potential for exposure continues to decline because of the elimination of asbestos products from the market. Sufficient evidence confirms that asbestos exposure in humans causes respiratory-tract cancer, pleural and peritoneal mesothelioma, lung cancer, laryngeal cancer, cancer of the digestive tract, and other cancers. azacitidine: RA. Has been used in treatment of acute myeloblastic anemia, acute lymphoblastic leukemia, and myelodysplastic syndromes. Has been used in combination with other antineoplastic agents in cancer treatment trial protocols, as well as in clinical trials for beta thalassemia, acute myeloid leukemia, myelodysplastic syndrome, advanced or metastatic solid tumors, non-Hodgkin lymphoma, multiple myeloma, non-smallcell lung cancer, and prostate cancer. Malignant tumor formation at multiple tissue sites occurred in laboratory animals when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. azathioprine: K. Used as an immunosuppressive agent, usually in combination with a corticosteroid, to prevent rejection following transplant surgery and to manage severe cases of rheumatoid arthritis in adults, and as a second-line treatment for some immunological diseases. A high occurrence of cancers in patients and others routinely treated with azathioprine confirms carcinogenicity in humans. benzene: K. Used primarily as a solvent in the chemical and pharmaceutical industries, in the synthesis of numerous chemicals, and in gasoline. Also used in the production of styrene, phenol, acetone, cyclohexane, nitrobenzene, detergent alkylate, and chlorobenzenes. Benzene is known to cause leukemia. benzidine and dyes metabolized to benzidine: K. Has been used in the production of azo dyes, fast-color salts, naphthols, sulfur dyes, and other dyeing compounds. Also used in clinical laboratories for detection of blood, as a rubber-compounding agent, in the manufacture of plastic films, for detection of hydrogen peroxide in milk, and for quantitative determination of nicotine. Most of these uses have been discontinued because of concerns about potential carcinogenicity. Although potential for exposure is low, human exposure may occur through inhalation, ingestion, or skin contact. Liver cancer has been reported in association with occupational exposure to benzidine, and limited evidence has associated it with a variety of other cancers. benzotrichloride: RA. Used as a chemical intermediate to stabilize plastics in the presence of ultraviolet light, 1363
Carcinogens in the preparation of specific dyes and pigments, and to make benzotrifluoride, hydroxybenzophenone, antiseptics, and antimicrobial agents. Human exposure is through inhalation, ingestion, and skin contact. A variety of cancers have developed in laboratory animals exposed to benzotrichloride. Increased risk of respiratory cancer has been reported in humans involved in the production of chlorinated toluenes, which involves potential exposure to benzotrichloride and other chemicals; otherwise, no data are available to evaluate the carcinogenicity in humans. beryllium and beryllium compounds: K. Used as an alloy, metal, and oxide in electrical components and in aerospace and defense applications. Also used in molds for injection-molded plastics, computers, home appliances, telecommunications devices, dental applications, bicycle frames, golf clubs, and many other applications. Inhalation of dusts and fumes is the primary route of human exposure, but it may also be ingested in drinking water or food. Studies showing an increased risk of lung cancer in occupational groups exposed to beryllium or beryllium compounds provide sufficient evidence of carcinogenicity in humans. bromodichloromethane: RA. Used in the synthesis of organic chemicals and as a reagent in laboratory research. Also has been used to separate minerals and salts, as a flame retardant, and in fire extinguishers. It is also formed as a result of the chlorination treatment of drinking, waste, or cooling water. Human exposure is through the consumption of contaminated drinking water, beverages, and food products, and inhalation of contaminated ambient air. Tumors in the kidney, intestine, and liver have been reported in laboratory animals when administered by stomach tube. Sufficient data are not available to evaluate the carcinogenic effects in humans. 2,2-bis-(bromoethyl)-1,3-propanediol (technical grade): RA. Used as a flame retardant, especially in unsaturated polyester resins, molded products, and rigid polyurethane foam. Tumor formation at multiple tissue sites and leukemia occurred in laboratory animals. No data are available to evaluate the carcinogenicity in humans. Contamination occurs in the environment as dust and through wastewater; therefore, human exposure is through inhalation and skin contact. 1,3-butadiene: K. Used in a variety of rubber products. Also used in a number of industrial chemicals and in the manufacture of fungicides. Also found in gasoline, automobile exhausts, and cigarette smoke. Human exposure is primarily through inhalation; some exposure may occur from ingesting contaminated food or water, 1364
Salem Health: Cancer or through skin contact. Lymphatic and hematopoietic cancers have been reported in humans who have been exposed to 1,3-butadiene. 1,4-butanediol dimethanesulfonate (Myleran): K. Used in chemotherapeutic treatment by ingestion or intravenous administration to treat some forms of leukemia. Also may be used in combination with cyclophosphamide before bone marrow transplants for chronic myelogenous leukemia. Cancer at different tissue sites has been reported among leukemia patients receiving 1,4-butanediol dimethanesulfonate. Also, leukemia was reported in a follow-up study of bronchial cancer patients treated with 1,4-butanediol dimethanesulfonate. butylated hydroxyanisole (BHA): RA. Used primarily as an antioxidant and preservative in an extensive list of foods (especially those containing vegetable oils and animal fats), food packaging, animal feed, and cosmetics, and in rubber and petroleum products. Administration in the diet induced tumors in the forestomach of laboratory animals. No data are available to evaluate the carcinogenicity in humans. Human exposure is through ingestion and skin contact. cadmium and cadmium compounds: K. Used primarily in batteries. Cadmium compounds are used in analytical chemistry, calico printing, dyeing, mirrors, electronbeam-pumped lasers, electroplating, fluorescent screens, lubricants, nuclear reactors, photocopying, photographic emulsions, radiation detectors, smoke detectors, solar cells, thin-film transistors and diodes, phosphors, photomultipliers, and vacuum tubes. Also used as a fungicide, nematocide, or ascaricide; to color glass and porcelain; and in the production of cadmium-containing stabilizers and pigments for paints, glass, ceramics, plastics, textiles, paper, and fireworks. Human exposure is through ingestion of contaminated food, drinking water, soil, and dust, and inhalation of particles of cadmium from ambient air or cigarette smoke. The largest intake of cadmium is estimated to come from cereal grain products, potatoes, and other vegetables. Studies have confirmed that exposure to various cadmium compounds increases the risk of lung cancer. Evidence also suggests an increased risk of prostate, kidney, and bladder cancer. carbon tetrachloride: RA. Used primarily in the production of Freon 11 and 12. Human exposure is through inhalation, ingestion, and skin contact. The general population is most likely exposed through air and drinking water. Liver tumors occurred in laboratory animals exposed to carbon tetrachloride. Although no adequate data are available to evaluate the carcinogenicity in hu-
Salem Health: Cancer mans, liver tumors, respiratory cancers, and leukemia have been reported in humans exposed to carbon tetrachloride. ceramic fibers (respirable size): RA. Used as insulation materials, primarily for lining furnaces and kilns and as replacement for asbestos. Products produced using ceramic fibers are blankets, boards, bulk fibers, felts, vacuum-formed or cast shapes, paper, and textile products. Human exposure is through inhalation, mainly in the manufacturing environment, during installation, and during removal. Tumors of the lung occurred in laboratory animals. No adequate studies have confirmed carcinogenicity in humans. chlorambucil: K. Used primarily in the treatment of chronic lymphocytic leukemia and primary (Waldenström) macroglobulinemia. Also used as an immunosuppressive agent in the treatment of systemic lupus erythematosus, acute and chronic glomerular nephritis, nephrotic syndrome, chronic active hepatitis, cold agglutinic disease, psoriasis, and Wegener granulomatosis. Human exposure is through ingestion, inhalation, and skin contact. Increased risk of cancers, especially acute nonlymphocytic leukemia, has been reported with exposure to chlorambucil. chloramphenicol: RA. An antimicrobial agent used to combat serious infections; has restricted use because it causes blood dyscrasia. Human exposure is primarily by the oral or topical route through its use as a drug; exposure also may occur through inhalation, ingestion, skin contact, or contact with contaminated water or soil. Although no adequate studies have confirmed cancers in laboratory animals exposed to chloramphenicol, many human case reports have implicated chloramphenicol as a cause of aplastic anemia and an increased risk of leukemia. chlorendic acid: RA. Used primarily as a flame retardant in polyester resins and coatings, epoxy resins, and polyurethane foams. Also used in the manufacture of corrosion-resistant polyester resins, oil-modified paints and coatings, flame-retardant additives, extreme pressure lubricants, and epoxy resins used in printed circuit boards. Human exposure is primarily through skin contact; small exposure may occur through inhalation. Tumors of the liver, pancreas, lung, and preputial gland occurred in laboratory animals in which chlorendic acid was administered in the diet. No data are available to evaluate the carcinogenicity in humans. chlorinated paraffins (C12, 60 percent chlorine): RA. Used primarily as extreme-pressure lubricant additives in metalworking and in flame retardants and plasticizers for plastics. Also used in rubber, paints, adhe-
Carcinogens sives, caulks, and sealants, and as a plasticizer in inks, paper and textile coatings, and flexible polyvinyl chloride. Tumors of the liver, kidney, and thyroid gland, as well as leukemia, occurred in laboratory animals in which chlorinated paraffins were administered by stomach tube. No data are available to evaluate the carcinogenicity in humans. 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU): RA. Has limited use in the treatment of Hodgkin disease, brain tumors, colorectal tumors, and specific pulmonary malignancies. Human exposure is through ingestion, inhalation, and skin contact. Tumors of the lung and lymphosarcomas occurred in laboratory animals in which CCNU was administered by injection. No adequate data are available to evaluate the carcinogenicity in humans; however, cases of leukemia have been reported in cancer patients who have received CCNU. 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (methyl-CCNU): K. Used an investigational drug in the treatment of several types of cancers. Clinical trials in which cancer patients were given adjuvant treatment with methyl-CCNU showed an increased risk of developing leukemia and preleukemia. bis(chloroethyl) nitrosourea (BCNU): RA. Used in the treatment of Hodgkin disease, multiple myeloma, and brain tumors. Human exposure is through injection, inhalation, and skin contact. Tumors of the lung and peritoneal cavity have occurred in laboratory animals administered BCNU by injection. Limited evidence of carcinogenicity in humans is available in that BCNU is associated with acute nonlymphocytic leukemia following its use with other anticancer therapies in the treatment of previously existing cancer. chloroform: RA. Primarily used to produce hydrochlorofluorocarbon-22; also used as a solvent and in certain medical procedures. Human exposure is through inhalation, skin contact with water, and ingestion, primarily drinking water. Tumors of the kidney and liver occurred in laboratory animals that were exposed to chloroform. There is no adequate evidence of carcinogenicity in humans; however, some studies indicate that there is an association between cancer of the large intestine, rectum, and urinary bladder and the components of chlorinated water. bis(chloromethyl) ether (BCME) and technical-grade chloromethyl methyl ether (CMME): K. Used primarily as chemical intermediates and alkylating agents. Human exposure is through inhalation and skin contact; however, probability of exposure is very low. Potential for exposure is greatest for chemical plant work1365
Carcinogens ers, ion-exchange resin makers, laboratory workers, and polymer makers. Studies have demonstrated that occupational exposure causes lung cancer. 3-chloro-2-methylpropene: RA. Used primarily in the production of carbofuran, an insecticide used mostly on corn. Also used in the production of plastics, pharmaceuticals, herbicides, and other organic chemicals; as a textile additive; and as a perfume additive. Human exposure is through inhalation, ingestion, and skin contact. Tumors of the forestomach occurred in laboratory animals when administered by stomach tube. No data are available to evaluate the carcinogenicity in humans. 4-chloro-o-phenylenediamine: RA. Patented as a hair dye component and used in the production of a photographic chemical, as a curing agent for epoxy resins, and as a reagent in gas chromatography. Human exposure is through ingestion, inhalation, and skin contact. Little exposure is expected in the general population due to its limited use in consumer products. Tumors of the urinary bladder and liver occurred in laboratory animals when administered in the diet. No data are available to evaluate the carcinogenicity in humans. chloroprene: RA. Used in the production of neoprene, a synthetic rubber used in the production of automotive and mechanical rubber goods, adhesives, caulks, construction goods, fiber binding, footwear, flame-resistant cushioning, fabric coatings, roof coatings, and sealants for dams or locks in waterways. Human exposure is through inhalation. Inhalation exposure in laboratory animals induced tumor formation at multiple tissue sites. Limited data demonstrating that occupational exposure to chloroprene increases the risk for various tumors may suggest carcinogenicity in humans. p-chloro-o-toluidine and p-chloro-o-toluidine hydrochloride: RA. Has been used to produce azo dyes for cotton, silk, acetate, and nylon, and to produce Pigment Red 7 and Pigment Yellow 49, as well as in the manufacture of the pesticide chlordimeform. Human exposure is through inhalation, ingestion, and skin contact. Increased incidences of urinary bladder tumors have been documented in workers exposed to p-chloroo-toluidine; however, as they were also exposed to numerous other compounds, this provides limited evidence of carcinogenicity in humans. Increased incidence of tumors occurred in laboratory animals exposed to p-chloro-o-toluidine hydrochloride. chlorozotocin: RA. Used in the investigational treatment of various cancers. Human exposure is through intravenous administration. An increased incidence of sarcoma and mesothelioma in the peritoneal cavity, and tumors of the nervous system, lungs, and forestomach, 1366
Salem Health: Cancer occurred in laboratory animals in which chlorozotocin was administered. No adequate data are available to evaluate the carcinogenicity in humans. chromium hexavalent compounds: K. Used as corrosion inhibitors, in wood preservatives, in leather tanning, in metal finishing and chrome plating, in stainlesssteel production, and in the manufacture of pigments. Also used in textile dyeing processes, printing inks, drilling muds, pyrotechnics, water treatment, and chemical synthesis. Residential uses as wood preservatives are expected to decrease because of a voluntary phaseout that went into effect December 31, 2003. Exposure for the general population is through inhalation of the ambient air, ingestion of water, or skin contact. Increased risks of lung cancer and a rare cancer of the sinonasal cavity among workers engaged in chromate production, chromate pigment production, and chromium plating have been reported. Other studies suggest that exposure to chromium may also be associated with cancer at other tissue sites, including leukemia and bone cancer. C.I. Basic Red 9 monohydrochloride: RA. Used primarily in a nutrient agar for bacterium identification; as a biological stain; in a commercial magenta dye used for coloring textiles, china clay products, leather, and printing inks; and as a filter dye in photography. Also used in tinting automobile antifreeze solutions and toilet sanitary preparations. Human exposure is primarily through skin contact. A variety of tumors have occurred in laboratory animals exposed to the compound. An increase in urinary bladder tumors in workers involved in the manufacture of magenta dye has been reported; however, inadequate evidence is available to determine if this is attributable to exposure to the magenta or to other intermediates and impurities. cisplatin: RA. Used in the treatment of various malignancies, often in combination with other cancer treatments. Human exposure is not only through treatment but also through skin absorption and inhalation. Significant increases in the incidence and number of lung adenomas and skin papillomas, as well as leukemia, occurred in laboratory animals in which cisplatin was administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. coal tars and coal tar pitches: K. Used primarily for the production of refined chemicals and coal tar products. Have also been used in surface-coating formulations, pesticides, and epoxy-resin surface coatings, and as fuel in open-hearth furnaces and blast furnaces in the steel industry. U.S. pharmacopeia-grade coal tar is used in denatured alcohol and in preparations used to treat
Salem Health: Cancer various skin conditions. Coal tar pitches are used primarily as the binder for aluminum-smelting electrodes and in roofing materials, refractory brick, and surface coatings; as a binder for foundry cores; and to produce pitch coke. Also used for road paving and construction, as well as in the production of naphthalene, recovery of benzene, production of anthracene paste, briquetting of smokeless solid fuel, impregnation of electrodes and fibers, and manufacture of electrodes and graphite. Human exposure is through inhalation, ingestion, and skin contact. Increased incidences of leukemia and a variety of other cancers have occurred in humans exposed to coal tars or coal tar pitches. Coal tars and coal tar pitches contain known and potential carcinogens, such as benzene, naphthalene, and other polycyclic aromatic hydrocarbons. cobalt sulfate: RA. Used in the electrochemical and electroplating industries; as a drier in lithographic inks, varnishes, paints, and linoleum; and in storage batteries, ceramics, enamels, glazes, and porcelain. Has been used in animal feeds as a mineral supplement and on pastures to supplement forage with cobalt, as well as in beers and to treat anemia in people not responsive to other treatments. Human exposure is through inhalation of ambient air and ingestion of food or drinking water. Occupational exposure also includes skin contact. Tumors of the lung and adrenal gland occurred in laboratory animals when administered by inhalation. No significant data are available to evaluate the carcinogenicity in humans. coke oven emissions: K. Used in iron-making blast furnaces, to synthesize calcium carbide, and to manufacture graphite and electrodes. Coke oven gas is used as a fuel. Coke by-products may be refined into commodity chemicals, such as benzene, toluene, naphthalene, sulfur, and ammonium sulfate. Human exposure to coke oven emissions is through inhalation and skin contact. A variety of cancers have been reported in humans exposed to coke oven emissions. p-cresidine: RA. Used exclusively in the production of azo dyes and pigments—such as Direct Orange 72, FD&C Red 40, and Direct Violet 9—to be used in the textile industry. Human exposure is through inhalation and skin contact. Increased incidences of urinary bladder cancer, liver cancer, and olfactory neuroblastomas occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. cupferron: RA. Used to separate and precipitate metals such as copper, iron, vanadium, and thorium; also used in analytical laboratories. Human exposure is through
Carcinogens ingestion and inhalation of dust from the dry salt, and through skin contact. Hemangiosarcomas and a variety of tumors have occurred in laboratory animals when administered in the diet. No data are available to evaluate the carcinogenicity in humans. cyclophosphamide: K. Used to treat a variety of cancers; also used as an immunosuppressive agent following organ transplants or to treat autoimmune disorders. Exposure for the general population is through medical treatment; occupational exposure is through skin contact or inhalation of dust. Bladder cancer and leukemia have been reported in patients administered cyclophosphamide. cyclosporin A: K. Used as an immunosuppressive agent in the prevention and treatment of graft-versus-host reactions in bone marrow transplantation and for the prevention of rejection of organ transplants. Has also been tested for the treatment of a variety of diseases. Human exposure is through intravenous and oral administration. Lymphoma and skin cancer have been reported in transplant recipients, psoriasis patients, and rheumatoid arthritis patients treated with cyclosporin A. dacarbazine: RA. Used in the treatment of Hodgkin disease, malignant melanomas, neuroblastomas, osteogenic sarcomas, and soft-tissue sarcomas, and occasionally in the therapy for other neoplastic diseases that have become resistant to alternative treatment. Human exposure is through injection, inhalation, and skin contact. A variety of cancers have resulted in laboratory animals when administered dacarbazine. No adequate data are available to evaluate the carcinogenicity in humans. danthron (1,8-dihydroxyanthraquinone): RA. Used in synthetic lubricants, experimental antitumor agents, a fungicide used to control powdery mildew, and certain dyes. Tumors of the colon, cecum, and liver occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. 2,4-diaminoanisole sulfate: RA. Used primarily in hair and fur dyes; also used in production of C.I. Basic Brown 2, which is used to dye clothing and is also an ingredient in shoe polishes. Human exposure is through skin contact and inhalation. Tumors at various tissue sites occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. 2,4-diaminotoluene: RA. Used primarily in the production of toluene diisocyanate, which is used to produce polyurethane. Also used to produce dyes for biological 1367
Carcinogens stains, furs, leathers, textiles, and wood. Human exposure is through skin contact and inhalation. Tumors of the liver and mammary gland and lymphomas occurred in laboratory animals when administered in the diet, and local tumors occurred when injected. No adequate data are available to evaluate the carcinogenicity in humans. diazoaminobenzene (DAAB): RA. Used in organic synthesis and in the manufacture of insecticides and dyes, particularly D&C Red no. 33, FD&C Yellow no. 5 (tartrazine), and FD&C Yellow no. 6, which are used in drugs and cosmetics; the latter two are allowed in food. Human exposure is through ingestion of products containing those dyes or skin contact with these products. DAAB is metabolized to benzene, a known human carcinogen that causes leukemia; evidence also shows that DAAB causes genetic damage. 1,2-dibromo-3-chloropropane: RA. Before being banned by the Environmental Protection Agency in 1985, 1,2dibromo-3-chloropropane was used as a pesticide; later used only for research purposes. Human exposure is probably minimal; however, ingestion of previously contaminated drinking water and food may occur. A variety of cancers have resulted in laboratory animals when exposed to 1,2-dibromo-3-chloropropane. There is inadequate evidence for the carcinogenicity in humans. 1,2-dibromoethane (ethylene dibromide): RA. Used to make vinyl bromide, a flame retardant in modacrylic fibers. Also used as a nonflammable solvent for resins, gums, and waxes, and used in the preparation of dyes and pharmaceuticals. Formerly used in lead gasoline and as a pesticide, it is still detected in ambient air, soil, groundwater, and food. Major source of human exposure is through the ingestion of contaminated drinking water. A variety of cancers have resulted in laboratory animals when exposed to 1,2-dibromoethane. There is inadequate evidence for the carcinogenicity in humans. 2,3-dibromo-1-propanol (DBP): RA. Used in the production of flame retardants, insecticides, and pharmaceuticals. Human exposure is through inhalation and skin contact. A variety of tumors have occurred in laboratory animals when painted onto the skin for numerous weeks. There is inadequate evidence for the carcinogenicity in humans. tris(2,3-dibromopropyl) phosphate: RA. Previously used as a flame-retardant additive for textiles and plastics. It was banned in 1977 for use in children’s clothing and in any textiles intended for use in clothing and is no longer used in the United States; however, in 1978, the Consumer Product Safety Commission identified twenty1368
Salem Health: Cancer two products containing the compound that were still commercially available. Human exposure is through inhalation, skin contact, and ingestion. A variety of cancers have resulted in laboratory animals exposed to tris(2,3-dibromopropyl) phosphate. There is inadequate evidence for the carcinogenicity in humans. 1,4-dichlorobenzene: RA. Used primarily as a space deodorant and as an insecticide fumigant for moth control. Also used in the production of polyphenylene sulfide and in the production of 1,2,4-trichlorobenzene; yellow, red, and orange pigments; air deodorizers; dyes; pharmaceuticals; and resin-bonded abrasives. Also used as a germicide/disinfectant, soil fumigant, insecticide, pesticide, animal repellent, and an agent to control mold and mildew growth. Human exposure is primarily through inhalation; skin contact and ingestion are also routes of potential exposure. Tumors of the kidney and liver occurred in laboratory animals when administered by stomach tube. No adequate data are available to evaluate the carcinogenicity in humans. 3,3 -dichlorobenzidine and 3,3 -dichlorobenzidine dihydrochloride: RA. Used primarily in the manufacture of pigments for printing ink, paint, paper, plastics, rubber, and textiles, and as a curing agent for isocyanate-containing polymers and solid urethane plastics. Human exposure is through inhalation of airborne dust, ingestion of contaminated well water near hazardous waste sites, and skin contact. Tumors at multiple tissue sites and leukemia occurred in laboratory animals administered the compound. No adequate data are available to evaluate the carcinogenicity in humans. dichlorodiphenyltrichloroethane (DDT): RA. Used extensively as an insecticide until 1972, when it was banned for the majority of uses in the United States. Later used only under official supervision for public health emergencies or for health quarantine. Although residue levels have been declining, DDT is still being detected in air, soil, rain, water, animal and plant tissues, food, and the work environment, and can be ingested in small amounts from some foods. Tumors at multiple tissue sites occurred in laboratory animals administered DDT. There is inadequate evidence for the carcinogenicity in humans. 1,2-dichloroethane (ethylene dichloride): RA. Used primarily to produce vinyl chloride, although it has been used as a solvent, degreaser, insect fumigant, and general anesthetic, among other uses. Human exposure is through inhalation, ingestion, and skin contact. Tumors at multiple tissue sites occurred in laboratory animals administered 1,2-dichloroethane. No adequate data are available to evaluate carcinogenicity in humans.
Salem Health: Cancer dichloromethane (methylene chloride): RA. Used primarily as a solvent in paint removers. Used also as an aerosol propellant; as a processing solvent in the manufacture of steroids, antibiotics, vitamins, and tablet coatings; as a degreasing agent; in electronics manufacturing, and as a polyurethane foam blowing agent. Also used in spray shoe polish, water repellents, spot removers, cleaners, glues, adhesive removers, and lubricants, among other products. Human exposure is through inhalation, ingestion, and, to a limited degree, skin absorption. Increased incidences of alveolar/bronchiolar neoplasms, hepatocellular neoplasms, and fibroadenoma of the mammary gland occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. 1,3-dichloropropene (technical grade): RA. Used in the manufacture of 3,3-dichloro-1-propene and other pesticides, such as Telone II, a widely used agricultural soil fumigant for parasitic nematodes. Human exposure is through inhalation of vapors, ingestion of contaminated foods and water, and skin contact. A variety of tumors occurred in laboratory animals when Telone II was administered by stomach tube, and injection-site fibrosarcomas occurred when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. diepoxybutane: RA. Not produced commercially in the United States since 1978; however, may be used in small quantities for research, as a curing agent for polymers, in textile fabrics, and to synthesize erythritol and other pharmaceuticals. Human exposure is through inhalation and skin contact. Skin cancer occurred in laboratory animals when applied topically; local fibrosarcomas and lung tumors occurred when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. diesel exhaust particulates: RA. Come from vehicles, oil and gas production facilities, stationary engines, repair yards, chemical manufacturing, and electric utilities. The type and condition of the engine, fuel composition and additives, operating conditions, and emission control devices determine the composition and quantity of the emissions from an engine. Limited evidence of increased risk for lung cancer has been found in human studies. diethyl sulfate: RA. Used primarily in dyes, pigments, textiles, and carbonless papers. Also used in cosmetics, household products, pharmaceuticals, agricultural chemicals, and some laboratory chemical processes. Human exposure is through inhalation and skin con-
Carcinogens tact. Administration by injection induced local sarcomas in laboratory animals and tumors of the nervous system in their offspring; tumors of the forestomach occurred when administered by stomach tube. Limited evidence is available for the carcinogenicity in humans; a study found excess mortality from laryngeal cancer in workers exposed to high concentrations of diethyl sulfate. diethylstilbestrol: K. Originally used as synthetic estrogen, and then widely prescribed for other uses in human medicine. Its use has since been reduced because of its cardiovascular toxicity and its link to a rare vaginal cancer in female offspring and possibly to testicular cancer among male offspring when given to pregnant mothers. Used in clinical trials for treatment of prostate and breast cancer and in biochemical research. diglycidyl resorcinol ether: RA. Used as a liquid spray epoxy resin and in other epoxy resins used in electrical, tooling, adhesive, and laminating applications. Also used in polysulfide rubber and in certain pavements, and as a coating for metal. Human exposure is through inhalation and skin contact. Tumors of the forestomach of laboratory animals occurred when administered by stomach tube. No adequate data is available to evaluate the carcinogenicity in humans. 3,3 -dimethoxybenzidine and dyes metabolized to 3,3 dimethoxybenzidine: RA. Used in production of dyes and pigments, as well as in the production of o-dianisidine diisocyanate for use in adhesives and as a component of polyurethanes. Human exposure is through inhalation and skin contact. Tumors at multiple tissue sites occurred in laboratory animals when administered 3,3′dimethoxybenzidine. No adequate data are available to evaluate the carcinogenicity in humans. 4-dimethylaminoazobenzene: RA. No longer produced or used commercially in the United States; previously used to color polishes and other wax products, polystyrene, and soap. Human exposure is through inhalation and skin contact. Tumors at multiple tissue sites occurred in laboratory animals when administered 4-dimethylaminoazobenzene. No adequate data are available to evaluate the carcinogenicity in humans. 3,3 -dimethylbenzidine and dyes metabolized to 3,3 dimethylbenzidine: RA. Used in production of dyes and pigments, as well as in the production of polyurethanebased high-strength elastomers, coatings, and rigid plastics. Also used in clinical laboratories in test tapes for the detection of blood and by water companies and swimming pool owners to test for chlorine in water or air. Human exposure is through inhalation, ingestion, and skin contact. Tumors at multiple tissue sites oc1369
Carcinogens curred in laboratory animals when administered 3,3′dimethylbenzidine. No adequate data are available to evaluate the carcinogenicity in humans. dimethylcarbamoyl chloride: RA. Used primarily in the production of dyes, pharmaceuticals, and pesticides. Human exposure is through inhalation and skin contact. Skin cancer was induced in laboratory animals when applied topically, local sarcomas when injected, and tumors of the nasal tract when inhaled. No adequate data are available to evaluate the carcinogenicity in humans. 1,1-dimethylhydrazine: RA. Used primarily as a component of jet and rocket fuels. Also used in organic peroxide fuel additives, in photography, as an absorbent for acid gases, and as a plant growth control agent. Human exposure is through inhalation, ingestion, and skin contact. Increased incidences of lung tumors occurred in laboratory animals when administered by stomach tube, and angiosarcomas in various organs and tumors of the kidneys, lungs, and liver when administered in drinking water. No adequate data are available to evaluate the carcinogenicity in humans. dimethyl sulfate: RA. Used in the manufacture of dyes, drugs, perfumes, pesticides, phenol derivatives, and other organic chemicals. Also used in polyurethanebased adhesives, in the analysis of auto fluids, and as a solvent for the separation of mineral oils. Human exposure is through inhalation and skin contact. Squamous cell carcinomas of the nasal cavity occurred in laboratory animals when administered by inhalation, local sarcomas when administered by injection, and tumors of the nervous system in offspring when administered by intravenous injection to pregnant animals. There is inadequate evidence for the carcinogenicity in humans; however, cases of bronchial carcinoma, pulmonary carcinoma, and choroidal melanoma have been reported in some humans exposed to dimethyl sulfate. dimethylvinyl chloride: RA. Not used commercially; only for research. Human exposure is through inhalation. Cancers of the nasal cavity, oral cavity, esophagus, and forestomach have occurred in laboratory animals when administered by stomach tube. No data are available to evaluate the carcinogenicity in humans. 1,6-dinitropyrene: RA. Not used commercially; available for research purposes. Found in particulate emissions from combustion sources, especially diesel exhaust. Studies have determined malignant tumor formation at multiple sites in laboratory animals when exposed to 1,6-dinitropyrene by multiple routes. Human studies show limited evidence of increased risk for lung cancer 1370
Salem Health: Cancer when exposed to diesel exhaust particulates; however, it has not been determined whether 1,6-dinitropyrene is responsible. 1,8-dinitropyrene: RA. Not used commercially; available for research purposes. Found in particulate emissions from combustion sources, especially diesel exhaust. Human studies show limited evidence of increased risk for lung cancer when exposed to diesel exhaust particulates; however, it has not been determined whether 1,8-dinitropyrene is responsible. Studies have determined malignant tumor formation at multiple sites in laboratory animals when exposed to 1,8-dinitropyrene by multiple routes. 1,4-dioxane: RA. Used primarily as a stabilizer in chlorinated solvents; also used as a solvent, in textile processing, and in laboratory research and testing. Human exposure is through inhalation, ingestion, and skin contact. Increased incidence of cancers of the nasal turbinates, liver, gallbladder, lung, and skin occurred in laboratory animals exposed to 1,4-dioxane. Inadequate evidence for the carcinogenicity in humans. Disperse Blue 1: RA. An anthraquinone dye used in hair color formulations and in coloring fabrics and plastics. Human exposure is through inhalation and skin contact. Tumor development in the urinary bladder and liver occurred in laboratory animals exposed to Disperse Blue 1. There is inadequate evidence for the carcinogenicity in humans. epichlorohydrin: RA. Used in the production of epoxy resins, synthetic glycerin, elastomers, and other synthetic materials. Has also been used to cure propylenebase rubbers, as a solvent for cellulose esters and ethers, and in resins for the paper industry; also widely used as a stabilizer. Human exposure is through ingestion, inhalation, and skin contact. Tumors of the forestomach occurred in laboratory animals when administered by stomach tube, tumors of the nasal cavity when administered by inhalation, and local sarcomas when administered by injection. There is inadequate evidence for the carcinogenicity in humans. erionite: K. Belonging to a group of minerals called zeolites, erionite is no longer mined or marketed for commercial purposes. Domestic uses for natural zeolite are pet litter, animal feed, horticultural applications, oil absorbent, odor control, desiccant, pesticide carrier, water purification, aquaculture, wastewater cleanup, gas absorbent, and other miscellaneous applications. The use of other zeolites may result in potential human exposure to erionite. Deposits of fibrous erionite are found in Arizona, Nevada, Oregon, and Utah, and
Salem Health: Cancer erionite fibers have been detected in road dust in Nevada, potentially exposing humans to erionite in ambient air. Mesothelioma and lung cancer have been linked to erionite exposure. estrogens, steroidal: K. Most commonly used for estrogen replacement therapy or in combination with a progestogen for hormone replacement therapy. Also used in oral contraceptives; to treat breast cancer, prostate cancer, and other medical conditions; and for biomedical research. Unopposed estrogens have been shown to cause uterine endometrial cancer; however, addition of a progestogen greatly diminishes that risk. Some evidence also suggests an increased risk of breast cancer. ethylene oxide: K. Used primarily in the production of several industrial chemicals, such as ethylene glycol (antifreeze), nonionic surfactants (detergents and dishwashing formulations), glycol ethers (solvents), ethanolamines (used in soaps, detergents, and textile chemicals), diethylene glycol (used in resins, plasticizers, and acrylate), triethylene glycol (used in dehydration of natural gas), polyethylene glycol (osmotic laxative), urethane polyols, fumigants, sterilizing agents, disinfectants, and insecticides. Human exposure is through inhalation and ingestion; very low risk of exposure from skin contact. An association between exposure to ethylene oxide and an increased risk of leukemia, stomach cancer, breast cancer, and lymphatic and hematopoietic cancers has been reported. ethylene thiourea: RA. Used primarily in neoprene and polyacrylate rubbers. Also used in pesticides, dyes, pharmaceuticals, and synthetic resins, and in electroplating baths and antioxidant production. Human exposure is through inhalation, ingestion, and skin contact. Cancer of the thyroid, liver, and pituitary gland occurred in laboratory animals exposed to ethylene thiourea. di(2-ethylhexyl) phthalate: RA. Used as a plasticizer in polyvinyl chloride (PVC) resins for fabricating flexible vinyl products; also used to manufacture non-PVC plasticizer. A variety of miscellaneous uses for di(2ethylhexyl) phthalate exist. Human exposure is through inhalation, ingestion, and skin contact, and through medical procedures. Tumors of the liver occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. ethyl methanesulfonate: RA. Used in laboratory research; not produced commercially in the United States. Tumors of the lung and kidney occurred in laboratory animals exposed to ethyl methanesulfonate. No adequate data are available to evaluate the carcinogenicity in humans.
Carcinogens formaldehyde (gas): RA. Used primarily for the production of urea-formaldehyde and phenolic resins (adhesives in pressed-wood products and building materials); also used to make other chemicals, household products, preservatives, permanent press fabrics, and paper product coatings. Human exposure is through inhalation and skin contact. Some studies have shown excess incidences of nasopharyngeal cancers in humans exposed to formaldehyde (gas). furan: RA. Used primarily in the production of tetrahydrofuran (solvent), pyrrole, and thiophene. Also used in the formation of lacquers, as a solvent for resins, and in the production of agricultural chemicals (insecticides), pharmaceuticals, and stabilizers. Human exposure is through inhalation. Liver cancers and leukemia occurred in laboratory animals when administered by stomach tube. No adequate data are available to evaluate the carcinogenicity in humans. glass wool (respirable size): RA. Used primarily in acoustical, electrical, and thermal insulation; filtration media; and weatherproofing. Human exposure is through inhalation and skin or eye contact. Various tumors and mesotheliomas occurred in laboratory animals when exposed to glass wool. There is inadequate evidence for the carcinogenicity in humans. glycidol: RA. Used in many pharmaceutical and fine chemical applications, in the manufacture of vinyl polymers and natural oils, and in the synthesis of glycerol, glycidyl ethers, and amines. Also used as an alkylating agent, as a demulsifer, as a dye-leveling agent, and for sterilizing milk of magnesia. Human exposure is through inhalation, skin and eye contact, and ingestion. Tumors at multiple sites occurred in laboratory animals when administered by stomach tube. No adequate data are available to evaluate the carcinogenicity in humans. hepatitis B virus (HBV): K. A virus that infects liver cells, causing acute or chronic hepatitis B. May be transmitted via injection or transfusion, via sexual contact, from mother to infant at time of birth, and through health care practices. Studies have demonstrated that chronic HBV infection causes liver cancer. hepatitis C virus (HCV): K. A virus that causes most non-B viral hepatitis, acute or chronic. May be transmitted via injection (intravenous drug use), transfusion, or sexual contact; from mother to infant at time of birth; and through health care practices. Studies have demonstrated that chronic HCV infection causes malignant tumors of the liver. 1371
Carcinogens heterocyclic amines (2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)): RA. Formed naturally when muscle-derived foods (meat and fish) are browned during cooking. Sufficient evidence of carcinogenicity in experimental animals exists, with tumors resulting at multiple tissue sites; however, no adequate epidemiology studies have been reported that indicate a human cancer risk. hexachlorobenzene: RA. Has not been produced commercially in the United States since the late 1970’s; however, it is produced as a by-product or impurity during the synthesis of several chlorinated solvents and pesticides. Human exposure is through ingestion, inhalation, and skin contact. Tumors of the liver and thyroid occurred in laboratory animals when administered in the diet. There is inadequate evidence for the carcinogenicity in humans. hexachloroethane: RA. Used to improve the quality of various metals and alloys, as an ignition suppressant, by the military for smoke munitions, and in various other applications. Human exposure is through inhalation, ingestion of contaminated drinking water or fish, and skin absorption. Increased incidences of tumors of the kidney, adrenal gland, and liver occurred in laboratory animals when administered by stomach tube. Few data are available to evaluate the carcinogenicity in humans. hexamethylphosphoramide: RA. Used as a solvent, a polymerization catalyst, a stabilizer against thermal degradation in polystyrene, an additive to resins to protect against degradation by ultraviolet light, a de-icing additive for jet fuels, and a rodenticide. Human exposure is through inhalation, ingestion, and skin contact. Nasal tumors occurred in laboratory animals when administered by inhalation. There is inadequate evidence for the carcinogenicity in humans. human papillomaviruses (HPV), some genital-mucosal types: K. Viruses that infect the genital skin and genital and nongenital mucosa; transmitted primarily through sexual contact. Low-risk HPV viruses can cause genital warts or cervical abnormalities; high-risk HPV viruses can cause cervical cancer. Evidence also suggests associations between HPV infection and cancer of the vulva, as well as some cancers of the head and neck, especially, the oropharynx (the soft palate, tonsils, and back of the tongue and throat). hydrazine and hydrazine sulfate: RA. Used primarily to produce agricultural chemicals, spandex fibers, and 1372
Salem Health: Cancer antioxidants. Also used as rocket fuel, a water treatment chemical, a polymerization catalyst, a reducing agent, and a blowing agent. Additionally used for plating metals on glass and plastics and in fuel cells, solder fluxes, photographic chemicals, pharmaceuticals, textile dyes, and various other products. Human exposure is through ingestion, inhalation, and skin contact. Potential for general population exposure is low. A variety of tumors occurred when administered to laboratory animals. There is inadequate evidence for the carcinogenicity in humans. hydrazobenzene: RA. Used primarily in the dye manufacturing industry; also used in the manufacture of pharmaceuticals and hydrogen peroxide, in the reclamation of rubber, as an additive in motor oil, as a desuckering agent for tobacco plants, in resin compositions, and in polymerization reactions. Human exposure is through inhalation, ingestion, and skin contact. A variety of tumors occurred in laboratory animals exposed to hydrazobenzene. iron dextran complex: RA. Used to treat iron-deficiency anemia when oral treatment has failed; also used in veterinary medicine to treat baby pigs. Human exposure is through inhalation, skin contact, and treatment by injection. Local tumors occurred in laboratory animals when administered by injection. There is inadequate evidence for the carcinogenicity in humans; however, tumors at probable sites of injection in humans have been reported. isoprene: RA. Used primarily to produce cis-1,4polyisoprene (rubber); also used to produce butyl rubber (isobutene-isoprene copolymer) and thermoplastic, elastomeric co-block (SIS) polymers. Isoprene is emitted through human breath, from tobacco smoke, and from plants and trees, resulting in low concentrations in the environment. A variety of tumors occurred in laboratory animals when exposed to isoprene through inhalation. There is inadequate evidence for the carcinogenicity in humans. Kepone (chlordecone): RA. No longer used in the United States; used until 1978 as an insecticide for leaf-eating insects, ants, and cockroaches, and as a larvicide for flies. Human exposure is through inhalation, ingestion, and skin contact. Tumors of the liver occurred in laboratory animals when administered in the diet. There is inadequate evidence for the carcinogenicity in humans. lead and lead compounds: RA. Lead is used largely in lead-acid storage batteries for motor vehicles and gen-
Salem Health: Cancer eral industry; also used for ammunition, cable covering, piping, brass and bronze, bearing metals for machinery, and sheet lead. There are many lead compounds (soluble, insoluble, and organic) with many and varied uses, such as in water repellant, cotton dyes, varnishes, chrome pigments, asbestos clutch or brake linings, flame retardants, matches, explosives, paints, rubber, and plastics. Human exposure is through inhalation, ingestion, and skin contact. Tumors of the kidney, brain, hematopoietic system, and lung were reported in laboratory animals exposed to lead; lead exposure has been associated with an increased risk of lung, stomach, and bladder cancer in humans. lindane and other hexachlorocyclohexane isomers: RA. Used primarily as an insecticidal treatment for hardwood logs and lumber, seed grains, and livestock. Also used as an insecticide for fruit and vegetable crops, and as a scabicide and pediculicide for humans in the form of a lotion, cream, or shampoo. Human exposure is through ingestion, inhalation, and skin contact. Tumors of the liver and thyroid occurred in laboratory animals when administered in the diet. There is inadequate evidence for the carcinogenicity in humans. melphalan: K. Used to treat cancer and other medical conditions; also used as an insect chemosterilant. Studies have found that patients treated with melphalan for bone marrow cancer, breast cancer, and ovarian cancer have an increased risk of leukemia. methoxsalen with ultraviolet A therapy (PUVA): K. Used to treat alopecia areata, atopic dermatitis, cutaneous T-cell lymphoma, lichen planus, mycosis fungoides, severe psoriasis, urticaria pigmentosa, vitiligo, and some forms of photosensitivity. Human exposure is through skin contact and ingestion. Studies have found that patients treated with PUVA have an increased risk of skin cancer. 2-methylaziridine (propylenimine): RA. Used in the adhesive, oil-additive, paper, pharmaceutical, rubber, and textile industries. Human exposure is through inhalation, ingestion, and skin contact. Leukemia and a variety of tumors have occurred in laboratory animals when administered by stomach tube or in the diet. No adequate data are available to evaluate the carcinogenicity in humans. 4,4 -methylenebis(2-chloroaniline): RA. Used primarily in the manufacture of castable urethane rubber products; has also been used in the laboratory as a model compound for studying carcinogens. Human exposure is through inhalation, skin contact, and ingestion. Liver cancer and a variety of tumors have occurred in laboratory animals exposed to 4,4′-methylenebis-
Carcinogens (2-chloroaniline). There is inadequate evidence for the carcinogenicity in humans. 4-4 -methylenebis(N,N-dimethyl)benzenamine: RA. Used in manufacture of dyes, including basic yellow 2, basic orange 14, and solvent yellow 34; also used to process hydrochloride salt and as an analytical reagent for lead. Human exposure is through inhalation and skin contact. Tumors of the liver and thyroid occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. 4,4 -methylenedianiline and its dihydrochloride salt: RA. 4,4′-Methylenedianiline is used in the production of 4,4′-methylenedianiline diisocyanate and polyisocyanates, which are used to produce a variety of polymers and resins. Dihydrochloride is used as a research chemical. Human exposure is through inhalation and skin contact. Increased incidences of tumors of the thyroid, liver, and adrenal gland occurred in laboratory animals when administered methylenedianiline dihydrochloride in the drinking water. No adequate data are available to evaluate the carcinogenicity in humans. methyleugenol: RA. Used as a flavoring agent in jellies, baked goods, candy, chewing gum, nonalcoholic beverages, pudding, relish, and ice cream. Has also been used as an anesthetic in rodents and as an insect attractant in combination with insecticides. Human exposure is through ingestion and inhalation. A variety of tumors occurred in laboratory animals when administered orally. No adequate data are available to evaluate the carcinogenicity in humans. methyl methanesulfonate: RA. Used experimentally as a research chemical and in the manufacturing of synthetic chemicals. Has been tested as a cancer treatment; potentially could be used to control insect populations and as a human male contraceptive. Human exposure is limited to laboratory research personnel. Studies have determined malignant tumor formation at multiple sites in laboratory animals exposed to methyl methanesulfonate by multiple routes. No adequate data are available to evaluate the carcinogenicity in humans. N-methyl-N-nitro-N-nitrosoguanidine (MNNG): RA. Has no known commercial use; it is used as a research chemical. Human exposure is most likely limited to research scientists. Studies have determined malignant tumor formation at multiple sites in laboratory animals exposed to MNNG by multiple routes. There is inadequate evidence available to evaluate the carcinogenicity in humans. 1373
Carcinogens metronidazole: RA. Used primarily for the treatment of infections due to protozoan parasites; has also been used to treat Vincent’s infection, acne rosacea, invasive intestinal amoebiasis, and amoebic hepatic abscess. Human exposure is through ingestion or topical application when used in medical treatment. Lymphomas as well as lung, mammary, pituitary, testicular, and liver tumors occurred in laboratory animals when administered orally. There is inadequate evidence available to evaluate the carcinogenicity in humans. Michler’s ketone [4,4 -(dimethylamino)benzophenone]: RA. Used in the production of at least thirteen dyes and pigments used to dye paper, leather, and textiles; one is also used as an antiseptic fungicide. Human exposure is through inhalation and skin contact. Increased incidences of liver tumors and hemangiosarcomas occurred in laboratory animals when administered orally in the diet. No adequate data are available to evaluate the carcinogenicity in humans. mineral oils (untreated and mildly treated): K. Used primarily as lubricant base oils to produce further refined oil products used in the manufacturing, automotive, mining, construction, and other miscellaneous industries. Human exposure is through inhalation, ingestion, and skin contact. Exposure to mineral oils is strongly associated with a variety of cancers. mirex: RA. All uses of mirex were suspended in 1977. Its primary use was as a fire-retardant additive under the name Dechlorane; it was also used as an insecticide to control fire ants in southeastern states. Mirex is very persistent in the environment and highly resistant to degradation; therefore, potential exposure to low concentrations still exists. Human exposure is through ingestion of fish caught from contaminated water, and for populations that live near a former manufacturing or waste disposal site, or live in areas where mirex was extensively used to control fire ants. Increased incidences of liver cancer, tumors of the adrenal gland, and leukemia occurred in laboratory animals when administered by stomach tube and then in the diet. No adequate data are available to evaluate the carcinogenicity in humans. mustard gas: K. A blister-inducing agent that has been used in chemical warfare; used in research. Human exposure is through inhalation and skin contact, with military personnel being at the greatest risk. Mustard gas is associated with an increased risk of lung, laryngeal, pharyngeal, and upper respiratory tract cancers. naphthalene: RA. Used in the production of insect repellents, phthalate plasticizers, pharmaceuticals, and other materials. Has also been used in the production of 1-naphthyl-N-methylcarbamate insecticides, beta1374
Salem Health: Cancer naphthol, moth repellents, surfactants, synthetic leather tanning chemicals, and toilet bowl deodorants. Human exposure is through inhalation and skin contact. Nasal tumors, neuroblastomas in the brain, and lung tumors occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. 2-naphthylamine: K. Used only in laboratory research; formerly used in the manufacture of dyes, rubber, and 2-chloronaphthylamine. Potential for human exposure is low; however, may occur through inhalation of emissions from sources where nitrogen-containing organic matter is burned, such as coal furnaces and cigarettes. Studies have shown that 2-naphthylamine causes bladder cancer. neutrons: K. Used medically in external beam therapy, in boron neutron capture therapy, and to make radioisotopes. Also used in oil-well logging, nuclear reactors, neutron activation analysis and radiography, sterilization of materials, radiometric dating of rocks, and scientific and engineering research. Human exposure occurs naturally from cosmic radiation originating from outer space; however, additional exposure occurs in cancer patients receiving radiation therapy, nuclearindustry workers, airline crews and passengers, and survivors of atomic bomb blasts. Studies show that neutron radiation induces chromosomal aberrations, mutations, deoxytibonucleic acid (DNA) damage, and many various tumors. nickel compounds: K. Includes stainless steel, copper– nickel alloys, and other corrosion-resistant alloys. Human exposure occurs through inhalation, ingestion, and skin contact. Studies have shown an increased risk of death from lung cancer and nasal cancer. nickel (metallic): RA. Used in alkaline batteries, coins, electrical contacts and electrodes, electroplating, machinery parts, magnets, spark plugs, surgical and dental prostheses, and welding products. Human exposure occurs through inhalation, ingestion, and skin contact. An increased incidence of malignant tumors at multiple tissue sites occurred in laboratory animals exposed to metallic nickel powder. No adequate data are available to evaluate the carcinogenicity in humans. nitrilotriacetic acid: RA. Used primarily as a chelating agent and as a laundry detergent builder. Also used in water and textile treatment, metal plating and cleaning, pulp and paper processing, leather tanning, the manufacture of pharmaceuticals, photographic development, synthetic rubber production, and herbicide formulations and micronutrient solutions in agriculture. Human exposure is through inhalation, ingestion, and skin
Salem Health: Cancer contact. Tumors of the kidney, ureter, urinary bladder, adrenal gland, and liver occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. o-nitroanisole: RA. Used primarily in the synthesis of azo dyes; has also been used in the pharmaceutical industry. Human exposure is through skin contact, ingestion, and inhalation. Leukemia and tumors of the urinary bladder, kidney, large intestine, and liver occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. nitrobenzene: RA. Used primarily in the manufacture of aniline; also used in the manufacture of azobenzene, benzidine, dyes, isocyanates, lubricating oils, pesticides, pharmaceuticals, pyroxylin compounds, quinoline, rubber chemicals, soaps, and shoe and metal polishes. Human exposure is through inhalation, ingestion, and skin contact. Increased incidences of tumors at multiple tissue sites occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. 6-nitrochrysene: RA. Not used commercially; available for research purposes. Found in particulate emissions from combustion sources, especially diesel exhaust. Limited evidence of increased risk for lung cancer when exposed to diesel exhaust particulates has been found in human studies. Studies have determined malignant tumor formation at multiple sites in laboratory animals exposed to 6-nitrochrysene. nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether): RA. No longer used commercially; was used as an herbicide to control annual grasses and broadleaf weeds on various food and ornamental crops. Human exposure is through inhalation, skin contact, and ingestion. Tumors of the liver, spleen, and pancreas occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. nitrogen mustard hydrochloride: RA. Used to treat neoplastic diseases; also used to control pleural, peritoneal, and pericardial effusions caused by metastatic tumors, and has been used in clinical trials for rheumatoid arthritis, in tissue transplantation studies, and for other nonmalignant diseases. Human exposure is through injection, inhalation, and skin contact. Tumors in various organs occurred in laboratory animals exposed to nitrogen mustard hydrochloride. There is limited evidence of carcinogenicity in humans, including skin cancer, leukemia, and various other malignant tumors. nitromethane: RA. Used primarily in the making of nitromethane derivatives, which are used as agricul-
Carcinogens tural soil fumigants, industrial antimicrobials, and pharmaceuticals. Also used as a fuel or fuel additive. Human exposure is through inhalation, especially of motor vehicle exhaust and cigarette smoke; ingestion of contaminated water; and skin contact. Tumors of the harderian gland, lung, liver, and mammary gland occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. 2-nitropropane: RA. Used primarily as a solvent in adhesives, inks, paints, polymers, varnishes, and synthetic materials, and used in the manufacture of 2-nitro-2methyl-1-propanol and 2-amino-2-methyl-1-propanol. Also used in explosives and propellants, and in fuels for internal combustion engines. Human exposure is through inhalation, ingestion, and skin contact. Liver cancer occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. 1-nitropyrene: RA. Limited use in the production of 1-azidopyrene, which is used in photosensitive printing; available for research purposes in the United States. Found in particulate emissions from combustion sources, especially diesel exhaust. Limited evidence of increased risk for lung cancer when exposed to diesel exhaust particulates has been found in human studies; however, it has not been determined whether 1-nitropyrene is responsible. Studies have determined malignant tumor formation at multiple sites in laboratory animals exposed to 1-nitropyrene by multiple routes. 4-nitropyrene: RA. Used only as a laboratory chemical. Found in particulate emissions from combustion sources, especially diesel exhaust. Limited evidence of increased risk for lung cancer when exposed to diesel exhaust particulates has been found in human studies; however, it has not been determined whether 4-nitropyrene is responsible. Studies have determined malignant tumor formation at multiple sites in laboratory animals exposed to 1-nitropyrene. N-nitrosodi-n-butylamine: RA. Used primarily as a research chemical; once used in the synthesis of di-nbutylhydrazine. Human exposure is through ingestion, inhalation, and skin contact. Leukemia and a variety of tumors occurred in laboratory animals exposed to N-nitrosodi-n-butylamine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosodiethanolamine: RA. No longer used commercially; however, it is widespread in the environment; used as a research chemical. Human exposure is through skin contact, ingestion, and inhalation. Nitrosodiethanolamine is a known contaminant of anti1375
Carcinogens freeze, cosmetics, lotions, cutting fluids, shampoos, some pesticides, and tobacco. Tumors of the liver and kidney occurred in laboratory animals when administered in the drinking water, and tumors of the nasal cavity, trachea, liver, and injection site occurred when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosodiethylamine: RA. Used primarily as a research chemical. Also used as an antioxidant, copolymer softener, gasoline and lubricant additive, fiber industry solvent, and stabilizer in plastics, and in the synthesis of 1,1-diethylhydrazine. Human exposure is through ingestion, inhalation, and skin contact. A variety of tumors occurred in laboratory animals exposed to N-nitrosodiethylamine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosodimethylamine: RA. Used primarily as a research chemical; also used to control nematodes (worms) and inhibit nitrification in soil. Used in rubber and acrylonitrile polymers, fluoride polymers, copolymers, high-energy batteries, and lubricants; as a solvent in the fiber and plastics industry; and as an antioxidant. Human exposure is through ingestion, inhalation, and skin contact. A variety of tumors occurred in animals exposed to N-nitrosodimethylamine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosodi-n-propylamine: RA. Not used commercially; used in laboratory research. Human exposure is through ingestion, inhalation, and skin contact. A variety of tumors occurred in laboratory animals exposed to Nnitrosodi-n-propylamine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitroso-N-ethylurea: RA. Used to synthesize diazoethane in the laboratory. Human exposure is limited; however, occupational exposure may occur through inhalation or skin contact. Leukemia and tumors at multiple sites occurred in laboratory animals when exposed to N-nitroso-N-ethylurea. No adequate data are available to evaluate the carcinogenicity in humans. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK): RA. Used as a laboratory chemical. Human exposure is through the inhalation of tobacco smoke or during tobacco chewing or oral snuff use. Tumors of the nasal cavity, lung, liver, and trachea occurred in laboratory animals when exposed to NNK. No adequate data are available to evaluate the carcinogenicity in humans. N-nitroso-N-methylurea: RA. Used in research; has been used to synthesize diazomethane in the laboratory and has been studied as a chemotherapeutic agent in cancer treatment. Human exposure is limited; however, 1376
Salem Health: Cancer occupational exposure may occur through inhalation or skin contact. Leukemia and tumors at multiple sites occurred in laboratory animals when exposed to N-nitroso-N-methylurea. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosomethylvinylamine: RA. Used as a research chemical. Human exposure is primarily limited to researchers; however, N-nitroso compounds have been identified in a variety of food products and can therefore be ingested. Tumors of the esophagus, tongue, pharynx, nasal cavity, and skin have occurred in laboratory animals when exposed to N-nitrosomethylvinylamine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosomorpholine: RA. Not used commercially; however, patents have been issued for its use in the production of N-aminomorpholine and as a solvent for polyacrylonitrile. A variety of tumors occurred in laboratory animals exposed to N-nitrosomorpholine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosonornicotine: RA. Used as a research chemical. Human exposure is through the use of tobacco products or the inhalation of sidestream smoke. Tumors of the esophagus, nasal cavity, trachea, and lung occurred in laboratory animals exposed to N-nitrosonornicotine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosopiperidine: RA. Used as a research chemical. Human exposure is limited; however, exposure may occur from cigarette smoke and certain meats and fish. Avariety of tumors occurred in animals exposed to N-nitrosopiperidine. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrosopyrrolidine: RA. Used primarily as a research chemical; not used commercially. N-nitrosopyrrolidine is produced when foods preserved or contaminated with nitrites, especially fatty foods, are heat prepared; human exposure occurs through ingestion of these foods or inhalation of vapors released during cooking. Leukemia and a variety of tumors occurred in laboratory animals when administered in the drinking water. No adequate data are available to evaluate the carcinogenicity in humans. N-nitrososarcosine: RA. Not used commercially; has limited use in research. Human exposure is through inhalation, ingestion, and skin contact. Skin cancer of the nasal region and tumors of the esophagus and liver occurred in laboratory animals when exposed to N-nitrososarcosine. No adequate data are available to evaluate the carcinogenicity in humans.
Salem Health: Cancer norethisterone: RA. Used primarily as the progestin in progestin-estrogen combination oral contraceptives. Also used in medicines used to treat amenorrhea, dysmenorrhea, dysfunctional uterine bleeding, endometriosis, premenstrual tension, and inoperable malignant tumors of the breast. Human exposure is through ingestion, skin contact, and inhalation. Tumors of the pituitary, mammary gland, and ovaries occurred in laboratory animals when exposed to norethisterone. No adequate data are available to evaluate the carcinogenicity in humans. ochratoxin A: RA. Not used commercially; it is an experimental teratogen and carcinogen. Human exposure is probably widespread through ingestion of food and handling of animal feed since ochratoxin A is a naturally occurring mycotoxin. Tumors of the liver, kidney, and mammary gland occurred in laboratory animals exposed to ochratoxin A. No adequate data are available to evaluate the carcinogenicity in humans. 4,4 -oxydianiline: RA. Used in the production of polyimide and poly(ester)imide resins, which are used in the manufacture of temperature-resistant products (such as wire enamels, coatings, and adhesives). Human exposure is through inhalation and through eye and skin contact. Tumors of the harderian gland, liver, and thyroid occurred in laboratory animals exposed to 4,4′oxydianiline. No adequate data are available to evaluate the carcinogenicity in humans. oxymetholone: RA. A steroid hormone used to treat many conditions, including hypogonadism, delayed puberty, hereditary angioneurotic edema, and carcinoma of the breast. Also used to stimulate the formation of red blood cells (especially to treat anemias), to promote a positive nitrogen balance following surgery or injury, and to counteract weakness and promote weight gain during debilitating diseases. Human exposure is through ingestion and skin contact. Increased incidences of liver tumors occurred in laboratory animals when exposed to oxymetholone. Cases of liver tumors have been reported in patients treated for long periods with oxymetholone; however, a causal relationship cannot be established. phenacetin: RA. Was used as an analgesic and feverreducing drug until it was implicated in kidney disease and withdrawn from the U.S. market in 1983; it was also once used in hair-bleaching preparations. Human exposure was through ingestion, with occupational exposure through inhalation and skin contact. Tumors of the urinary tract and nasal cavity occurred in laboratory animals when phenacetin was administered in the diet.
Carcinogens There is limited evidence for the carcinogenicity in humans because phenacetin was usually taken mixed with other drugs. phenacetin-containing analgesic mixtures: K. Was used as an analgesic and fever-reducing drug until it was implicated in kidney disease and withdrawn from the U.S. market in 1983; cancers of the urinary tract, renal pelvis, and bladder have also been reported in patients using large amounts of phenacetin-containing analgesic mixtures. phenazopyridine hydrochloride: RA. Has been used as an analgesic drug to reduce pain associated with urinary tract infections or irritation; often combined with sulfonamides and antibiotics. Human exposure is through ingestion, with occupational exposure through inhalation and skin contact. Tumors of the liver, colon, and rectum occurred in laboratory animals when administered in the diet. There is inadequate evidence for the carcinogenicity in humans. phenolphthalein: RA. Used in various ingested products, including laxatives, as well as in some scientific applications. Human exposure is through ingestion, skin contact, and inhalation. Increased incidences of tumors in multiple tissue sites occurred in laboratory animals when exposed to phenolphthalein. There is inadequate evidence for the carcinogenicity in humans. phenoxybenzamine hydrochloride: RA. Used primarily to treat hypertension caused by pheochromocytoma; also used to treat benign prostatic hypertrophy under certain conditions. Has been used to treat peripheral vascular disorders, hypertension, and shock. Human exposure is through ingestion during its medical use and skin contact during its production. Peritoneal tumors and lung tumors occurred in laboratory animals when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. phenytoin: RA. An anticonvulsant drug used to treat grand mal epileptic patients with focal and psychomotor seizures; has been used to treat varous other conditions. Also used to control seizures occurring during neurosurgery, to prevent postcountershock arrhythmias in digitalized patients, and to reverse digitalis-induced arrhythmias. Human exposure is through injection, ingestion, inhalation, and skin contact. Thymic, generalized, and mesenteric lymphomas; liver tumors; and leukemias occurred in laboratory animals exposed to phenytoin. There is inadequate evidence for the carcinogenicity in humans; however, there is limited evidence suggesting that phenytoin may be a transplacental carcinogen in humans. polybrominated biphenyls (PBBs): RA. Used as flameretardant additives in synthetic fibers and molded plas1377
Carcinogens tics. Human exposure is through ingestion, inhalation, and skin contact. Liver tumors occurred in laboratory animals when exposed to a PBB. No adequate data are available to evaluate the carcinogenicity in humans. polychlorinated biphenyls (PCBs): RA. Uses are confined to closed systems, such as electrical capacitors, gas-transmission turbines, and vacuum pumps; exemptions are granted to individual petitioners for use as a mounting medium in microscopy, an immersion oil in low fluorescence microscopy, or an optical liquid, and for research and development. Human exposure is through ingestion, inhalation, and skin contact. Liver tumors occurred in laboratory animals when exposed to Aroclor 1260, Aroclor 1254, and Kanechlor 500 (all PCBs). There is inadequate evidence for the carcinogenicity in humans; however, an increase in the incidence of cancer, particularly skin cancer and cancers of the digestive system and of the lymphatic and hematopoietic tissues, has been reported in men exposed to PCBs. polycyclic aromatic hydrocarbons (PAHs) (benz[a]anthracene, benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]acridine, dibenz[a,j]acridine, dibenz[a,h]anthracene, 7H-dibenzo[c,g]carbazole, dibenzo[a,e]pyrene, dibenzo[a,h]pyrene, dibenzo[a,i]pyrene, dibenzo[a,l]pyrene, indeno[1,2,3-cd]pyrene, 5-methylchrysene): RA. Other than dibenzo[a,h]pyrene, dibenzo[a,i]pyrene, and 5-methylchrysene, which have no known uses, the other PAHs are used only in biomedical, biochemical, laboratory, and cancer research. At least eight of those are found in coal tar and coal tar products, which include coal tar pitch and creosote. Human exposure is through inhalation of contaminated air, tobacco smoke, and wood smoke, and ingestion of contaminated water and foods, especially smoked, barbecued, and charcoal-broiled foods. Studies have determined malignant tumor formation at multiple sites in laboratory animals exposed to PAHs by multiple routes. There is inadequate evidence for the carcinogenicity in humans; however, many studies show increased incidences of cancer, including lung, skin, and genitourinary cancers, in humans exposed to mixtures of PAHs. procarbazine hydrochloride: RA. Used in combination with other anticancer medications to treat Hodgkin disease, non-Hodgkin lymphoma, malignant melanoma, and small-cell carcinomas of the lung. Human exposure is through ingestion, inhalation, and skin contact. Leukemia, lymphomas, hemangiosarcomas, and tumors at multiple sites occurred in laboratory animals when 1378
Salem Health: Cancer exposed to procarbazine hydrochloride. There is inadequate evidence for the carcinogenicity in humans; however, the use of procarbazine hydrochloride in combination with other chemotherapeutic medications for the treatment of Hodgkin disease has repeatedly been shown to lead to the appearance of acute nonlymphocytic leukemia. progesterone: RA. A naturally occurring steroidal hormone secreted by female ovaries, the placenta in pregnant females, and the adrenal cortex; used as a contraception and to treat secondary amenorrhea and dysfunctional uterine bleeding. Has also been used to treat dysmenorrhea and premenstrual tension, habitual and threatened abortion, preeclampsia and toxemia of pregnancy, female hypogonadism, mastodynia, uterine fibroma, and tumors of the breast and endometrium. Human exposure is through ingestion, injection, implantation, skin contact, and inhalation. Cancers of the breast, ovaries, endometrium, cervix, vagina, and genital tract occurred in female laboratory animals, including neonatal and newborn animals, when exposed to progesterone through injections and implants. No adequate data are available to evaluate the carcinogenicity in humans. 1,3-propane sultone: RA. Used in the production of fungicides, insecticides, some resins, dyes, detergents, lathering agents, bacteriostats, a variety of other chemicals, and untempered steel. Human exposure is through ingestion and inhalation. Brain tumors, breast tumors, and increased incidences of leukemia, tumors of the small intestine, and skin cancer of the ear occurred in laboratory animals when administered by stomach tube, and injection site tumors occurred when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. -propiolactone: RA. Has been used to sterilize blood plasma, vaccines, tissue grafts, surgical instruments, and enzymes; to kill spores of vegetative bacteria, pathogenic fungi, and viruses; and to manufacture acrylic acid and esters. Has also been used as a vapor-phase disinfectant in enclosed spaces, and in organic synthesis. Human exposure is limited because it is no longer used as a sterilant in medical procedures or in food; however, occupational exposure may occur through inhalation and skin contact when used as a chemical intermediate in industrial facilities. Tumors of the forestomach and skin cancer occurred in laboratory animals exposed to β-propiolactone. No adequate data are available to evaluate the carcinogenicity in humans. propylene oxide: RA. Used primarily in the production of polyurethane polyols (used to make polyurethane
Salem Health: Cancer foams), propylene glycols (used to make polyester resins for the textile and construction industries, as well as in drugs, cosmetics, solvents and emollients in food, plasticizers, heat transfer and hydraulic fluids, and antifreezes), glycol ethers, and specialty chemicals, including pesticides. May also be used in fumigation chambers for the sterilization of packaged foods. Human exposure is through ingestion; inhalation, and skin contact. Tumors of the nasal cavity, adrenal gland, and peritoneum occurred in laboratory animals when administered by inhalation; local tumors and tumors of the forestomach when administered by stomach tube; and local tumors when administered by injection. No adequate data are available to evaluate the carcinogenicity in humans. propylthiouracil: RA. Used as an antithyroid agent for the treatment of hyperthyroidism. Human exposure is primarily through ingestion as a drug. Tumors of the pituitary gland and thyroid occurred in laboratory animals when ingested. No adequate data are available to evaluate the carcinogenicity in humans. radon: K. Used primarily for research; however, it is produced in nature by radioactive decay of radium and is released from soil into the air and groundwater. Human exposure is through inhalation and ingestion. An increased risk of lung cancer, as well as tracheal and bronchial cancer, is associated with exposure to radon. reserpine: RA. A naturally occurring alkaloid used to lower blood pressure and reduce the heart rate and as a tranquilizer and sedative. Human exposure is through ingestion and skin contact. Tumors of the adrenal gland, breast, and seminal vesicles occurred in laboratory animals when resperine was administered in the diet and by injection. No adequate data are available to evaluate the carcinogenicity in humans. safrole: RA. Has been used in drugs, beverages, foods, soap, and perfumes, and in the manufacture of heliotropin and piperonyl butoxide. Human exposure is through ingestion and skin contact. Liver tumors and lung tumors occurred in laboratory animals when administered safrole. No adequate data are available to evaluate the carcinogenicity in humans. selenium sulfide: RA. Used in antidandruff shampoos and fungicides. Human exposure is through skin contact and inhalation. Liver tumors and alveolar/bronchiolar tumors occurred in laboratory animals when administered by stomach tube. No adequate data are available to evaluate the carcinogenicity in humans.
Carcinogens silica, crystalline (respirable size): K. Used in the production of quartzite, tripoli, gannister, chert, and novaculite; occurs naturally as agate, amethyst, chalcedony, cristobalite, flint, quartz, tridymite, and sand. Sand is used in the manufacture of glass, ceramics, foundry castings, abrasives, sandblasting materials, silicon, and ferrosilicon metals; as a filter in municipal water and sewage treatment plants; and in hydraulic fracturing in oil and gas recovery. Human exposure is through inhalation and ingestion. An increased risk of lung cancer is associated with exposure to respirable crystalline silica. solar radiation: K. Emitted by the sun; has been determined to cause skin cancer and may also cause melanoma of the eye and non-Hodgkin lymphoma. soots: K. Unwanted by-products of the incomplete combustion or burning of organic materials; have been used as fertilizer to provide small amounts of nitrogen and essential trace metals to plants, as a slug deterrent, as a soil conditioner, and in the recovery of trace metals in the metallurgical industry. Human exposure is through inhalation, ingestion, and skin contact. Increased risks, of scrotal cancer, lung cancer, and leukemia, as well as total lymphatic and hematopoietic cancer and cancer of the esophagus, liver, prostate, and bladder, are associated with exposure to soots. streptozotocin: RA. Used in the treatment of metastasizing pancreatic islet cell tumors and malignant carcinoid tumors. Tumors of the kidney, lung, uterus, pancreas, liver, peritoneum, and bile ducts occurred in laboratory animals when exposed to streptozotocin. No adequate data are available to evaluate the carcinogenicity in humans. strong inorganic acid mists containing sulfuric acid: K. Produced during the manufacture or use of sulfuric acid, sulfur trioxide, or oleum. The following industries use sulfuric acid: fertilizer, mining and metallurgy, ore processing, petroleum refining, inorganic and organic chemicals, cellulose fibers and films, inorganic pigments and paints, synthetic rubber and plastics, pulp and paper, soap and detergents, and water treatment. Lead-acid batteries are the primary consumer products containing sulfuric acid, which is also used as a general purpose food additive. Human exposure is through inhalation, ingestion, and skin contact. Exposure to strong inorganic acid mists containing sulfuric acid is associated with laryngeal and lung cancer in humans. styrene-7,8-oxide: RA. Used in the production of styrene glycol and its derivatives, cosmetics, surface coatings, agricultural and biological chemicals, epoxy resins, and cross-linked polyesters and polyurethanes. Has 1379
Carcinogens also been used in the production of 2-phenylethanol used in perfumes, in the treatment of fibers and textiles, and in hydraulic fluids, chlorinated cleaning compositions, petroleum distillates, dielectric fluids, and acidsensitive polymers and copolymers. Human exposure is through contact with contaminated air or water. Tumors of the forestomach and liver occurred in laboratory animals when administered by stomach tube. No adequate data are available to evaluate the carcinogenicity in humans. sulfallate: RA. Was used as an herbicide to control particular annual grasses and broadleaf weeds around vegetable and fruit crops; however, manufacture of sulfallate products was discontinued in the early 1990’s. Potential for further human exposure is low. Tumors of the breast, forestomach, and lung occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. sunlamps or sun beds, exposure to: K. Emit primarily ultraviolet A (UVA) and ultraviolet B (UVB) radiation; have been determined to increase risk of skin cancer. tamoxifen: K. Used primarily in the treatment of breast cancer; has also been tested as a possible treatment for other cancers. Human exposure is through ingestion and inhalation. An increased risk of endometrial cancer (cancer of the uterus) has been associated with exposure to tamoxifen. 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD);“Dioxin”:K. Used as a research chemical. Has no known commercial applications; however, is inadvertently produced by incineration of municipal, toxic, and hospital wastes; by paper and pulp bleaching; in PCB-filled electrical transformer fires; in smelters; and during production of chlorophenoxy herbicides. Human exposure is through inhalation, ingestion (especially of meat, fish, and dairy products), and skin contact. Studies have determined that a significant increased risk for all cancers combined, lung cancer, and non-Hodgkin lymphoma is associated with exposure to TCDD. tetrachloroethylene (perchloroethylene): RA. Used primarily as a cleaning solvent (especially in the dry cleaning industry) and as a chemical precursor for fluorocarbons. Also used as an insulating fluid and cooling gas in electrical transformers; in adhesive formulations, leather treatments, paint removers, printing inks, and paper coatings; in aerosol formulations such as water repellants, automotive cleaners, spot removers, and silicone lubricants; as an extractant for pharmaceuticals; and as an agent that kills parasitic worms. As 1380
Salem Health: Cancer tetrachloroethylene is widely distributed in the environment, human exposure is through inhalation and ingestion of contaminated water or food; skin contact may also occur. Leukemia and tumors of the liver and kidney occurred in laboratory animals exposed to tetrachloroethylene. There is limited evidence for the carcinogenicity in humans. Studies have reported increased incidences of lymphosarcomas, leukemias, and cancers of the skin, colon, lung, urogenital tract, larynx, and urinary bladder in laundry and dry cleaning workers, however, these workers are also exposed to petroleum solvents and other dry cleaning agents. There is evidence as well for consistent positive associations between tetrachloroethylene exposure and nonHodgkin lymphoma and esophageal and cervical cancer. tetrafluoroethylene (TFE): RA. Used primarily in the synthesis of polytetrafluoroethylene; also used to produce copolymers with monomers such as ethylene and hexafluoropropylene. Human exposure is primarily through inhalation. Leukemia and tumors of the liver and kidney occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. tetranitromethane: RA. Used in rocket propellants, explosives, and diesel fuel, and as an organic reagent. Human exposure is through inhalation. A dose-related increase in alveolar/bronchiolar tumors occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. thioacetamide: RA. Used as a replacement for hydrogen sulfide in qualitative analyses; has also been used as an organic solvent. Human exposure is through inhalation and skin contact. Tumors of the liver and bile duct have occurred in laboratory animals. No adequate data are available to evaluate the carcinogenicity in humans. 4,4 -thiodianaline: RA. Was used in the production of C.I. Mordant Yellow 16 dye, Milling Red G dye, and Milling Red FR dye; however, has not been used since the early 1990’s. Human exposure may have been through skin contact, accidental ingestion, and inhalation. Tumors of the liver, thyroid, Zymbal gland, uterus, and colon occurred in laboratory animals when exposed to 4,4′-thiodianaline. No adequate data are available to evaluate the carcinogenicity in humans. thiotepa: K. Used to treat a variety of cancers, including bladder, brain, breast, ovarian, and lung, and lymphomas. Studies have determined that patients treated with thiotepa are at increased risk to develop secondary leukemia.
Salem Health: Cancer thiourea: RA. Has been used in the synthesis of pharmaceuticals and insecticides, in boiler water treatment, as a photographic toning agent, as a dry cleaning agent, in hair preparations, and as a reagent for bismuth and selenite. Human exposure is through inhalation and skin contact. No adequate data are available to evaluate the carcinogenicity in humans. thorium dioxide: K. Used in high-temperature ceramics, gas mantles, crucibles, nuclear fuel, flame spraying, medicines, nonsilica optical glass, and thoriated tungsten filaments. Concerns over its naturally occurring radioactivity have led to its substantially decreased use. Human exposure is through inhalation, intravenous injection, ingestion, and skin contact. Studies have determined a significantly increased risk of liver tumors, leukemia, and bone cancer for those exposed to thorium dioxide. tobacco, smokeless: K. Main forms are chewing tobacco and snuff. Has been determined to cause tumors of the oral cavity, especially at the site of placement. tobacco, smoking: K. Used in cigarettes, pipes, cigars, and bidis. Has been determined to cause cancer of the lung, urinary bladder, renal pelvis, oral cavity, pharynx, larynx, esophagus, lip, and pancreas. Sufficient evidence exists for the carcinogenicity of cigarette smoking and cancers of the nasal cavities and nasal sinus, stomach, liver, kidney, and uterine cervix, as well as myeloid leukemia. tobacco smoke, environmental: K. Passive exposure (sidestream smoke) produced from tobacco products (cigarettes, pipes, cigars, and bidis) has been determined to cause lung cancer and cancers of the nasal cavity. toluene diisocyanate: RA. Used primarily in the synthesis of polyurethane foams, which are used in furniture, bedding, and insulation. Also used in floor finishes, wood finishes, paints, concrete sealants, adhesive and sealant compounds, automobile parts, shoe soles, roller skate wheels, pond liners, and blood bags, and in oil fields and mines. Human exposure is through inhalation and skin contact. Tumors at multiple sites occurred in laboratory animals exposed to toluene diisocyanate. No adequate data are available to evaluate the carcinogenicity in humans. o-toluidine and o-toluidine hydrochloride: RA. Used primarily in the manufacture of dyes and pigments; also used in the manufacture of synthetic rubber, rubber vulcanizing chemicals, pharmaceuticals, and pesticides, as well as in organic synthesis and glucose analysis. Human exposure is through inhalation and skin contact. Tumors at multiple sites occurred in laboratory
Carcinogens animals when administered in the diet. There is limited evidence for the carcinogenicity in humans. An excess of bladder cancers has been reported in workers exposed to o-toluidine; however, they were also exposed to other potential bladder carcinogens at the same time. toxaphene: RA. Was used primarily as a pesticide, especially on cotton crops, until it was banned in the United States in 1990; was also used to control insect pests on livestock and poultry. Human exposure is through ingestion of contaminated food and water, skin contact, and inhalation. Tumors of the liver and thyroid occurred in laboratory animals when administered in the diet. No adequate data are available to evaluate the carcinogenicity in humans. trichloroethylene (TCE): RA. Used primarily as a degreaser for metal parts, mainly by industries that manufacture furniture and fixtures, fabricated metal products, electrical and electronic equipment, transport equipment, and other miscellaneous products; it is also used in adhesives, lubricants, paint strippers, paints, varnishes, pesticides, and cold metal cleaners. Human exposure is through ingestion of food and water and through inhalation. Malignant tumor formation at multiple sites occurred in laboratory animals when exposed to TCE. There is limited evidence for the carcinogenicity in humans; studies have consistently showed an increased risk for kidney cancer, liver cancer, Hodgkin disease, non-Hodgkin lymphoma, and cervical cancer with occupational exposure to TCE. 2,4,6-trichlorophenol: RA. Has been used primarily in pesticides and wood preservatives; has also been used in fungicides, glue preservatives, insecticides, bactericides, and antimildew agents for textiles; however, most uses have been discontinued in the United States except in fungicides. Human exposure is through ingestion of contaminated food and water, inhalation of contaminated air, and skin contact. Increased incidences of leukemias, lymphomas, and liver cancer occurred in laboratory animals when administered in the diet. There is limited evidence for the carcinogenicity in humans, including soft-tissue sarcomas and non-Hodgkin lymphomas, when exposed to chlorophenols, which contain 2,4,6-trichlorophenol as well as tetrachlorodibenzo-p-dioxin (TCDD), which is a known carcinogen. 1,2,3-trichloropropane: RA. Used in the production of polysulfone liquid polymers and dichloropropene, and in the synthesis of hexafluoropropylene and polysulfides; it also was used as a solvent and extractive agent, and in the manufacture of a soil fumigant. Hu1381
Carcinogens man exposure is through inhalation of vapors, skin contact, and ingestion of contaminated water. Malignant tumor formation at multiple sites occurred in laboratory animals when administered by stomach tube. No adequate data are available to evaluate the carcinogenicity in humans. ultraviolet A radiation (UVA), ultraviolet B radiation (UVB), and ultraviolet C radiation (UVC): RA. All are components of broad-spectrum ultraviolet radiation (UVR); exposure is through solar radiation (except for UVC, which is absorbed by the ozone layer) and artificial devices emitting broad-spectrum UVR, such as sunlamps and sun beds. Exposure to each of these components induced skin tumors in laboratory animals; limited evidence shows that each of these components causes DNA damage in human tissue, which may lead to skin cancer. ultraviolet radiation (UVR), broad spectrum: K. Exposure is through solar radiation and artificial devices emitting broad-spectrum UVR, such as sunlamps and sun beds. Has been determined to cause skin cancer. urethane: RA. Used in the preparation of amino resins, which are used in permanent press textiles; also used in the manufacture of pesticides, fumigants, cosmetics, and pharmaceuticals, and in biochemical research. Human exposure is through inhalation, ingestion, and skin contact. Leukemias and tumors at multiple sites occurred in laboratory animals when exposed to urethane. No adequate data are available to evaluate the carcinogenicity in humans. vinyl bromide: RA. Used primarily in the production of polymers and copolymers, which are used as flame retardants, and in the production of carpet-backing material, fabrics, home furnishings, granular products, films, laminated fibers, and rubber substitutes; also used in leather and fabricated metal products and in the production of pharmaceuticals and fumigants. Human exposure is through inhalation and skin contact. Tumors of the liver and Zymbal gland occurred in laboratory animals when vinyl bromide was administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. vinyl chloride: K. Used mainly by the plastics industry to produce polyvinyl chloride (PVC) and copolymers. Common items containing PVC include automotive
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Salem Health: Cancer parts and accessories, battery cell separators, containers, credit cards, electrical insulation, flooring, furniture, medical supplies, windows, wrapping film, and videodiscs. Vinyl chloride-vinyl acetate copolymers are used to produce films and resins. Human exposure is through inhalation of contaminated air, ingestion of contaminated foods and water, and skin contact. Studies indicate that vinyl chloride causes a rare tumor of the liver (angiosarcoma), as well as other tumors. 4-vinyl-1-cyclohexene diepoxide: RA. Used to dilute other diepoxides and for epoxy resins. Exposure is through inhalation and especially through skin contact. Skin cancer at the site of application and tumors of the ovary occurred in laboratory animals when exposed to 4-vinyl-1-cyclohexene diepoxide. No adequate data are available to evaluate the carcinogenicity in humans. vinyl fluoride: RA. Used primarily in the production of polyvinyl fluoride and other fluoropolymers, which are commonly used as building materials. Human exposure is primarily by inhalation, but skin and eye contact may also occur. A variety of tumors have occurred in laboratory animals when administered by inhalation. No adequate data are available to evaluate the carcinogenicity in humans. wood dust: K. Usually produced as a by-product of manufacturing wood products; commercially used in wood composts. Human exposure is through inhalation. Studies have determined that cancer of the nasal cavities and paranasal sinuses is associated with wood dust exposure, with limited evidence for cancer of the nasopharynx and larynx and Hodgkin disease. X radiation and gamma radiation: K. Used in medicine (radiotherapy, computed tomography, positron emission tomography), the nuclear power industry, the military (nuclear weapons), scientific research, industry (well logging, sterilizing products, irradiating foods), and various consumer products (smoke detectors, televisions, radioluminescent clocks and watches, selfluminous signs). Exposure to X radiation and gamma radiation is strongly associated with leukemia and cancer of the thyroid, breast, and lung; cancer of the bladder, central nervous system, colon, salivary glands, skin, stomach, and ovary have also been reported.
u
Glossary
ABCD rating: A system used to describe the stages of prostate cancer, with “A” and “B” describing cancer that is confined to the prostate, “C” for cancer that has grown out of the prostate but has not metastasized or spread to lymph nodes, and “D” for cancer that has metastasized or spread to lymph nodes. ablation: The removal, destruction, or severing of diseased or damaged tissue, body part, or its functionality through surgery, drugs, heat, hormones, radiofrequency, or other means. abscess: A pus-filled cavity that is usually swollen and inflamed and is a result of bacterial infection. acquired immunodeficiency syndrome (AIDS): A disease of the immune system, caused by the human immunodeficiency virus (HIV), that causes a substantially increased risk for developing certain cancers and infections. acromegaly: A rare disorder of adults in which an overproduction of growth hormones causes an enlargement of the bones of the hands, feet, nose, jaw, and head, as well as various other signs and symptoms. actinic keratosis: Precancerous patches of skin that are thick and scaly. (Also called solar keratosis and senile keratosis.) acute: That which begins and worsens quickly. adeno-: Referring to a gland. adenoma: A tumor of glandular origin or of a glandular structure that is not cancerous. adenopathy: Swollen or large lymph glands. adenosine triphosphate (ATP): The chemical compound in all living cells that provides the energy needed for metabolic processes. adenosquamous carcinoma: A malignant tumor that contains both glandular cells and squamous cells. adjunct therapy: Another treatment used in addition to a primary treatment to aid the primary treatment and increase the chance for a cure, such as chemotherapy used in addition to surgery. adnexal mass: A growth of tissue in the uterine adnexa, usually in the ovary or Fallopian tube; it includes ovarian cysts, benign or malignant tumors, and ectopic (tubal) pregnancies. adrenal glands: Small endocrine glands located on top of both kidneys that make and secrete adrenaline and noradrenaline, the steroid hormones that help control heart rate, blood pressure, and other body functions. (Also called suprarenal glands.) adrenalectomy: Surgical removal of one or both adrenal glands.
adrenocortical: Pertaining to the outer layer of the adrenal gland. adult T-cell leukemia/lymphoma (ATLL): A fast-growing T-cell non-Hodgkin lymphoma, which is a cancer of the immune system’s T cells; it is believed to be caused by the human T-cell leukemia/lymphotropic virus type 1 (HTLV-1). aggravating factor: Something that makes a medical condition worse, more serious, or more severe. aggressive: That which grows, develops, or spreads quickly. agnogenic myeloid metaplasia (AMM): Aslow-developing, long-term disease that occurs when bone marrow is replaced by fibrous tissue, making the bone marrow unable to manufacture blood cells properly and creating a condition in which blood is then made in organs such as the liver and the spleen; this may lead to the enlargement of these organs and progressive anemia. AIDS: See aquired immunodeficiency syndrome. AJCC staging system: Developed by the American Joint Committee on Cancer, this system describes the extent of cancer in a patient’s body using T to describe the size of the tumor and if it has invaded nearby tissue, N to describe any nearby lymph nodes that are involved, and M to describe distant metastasis (spread of the cancer to another part of the body). alanine aminopeptidase (AAP): An enzyme that is used as a biomarker to detect kidney damage and that can be used to help diagnose certain kidney disorders; high levels occur in the urine when there are problems with the kidney. alanine transferase: An enzyme found in the liver and various bodily tissues and which, when present in abnormally high levels in the blood, may be a sign of liver damage, cancer, or other diseases. allogeneic bone marrow transplantation: A procedure in which stem cells derived from the bone marrow are transferred to the cancer patient from a genetically similar but not identical donor, such as a brother or sister. allogeneic stem cell transplantation: A procedure in which blood-forming stem cells are transferred to the cancer patient from a genetically similar but not identical donor, such as a brother or sister. allopathic medicine: See conventional medicine. amelanotic melanoma: A cancerous skin lesion that has little or no color, although it may appear red, pink, or white, and has an asymmetrical shape with an irregular faintly pigmented border that may be light brown, tan, or gray. 1383
Glossary ampullary cancer: Cancer of the ampulla of Vater, which is the area where the pancreatic duct and the common bile duct (from the liver) join together and enter the small intestine. analgesic: A drug, such as aspirin, acetaminophen, and ibuprofen, that reduces pain. anaphylactic shock: The most severe and sometimes lifethreatening whole-body allergic reaction during which a person may experience itchy skin, edema, collapsed blood vessels, fainting, difficulty in breathing, and then death if medical treatment is not received promptly. anaplastic: Rapidly dividing cancer cells with an abnormal appearance. anaplastic large cell lymphoma (ALCL): A fast-growing non-Hodgkin lymphoma, that is usually a cancer of the immune system’s T cells and that may occur in the lymph nodes of the neck, armpit, or groin, as well as in the bones, liver, lungs, soft tissues, or skin. anaplastic thyroid cancer: A rare and aggressive thyroid cancer consisting of abnormal-looking cancer cells. anastomosis: A surgical procedure in which healthy sections of tubular structures in the body are connected together after a diseased portion has been surgically removed. androblastoma: A rare ovarian tumor that secretes a male sex hormone, usually causing physical characteristics of men to appear in women. anesthetic: A medical substance that puts the patient to sleep, causing a loss of feeling and awareness when administered systemically (general anesthetics) or causing a loss of feeling in only part of the body when applied locally. angioimmunoblastic T-cell lymphoma: A fast-growing T-cell non-Hodgkin lymphoma that causes enlarged lymph nodes and increased antibodies in the blood, and may also cause a skin rash, fever, weight loss, and night sweats. angiomyolipoma: A benign tumor of fat and muscle tissue usually found in the kidney and that may bleed or grow painfully large enough to cause kidney failure but otherwise rarely causes any symptoms. anorexia: An abnormal loss of appetite. anterior mediastinotomy: A procedure in which a tube is inserted through an incision next the breastbone to view the tissues and organs in the area between the breastbone and heart and between the lungs. anterior pelvic exenteration: The surgical removal of the uterus, cervix, vagina, urethra, lower part of the ureters, and bladder. anterior urethral cancer: Cancer of the part of the urethra (the tube that carries urine from the bladder to the 1384
Salem Health: Cancer outside of the body) that is closest to the outside of the body. antiangiogenic: That which reduces the growth of new blood vessels. antibody: A specific type of protein created by plasma cells (white blood cells) as an immune response to a specific antigen (foreign substance, such as a virus or bacterium) that may be a threat to the body, to neutralize or destroy that antigen. (Also called an immunoglobulin.) antibody therapy: A medical treatment that uses an antibody to kill specific tumor cells, either directly or by stimulating the immune system to kill the tumor cells. anticoagulant: A drug used to aid in the prevention of blood clots. (Also called a blood thinner.) antiemetic: A drug used to prevent or reduce nausea and vomiting. antigen: A substance that stimulates a specific immune response, namely the production of antibodies. antiglobulin test: A laboratory test used to determine blood type and to diagnose blood disorders in which antibodies are produced that destroy a patient’s own red blood cells or platelets. antimitotic agent: A drug used to treat cancer by stopping cell division (mitosis) and thereby blocking cell growth. apheresis: A procedure in which blood is withdrawn from a patient or donor, the blood is passed through an apparatus that separates out one or more components from the blood, and then the remaining blood is transfused back into the patient or donor. aromatase inhibitor: A drug that interferes with the role of the aromatase enzyme in the production of estradiol, a female hormone; it is used as hormone therapy for postmenopausal women who have hormone-dependent breast cancer. arterial access device: A semipermanent implantable device, such as a port, chemo-port, port-a-cath, or PICC line, that allows a medical professional direct access to an artery without having to put a needle into the artery every time treatment is given, making administration of chemotherapy easier and reducing the risk of certain chemotherapy-related complications. arteriogram: An X ray of arteries taken after the injection into the arteries of a special dye. aspiration: The removal of a sample of tissue or fluid for examination by suctioning through a needle attached to a syringe, or the accidental inhalation of a foreign substance into the lungs. assay: A laboratory test that finds and measures the quantity of one or more components within a specific substance.
Salem Health: Cancer ataxia: Loss of the ability to coordinate voluntary muscle movements. atypical teratoid/rhabdoid tumor: An aggressive and rare pediatric cancer involving the central nervous system, kidney, or liver. autoimmune hemolytic anemia: A condition in which the body’s immune system interferes with the formation of red blood cells; it may occur in patients with chronic lymphocytic leukemia (CLL). autologous bone marrow transplantation: A procedure in which a patient’s own bone marrow is removed, stored, and then returned back to that person’s body after intensive treatment, such as high-dose chemotherapy. autologous stem cell transplantation: A procedure in which a patient’s own blood-forming stem cells are removed, stored, and then returned back to that person’s body. autonomic nervous system (ANS): The part of the nervous system that controls muscles of internal organs (such as the blood vessels, heart, lungs, intestines, and stomach) and glands (such as sweat glands and salivary glands) and affects involuntary, reflexive functions, such as heart rate, respiration rate, digestion, perspiration, and salivation. It consists of three parts: the parasympathetic nervous system, which induces fight-orflight responses in emergencies or stressful situations; the sympathetic nervous system, which allows the body to rest and digest; and the enteric nervous system, which controls the gastrointestinal system. B cell: A white blood cell that makes antibodies and helps fight infections. B-cell acute lymphocytic leukemia: With this leukemia, the most common type of acute lymphoblastic leukemia (ALL), abnormal immature white blood cells (B-cell lymphoblasts) crowd out the normal white blood cells, red blood cells, and platelets the body needs. (Also called B-cell acute lymphoblastic leukemia and precursor B-lymphoblastic leukemia.) B-cell lymphoma: A type of non-Hodgkin lymphoma that affects B cells (immature white blood cells) and may be either slow-growing or fast-growing; there are many types of B-cell lymphomas. barbiturate: A drug that depresses the central nervous system, causing a sedative effect that can be used to relieve anxiety before surgery and to treat insomnia, seizures, and convulsions. barium swallow: See esophagram. Bellini duct carcinoma (BDC): A rare, fast-growing, and fast-spreading kidney cancer that begins in the duct of Bellini in the kidney.
Glossary Bench Jones protein: A protein produced by plasma cells that is found in the urine of patients with certain diseases, especially multiple myeloma. benign: Not cancerous. Biafine cream: A cream applied topically by patients receiving radiation treatment to reduce the risk of and to treat skin reactions to the radiation. bilateral cancer: Cancer that occurs in both the left and right organs, such as both breasts or both ovaries. biliary: Pertaining to the liver, bile ducts, and gallbladder. biological response modifier (BRM) therapy: A treatment that uses monoclonal antibodies, growth factors, and vaccines to enhance or restore the immune system’s ability to fight infections, cancer, and other diseases, as well as to reduce certain side effects that may be caused by some cancer treatments. biomedicine: See conventional medicine. biopsy: The removal of cells, tissues, or entire lumps or suspicious areas for microscopic examination by a pathologist. blood-brain barrier (BBB): A network of blood vessels with closely spaced cells that prevents many potentially toxic substances, including anticancer drugs, from leaving the bloodstream and crossing the protective blood vessel walls into the brain tissues. blood-brain barrier disruption (BBBD): The use of drugs to create gaps between the cells of the barrier so that anticancer drugs may be delivered to a brain tumor via an artery that goes into the brain. blood cell count: See complete blood count (CBC). blood thinner: See anticoagulant. blood urea nitrogen (BUN): A substance in the blood that occurs naturally as a result of the breakdown of protein in liver and that is usually filtered out of the blood and into the urine by the kidneys; a high level of urea nitrogen in the blood may indicate a kidney problem. bolus infusion: A single dose of drug given quickly by intravenous injection. bone metastasis: Cancer that has spread to the bone from the original tumor. bone-seeking radioisotope: A substance that gives off low-level radiation, which kills cancer cells; it is administered through a vein, then collects in bone cells and tumor cells that have spread to the bone. brain stem gliomas: Tumors of the brain stem (the part of the brain that connects to the spinal cord). breast-conserving surgery: The surgical removal of the breast cancer without removing all of the breast. The surgery may involve the removal of the lump (lumpectomy); the removal of one quarter, or quadrant, of the breast (quadrantectomy); or the removal of the tumor 1385
Glossary and some of the breast tissue around the tumor, as well as the lining over the chest muscles below the tumor (segmental mastectomy). (Also called breast-sparing surgery.) breast duct endoscopy: A procedure in which a thin, flexible tube attached to a camera is inserted through the nipple and into the breast ducts deep into the breast to look for abnormal tissue in the lining of the breast ducts; samples of tissue and fluid may be removed during the procedure. bronchogenic carcinoma: Lung cancer that begins in the lining of the airways of the lungs (bronchi) and includes small-cell and non-small cell lung cancer. bronchoscopy: A procedure in which a thin, flexible tube with a light and lens is inserted through the nose or mouth and into the trachea, bronchi (airways of the lungs), and lungs to look for signs of cancer, remove tissue for microscopic examination by a pathologist, or perform treatment procedures. Burkitt lymphoma: A rare, aggressive leukemia (cancer of the blood) in which an excess of white blood cells (B lymphocytes) forms in the blood and bone marrow; it has been linked to infection with the Epstein-Barr virus. cancer: A group of diseases in which abnormal cells divide without control and then can invade nearby tissues and may even spread to other locations in the body via the blood and lymph systems. cancer of the adrenal cortex: A rare cancer of the outer part of the adrenal gland that may or may not make more than a normal amount of certain hormones (aldosterone, cortisol, estrogen, or testosterone). carbogen: A mixture of oxygen and carbon dioxide that is inhaled and induces an increased sensitivity of tumor cells to the effects of radiation therapy. carcinogen: A substance that causes cancer. carcinogenesis: The process in which normal cells are transformed into cancer cells. carcinoma: Amalignant tumor that begins in the skin or in the tissues that line or cover the internal organs (epithelial tissue). carcinoma of unknown primary origin (CUP): A cancer in which cancer cells have spread and been found in the body; however, the initial location where the cells first started growing cannot be established. carcinosarcoma: A malignant tumor containing both epithelial tissue (such as skin or tissue that lines or covers internal organs) and connective tissue (such as bone, cartilage, or fat). cardiac sarcoma: A rare cancer in heart tissue. (Also called heart cancer.) 1386
Salem Health: Cancer catheter: A flexible tube used to inject or withdraw fluids from the body. cauterize: To destroy tissue by using extreme heat or cold, an electric current, or caustic chemicals. CBC: See complete blood count (CBC). cellular adoptive immunotherapy: A treatment in which the T cells (white blood cells) of a cancer patient are collected, grown, and multiplied in number in the laboratory, then given back to the patient to help the patient’s immune system fight the cancer. central nervous system primitive neuroectodermal tumor: A cancer that originates from a particular type of cell in the brain or spinal cord. central nervous system prophylaxis:A preventive medical treatment in which chemotherapy or radiation is administered to the central nervous system to kill cancer cells that may be undetectable in the brain and spinal cord. cerebellar hemangioblastoma: A benign, slow-growing tumor in the posterior part of the brain (cerebellum). cervical intraepithelial neoplasia (CIN): The formation of abnormal cells on the surface of the cervix. chemoimmunotherapy: The use of chemotherapy to kill or slow cancer cell growth, combined with immunotherapy to restore the immune system’s ability to fight cancer. chemoprotective agent: A drug used to protect healthy tissues in the body from the toxic effects of anticancer drugs. chemoradiation: A medical treatment that combines chemotherapy and radiation therapy. chemotherapy: Adrug treatment used to kill cancer cells. chloroma: See granulocytic sarcoma. cholangiocarcinoma: A rare cancer that occurs in the lining of the bile ducts in the liver. cholangiosarcoma: A tumor of the connective tissues of the bile ducts in the liver. chondrosarcoma: A cancer that forms in cartilage. chorioadenoma destruens: A cancer that typically forms after fertilization of an egg and that grows into the muscular wall of the uterus. choroid plexus tumor: A rare cancer that develops in the ventricles of the brain and usually occurs in children younger than two years old. chronic: A disease or condition that continues, slowly progresses, or returns, often over a long period of time. clear cell adenocarcinoma: A rare tumor, especially of the female genital tract, that contains cells that look clear inside when viewed under a microscope. clinical resistance: An unsuccessful reduction in the amount of a cancer after treatment. colorectal: Pertaining to the colon and the rectum.
Salem Health: Cancer complete blood count (CBC): A laboratory test that determines the number of red blood cells, white blood cells, and platelets in a sample of blood. (Also called blood cell count.) complete hysterectomy: The surgical removal of the uterus and the cervix. complete metastasectomy: The surgical removal of all tumors formed from cancerous cells that have spread from the original tumor. complete remission: A period during which any clinical signs of a disease disappear in response to a treatment; however, this does not necessarily mean that the disease has been cured. computed tomography (CT) scan: A series of detailed pictures of structures within the body, created by a computer that takes the data from multiple X-ray images taken from different angles and turns them into pictures on a screen. (Also called computerized axial tomography scan, tomography scan, computerized tomography, and CAT scan.) concurrent therapy: A medical treatment given at the same time as another. congenital mesoblastic nephroma: A kidney tumor, containing connective tissue cells, that may spread to nearby tissue or the other kidney and that is found in a fetus before birth or in an infant within the first three months of life. consolidation therapy: A high-dose chemotherapy given after induction therapy as the second phase of a cancer treatment regimen, to help further reduce the presence of cancer cells in the body. (Also called intensification therapy.) contraindication: Something, such as a medical condition or a symptom, that makes a particular treatment inadvisable because of the increased likelihood of a bad reaction. contrast material: A dye or other substance that is given to a patient by intravenous injection, enema, or mouth and used with X rays, computed tomography (CT) scans, magnetic resonance imaging (MRI), or other imaging tests to show abnormal areas inside the body. conventional medicine: A system of medicine in which symptoms and diseases are treated using drugs, radiation, or surgery by medical doctors with the assistance of other health care professionals, such as nurses, pharmacists, and therapists. (Also called allopathic medicine and biomedicine.) CT scan: See computed tomography (CT) scan. cystoprostatectomy: The surgical removal of the bladder and the prostate; the seminal vesicles are also removed in a radical cystoprostatectomy.
Glossary cystosarcoma phyllodes (CSP): Tumors that occur in breast tissue and are usually benign but may be malignant. cystourethrectomy: The surgical removal of the bladder and the urethra. cytopenia: A deficiency of blood cells. debulking: Surgically removing as much of a tumor as possible. desmoplastic melanoma: A rare form of skin cancer, specifically a variant of malignant melanoma, that is characterized by nonpigmented lesions on sun-exposed areas of the body, especially on the head and neck. diffuse hyperplastic perilobar nephroblastomatosis (DHPLN): Abnormal tissue growth on the outer part of one or both kidneys that occurs during childhood and that may develop into Wilms’ tumor (childhood kidney cancer) if not treated. diffuse large B-cell lymphoma: A fast-growing cancer of the immune system (a non-Hodgkin lymphoma) that is characterized by tumors in the lymph nodes, bone marrow, liver, spleen, and other organs, as well as fever, night sweats, and weight loss. distant metastasis: The spread of cancer from the original site to distant organs or distant lymph nodes. donor lymphocyte infusion: A therapy in which lymphocytes (a type of white blood cell) are taken from the blood of the stem cell transplant donor and given to the recipient patient to kill remaining cancer cells. ductal carcinoma: Cancer that begins in the cells that line the milk ducts in the breast, which is the most common type of breast cancer. durable power of attorney: A legal document that gives one person the authority to make medical, legal, or financial decisions for another person until that person dies or cancels it; it may go into effect immediately or when that person is incapable of making those decisions. early-stage cancer: Cancer that is in the beginning stage of its growth and has not spread to other parts of the body. ectomesenchymoma: A rare, fast-growing tumor of the nervous system or soft tissue that may form in the abdomen, head, neck, limbs, perineum, or scrotum in children and young adults. -ectomy: Surgical removal. endocrine: Pertaining to tissues, such as the pituitary, thyroid, and adrenal glands, which make hormones and release them throughout the body via the bloodstream; these hormones control the actions of other cells or organs. endoscopic ultrasound (EUS): A procedure in which a thin, tubelike instrument (an endoscope) is inserted 1387
Glossary into the body and a probe at the end of the endoscope uses high-energy sound waves (ultrasound) to make a picture (sonogram) of internal organs. (Also called endosonography.) epithelial carcinoma: Cancer that originates in the cells that line an organ. epithelial ovarian cancer: Cancer that occurs in the cells on the outside of the ovary. erythrocyte sedimentation rate (ESR): The distance red blood cells travel in one hour in a sample of blood as they settle to the bottom of a test tube; this rate increases when inflammation, infection, cancer, diseases of the blood and bone marrow, and rheumatic diseases are present. erythroleukemia: Cancer of the blood-forming tissues in which an excess of immature, abnormal red blood cells is found in the blood and bone marrow. erythroleukoplakia: Potentially cancerous patches of red and white tissue that form on mucous membranes in the mouth; alcohol and tobacco (smoking or chewing) increase the risk of erythroleukoplakia. esophageal stent: A metal mesh, plastic, or silicone tube that is placed in the esophagus to keep a blocked area open so that the patient can swallow soft food and liquids; it may be used in the treatment of esophageal cancer. esophagram: A series of X rays of the esophagus taken after the patient drinks a barium solution. (Also called barium swallow and upper GI series.) Ewing family of tumors (EFTs): A group of tumors that all come from the same type of stem cell and include Ewing tumor of bone (ETB or Ewing sarcoma of bone), extraosseous Ewing (EOE) tumors, Askin tumors (PNET of the chest wall), and primitive neuroectodermal tumors (PNET or peripheral neuroepithelioma). excision: Removal by surgery. excisional biopsy: The surgical removal of a lump or suspicious area for microscopic examination by a pathologist. excisional skin surgery: The surgical removal of cysts, moles, other skin growths, and skin cancer (including some of the healthy tissue around it) using local anesthesia. extracranial germ-cell tumor: A rare cancer that originates in reproductive cells (germ cells) in the ovary or testicle, or in germ cells that have traveled to areas of the body other than the brain, such as the abdomen, chest, or tailbone. extrahepatic bile duct cancer: A rare cancer that occurs in the part of the bile duct that is outside the liver. extrapleural pneumonectomy: The surgical removal of a diseased lung, part of the membrane covering the 1388
Salem Health: Cancer heart (pericardium), part of the muscle between the lungs and the abdomen (diaphragm), and part of the membrane lining the chest (parietal pleura); this surgery is often used to treat malignant mesothelioma. familial adenomatous polyposis (FAP): An inherited condition in which many growths (polyps) form on the inside walls of the colon and rectum; this condition increases the risk for colorectal cancer. familial dysplastic nevi: A hereditary condition in which at least two members of a family have atypical moles (dysplastic nevi) and are at very high risk for developing melanoma. familial isolated hyperparathyroidism (FIHP): A rare inherited condition characterized by a loss of calcium in the bones, an elevated calcium level in the blood (hypercalcemia), and an excessive amount of parathyroid hormone (PTH) being produced because of one or more tumors in the parathyroid glands. familial medullary thyroid cancer: An inherited form of cancer that develops in the cells of the thyroid that make the hormone calcitonin. fast-neutron beam radiation: A type of radiation therapy in which a machine (a cyclotron) focuses a beam of high-energy neutrons to kill cancer cells. fibroid: A benign smooth-muscle tumor most often found in the uterus or gastrointestinal tract. (Also called leiomyoma.) fibromatosis: A condition in which many benign tumors grow in connective tissues. fine needle aspiration (FNA) biopsy: The removal of a sample of tissue or fluid for examination under a microscope by suctioning through a thin needle attached to a syringe. fluoroscopy: An imaging technique that allows a physician to see internal organs in motion by the use of a fluoroscope (a machine that transmits an X-ray beam through a patient so that it strikes a fluorescent plate that is attached to a television camera, causing the images to be visible live on a television monitor); this technique is often used to observe the digestive tract. FOLFOX: A chemotherapy drug combination of folinic acid (leucovorin), fluorouracil, and oxaliplatin that is used to treat colorectal cancer. follicular large-cell lymphoma: A rare, slow-growing cancer of the lymphatic system (a non-Hodgkin lymphoma) with large cancer cells. follicular lymphoma: A cancer of the immune system (a B-cell non-Hodgkin lymphoma) in which tumor cells grow as groups to form nodules.
Salem Health: Cancer follicular mixed-cell lymphoma: A slow-growing cancer of the lymphatic system (a B-cell non-Hodgkin lymphoma) with both large and small cancer cells. follicular thyroid cancer: A slow-growing, highly treatable cancer of the follicular cells in the thyroid. functional magnetic resonance imaging (fMRI): A noninvasive diagnostic tool that uses a powerful magnetic field, radio waves, and a computer to produce detailed pictures of the brain, spinal cord, or other organs and allows physicians to measure the metabolic changes that are taking place by detecting changes in blood flow and blood oxygenation. fungating lesion: A type of skin lesion that develops when an underlying malignant tumor increases in size and extends through the epithelium, leaving a visible ulceration with tissue necrosis (death of living tissue), infection, and odor, and that may occur in many types of cancer, especially in advanced disease. gamma irradiation: A type of radiation therapy that uses a high-energy radiation different from X rays called gamma radiation. gastrectomy: Surgical removal of all or part of the stomach. gastroscopy: Examination of the inside of the stomach by passing a thin, tubelike instrument with a light and lens for viewing through the mouth and esophagus into the stomach. (Also called upper endoscopy.) germinoma: A germ-cell tumor that is most often found in the brain. glial tumors: Tumors of the central nervous system, which include astrocytomas, ependymal tumors, glioblastoma multiforme, and primitive neuroectodermal tumors. glucagonoma: A fast-growing tumor of the central nervous system originating in the glial tissue of the brain and spinal cord. graft-versus-host (GVD) disease: An antitumor effect in which immune system cells in transplanted tissue from a donor (for example, bone marrow or peripheral blood) attack and help eliminate the recipient patient’s tumor cells. granulocytic sarcoma: A malignant, green-colored tumor composed of immature white blood cells (myeloblasts) and often associated with myelogenous leukemia. (Also called chloroma.) health care proxy (HCP): A legal document that gives one person the authority to make health care decisions for another person when that person loses the ability to make those decisions. heart cancer: See cardiac sarcoma. hematoma: A mass of clotted or partially clotted blood
Glossary that forms in a tissue, an organ, or a body space as a result of a broken blood vessel. hematopoiesis: The production of new blood cells. hemilaryngectomy: The surgical removal of one side of the larynx (voice box). hemorrhage: Extensive blood loss from damaged blood vessels, usually within a short amount of time. hepatectomy: Surgical removal of all or part of the liver. hepatic: Pertaining to the liver. hepatic arterial occlusion: A blockage in the blood flow to the liver; can be caused intentionally using drugs or other agents to help kill cancer cells growing in the liver or inadvertently while providing chemotherapy through a catheter in the hepatic artery. hepatic veno-occlusive disease: A blockage in some of the veins in the liver, which is a common complication of high-dose chemotherapy given before a bone marrow transplant and which causes increases in weight, liver size, and blood levels of bilirubin. hepatobiliary: Pertaining to the liver, bile ducts, and gallbladder. hepatoblastoma: A malignant liver tumor of infants and young children. hepatocellular carcinoma: The most common type of liver tumor; it originates in the hepatocytes, the major type of cell in the liver, and is usually caused by cirrhosis (scarring of the liver). hepatoma: A tumor of the liver. hereditary nonpolyposis colorectal cancer (HNPCC): An inherited cancer syndrome in which a person has a very high risk of developing colorectal cancer and an above-normal risk of other cancers, including uterus, ovary, stomach, small intestine, biliary system, urinary tract, brain, and skin. (Also called Lynch syndrome.) high-dose chemotherapy: An intensive anticancer drug treatment that also destroys bone marrow and may cause other severe side effects; bone marrow or stem cell transplantation to rebuild the bone marrow usually follows this type of chemotherapy. high-dose radiation (HDR) therapy: A greater amount of radiation than in typical radiation therapy is directed precisely at the tumor, so as to kill more cancer cells in fewer treatments without damaging healthy tissue. high dose rate remote radiation therapy: A radiation treatment that involves placing a radiation source inside the body as close as possible to the cancer cells and then removing it between treatments. high-energy photon therapy: Aradiation therapy in which high-energy photons (units of light energy) penetrate deeply into tissues to attack tumors while impart1389
Glossary ing less radiation to superficial tissues, such as the skin. high-grade lymphoma: A cancerous tumor of lymphoid tissue that grows and spreads quickly and has severe symptoms. high-grade squamous intraepithelial lesion (HSIL): A precancerous condition in which there are abnormal cells of the uterine cervix. high-risk cancer: A cancer that is likely to spread or come back. homeopathic medicine: An alternative system of medicine based on the belief that a substance that causes particular symptoms in a healthy person can be used in minute doses to cure those symptoms in an ill person. Hurthle cell neoplasm: A type of thyroid tumor that is uncommon and may be either benign or malignant. hyper-: Excessive; above normal. hyperalimentation: The intravenous feeding of nutrients to patients who cannot ingest or digest food through the alimentary tract. hyperfractionation: The practice of giving smaller doses (fractions) of radiation more often than the standard radiation dose of once a day, resulting in fewer side effects. hypernephroma: Kidney cancer that originates in the lining of the renal tubules in the kidney; it is the most common type of kidney cancer. (Also called renal cell cancer.) hypersensitivity: An abnormal or excessive response by the immune system to a drug or other substance. hyperuricemia: Presence of an excessive amount of uric acid in the blood, which is sometimes a side effect of anticancer drugs. hypo-: Less than normal. hypofractionation: The practice of giving larger doses (fractions) of radiation less often and over a shorter period of time than the standard radiation dose of once a day. hypopharyngeal cancer: Cancer that originates in the bottom part of the throat (hypopharynx). idiopathic pneumonia syndrome: A condition characterized by pneumonia-like symptoms, such as fever, chills, coughing, and breathing difficulties, with no obvious infection in the lung; it can occur after a stem cell transplant. immature teratoma: A rare germ-cell tumor often containing different tissues, such as bone, hair, and muscle. immunoglobulin: See antibody. implantable pump: A small device that is implanted under the skin and that administers a steady dose of drugs. incidence: The number of new cases of a disease diag1390
Salem Health: Cancer nosed in a specific population during a specified period (usually a year). incision: A cut or wound in body tissue, especially that made with a surgical instrument. incisional biopsy: Surgical removal of a part of a lump or suspicious area for examination under a microscope. incontinence: Inability to control the discharge of urine (urinary incontinence) or feces (fecal incontinence). indolent: Slow to develop or progress. indolent lymphoma: See low-grade lymphoma. induction therapy: The initial treatment used in an effort to make subsequent treatments, such as surgery or radiotherapy, more effective and to evaluate the response to drugs or other agents. infiltrating cancer: Cancer that has spread into nearby, healthy tissue. (Also called invasive cancer.) intensification therapy: See consolidation therapy. inter-: Between or among. interstitial radiation therapy: Radiation treatment in which radioactive material sealed in needles, wires, seeds, or catheters is inserted into tissue at or near the tumor site. intra-: Within, during, or between layers of. intracranial tumor: A tumor situated in the brain. intrahepatic infusion: The administration of drugs directly into the blood vessels of the liver. intraluminal intubation and dilation: A procedure in which a tube (plastic or metal) is inserted through the mouth into the esophagus to keep it open; it is used especially during radiation therapy for esophageal cancer. intramuscular (IM): Within or into muscle. intraoperative radiation therapy (IORT): A procedure in which a concentrated beam of radiation is aimed directly at a tumor while it is exposed during surgery. intraperitoneal (IP): Within the peritoneal (abdominal) cavity. intraperitoneal chemotherapy: Treatment in which anticancer drugs are delivered directly into the peritoneal (abdominal) cavity through a thin tube. intraperitoneal infusion: The administration of drugs and fluids directly into the peritoneal (abdominal) cavity through a thin tube. intraperitoneal radiation therapy: Treatment in which a radioactive liquid is delivered directly into the peritoneal (abdominal) cavity through a thin tube. intrathecal chemotherapy: Treatment in which anticancer drugs are delivered by injection directly into the fluidfilled space between the thin layers of tissue that cover the brain and spinal cord. intravenous pyelogram (IVP): A series of X rays taken
Salem Health: Cancer of the kidneys, ureters, and bladder after intravenous administration of a dye that collects in and is excreted by the kidneys. intraventricular infusion: The administration of a drug into the fluid-filled cavity within the heart or brain. invasive cancer: See infiltrating cancer. inverted papilloma: A tumor of the mucosal membrane of the nasal cavity, paranasal sinus, or urinary tract in which the epithelial cells grow downward into the underlying supportive tissue. irradiation: The use of high-energy radiation to kill cancer cells and shrink tumors. (Also called radiation therapy.) isolated hepatic perfusion: A procedure in which the liver’s blood supply is temporarily separated from blood circulating throughout the rest of the body by the placement of a catheter into the artery that provides blood to the liver and the placement of a second catheter into the vein that takes blood away from the liver, so that high doses of anticancer drugs can be directed to the liver only. isolated limb perfusion: A procedure in which a tourniquet is used to stop the flow of blood to and from a limb (arm or leg) temporarily so that high-dose anticancer drugs can be delivered directly to the limb where the cancer is situated. isolated lung perfusion: A surgical procedure during which high-dose anticancer drugs are delivered directly to tumors in the lungs after separating the circulation of blood to the lungs from the circulation of blood through the rest of the body. -itis: A suffix denoting inflammation or inflammatory disease. J-pouch coloanal anastomosis: The surgical attachment of the colon to the anus after the removal of the rectum, performed by forming a J-shaped pouch from a 2to 4-inch section of the colon as a replacement for the rectum. jaundice: A condition in which the liver is not working properly or a bile duct is blocked, causing the skin and the whites of the eyes to yellow, the urine to darken, and the color of the stool to become lighter than normal. juvenile myelomonocytic leukemia (JMML): A rare childhood cancer of the blood or bone marrow in which cancer cells spread into tissues such as the skin, lungs, and intestines. Kahler disease: A cancer of plasma cells (immune system cells in bone marrow that produce antibodies). keratoacanthoma: A quick-growing, rounded skin tumor
Glossary that occurs on sun-exposed areas of the body, especially on the head and neck, and that tends to heal on its own. Klatskin tumor: A cancer of the lining of the bile ducts in the liver at the junction where the left and right ducts meet; it is a type of cholangiocarcinoma. large-cell carcinoma: The uncontrolled growth of large, cancerous cells of the lung. late-stage cancer: A cancer that has been growing for a while and has spread to the lymph nodes or other parts of the body. leiomyoma: See fibroid. leukemia: A cancer of the blood or bone marrow that is characterized by an abnormal increase in the number of white blood cells in the tissues of the body and may also include an increase of those in the circulating blood; leukemias are classified according to the type of white blood cell most noticeably involved. ligation: The surgical process of tying up a blood vessel to stop blood from reaching a tumor or part of the body. light-emitting diode (LED) therapy: A therapy in which a special type of light is used to activate specific drugs that react when exposed to the light, enabling them to kill the cancer cells. limited-stage small-cell lung cancer: Lung cancer in which cancer cells are found in one lung, only nearby lymph nodes, and the tissues between the lungs. lipoma: A benign tumor consisting of fat cells. localized cancer: Cancer that is confined to the original site without evidence of having spread. locally advanced cancer: Cancer that has spread to nearby tissue or lymph nodes. low-grade lymphoma: Cancer of immune system cells that grows and spreads slowly, inducing few symptoms. (Also called indolent lymphoma.) low-grade squamous intraepithelial lesion (LSIL): Slight changes in the size and shape of the cells on the surface of the uterine cervix that are considered mild abnormalities caused by human papillomavirus (HPV) infection. lower gastrointestinal (GI) series: A group of X rays taken of the colon and rectum following a barium enema; it is used to diagnose abnormalities in the large intestine. lymph nodes: Glands that are located along the lymphatic system in many areas throughout the body and that filter impurities, such as cancer cells or bacteria, from the lymphatic fluid that flows through the nodes. lymphoepithelioma: A cancer that originates in the tissues covering the nasopharynx (the upper part of the throat behind the nose). 1391
Glossary lymphography: An X-ray study of lymphatic vessels and lymph nodes after injection of a special dye. lymphoma: A malignant tumor of the lymph nodes or other lymphatic tissues. lymphoscintigraphy: An imaging technique used in conjunction with a radioactive substance injected at the site of the tumor to identify the first draining lymph node near a tumor so that a physician can determine which lymph node to remove for examination. Lynch syndrome: See hereditary nonpolyposis colon cancer (HNPCC). lytic lesion: An area of bone that has been destroyed from a disease process, such as cancer. magnetic resonance imaging (MRI): An imaging method using magnetism, radio waves, and a computer to produce images of organs and soft tissues; it provides spatial information about the size and shape of a tumor. magnetic resonance perfusion imaging: A diagnostic technique that is used in conjunction with an injected dye to produce computerized images of blood flow through tissues; it is a special type of magnetic resonance imaging (MRI). magnetic resonance spectroscopic imaging (MRSI): An imaging method that detects and measures activity at the cellular level, providing metabolic information; it is used in conjunction with magnetic resonance imaging (MRI). magnetic-targeted carrier: A tiny bead containing iron and carbon particles that is attached to an anticancer drug and used to direct the drug to the tumor site with the use of a magnet outside the body, allowing a larger dose of the drug at the tumor site for a longer period of time, and protecting healthy tissue from the side effects of chemotherapy. maintenance therapy: Treatment that is given to help a primary treatment continue working and to help keep cancer in remission. malignant: Cancerous. malignant ascites: An accumulation in the abdomen of fluid containing cancer cells. malignant meningioma: A rare, fast-growing tumor that arises from the meninges (membranes that cover and protect the brain and spinal cord) and that may spread to other areas of the body. malignant mesothelioma: A cancerous tumor of the lining of the lung and chest cavity (pleura) or lining of the abdomen (peritoneum); it is often caused by sustained exposure to airborne particles of asbestos. malignant mixed Müllerian tumor (MMMT): A rare tumor containing carcinoma and sarcoma cells and often occurring in the uterus. 1392
Salem Health: Cancer malignant peripheral nerve sheath tumor (MPNST): A soft-tissue tumor arising from a protective sheath (covering) around peripheral nerves (nerves outside the central nervous system). malignant pleural effusion: A condition in which cancer, most often lung cancer, breast cancer, lymphoma, and leukemia, causes an abnormal accumulation of fluid in the lining of the lung and the wall of the chest cavity. MALT: See mucosa-associated lymphoid tissue lymphoma. Mammotome: A minimally invasive device used to perform a breast biopsy. margin: The edge of the tissue removed in cancer surgery, which is examined for cancer cells to determine whether all the cancer has been removed. marginal zone lymphoma (MZL): Aslow-growing B-cell non-Hodgkin lymphoma that originates in the outer edges of lymph tissue. mature T-cell lymphoma: A fast-growing non-Hodgkin lymphoma (malignant tumor of the lymphoid tissue) that originates in mature T lymphocytes. mature teratoma: A benign germ-cell tumor often containing different tissues, such as bone, hair, and muscle. maximum inspiratory pressure test (MIP test): A test in which a person inhales and exhales through a manometer, a device that measures the strength of the muscles used in breathing. maximum tolerated dose: The highest dose of a drug or treatment that a person can tolerate before unacceptable side effects begin to occur. mean survival time: The average time that patients in a clinical study stayed alive, beginning with the time of diagnosis or with the start of treatment. median survival time: The length of time from diagnosis or start of treatment by which half of the patients with a specific disease have died. medical nutrition therapy: Therapy in which appropriate foods or nutrients are used in the treatment of conditions such as diabetes, heart disease, and cancer, and which may include changes in a person’s diet or intravenous or tube feeding. medullary thyroid cancer: Cancer of the C cells of the thyroid, which make calcitonin (a hormone that helps maintain a healthy blood calcium level). Merkel cell cancer: See trabecular cancer. melanoma: A cancer that originates in pigmented tissues, such as the skin (in the form of a mole), in the eye, or in the intestines. metaplastic carcinoma: A cancer that originates in cells that have changed into an abnormal form for that tissue; it is usually found in the alimentary or upper respiratory tract or in the breast.
Salem Health: Cancer metastasectomy: Surgical removal of one or more tumors that have formed from cells that have spread from the original (primary) tumor. metastasize: To spread, especially cancer cells, from the original site in the body to another area of the body. metronomic therapy: Low doses of anticancer drugs given continuously or frequently, usually in conjunction with other therapy methods. mixed glioma: A brain tumor consisting of more than one type of cell. modified radical mastectomy: Surgical removal of the breast, lymph nodes under the arm, the lining over the chest muscles, and sometimes part of the chest wall muscles. molar pregnancy: A slow-growing tumor that originates in the cells (trophoblastic) that aid in embryo attachment to the uterus and in placenta formation after fertilization of an egg by a sperm; it is usually benign but can become invasive, as well as malignant (then called a choriocarcinoma). molecular marker: A distinctive biological molecule found in the body that indicates a specific process, condition, or disease, and that may be used to determine the body’s response to a treatment for that disease or condition. MRI: See magnetic resonance imaging. mucosa-associated lymphoid tissue (MALT) lymphoma: A cancer (non-Hodgkin lymphoma) that originates in B cells in mucosal tissue that are involved in antibody production. Müllerian tumor: A rare cancer of the uterus, ovary, or Fallopian tubes. multidisciplinary: Involving a number of different specialties (disciplines), especially in the approach to planning treatment and the team of experts who oversee that treatment. neck dissection: Surgical removal of lymph nodes and other tissues in the neck. necrosis: Death of living tissues. negative axillary lymph node: A cancer-free lymph node in the armpit. neoadjuvant therapy: Treatment given before the primary treatment to help the primary treatment, such as drugs given to shrink an inoperable tumor so that surgery is possible. neoplasm: See tumor. nephrectomy: Surgical removal of a kidney. nephrotomogram: A series of X rays of the kidneys taken from different angles. nephrotoxic: Poisonous to the kidney.
Glossary nephroureterectomy: Surgical removal of a kidney and its ureter. nerve block: The injection of a local anesthetic around a nerve or into the spine to block pain. nerve-sparing radical prostatectomy: Surgical removal of the prostate with an attempt at saving the nerves that help cause penile erections. neuroendocrine carcinoma of the skin: See trabecular cancer. neuroma: A tumor that originates in nerve cells. neuropathy: An abnormal or degenerative condition of the nervous system that causes pain, tingling, numbness, swelling, or muscle weakness, usually beginning in the hands or feet and spreading to different parts of the body over time; physical injury, infection, toxic substances, disease (including cancer), or drugs (including anticancer drugs) may be the cause. neurotoxic: Poisonous or damaging to the nervous system. non-small-cell lung cancer: A group of lung cancers in which the cells, when viewed under a microscope, are not the small-cell type, and which include adenocarcinoma, large-cell carcinoma, and squamous cell carcinoma. nonfunctioning tumor: A tumor occurring in the endocrine tissue that does not make hormones. nonseminoma: A group of testicular cancers that begin in the cells that give rise to sperm (germ cells) and include choriocarcinoma, embryonal carcinoma, teratoma, and yolk sac carcinoma. occult primary tumor: Cancer in which the original tumor site is unknown, and the metastases of which are mostly found in the head and neck. ocular melanoma: A rare cancer of the eye occurring in the cells that produce the pigment melanin (melanocytes). oligoastrocytoma: A brain tumor that is a type of mixed glioma (consists of more than one type of cell). omentectomy: Surgical removal of all or part of the omentum (a fold of the lining of the abdomen). open biopsy: A procedure in which tissues or lumps are removed through an incision in the skin to be examined by a pathologist. open colectomy: Surgical removal of all or part of the colon through an incision in the wall of the abdomen. operable: Referring to a condition that can be treated by surgery. opportunistic infection: An infection caused by an organism that usually does not cause disease but can do so in people with weakened immune systems. oral: Pertaining to the mouth. 1393
Glossary osteosarcoma: Bone cancer, usually of the large bones of the arm or leg. ostomy: An operation in which an artificial passage is created from an area inside the body to the outside for bodily elimination, such as in a colostomy, ileostomy, or urostomy. ovarian ablation: Surgery, a drug treatment, or radiation therapy to prevent the functioning of the ovaries. oxygen therapy: The administration of oxygen through a nose tube, mask, or tent. Pancoast tumor: A type of lung cancer that forms at the very top (apex) of a lung and invades nearby tissues, such as the chest wall, ribs, and vertebrae. papillary serous carcinoma: A fast-growing cancer that spreads rapidly and usually affects the uterus/endometrium, ovary, or peritoneum. papillary thyroid cancer: A common type of slowgrowing thyroid cancer that originates in the follicular cells in the thyroid. papillary tumor: A mushroom-shaped tumor, the stem of which is attached to the inner lining (epithelial layer) of an organ. papilledema: Swelling around the optic disk as a result of increased brain pressure, sometimes caused by a brain tumor. paraganglioma: A rare tumor that arises from cells of the paraganglia and is usually found in the abdomen, thorax, or head or neck region. parathyroidectomy: Surgical removal of one or more of the parathyroid glands. parotidectomy: Surgical removal of all or part of the parotid gland (a salivary gland). partial cystectomy: Surgical removal of part of the bladder. partial hysterectomy: Surgical removal of the uterus only. partial laryngectomy: Surgical removal of part of the larynx (voice box). partial mastectomy: Surgical removal of a tumor of the breast, as well as some of the tissue around the tumor, the lining over the chest muscles below the tumor, and usually some of the lymph nodes under the arm. (Also called segmental mastectomy.) partial nephrectomy: Surgical removal of part of a kidney or a kidney tumor. partial oophorectomy: Surgical removal of part of one ovary or part of both ovaries. partial remission: A decrease in the amount of cancer in the body or the size of a tumor as a result of treatment received. partial vulvectomy: Surgical removal of part of the vulva. 1394
Salem Health: Cancer pathologic fracture: A break in the bone due to a disease, especially the spread of cancer to the bone. pathology report: A written report prepared by a pathologist describing the cells and tissues of a biopsy specimen after viewing under a microscope; it is used to help the primary physician make a diagnosis of a patient’s condition. patient advocate: A person who speaks on behalf of a patient to doctors, insurance companies, employers, case managers, or lawyers to protect the patient’s rights and to help that patient resolve issues about health care, medical bills, and job discrimination as a result of the patient’s medical condition. patient-controlled analgesia (PCA): A method of pain relief in which a preset dose of pain medicine is automatically administered to the patient when that patient presses a button on a computerized pump, allowing pain relief as needed. The pump also monitors the amount of medicine the patient is receiving within a certain time period and limits that amount when needed to prohibit an overdose. pelvic exenteration: Surgical removal of the lower colon, rectum, and bladder, as well as the cervix, vagina, ovaries, and nearby lymph nodes in women; then an opening is created through which urine and stool can pass out of the body. pelvic lymphadenectomy: Surgical removal of lymph nodes in the pelvis for microscopic examination by a pathologist. penectomy: Surgical removal of part or all of the penis. percutaneous ethanol injection: An injection of ethanol (pure alcohol) through the skin directly into the tumor, using a very thin needle with the help of ultrasound or computed tomography visual guidance, to destroy cancer cells. percutaneous transhepatic cholangiodrainage (PTCD): A procedure in which a stent is placed in the liver to drain bile and to relieve pressure in the bile ducts caused by a blockage; the bile may then drain through the stent into the small intestine or into a collection bag outside the body. periampullary cancer: A cancer that occurs near the ampulla of Vater (the area where the pancreatic duct and the common bile duct from the liver join together and enter the small intestine). perineal colostomy: An operation in which an artificial passage is created surgically to allow the colon to exit the body through the perineum (the area between the anus and the vulva in females and between the anus and the scrotum in males) after part of the colon has been removed. perineal prostatectomy: Surgical removal of the prostate
Salem Health: Cancer through an incision in the perineum (the area between the scrotum and the anus). peripheral blood lymphocyte therapy: A treatment in which lymphocytes from a sibling donor are infused into a patient who is suffering from Epstein-Barr virus infection or overgrowth of white blood cells after an organ or bone marrow transplant. peripheral venous catheter: A small, flexible tube inserted into a vein, usually in the back of the hand or forearm, taped in place and used to administer fluids into the body. peritoneal cancer: A rare cancer that originates in the tissues that line the inside of the abdomen and cover the organs in the abdomen. peritonitis: Inflammation of the peritoneum (the tissues that line the inside of the abdomen and cover the organs in the abdomen) as a result of infection, injury, or a disease. photo-beam radiation: A radiation treatment that uses high-energy X rays to reach deep tumors. photocoagulation: Sealing off blood vessels or destroying tissue with a high-energy beam of light. photopheresis: A procedure in which blood is removed from the body so that it can be treated with ultraviolet light and drugs that become active when exposed to light, and then is returned to the body. pineocytoma: A slow-growing brain tumor occurring in or near the pineal gland, which is near the center of the brain. plaque radiotherapy: A type of radiation therapy used to treat eye tumors that involves sewing to the outside wall of the eye a thin piece of metal with radioactive seeds attached, leaving it there for several days, and then removing it at the end of treatment. plasma cell myeloma: A cancer that originates in plasma cells (white blood cells that produce antibodies). plasma cell tumor: A tumor that originates in plasma cells (white blood cells that produce antibodies); includes multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), and plasmacytoma. plasmacytoma: A tumor that originates in plasma cells (white blood cells that produce antibodies) and may turn into multiple myeloma. pleurectomy: Surgical removal of part of the pleura (the thin layer of tissues that covers, protects, and cushions the lungs). pneumatic larynx: A device that uses air to produce sound to help a person whose larynx (voice box) has been removed to talk. port: An implantable device that allows a medical profes-
Glossary sional direct access to an artery without having to put a needle into the artery every time treatment is given or blood is withdrawn. positive axillary lymph node: Alymph node in the armpit area in which cancer cells are detected. posterior pelvic exenteration: Surgical removal of the lower part of the bowel, rectum, cervix, uterus, ovaries, Fallopian tubes, and vagina; some pelvic lymph nodes may also be removed. posterior urethral cancer: Cancer in the part of the urethra that connects to the bladder. postremission therapy: Anticancer drugs given after remission induction therapy to kill any remaining cancer cells. post-transplant lymphoproliferative disorder (PTLD): A condition in which a group of B-cell lymphomas occurs in a patient with a weakened immune system after an organ transplant; it is usually associated with patients who have also been infected with Epstein-Barr virus and may progress to non-Hodgkin lymphoma. power of attorney: A legal document that gives one person the authority to make medical, legal, or financial decisions for another person; it may go into effect immediately or when that person is incapable of making those decisions. precancerous: Pertaining to a condition that may become cancer. precancerous dermatitis: A skin disease characterized by thickened or scaly patches on the skin, usually on sun-exposed areas, and often caused by prolonged exposure to arsenic. precursor B-lymphoblastic leukemia: See B-cell acute lymphocytic leukemia. preventive mastectomy: Surgical removal of one or both breasts to reduce the risk of developing breast cancer. primary tumor: The original tumor. primitive neuroectodermal tumor (PNET): A tumor that may develop in the brain or central nervous system (CNS-PNET), or in sites outside the brain such as the limbs, pelvis, and chest wall (peripheral PNET). proctoscopy: Visual examination of the rectum by inserting a thin, tubelike instrument with a light and lens (a proctoscope) into the rectum. proctosigmoidoscopy: Visual examination of the lower colon by inserting a thin, tubelike instrument with a light and lens (a sigmoidoscope) into the rectum. prognosis: The most likely outcome of a disease, including the probability of recovery or recurrence. progression-free survival: The length of time for which a patient’s disease remains stable and does not progress both during and after treatment, often used in a clinical 1395
Glossary study or trial as a measure of how well a new treatment works. prophylactic cranial irradiation: Radiation therapy to the head to prevent the spread of cancer to the brain. prophylactic surgery: Surgical removal of a cancer-free organ or gland as a preventive step for a person with a high risk of developing cancer in that organ or gland. prostate-specific antigen (PSA) bounce: A brief increase and then decrease in the blood level of PSA; an increased level of PSA occurs in men with disease or infection of the prostate, and that level may briefly rise and fall again one to three years after receiving radiation treatment for prostate cancer as a result of PSA being released from destroyed cancer cells or from normal prostate tissue exposed to the radiation treatment, not because the cancer has come back. prostate-specific antigen (PSA) failure: An increase in the blood level of PSA after treatment with surgery or radiation for prostate cancer; it may indicate a recurrence of the cancer. prosthesis: An artificial replacement for part of the body, such as a leg or an arm. pruritus: Itching. psoralen and ultraviolet A therapy (PUVA therapy): A type of photodynamic therapy in which psoralen (a drug that becomes active when exposed to light) is administered either by mouth or topically to the skin and then followed by ultraviolet A radiation to treat skin conditions such as psoriasis, vitiligo, and skin nodules of cutaneous T-cell lymphoma. punch biopsy: Removal of a small cylinder of tissue, using a sharp, hollow instrument, for microscopic examination by a pathologist. quadrantectomy: Surgical removal of approximately onequarter of the breast—the quarter that contains the cancer. quality of life: Degree of well-being and ability to perform daily activities. radiation dermatitis: A painful skin condition in which the skin becomes red, itchy, and blistered as a side effect of radiation therapy. radiation enteritis: A complication of radiation therapy to the abdomen, pelvis, or rectum in which the small intestine becomes inflamed, causing nausea, vomiting, abdominal pain and cramping, watery or bloody diarrhea, fatty stools, and weight loss. radiation fibrosis: Scar tissue caused by radiation therapy. radiation necrosis: Death of healthy tissue as a result of radiation therapy; this dead tissue may form at the site of an irradiated tumor months or even years after the ra1396
Salem Health: Cancer diation therapy has ended and may require surgery to be removed. radiation surgery: A type of radiation therapy in which special equipment is used to position the patient so that a single large dose of radiation can accurately target a tumor; it is often used to treat brain tumors. radiation therapy: See irradiation. radical cystectomy: Surgical removal of the bladder and nearby tissues and organs. radical hysterectomy: Surgical removal of the uterus, cervix, and part of the vagina; may also include removal of the ovaries, Fallopian tubes, and nearby lymph nodes. radical local excision: Surgical removal of a tumor and a large area of surrounding normal tissue; nearby lymph nodes may also be removed. radical lymph node dissection: Surgical removal of most or all of the lymph nodes that drain lymph from the area around a tumor for microscopic examination by a pathologist. radical nephrectomy: Surgical removal of a kidney, the nearby adrenal gland and lymph nodes, and surrounding tissue. radical perineal prostatectomy: Surgical removal of the prostate through an incision in the perineum (the area between the scrotum and the anus); nearby lymph nodes may also be removed through another incision in the wall of the abdomen. radical retropubic prostatectomy: Surgical removal of the prostate and nearby lymph nodes through an incision in the wall of the abdomen. radical vulvectomy: Surgical removal of the vulva and nearby lymph nodes. radioimmunoguided surgery: Surgical removal of tumors that have been located using radioactive substances. radiologic exam: An imaging procedure that uses radiation (such as X rays) to help diagnose certain cancers and other abnormalities. radiology: The branch of medicine in which X rays, ultrasound, magnetic resonance imaging, and other imaging technologies are used to diagnose and sometimes treat certain diseases, such as cancer. rectal reconstruction: Surgery in which the rectum is rebuilt using a section of the colon following the surgical removal of the rectum due to cancer or other diseases. refractory cancer: Cancer that is resistant to treatment. regional lymph node dissection: Surgical removal of some of the lymph nodes that drain lymph from the area around a tumor for microscopic examination by a pathologist.
Salem Health: Cancer regression: Adecrease in the amount of cancer in the body or the size of a tumor. remission: A reduction or cessation of any signs and symptoms of cancer, even though the cancer may still exist. remission induction therapy: The initial treatment with anticancer drugs to bring about a reduction or cessation of signs and symptoms of cancer. renal cell cancer: See hypernephroma. resection: Surgical removal of tissue or part or all of an organ. retropubic prostatectomy: Surgical removal of the prostate through an incision in the wall of the abdomen. rhabdoid tumor: A malignant tumor found in either the kidney or the central nervous system. risk factor: Something that increases the likelihood of developing a certain disease, such as family history, exposure to tobacco products or other cancer-causing agents, obesity, and age. sarcoma: A malignant tumor of bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. sarcomatoid carcinoma: Cancer that contains long spindle-shaped cells and that originates in the skin or in the lining or covering of internal organs. (Also called spindle cell cancer.) scintimammography: A supplemental imaging technique that uses a radioactive substance (technetium 99) and a gamma camera to detect cancer cells in a breast with dense breast tissue or that has produced an abnormal mammogram. segmental mastectomy: See partial mastectomy. segmental resection: Surgical removal of part of an organ or gland. seminal vesicle biopsy: Needle aspiration of fluid or tissue from the seminal vesicles (glands in the male reproductive tract that produce part of the semen) for microscopic examination by a pathologist. seminoma: Cancer of the testicles that has the potential to spread to the bone, brain, liver, or lung. senile keratosis: See actinic keratosis. sestamibi scan: An imaging technique in which a radioactive substance (technetium bound to sestamibi) injected into a patient can be detected by a gamma camera when it collects in overactive parathyroid glands, cancer cells in the breast, or diseased heart muscle. shave biopsy: Removal of a skin abnormality with a thin layer of surrounding skin for microscopic examination by a pathologist by using a small blade in such a way that stitches are not needed.
Glossary shunt: A passage that diverts a bodily fluid from one area of the body to another. side-to-end coloanal anastomosis: The surgical attachment of the side of the colon to the anus after the removal of the rectum, by forming a small J-shaped pouch from a 2-inch section of the colon as a replacement for the rectum. signet ring cell carcinoma: A highly malignant cancer containing cells that resemble signet rings and are usually found in the glandular cells that line the digestive organs. skinning vulvectomy: Surgical removal of the top layer of skin of the vulva. sleeve lobectomy: A lung-saving procedure in which a tumor in a central lobe of the lung is surgically removed along with a part of the main bronchus; then the ends of the bronchus are rejoined and remaining lobes are reattached to the bronchus. small-cell lung cancer: A fast-growing cancer of the lung that can spread to other parts of the body. smoldering myeloma: A slow-growing myeloma in which abnormal plasma cells produce too much of a specific protein (monoclonal antibody); this is an asymptomatic condition that could progress to fully developed multiple myeloma. soft-tissue sarcoma: A malignant tumor that originates in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. solar keratosis: See actinic keratosis. solid tumor: A benign or malignant mass of tissue, usually free of any cysts or liquid areas; includes carcinomas, sarcomas, and lymphomas. somatostatin receptor scintigraphy (SRS): An imaging technique in which a radioactive drug (octreotide) injected into a patient attaches to tumor cells, which can then be detected by a radiation-measuring device; a picture is then created that shows where the tumor cells are in the body. spindle cell cancer: See sarcomatoid carcinoma. spiral computed tomography (CT) scan: A series of detailed pictures of structures within the body, created by a computer linked to an X-ray machine that scans the body in a spiral path. stromal tumor: A tumor that occurs in the supporting connective tissue of an organ. subcutaneous port: A semipermanent device implanted just under the skin that allows a medical professional direct access to an artery without having to put a needle into the artery every time intravenous fluids or drugs need to be administered or blood samples need to be taken. 1397
Glossary supraglottic laryngectomy: Surgical removal of the supraglottis (the part of the larynx that is above the vocal cords). suprarenal glands: See adrenal glands. syngeneic: Pertaining to individuals or tissues from those individuals containing identical genes, such as identical twins. systemic therapy: Treatment that affects cells all over the body by traveling through the bloodstream. T-cell depletion: Treatment that destroys T cells, especially from a donor’s bone marrow graft, to reduce the risk of an immune reaction against the recipient’s tissues. T-cell lymphoma: Cancer of T-lymphocytes (cells of the lymph system). terminal disease: An incurable disease that will lead to death. thermal ablation: The removal, destruction, or severing of a diseased or damaged tissue, body part, or its function through the use of heat. thermotherapy: The use of heat in the treatment of a disease. third-line therapy: Treatment that is given after both an initial and a subsequent treatment fail or become ineffective. three-dimensional conformal radiation therapy: A procedure in which a tumor is subjected to the highest possible dose of radiation while surrounding tissue is spared; accomplished by using a computer-generated three-dimensional picture of the tumor. thrombectomy: Surgical removal of a thrombus (blood clot) from a blood vessel. thrombolysis: Dissolving or breaking up a thrombus (blood clot), especially through the use of drugs. thyroidectomy: Surgical removal of part or all of the thyroid. time to progression: The length of time following diagnosis or treatment until the disease begins to get worse. tissue flap reconstruction: Breast reconstruction using a flap of tissue surgically removed from another area of the body and formed into a new breast mound. tomography: The process of creating a series of detailed pictures of structures within the body, by a computer linked to an X-ray machine. tongue cancer: Cancer that originates in the tongue. topical: Pertaining to the surface of the body. topical chemotherapy: The application of anticancer drugs directly on the skin in the form of a lotion, an ointment, or a cream. total-body irradiation: Radiation therapy to the whole body to kill cancer cells throughout the body and to de1398
Salem Health: Cancer stroy the bone marrow and immune system in preparation for bone marrow or stem cell transplantation. total mastectomy: Surgical removal of the breast. total nodal irradiation: Radiation therapy to the neck, chest, spleen, and lymph nodes under the arms, in the upper abdomen, and in the pelvic area. total pancreatectomy: Surgical removal of the pancreas, as well as nearby lymph nodes, the common bile duct, the gallbladder, the spleen, and part of the stomach and small intestine. total parenteral nutrition (TPN): The intravenous feeding of nutrients to patients who cannot ingest or digest food through the alimentary tract. total skin electron beam radiation therapy (TSEB radiation therapy): Radiation therapy that directs electrons at the entire surface of the body, allowing the radiation into the outer layers of the skin but not penetrating deeper into the tissues or organs below the skin. trabecular cancer: A rare cancer of the skin that may form on or just below the skin, especially in parts of the body exposed to the sun and in older people and those with weakened immune systems. (Also called Merkel cell cancer and neuroendocrine carcinoma of the skin.) transperineal biopsy: Removal of a sample of tissue from the prostate, using a thin needle inserted through the skin between the scrotum and the rectum, for microscopic examination by a pathologist. transrectal biopsy: Removal of a sample of tissue from the prostate, using a thin needle inserted through the rectum, for microscopic examination by a pathologist. transsphenoidal surgery: Surgery in which part of the brain is accessed through the nose and the sphenoid bone (a bone at the base of the skull); this type of surgery is common when removing tumors of the pituitary gland. transurethral biopsy: Removal of a sample of tissue from the prostate by inserting a thin tube with a cutting loop attachment through the urethra and into the prostate; the sample is then examined under a microscope by a pathologist. transurethral resection of the prostate (TURP): Surgical removal of tissue from the prostate using an instrument inserted through the urethra. treatment field: The area of the body at which the radiation beam is aimed during radiation therapy. tubulovillous adenoma: An abnormal growth of tissue (polyp), in the colon, the gastrointestinal tract, or other parts of the body, that may become cancerous. tumor: A new mass of tissue resulting from uncontrolled cell division and that serves no physiological function; it may be benign or malignant. (Also called neoplasm.)
Salem Health: Cancer tumor load: Pertaining to the size of a tumor, the number of cancer cells, or the amount of cancer in the body. tumor volume: The amount of space taken up by a tumor.
Glossary ventilator: A machine that helps a patient breathe. video-assisted resection: Surgery in which a video camera projects and enlarges the surgical field onto a television screen, allowing the surgeon an enhanced view of the surgical field. villous adenoma: An abnormal growth of tissue (polyp) in the colon, the gastrointestinal tract, or other parts of the body that may become cancerous. visual pathway glioma: A tumor that occurs along the optic nerve (the nerve that sends messages from the eye to the brain).
ultrasound-guided biopsy: Surgical removal of a sample of tissue, using an ultrasound imaging device to locate and guide the removal of that tissue, for microscopic examination by a pathologist. unilateral: Pertaining to one side of the body. unilateral salpingo-oophorectomy: Surgical removal of the ovary and Fallopian tube on one side of the body. unresectable gallbladder cancer: Gallbladder cancer that has spread to nearby areas, such as the lymph nodes, liver, stomach, pancreas, and intestine, so that it cannot be surgically removed. unsealed internal radiation therapy: Radiation therapy in which a radioactive substance that has not been sealed in a container is injected into the body or swallowed. upper endoscopy: See gastroscopy. upper GI series: See esophagram. urinary diversion: Asurgical procedure to create an alternative passage for urine to exit the body; it may include redirecting urine into the colon, draining the bladder through the use of catheters, or making an incision in the abdomen and collecting urine in a bag outside the body.
wedge resection: Surgical removal of a triangle-shaped piece of tissue or a tumor with some of the normal tissue around it. Whipple procedure: Surgical removal of the head of the pancreas, the duodenum, part of the stomach, and other nearby tissues to treat pancreatic cancer. whole genome association study (WGA study): A study in which the deoxyribonucleic acid (DNA) of people with a disease or medical condition is compared to the DNA of people without it in an effort to discover the genes that are involved in the disease and to aid medical professionals in the prevention, diagnosis, and treatment of the disease. wide local excision: Surgical removal of the cancer along with healthy tissue around it.
vaginectomy: Surgical removal of part or all of the vagina.
X-ray therapy: Radiation therapy that uses X rays to shrink tumors and kill cancer cells.
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Bibliography
General Studies and Reference Works Altman, Roberta, and Michael J. Sarg. The Cancer Dictionary. New York: Facts On File, 1994. American Cancer Society. Quick Facts on Advanced Cancer. Atlanta: Author, 2008. Bloch, Annette, and Richard Bloch. Fighting Cancer: A Step-by-Step Guide to Helping Yourself Fight Cancer. Kansas City, Mo.: R. A. Bloch Cancer Foundation, 1990. _______. Guide for Cancer Supporters: Step-by-Step Ways to Help a Relative or Friend Fight Cancer. Kansas City, Mo.: R. A. Bloch Cancer Foundation, 1995. Bognar, David, and Walter Cronkite. Cancer, Increasing Your Odds for Survival: A Resource Guide for Integrating Mainstream, Alternative and Complementary Therapies. Alameda, Calif.: Hunter House, 1998. Brownworth, Victoria A., ed. Coming Out of Cancer: Writings from the Lesbian Cancer Epidemic. Seattle: Seal Press, 2000. Cancercare. A Helping Hand: The Resource Guide for People with Cancer. New York: Author, 2008. Epps, Roselyn Payne, and Susan Cobb Stewart, eds. The American Medical Women’s Association Guide to Cancer and Pain Management. New York: Dell, 1996. Fischer, William L. How to Fight Cancer and Win: Scientific Guidelines and Documented Facts for the Successful Treatment and Prevention of Cancer and Other Health Related Problems. Baltimore, Md.: Agora Health Books, 1992. Friedberg, Errol C. Cancer Answers: Encouraging Answers to Twenty-five Questions You Were Always Afraid to Ask. New York: W. H. Freeman, 1992. Getz, Kenneth, and Deborah Borfitz. Informed Consent: The Consumer’s Guide to the Risks and Benefits of Volunteering for Clinical Trials. Boston: CenterWatch, 2002. Haylock, Pamela J., and Carol P. Curtiss. Cancer Doesn’t Have to Hurt: How to Conquer the Pain Caused by Cancer and Cancer Treatment. Alameda, Calif.: Hunter House, 1997. Kneece, Judy C. Helping Your Mate Face Breast Cancer: Tips for Becoming an Effective Support Partner. North Charleston, S.C.: Educare, 2001. Moritz, Cynthia. About Cancer. Syracuse, N.Y.: New Readers Press, 1994. Oster, Nancy, Lucy Thomas, and Darol Joseff. Making Informed Medical Decisions: Where to Look and How to Use What You Find. Foreword by Susan Love. Sebastopol, Calif.: Patient-Centered Guides, 2000. 1400
Schimmel, Selma R., with Barry Fox. Cancer Talk: Voices of Hope and Endurance from “The Group Room,” the World’s Largest Cancer Support Group. New York: Broadway, 1999. Schine, Gary L., and Ellen B. Berlinsky. Cancer Cure: The Complete Guide to Finding and Getting the Best Care There Is. New York: Kensington, 1996. Souhami, Robert, and Jeffrey Tobias. Cancer and Its Management. Malden, Mass.: Blackwell Science, 2005. Zakarian, Beverly, and Ezra M. Greenspan. The Activist Cancer Patient: How to Take Charge of Your Treatment. Hoboken, N.J.: John Wiley and Sons, 1996. Abdominal Cancers Abbruzzese, James, and Ben Ebrahimi. Myths and Facts About Pancreatic Cancer: What You Need to Know. Melville, N.Y.: PRR, 2002. Alschuler, Lise N., and Karolyn A. Gazella, eds. Alternative Medicine Magazine’s Definitive Guide to Cancer: An Integrative Approach to Prevention, Treatment, and Healing. Berkeley, Calif.: Celestial Arts, 2007. American Cancer Society. Quickfacts Pancreatic Cancer. Atlanta: Author, 2008. Brunschwig, Alexander. Radical Surgery in Advanced Abdominal Cancer. Chicago: University of Chicago Press, 1947. Cameron, John L. Pancreatic Cancer. Hamilton, Ont.: BC Decker, 2001. Cohen, Isaac, O.M.D. Breast Cancer: Beyond Convention: The World’s Foremost Authorities on Complementary and Alternative Medicine Offer Advice on Healing. New York: Atria, 2003. Henderson, Bill. Cancer-Free: Your Guide to Gentle, Non-toxic Healing. 2d ed. Bangor, Maine: Booklocker, 2007. Icon Health Publications. The Official Patient’s Sourcebook on Pancreatic Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2002. Morra, Marion, and Eve Potts. Choices: Realistic Alternatives in Cancer Treatment. New York: Avon, 1987. Murray, Michael. Encyclopedia of Natural Medicine. 2d ed. Roseville, Calif.: Prima, 1998. _______. How to Prevent and Treat Cancer with Natural Medicine. New York: Riverhead Trade, 2003. O’Reilly, Eileen, and Joanne Frankel Kelvin. One Hundred Questions and Answers About Pancreatic Cancer. Sudbury, Mass.: Jones and Bartlett, 2002.
Salem Health: Cancer Pierce, Tanya Harter. Outsmart Your Cancer: Alternative Non-toxic Treatments That Work. Stateline, Nev.: Thoughtworks, 2004. Rains, Calvin E., Sr. My Journey with Pancreatic Cancer. Bloomington, Ind.: AuthorHouse, 2006. Reber, Howard, ed. Pancreatic Cancer: Pathogenesis, Diagnosis, and Treatment. Totowa, N.J.: Humana, 1998. Riess, H., A. Goerke, and H. Oettle. Pancreatic Cancer. Berlin: Springer, 2007. Rossman, Martin L. Fighting Cancer from Within: How to Use the Power of Your Mind for Healing. New York: Holt, 2003. Smith, Tom. Coping with Bowel Cancer. London: Sheldon Press, 2006. Von Hoff, Daniel D., Douglas B. Evans, and Ralph H. Hruban. Pancreatic Cancer. Sudbury, Mass.: Jones and Bartlett, 2005. Bone Cancers American Cancer Society. Quick FACTS Bone Metastasis. Atlanta: Author, 2008. Body, Jean-Jac. Tumor Bone Diseases and Osteoporosis in Cancer Patients: Pathophysiology, Diagnosis, and Therapy. New York: Informa Healthcare, 2000. Davies, Andrew. Cancer-Related Bone Pain. New York: Oxford University Press, 2007. Orr, Tamra. Frequently Asked Questions About Bone Cancer. New York: Rosen Publishing Group, 2007. Shaffer, Marianne. Bone Marrow Transplants: A Guide for Cancer Patients and Their Families. Blue Ridge Summit, Pa.: Taylor Trade Publishing, 1994. Singh, Gurmit, and Shafaat A. Rabbani. Bone Metastasis: Cancer Drug Discovery and Development. Totowa, N.J.: Humana Press, 2005. Brain Cancers Ali-Osman, Francis. Brain Tumors: Contemporary Cancer Research. Totowa, N.J.: Humana, 2005. Black, Peter. Living with a Brain Tumor: Dr. Peter Black’s Guide to Taking Control of Your Treatment. New York: Holt, 2006. Raizer, Jeffrey J., and Lauren E. Abrey. Brain Metastases: Cancer Treatment and Research. New York: Springer, 2007. Sawaya, R., W. K. A. Yung, Franco DeMonte, and Mark R. Gilbert. Tumors of the Brain and Spine. New York: Springer, 2007. Zeltzer, Paul M. Brain Tumors: Leaving the Garden of Eden—A Survival Guide to Diagnosis, Learning the Basics, Getting Organized, and Finding Your Medical Team. Encino, Calif.: Shilysca Press, 2004.
Bibliography Breast Cancers American Cancer Society. Breast Cancer Clear and Simple. Atlanta: Author, 2007. Batt, Sharon. Patient No More: The Politics of Breast Cancer. Charlottetown, P.E.I.: Gynergy, 1994. Burt, Jeannie, and Gwen White. Lymphedema: A Breast Cancer Patient’s Guide to Prevention and Healing. Alameda, Calif.: Hunter House, 2005. Chang, Alice F., with Karen Mang Spruill. A Survivor’s Guide to Breast Cancer. Oakland, Calif.: New Harbinger, 2000. Eisenpreis, Bettijane. Coping: A Young Woman’s Guide to Breast Cancer Prevention. New York: Rosen, 1996. Elk, Ronit. Breast Cancer for Dummies. Hoboken, N.J.: Wiley, 2003. Friedewald, Vincent E., Aman U. Buzdar, and Michael Bokulich. Ask the Doctor: Breast Cancer. Kansas City, Mo.: Andrews and McMeel, 1997. Haber, Sandra, Catherine Acuff, and Lauren Ayers. Breast Cancer: A Psychological Treatment Manual. New York: Springer, 1995. Hirshaut, Yashar, and Peter I. Pressman. Breast Cancer: The Complete Guide. New York: Bantam, 2000. Jacobson, Nora. Cleavage Technology, Controversy, and the Ironies of the Man-made Breast. Piscataway, N.J.: Rutgers University Press, 2000. Kneece, Judy C. Finding A Lump in Your Breast: Where to Go . . . What to Do. North Charleston, S.C.: Educare, 1996. _______. Your Breast Cancer Treatment Handbook: Your Guide to Understanding the Disease, Treatments, Emotions, and Recovery from Breast Cancer. West Columbia, S.C.: Educare, 2004. Lange, Vladimir. Be a Survivor: Your Guide to Breast Cancer Treatment. Atlanta: Lange, 2007. Leopold, Ellen. A Darker Ribbon: A Twentieth-Century Story of Breast Cancer, Women, and Their Doctors. Boston: Beacon Press, 2000. Link, John. Take Charge of Your Breast Cancer: A Guide to Getting the Best Possible Treatment. New York: Holt, 2002. Love, Susan M. Dr. Susan Love’s Breast Book. 4th ed. New York: Da Capo Lifelong Books, 2005. McTiernan, Anne, Julie Gralow, and Lisa Talbott. Breast Fitness: An Optimal Exercise and Health Plan for Reducing Your Risk of Breast Cancer. New York: St. Martin’s Griffin, 2001. Maslin, Anna, ed. Breast Cancer: Sharing the Decision. New York: Oxford University Press, 1999. Mayer, Musa. Examining Myself: One Woman’s Story of Breast Cancer Treatment and Recovery. London: Faber and Faber, 1993. 1401
Bibliography Olivotto, Ivo, Karen Gelmon, and Urve Kuusk. Intelligent Patient Guide to Breast Cancer. Seattle: Gordon Soules, 2001. Raz, Hilda, ed. Living on the Margins: Women Writers on Breast Cancer. New York: Persea Books, 2000. Shockney, Lillie. Breast Cancer Survivor’s Club: A Nurse’s Experience. Loveland, Colo.: Real Health Books, 2001. Steligo, Kathy. The Breast Reconstruction Guidebook: Issues and Answers from Research to Recovery. San Carlos, Calif.: Carlo Press, 2005. Stumm, Diane, P.T. Recovering from Breast Surgery: Exercises to Strengthen Your Body and Relieve Pain. Alameda, Calif.: Hunter House, 1995. Cancer Screening and Testing Procedures Finkel, Madelon L. Understanding the Mammography Controversy: Science, Politics, and Breast Cancer Screening. Westport, Conn.: Praeger, 2005. International Agency for Research on Cancer. IARC Handbooks on Cancer Prevention: Cervix Cancer Screening. Geneva: World Health Organization, 2005. Morrison, Patrick J., Shirley V. Hodgson, and Neva E. Haites. Familial Breast and Ovarian Cancer: Genetics, Screening and Management. Cambridge, England: Cambridge University Press, 2005. Parvin, Elizabeth. Screening for Breast Cancer. New York: Oxford University Press, 2007. Reintgen, Douglas S., and Robert A. Clark. Cancer Screening. St. Louis, Mo.: Mosby-Year Book, 1996. Thompson, Ian M., Jr., Martin I. Resnick, and Eric A. Klein. Prostate Cancer Screening. Totowa, N.J.: Humana, 2001. World Health Organization. Cervical Cancer Screening in Developing Countries. Geneva: Author, 2002. Cervical, Ovarian, and Uterine Cancers Conner, Kristine, and Lauren Langford. Ovarian Cancer. Sebastopol, Calif.: Patient-Centered Guides, 2003. Dizon, Don S. One Hundred Questions and Answers About Cervical Cancer. Sudbury, Mass.: Jones and Bartlett, 2008. Fuller, Arlan F., Jr., Robert H. Young, and Michael V. Seiden. Uterine Cancer. Hamilton, Ont.: BC Decker, 2004. Luesley, David M., Frank Lawton, and Andrew Berchuck. Uterine Cancer. New York: Informa Healthcare, 2005. Piver, M. Steven, Gamal Abbakh, and Harriet Phillips. Myths and Facts About Ovarian Cancer: What You Need to Know. 2d ed. Melville, N.Y.: PRR, 2000. Rohan, Thomas E., and Keerti V. Shah. Cervical Cancer: From Etiology to Prevention. New York: Springer, 2004. 1402
Salem Health: Cancer Sheen, Barbara. Diseases and Disorders: Ovarian Cancer. Farmington Hills, Mich.: Lucent, 2005. Chemotherapy Bruning, Nancy. Coping with Chemotherapy: Compassionate Advice and Authoritative Information from a Chemotherapy Survivor. Rev. ed. New York: Avery, 2002. Chu, Edward, and Vincent T. DeVita, Jr. Physician’s Cancer Chemotherapy Drug Manual 2008. Sudbury, Mass.: Jones and Bartlett, 2008. Cukier, Daniel. Coping with Chemotherapy and Radiation Therapy. New York: McGraw-Hill, 2004. Dodd, Marilyn J. Managing the Side Effects of Chemotherapy and Radiation Therapy. San Francisco: University of California, 2001. Fischer, David S., Henry J. Durivage, M. Tish Knobf, and Nancy Beaulieu. The Cancer Chemotherapy Handbook. 6th ed. Philadelphia: Mosby, 2003. Geier, Mary Alice. Cancer, What’s It Doing in My Life? A Personal Journal of the First Two Years of Chemotherapy in the Career of a Cancer Patient. Pasadena, Calif.: Hope Publishing House, 1997. Lyss, Alan P., Humberto Fagundes, and Patricia Corrigan. Chemotherapy and Radiation for Dummies. Hoboken, N.J.: Wiley, 2005. McKay, Judith. The Chemotherapy and Radiation Therapy Survival Guide. Oakland, Calif.: New Harbinger, 1998. Moss, Ralph W. Questioning Chemotherapy. Lanham, Md.: Equinox Press, 1995. Naparstek, Belleruth. Health Journeys: A Meditation to Help You with Radiation Therapy. Akron, Ohio: Health Journeys, 1999. Perry, Michael C. The Chemotherapy Source Book. Philadelphia: Lippincott Williams and Wilkins, 2007. Polovich, Martha, Julie M. White, and Linda O. Kelleher. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 2d ed. Pittsburgh: Oncology Nursing Society, 2005. Raftopoulous, Harry, and Erin O’Driscoll. Exercises for Chemotherapy Patients. Long Island City, N.Y.: Hatherleigh Press, 2003. Skeel, Roland T. Handbook of Cancer Chemotherapy. Philadelphia: Lippincott Williams and Wilkins, 2007. Children and Cancer Ackermann, Adrienne, and Abigail Ackermann. Our Mom Has Cancer. Atlanta: American Cancer Society, 2002. Blake, Claire, Eliza Blanchard, and Kathy Parkinson. Paper Chain. Santa Fe, N.M.: Health Press, 1998. Brack, Pat, with Ben Brack. Moms Don’t Get Sick. Pierre, S.D.: Melius, 1990.
Salem Health: Cancer Buscaglia, Leo. The Fall of Freddie the Leaf. Thorofare, N.J.: Slack, 2002. Carney, Karen L. What Is Cancer Anyway? Explaining Cancer to Children of All Ages. Wethersfield, Conn.: Dragonfly, 1998. Harpham, Wendy S. When a Parent Has Cancer: A Guide to Caring for Your Children. New York: Harper, 2004. Janes-Hodder, Honna, and Nancy Keene. Childhood Cancer: A Parent’s Guide to Solid Tumor Cancers. Sebastopol, Calif.: Patient Center Guides, 2002. Jones, Susan. Until We Meet Again. Illustrated by Shirley Antak. Minneapolis: 50-50 Publishing, 2007. Karu, Tim. Henry and the White Wolf. Illustrated by Tyler Karu. New York: Workman, 2000. Keene, Nancy, Wendy Hobbie, and Kathy Ruccione. Childhood Cancer Survivors: A Practical Guide to Your Future. Sebastopol, Calif.: O’Reilly Media, 2006. Kohlenberg, Sherry. Sammy’s Mommy Has Cancer. Illustrated by Lauri Crow. Washington, D.C.: Magination Press, 1993. Krishner, Trudy. Kathy’s Hats: A Story of Hope. Illustrated by Nadine Bernard Westcott. Morton Grove, Ill.: Albert Whitman, 1992. Martin, Kim. H is for Hair Fairy: An Alphabet of Encouragement and Insight for Kids—and Kids at Heart!— with Cancer. Illustrated by Wend Broomhower. Victoria, B.C.: Trafford, 2005. Mills, Joyce C.. Gentle Willow: A Story for Children About Dying. Illustrated by Cary Pillo. Washington, D.C.: Magination Press, 2003. Mundy, Michaelene. Sad Isn’t Bad: A Good-Grief Guidebook for Kids Dealing with Loss. Illustrated by R. W. Alley. St. Meinrad, Ind.: Abbey Press, 1998. Murray, Lisa, and Billy Howard. Angels and Monsters. Atlanta: American Cancer Society, 2002. Pennebaker, Ruth. Both Sides Now. New York: Laurel Leaf, 2002. Richmond, Christina. Chemo Girl: Saving the World One Treatment at a Time. Sudbury, Mass.: Jones and Bartlett, 1996. Schulz, Charles M. Why, Charlie Brown, Why? A Story About What Happens When a Friend Is Very Ill. New York: Ballantine Books, 2002. Schweibert, Pat, and Chuck DeKlyen. Tear Soup. Illustrated by Taylor Bills. Portland, Ore.: Grief Watch, 2005. Silverman, Janis. Help Me Say Goodbye: Activities for Helping Kids Cope When a Special Person Dies. Minneapolis: Fairview Press, 1999. Speltz, Ann. The Year My Mother Was Bald. Illustrated by Kate Sternberg. Washington, D.C.: Magination Press, 2002.
Bibliography Torrey, Lisa. Michael’s Mommy Has Breast Cancer. Illustrated by Barbara W. Watler. Tallahassee, Fla.: Hibiscus Press, 1999. Colon and Rectal Cancers Adrouny, A. Richard. Understanding Colon Cancer. Jackson: University Press of Mississippi, 2002. American Cancer Society. American Cancer Society’s Complete Guide to Colorectal Cancer. Atlanta: Author, 2005. Bub, David, Susannah Rose, and Douglas Wong. One Hundred Questions and Answers About Colorectal Cancer. Sudbury, Mass.: Jones and Bartlett, 2002. Cassidy, Jim, Patrick Johnston, and Eric Van Cutsem, eds. Colorectal Cancer. New York: Informa Healthcare, 2006. Donehower, Ross C. Colon Cancer 2007: Johns Hopkins White Papers. Baltimore, Md.: Johns Hopkins Medicine, 2007. Holen, Kyle. Dx/Rx: Colorectal Cancer. Sudbury, Mass.: Jones and Bartlett, 2007. Johnston, Lorraine. Colon and Rectal Cancer: A Comprehensive Guide for Patients and Families. Sebastopol, Calif.: Patient-Centered Guides, 2000. Lange, Vladimir. Be a Survivor: Colorectal Cancer Treatment Guide. Atlanta: Lange Productions, 2006. Larson, Carol Ann, and Kathleen Ogle. Positive Options for Colorectal Cancer: Self-Help and Treatment. Alameda, Calif.: Hunter House, 2005. Pochapin, Mark Bennett. What Your Doctor May Not Tell You About Colorectal Cancer: New Tests, New Treatments, New Hope. New York: Grand Central, 2005. Rozen, Paul, Graham Young, Bernard Levin, and Stephen J. Spann, eds. Colorectal Cancer in Clinical Practice: Prevention, Early Detection and Management. Florence, Ky.: Taylor and Francis, 2002. Scholefield, John, Herand Abcarian, Tim Maughan, and Axel Grothey, eds. Challenges in Colorectal Cancer. Malden, Mass.: Wiley-Blackwell, 2008. Smith, Tom. Coping with Bowel Cancer. London: Sheldon Press, 2006. Coping and Survivorship Anderson, Greg. Fifty Essential Things to Do When the Doctor Says It’s Cancer. New York: Plume, 1993. Armstrong, Lance. It’s Not About the Bike: My Journey Back to Life. New York: Putnam, 2000. Canfield, Jack. Chicken Soup for the Breast Cancer Survivor’s Soul: Stories to Inspire, Support, and Heal. Deerfield Beach, Fla.: HCI, 2006. Clifford, Christine. Not Now—I’m Having a No Hair Day. Minneapolis: University of Minnesota Press, 2003. 1403
Bibliography Cohen, Deborah A., with Robert M. Gelfand. Just Get Me Through This! The Practical Guide to Breast Cancer. New York: Kensington, 2000. Cousins, Norman. Head First: The Biology of Hope and the Healing Power of the Human Spirit. New York: Penguin, 1990. Dunstone, Carol, and Ann Bennett. Trilogy: How to Help the Mind, Body, and Spirit Survive Mouth, Head, and Neck Cancer. Bloomington, Ind.: AuthorHouse, 2006. Goleman, Daniel, and Joel Gurin. Mind/Body Medicine: How to Use Your Mind for Better Health. Yonkers, N.Y.: Consumer Reports, 1995. Gottlieb, Bert. The Men’s Club: How to Lose Your Prostate Without Losing Your Sense of Humor. Oxnard, Calif.: Pathfinder, 2000. Granet, Roger. Surviving Cancer Emotionally: Learning How to Heal. New York: Wiley, 2001. Halverstadt, Amy, and Andrea Leonard. Essential Exercises for Breast Cancer Survivors . Boston: Harvard Common Press, 2000. Harpham, Wendy Schlessel. After Cancer: A Guide to Your New Life. New York: W. W. Norton, 1994. Harwell, Amy, with Kristine Tomasik. When Your Friend Gets Cancer: How You Can Help. Wheaton, Ill.: Shaw, 1987. Holland, Jimmie C., and Sheldon Lewis. The Human Side of Cancer: Living with Hope, Coping with Uncertainty. New York: HarperCollins, 2000. Hope, Lori. Help Me Live: Twenty Things People with Cancer Want You to Know. Berkeley, Calif.: Celestial Arts, 2005. Kahane, Deborah Hobler. No Less a Woman: Femininity, Sexuality, and Breast Cancer. Alameda, Calif.: Hunter House, 1995. Korda, Michael. Man to Man: Surviving Prostate Cancer. New York: Vintage, 1997. McCoy, Linda P. Twenty-Something and Breast Cancer. Sedona, Ariz.: In Print, 1995. Marchetto, Marisa Acocella. Cancer Vixen. New York: Knopf, 2006. Pesmen, Curtis. The Colon Cancer Survivors’ Guide: Living Stronger, Longer. Suffern, N.Y.: Tatra Press, 2005. Phillips, Robert H., and Paula Goldstein. Coping with Breast Cancer: A Practical Guide to Understanding, Treating, and Living with Breast Cancer. New York: Avery, 1998. Ratner, Elaine. The Feisty Woman’s Breast Cancer Book. Alameda, Calif.: Hunter House, 1999. Rollin, Betty. First, You Cry. New York: Harper, 1976. Seligman, Linda. Promoting a Fighting Spirit: Psychotherapy for Cancer Patients, Survivors, and Their Families. Hoboken, N.J.: Jossey-Bass, 1996. 1404
Salem Health: Cancer Soffa, Virginia M. The Journey Beyond Breast Cancer: From the Personal to the Political—Taking an Active Role in the Prevention, Diagnosis, and Your Own Healing. Rochester, Vt.: Healing Arts Press, 1994. Walker, Laura Jensen. Thanks for the Mammogram!: Fighting Cancer with Faith, Hope, and a Healthy Dose of Laughter. Grand Rapids, Mich.: Revell, 2006. Weiss, Marisa C., and Ellen Weiss. Living Beyond Breast Cancer: A Survivor’s Guide for When Treatment Ends and the Rest of Your Life Begins. New York: Crown, 1997. Endocrine Cancers Arnold, Andrew. Endocrine Neoplasms. New York: Springer, 1997. Horwitz, Kathryn B. Endocrine Aspects of Cancer. Chevy Chase, Md.: Endocrine Society, 1993. Santen, Richard J., and Andrea Manni. Diagnosis and Management of Endocrine-Related Tumors. New York: Springer, 1984. Head, Neck, and Oral Cancers Ahuja, A. T., R. M. Evans, A. D. King, and C. A. van Hasselt. Imaging of Head and Neck Cancer. San Francisco: Greenwich Medical Media, 2003. Baert, A. L., and Robert Hermans. Head and Neck Cancer Imaging. New York: Springer, 2006. Brockstein, Bruce, and Gregory Masters. Head and Neck Cancer. New York: Springer, 2003. Ensley, John Frederick, Silvio Gutkind, John A. Jacobs, and Scott Lippman. Head and Neck Cancer: Emerging Perspectives. San Diego: Academic Press, 2002. Hong, Waun Ki, and Randal S. Weber. Head and Neck Cancer: Basic and Clinical Aspects. New York: Springer, 1995. Leupold, Nancy E. Meeting the Challenges of Oral and Head and Neck Cancer: A Survivor’s Guide. San Diego: Plural, 2008. Silverman, Sol, and American Cancer Society. Oral Cancer. Hamilton, Ont.: BC Decker, 2003. Stafford, Nicholas, and John Waldron. Management of Oral Cancer. New York: Oxford University Press, 1990. Werner, Jochen A., and R. Kim Davis. Metastases in Head and Neck Cancer. Berlin: Springer, 2005. Leukemias, Lymphomas, and Myelomas Adler, Elizabeth M. Living with Lymphoma: A Patient’s Guide. Baltimore, Md.: Johns Hopkins University Press, 2005. Ball, Edward D. One Hundred Questions and Answers About Leukemia. Sudbury, Mass.: Jones and Bartlett, 2002.
Salem Health: Cancer Bashey, Asad, and James W. Huston. One Hundred Questions and Answers About Myeloma. Sudbury, Mass.: Jones and Bartlett, 2004. Burke, John, and Manish A. Shah. Dx/Rx: Leukemia. Sudbury, Mass.: Jones and Bartlett, 2004. Holman, Peter, Jodi Garrett, and William D. Jansen. One Hundred Questions and Answers About Lymphoma. Sudbury, Mass.: Jones and Bartlett, 2003. Icon Health Publications. The Official Patient’s Sourcebook on Adult Non-Hodgkin’s Lymphoma: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2002. Johnston, Lorraine. Non-Hodgkin’s Lymphomas: Making Sense of Diagnosis, Treatment, and Options. Sebastopol, Calif.: Patient-Centered Guides, 1999. Lackritz, Barbara. Adult Leukemia: A Comprehensive Guide for Patients and Families. Sebastopol, Calif.: Patient-Centered Guides, 2001. Leonard, John P., and Morton Coleman, eds. Hodgkin’s and Non-Hodgkin’s Lymphoma. New York: Springer, 2006. Marcus, Robert, John W. Sweetenham, and Michael E. Williams. Lymphoma: Pathology, Diagnosis, and Treatment. Cambridge, England: Cambridge University Press: 2007. Mauch, Peter M., et al., eds. Non-Hodgkin’s Lymphomas: A Self-Study Program. Philadelphia: Lippincott Williams and Wilkins, 2003. Mughal, Tariq, John M. Goldman, and Sabena Mughal. Understanding Leukemias, Lymphomas, and Myelomas. New York: Informa Healthcare, 2005. Parker, James N., and Philip M. Parker. The Official Patient’s Sourcebook on Adult Acute Myeloid Leukemia. San Diego, Calif.: Icon Health Publications, 2002. Tanner, Jerome E. Myeloma. New York: Chelsea House, 2008. Lung Cancers Henschke, Claudia I., Peggy McCarthy, and Sarah Wernick. Lung Cancer: Myths, Facts, Choices—and Hope. New York: W. W. Norton, 2003. Johnston, Lorraine. Lung Cancer: Making Sense of Diagnosis, Treatment, and Options. Sebastopol, Calif.: Patient-Centered Guides, 2001. Parles, Karen, and Joan H. Schiller. One Hundred Questions and Answers About Lung Cancer. Sudbury, Mass.: Jones and Bartlett, 2002. Roth, Jack A., James D. Cox, and Waun Ki Hong. Lung Cancer. Malden, Mass.: Blackwell, 1998. Scott, Walter. Lung Cancer: A Guide to Diagnosis and Treatment. Omaha, Neb.: Addicus Books, 2000.
Bibliography Nutrition and Cancer Budwig, Johanna. Flax Oil as a True Aid Against Arthritis, Heart Infarction, Cancer, and Other Diseases. Ferndale, Wash.: Apple, 1996. Ghosh, Kris, Linda Carson, and Elyse Cohen. Betty Crocker’s Living with Cancer Cookbook. Minneapolis: Betty Crocker, 2001. Keane, Maureen, and Daniella Chace. What to Eat if You Have Cancer: A Guide to Adding Nutritional Therapy to Your Treatment Plan. Lincolnwood, Ill.: NTC Publishing Group, 1996. Keim, Rachel, with Ginny Smith. What to Eat Now: The Cancer Lifeline Cookbook. Seattle: Sasquatch Books, 1996. Quillin, Patrick. Beating Cancer with Nutrition: Clinically Proven and Easy-to-Follow Strategies to Dramatically Improve Your Quality and Quantity of Life and Chances. Tulsa, Okla.: Nutrition Times Press, 1998. Reuben, Carolyn. Antioxidants: Your Complete Guide— Fight Cancer and Heart Disease, Improve Your Memory, and Slow the Aging Process. Roseville, Calif.: Prima Lifestyles, 1994. Ricketts, David. Eat to Beat Prostate Cancer Cookbook. New York: Harry A. Abrams, 2006. Sanders, Buffy. The Prostate Diet Cookbook: CancerFighting Foods for a Healthy Prostate. Gig Harbor, Wash.: Harbor Press, 2001. Weihofen, Donna, with Christina Marino. The Cancer Survival Cookbook: Two Hundred Quick and Easy Recipes with Helpful Eating Hints. New York: John Wiley and Sons, 1997. Prostate and Testicular Cancers Dattoli, Michael J. Surviving Prostate Cancer Without Surgery: The New Gold Standard Treatment That Can Save Your Life and Lifestyle. Sarasota, Fla.: Seneca House Press, 2005. Grimm, Peter. The Prostate Cancer Treatment Book. New York: McGraw-Hill, 2003. Icon Health Publications. The Official Patient’s Sourcebook on Testicular Cancer: A Revised and Updated Directory for the Internet Age. San Diego, Calif.: Author, 2002. Johanson, Paula. Frequently Asked Questions About Testicular Cancer. New York: Rosen Publishing Group, 2007. Lange, Paul H. Prostate Cancer for Dummies. Hoboken, N.J.: Wiley, 2003. Marks, Sheldon. Prostate and Cancer: A Family Guide to Diagnosis, Treatment, and Survival. 3d ed. Cambridge, Mass.: Da Capo Press, 1999. 1405
Bibliography Oesterling, Joseph. The ABC’s of Prostate Cancer: The Book That Could Save Your Life. Ann Arbor, Mich.: J. W. Edwards, 1997. Rous, Stephen N. The Prostate Book: Sound Advice on Symptoms and Treatment. New York: W. W. Norton, 1995. Strum, Stephen. A Primer on Prostate Cancer: The Empowered Patient’s Guide. Hollywood, Fla.: Life Extension Media, 2002. Torrey, E. Fuller. Surviving Prostate Cancer: What You Need to Know to Make Informed Decisions. New Haven, Conn.: Yale University Press, 2008. Walsh, Patrick C. Dr. Patrick Walsh’s Guide to Surviving Prostate Cancer. New York: Grand Central, 2002.
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Salem Health: Cancer Skin Cancers Buckmaster, Majorie L. Skin Cancer. New York: Benchmark Books, 2007. Kenet, Barney J., and Patricia Lawler. Saving Your Skin: Prevention, Early Detection, and Treatment of Melanoma and Other Skin Cancers. New York: Four Walls Eight Windows, 1998. McClay, Edward F., Mary-Eileen T. McClay, and Jodie Smith. One Hundred Questions and Answers About Melanoma and Other Skin Cancers. Sudbury, Mass.: Jones and Bartlett, 2003. Schofield, Jill R., and William A. Robinson. What You Really Need to Know About Moles and Melanoma. Baltimore, Md.: Johns Hopkins University Press, 2000. Schwartz, Robert A. Skin Cancer. Malden, Mass.: WileyBlackwell, 2008.
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Category List
Cancer biology Angiogenesis, 64 BRAF gene, 172 BRCA1 and BRCA2 genes, 178 Cancer biology, 213 Chromosomes and cancer, 274 Cyclin-dependent kinase inhibitor-2A (CDKN2A), 344 Cytokines, 350 Epidemiology of cancer, 426 Estrogen receptor downregulator (ERD), 441 Genetics of cancer, 519 Human chorionic gonadotropin (HCG), 609 Immune response to cancer, 629 Mitochondrial DNA mutations, 794 MLH1 gene, 795 MSH genes, 803 Mutagenesis and cancer, 813 MYC oncogene, 817 Oncogenes, 878 Placental alkaline phosphatase (PALP), 968 PMS genes, 976 Proteomics and cancer research, 1012 Proto-oncogenes and carcinogenesis, 1015 RB1 gene, 1032 RhoGD12 gene, 1050 SCLC1 gene, 1067 TP53 protein, 1177 Tumor necrosis factor (TNF), 1193 Tumor-suppressor genes, 1194
Bisphenol A (BPA), 149 1,3-Butadiene, 202 1,4-Butanediol dimethanesulfonate, 203 Cadmium and cadmium compounds, 208 Caffeine, 209 Carcinogens, known, 224 Carcinogens, reasonably anticipated, 227 Cell phones, 249 Chewing tobacco, 261 Chlorambucil, 268 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU), 269 Chromium hexavalent compounds, 274 Cigarettes and cigars, 281 Coal tars and coal tar pitches, 288 Coke oven emissions, 292 Cyclophosphamide, 345 Cyclosporin A, 346 Di(2-ethylhexyl) phthalate (DEHP), 368 Diethanolamine (DEA), 373 Diethylstilbestrol (DES), 373 Dioxins, 376 Electromagnetic radiation, 399 Epstein-Barr virus, 431 Erionite, 433 Ethylene oxide, 447 Fertility drugs and cancer, 469 Formaldehyde, 486 Free radicals, 490 Hair dye, 550 Helicobacter pylori, 558 Hepatitis B virus (HBV), 569 Hepatitis C virus (HCV), 570 HER2/neu protein, 573 Herpes simplex virus, 584 Herpes zoster virus, 586 HIV/AIDS-related cancers, 590 Hormone replacement therapy (HRT), 603 Human growth factors and tumor growth, 610 Human papillomavirus (HPV), 611 Human T-cell leukemia virus (HTLV), 612 Ionizing radiation, 657 Melphalan, 779 Mineral oils, 792 Mustard gas, 812 2-Naphthylamine, 826 Nickel compounds and metallic nickel, 851
Carcinogens and suspected carcinogens Acrylamides, 6 Aflatoxins, 26 Agent Orange, 34 Air pollution, 39 Alcohol, alcoholism, and cancer, 42 4-Aminobiphenyl, 56 Arsenic compounds, 100 Asbestos, 103 Azathioprine, 117 Bacteria as causes of cancer, 118 Benzene, 130 Benzidine and dyes metabolized to benzidine, 131 Beryllium and beryllium compounds, 133 Birth control pills and cancer, 146 Bis(chloromethyl) ether and technical-grade chloromethyl methyl ether, 148 1409
Salem Health: Cancer Oncogenes, 878 Oncogenic viruses, 881 Organochlorines (OCs), 901 Pesticides and the food chain, 948 Phenacetin, 955 Plasticizers, 971 Polycyclic aromatic hydrocarbons, 981 Radon, 1032 Report on Carcinogens (RoC), 1044 Silica, crystalline, 1083 Simian virus 40, 1084 Soots, 1097 Sunlamps, 1127 Thiotepa, 1158 Ultraviolet radiation and related exposures, 1200 Vinyl chloride, 1230 Wood dust, 1251
Diethylstilbestrol (DES), 373 Drug resistance and multidrug resistance (MDR), 383 Estrogen receptor downregulator (ERD), 441 Glutamine, 536 Histamine 2 antagonists, 587 Hormonal therapies, 599 Immunotherapy, 635 Interferon, 653 Interleukins, 654 Laxatives, 692 Matrix metalloproteinase inhibitors, 764 Monoclonal antibodies, 800 Nonsteroidal anti-inflammatory drugs (NSAIDs), 858 Opioids, 892 Pain management medications, 914 Palliative treatment, 917 Phenacetin, 955 Photodynamic therapy (PDT), 959 Plant alkaloids and terpenoids in chemotherapy, 968 Proteasome inhibitors, 1010 Radiopharmaceuticals, 1030 Topoisomerase inhibitors, 1175 Tumor necrosis factor (TNF), 1193 Tyrosine kinase inhibitors, 1196 Vaccines, preventive, 1220 Vaccines, therapeutic, 1221
Chemotherapy and other drugs Adenoviruses, 19 Alkylating agents in chemotherapy, 45 Androgen drugs, 61 Angiogenesis inhibitors, 66 Anthraquinones, 71 Anthrax, 71 Antiandrogens, 72 Antidiarrheal agents, 73 Antiestrogens, 75 Antifungal therapies, 76 Antimetabolites in chemotherapy, 78 Antinausea medications, 81 Antineoplastics in chemotherapy, 83 Antiviral therapies, 90 Bacillus Calmette Guérin (BCG), 118 Benzodiazepines, 132 Biological therapy, 139 Bisphosphonates, 151 Brompton cocktail, 196 1,4-Butanediol dimethanesulfonate, 203 Cancell, 212 Cartilage supplements, 246 Chemoprevention, 254 Chemotherapy, 257 Chlorambucil, 268 Colony-stimulating factors (CSFs), 299 Corticosteroids, 321 Cyclooxygenase 2 (COX-2) inhibitors, 344 Cyclophosphamide, 345 Cyclosporin A, 346 Cytokines, 350 Delta-9-tetrahydrocannabinol, 355
Complementary and alternative therapies Anthraquinones, 71 Antioxidants, 86 Cancell, 212 Cartilage supplements, 246 Coenzyme Q10, 289 Complementary and alternative therapies, 309 Curcumin, 339 Delta-9-tetrahydrocannabinol, 355 Dietary supplements, 370 Electroporation therapy, 400 Essiac, 441 Gerson therapy, 527 Ginseng, panax, 531 Green tea, 540 Herbs as antioxidants, 573 Integrative oncology, 651 Laetrile, 679 Mistletoe, 793 Motion sickness devices, 802 PC-SPES, 937 Phenolics, 955 Saw palmetto, 1065 Sun’s soup, 1128 1410
Category List Diseases, symptoms, and conditions Achlorhydria, 4 Acoustic neuromas, 4 Acute lymphocytic leukemia (ALL), 11 Acute myelocytic leukemia (AML), 13 Adenocarcinomas, 16 Adenoid cystic carcinoma (ACC), 17 Adenomatoid tumors, 18 Adenomatous polyps, 18 Adrenal gland cancers, 21 Adrenocortical cancer, 23 Aleukemia, 43 Alopecia, 47 Alveolar soft-part sarcomas, 49 Amenorrhea, 50 Amyloidosis, 58 Anal cancer, 59 Anemia, 62 Angiosarcomas, 69 Aplastic anemia, 95 Appendix cancer, 97 Appetite loss, 98 Ascites, 105 Astrocytomas, 112 Ataxia telangiectasia (AT), 114 Barrett esophagus, 123 Basal cell carcinomas, 124 Beckwith-Wiedemann syndrome (BWS), 126 Benign prostatic hyperplasia (BPH), 128 Benign tumors, 128 Bile duct cancer, 136 Birt-Hogg-Dubé syndrome (BHDS), 145 Bladder cancer, 151 Blood cancers, 154 Bone cancers, 158 Bone pain, 165 Bowen disease, 168 Brain and central nervous system cancers, 173 Breakthrough pain, 180 Breast cancer in children and adolescents, 180 Breast cancer in men, 182 Breast cancer in pregnant women, 184 Breast cancers, 185 Bronchial adenomas, 197 Bronchoalveolar lung cancer, 197 Burkitt lymphoma, 200 Cachexia, 207 Calcifications of the breast, 211 Candidiasis, 221 Carcinoid tumors and carcinoid syndrome, 230 Carcinoma of unknown primary origin (CUP), 232
Carcinomas, 233 Carcinomatosis, 235 Carcinomatous meningitis, 237 Carcinosarcomas, 238 Cardiomyopathy in cancer patients, 239 Carney complex, 245 Castleman disease, 248 Cervical cancer, 251 Childhood cancers, 264 Chordomas, 271 Choriocarcinomas, 272 Chronic lymphocytic leukemia (CLL), 276 Chronic myeloid leukemia (CML), 279 Cold nodule, 292 Colon polyps, 296 Colorectal cancer, 300 Comedo carcinomas, 309 Coughing, 322 Cowden syndrome, 326 Craniopharyngiomas, 327 Craniosynostosis, 329 Crohn disease, 332 Cryptorchidism, 338 Cushing syndrome and cancer, 340 Cutaneous breast cancer, 341 Cutaneous T-cell lymphoma (CTCL), 342 Denys-Drash syndrome and cancer, 357 Depression, 357 Dermatofibrosarcoma protuberans (DFSP), 360 Desmoid tumors, 365 Desmoplastic small round cell tumor (DSRCT), 365 Diarrhea, 369 Disseminated intravascular coagulation (DIC), 378 Diverticulosis and diverticulitis, 378 Down syndrome and leukemia, 381 Dry mouth, 385 Duct ectasia, 386 Ductal carcinoma in situ (DCIS), 387 Duodenal carcinomas, 393 Dysplastic nevus syndrome, 394 Edema, 395 Embryonal cell cancer, 403 Endocrine cancers, 406 Endometrial cancer, 412 Endometrial hyperplasia, 414 Endotheliomas, 420 Enteritis, 421 Eosinophilic leukemia, 424 Ependymomas, 425 Epidermoid cancers of mucous membranes, 429 Erythroplakia, 433 1411
Salem Health: Cancer Esophageal cancer, 434 Esophagitis, 439 Estrogen-receptor-sensitive breast cancer, 442 Ewing sarcoma, 447 Eye cancers, 455 Eyelid cancer, 458 Fallopian tube cancer, 460 Fanconi anemia, 464 Fatigue, 466 Fever, 472 Fibroadenomas, 475 Fibrocystic breast changes, 476 Fibrosarcomas, soft-tissue, 478 5Q minus syndrome, 484 Gallbladder cancer, 493 Gardner syndrome, 498 Gastric polyps, 500 Gastrinomas, 501 Gastrointestinal cancers, 502 Gastrointestinal complications of cancer treatment, 506 Gastrointestinal stromal tumors (GISTs), 511 Germ-cell tumors, 525 Gestational trophoblastic tumors (GTTs), 527 Giant cell tumors (GCTs), 530 Gliomas, 533 Glomus tumors, 534 Graft-versus-host disease (GVHD), 538 Granulosa cell tumors, 540 Gynecologic cancers, 543 Hairy cell leukemia, 550 Hand-foot syndrome (HFS), 552 Head and neck cancers, 554 Hemangioblastomas, 559 Hemangiopericytomas, 559 Hemangiosarcomas, 560 Hematemesis, 561 Hematuria, 564 Hemochromatosis, 565 Hemolytic anemia, 566 Hemoptysis, 566 Hemorrhoids, 567 Hepatomegaly, 571 Hereditary diffuse gastric cancer, 576 Hereditary leiomyomatosis and renal cell cancer (HLRCC), 577 Hereditary mixed polyposis syndrome, 579 Hereditary non-VHL clear cell renal cell carcinomas, 580 Hereditary pancreatitis, 580 Hereditary papillary renal cell carcinomas, 581 Hereditary polyposis syndromes, 582
Herpes simplex virus, 584 Herpes zoster virus, 586 Histiocytosis X, 588 HIV/AIDS-related cancers, 590 Hodgkin disease, 593 Horner syndrome, 605 Hot flashes, 608 Hydatidiform mole, 612 Hypercalcemia, 614 Hypercoagulation disorders, 615 Hypopharyngeal cancer, 619 Infection and sepsis, 638 Infectious cancers, 641 Infertility and cancer, 643 Inflammatory bowel disease, 645 Invasive cancer, 655 Invasive ductal carcinomas, 656 Invasive lobular carcinomas, 657 Islet cell tumors, 659 Itching, 661 Juvenile polyposis syndrome, 665 Kaposi sarcoma, 667 Keratosis, 670 Kidney cancer, 671 Klinefelter syndrome and cancer, 674 Krukenberg tumors, 675 Lacrimal gland tumors, 677 Lambert-Eaton myasthenic syndrome (LEMS), 679 Laryngeal cancer, 682 Laryngeal nerve palsy, 685 Leiomyomas, 693 Leiomyosarcomas, 694 Leptomeningeal carcinomas, 696 Leukemias, 698 Leukoencephalopathy, 702 Leukopenia, 704 Leukoplakia, 704 Leydig cell tumors, 706 Li-Fraumeni syndrome (LFS), 706 Lip cancers, 710 Liposarcomas, 712 Liver cancers, 715 Lobular carcinoma in situ (LCIS), 725 Lumps, 732 Lung cancers, 733 Lymphangiosarcomas, 741 Lymphedema, 742 Lymphocytosis, 743 Lymphomas, 744 Malignant fibrous histiocytoma (MFH), 752 Malignant rhabdoid tumor of the kidney, 753 1412
Category List Malignant tumors, 754 Mantle cell lymphoma (MCL), 759 Mastocytomas, 763 Mediastinal tumors, 766 Medullary carcinoma of the breast, 774 Medulloblastomas, 775 Melanomas, 776 Meningeal carcinomatosis, 781 Meningiomas, 782 Merkel cell carcinomas (MCC), 783 Mesenchymomas, malignant, 785 Mesothelioma, 786 Metastasis, 788 Metastatic squamous neck cancer with occult primary, 790 Microcalcifications, 790 Moles, 798 Mucinous carcinomas, 803 Mucosa-associated lymphoid tissue (MALT) lymphomas, 804 Mucositis, 806 Multiple endocrine neoplasia type 1 (MEN 1), 807 Multiple endocrine neoplasia type 2 (MEN 2), 808 Multiple myeloma, 809 Myasthenia gravis, 815 Mycosis fungoides, 817 Myelodysplastic syndromes, 819 Myelofibrosis, 820 Myeloma, 822 Myeloproliferative disorders, 823 Myelosuppression, 825 Nasal cavity and paranasal sinus cancers, 826 Nausea and vomiting, 834 Nephroblastomas, 839 Neuroblastomas, 841 Neuroectodermal tumors, 842 Neuroendocrine tumors, 844 Neurofibromatosis type 1 (NF1), 845 Neutropenia, 849 Night sweats, 852 Nijmegen breakage syndrome, 853 Nipple discharge, 854 Non-Hodgkin lymphoma, 855 Obesity-associated cancers, 868 Oligodendrogliomas, 875 Oral and oropharyngeal cancers, 894 Orbit tumors, 897 Organ transplantation and cancer, 899 Ovarian cancers, 905 Ovarian cysts, 908 Ovarian epithelial cancer, 909
Paget disease of bone, 912 Pancolitis, 920 Pancreatic cancers, 923 Pancreatitis, 927 Paraneoplastic syndromes, 931 Parathyroid cancer, 932 Penile cancer, 941 Pericardial effusion, 944 Peutz-Jeghers syndrome (PJS), 951 Pheochromocytomas, 956 Phyllodes tumors, 960 Pineoblastomas, 963 Pituitary tumors, 965 Pleural effusion, 973 Pleuropulmonary blastomas, 975 Pneumonia, 979 Polycythemia vera, 981 Polyps, 983 Premalignancies, 994 Primary central nervous system lymphomas, 1003 Prostate cancer, 1004 Prostatitis, 1009 Rectal cancer, 1036 Recurrence, 1038 Renal pelvis tumors, 1043 Retinoblastomas, 1046 Rhabdomyosarcomas, 1048 Richter syndrome, 1050 Rothmund-Thomson syndrome, 1056 Salivary gland cancer, 1058 Sarcomas, soft-tissue, 1062 Schwannoma tumors, 1066 Sertoli cell tumors, 1073 Sézary syndrome, 1076 Side effects, 1078 Sjögren syndrome, 1086 Skin cancers, 1088 Small intestine cancer, 1091 Spermatocytomas, 1099 Spinal axis tumors, 1100 Spinal cord compression, 1102 Squamous cell carcinomas, 1106 Sterility, 1120 Stomach cancers, 1121 Stomatitis, 1124 Superior vena cava syndrome, 1130 Symptoms and cancer, 1144 Syndrome of inappropriate antidiuretic hormone production (SIADH), 1147 Synovial sarcomas, 1149 Taste alteration, 1151 1413
Salem Health: Cancer Teratocarcinomas, 1152 Teratomas, 1153 Testicular cancer, 1154 Throat cancer, 1162 Thrombocytopenia, 1164 Thymomas, 1166 Thymus cancer, 1167 Thyroid cancer, 1169 Tobacco-related cancers, 1174 Transitional cell carcinomas, 1183 Trichilemmal carcinomas, 1187 Tuberous sclerosis, 1187 Tubular carcinomas, 1188 Tumor flare, 1189 Tumor lysis syndrome, 1189 Turcot syndrome, 1195 Urethral cancer, 1205 Urinary system cancers, 1209 Uterine cancer, 1217 Vaginal cancer, 1223 Virus-related cancers, 1232 Von Hippel-Lindau (VHL) disease , 1235 Vulvar cancer, 1237 Waldenström macroglobulinemia (WM), 1240 Weight loss, 1243 Wilms’ tumor, 1245 Wilms’ tumor aniridia-genitorurinary anomalies-mental retardation (WAGR) syndrome and cancer, 1248 Xeroderma pigmentosa, 1254 Yolk sac carcinomas, 1256 Young adult cancers, 1256 Zollinger-Ellison syndrome, 1260
Fruits, 491 Garlic and allicin, 499 Ginseng, panax, 531 Glutamine, 536 Green tea, 540 Herbs as antioxidants, 573 Indoles, 638 Isoflavones, 661 Lutein, 737 Lycopene, 737 Macrobiotic diet, 750 Nutrition and cancer prevention, 861 Nutrition and cancer treatment, 864 Omega-3 fatty acids, 877 Phytoestrogens, 962 Prevention, 999 Resveratrol, 1045 Risks for cancer, 1052 Saw palmetto, 1065 Screening for cancer, 1067 Smoking cessation, 1093 Soy foods, 1098 Sun’s soup, 1128 Sunscreens, 1129 Wine and cancer, 1250 Medical specialties Cancer care team, 216 Cancer education, 220 Clinical trials, 285 Cytogenetics, 348 Cytology, 350 Dermatology oncology, 362 Endocrinology oncology, 409 Family history and risk assessment, 461 Gastrointestinal oncology, 508 Genetic counseling, 515 Gynecologic oncology, 547 Hematologic oncology, 562 Immunocytochemistry and immunohistochemistry, 633 Medical oncology, 770 Molecular oncology, 796 Neurologic oncology, 847 Occupational therapy, 873 Oncology, 882 Oncology clinical nurse specialist, 885 Oncology social worker, 887 Ophthalmic oncology, 889 Orthopedic surgery, 902 Otolaryngology, 903 Pathology, 934
Lifestyle and prevention Antioxidants, 86 Artificial sweeteners, 102 Beta-carotene, 135 Bioflavonoids, 138 Caffeine, 209 Calcium, 212 Carotenoids, 245 Cartilage supplements, 246 Chemoprevention, 254 Chewing tobacco, 261 Coenzyme Q10, 289 Cruciferous vegetables, 335 Dietary supplements, 370 Esophageal speech, 436 Exercise and cancer, 451 Fiber, 474 Folic acid, 486 1414
Category List Pediatric oncology and hematology, 938 Pharmacy oncology, 952 Primary care physician, 1001 Psycho-oncology, 1016 Radiation oncology, 1021 Surgical oncology, 1138 Urologic oncology, 1214 Veterinary oncology, 1226 Viral oncology, 1230
Boron neutron capture therapy (BNCT), 167 Brachytherapy, 170 Brain scan, 176 Breast implants, 188 Breast reconstruction, 190 Breast self-examination (BSE), 193 Breast ultrasound, 194 Breslow’s staging, 195 Brief Pain Inventory (BPI), 196 Bronchography, 199 Bronchoscopy, 199 CA 15-3 test, 205 CA 19-9 test, 205 CA 27-29 test, 206 CA 125 test, 206 Carcinoembryonic antigen antibody (CEA) test, 223 Cardiopulmonary resuscitation (CPR), 240 Chemoembolization, 253 Cholecystectomy, 269 Clinical breast exam (CBE), 283 Cobalt 60 radiation, 289 Colectomy, 293 Coloanal anastomosis, 294 Colonoscopy and virtual colonoscopy, 297 Colorectal cancer screening, 304 Colostomy, 306 Colposcopy, 308 Complete blood count (CBC), 312 Computed tomography (CT)-guided biopsy, 313 Computed tomography (CT) scan, 315 Conization, 317 Continuous hyperthermic peritoneal perfusion (CHPP), 318 Cordectomy, 318 Cordotomy, 319 Core needle biopsy, 321 Craniotomy, 331 Cryoablation, 336 Culdoscopy, 339 Cystography, 347 Cystoscopy, 347 Digital rectal exam (DRE), 374 Dilation and curettage (D&C), 375 DPC4 gene testing, 382 Ductal lavage, 389 Ductogram, 389 Dukes’ classification, 392 Electroporation therapy, 400 Electrosurgery, 401 Embolization, 402 Endorectal ultrasound, 416
Organizations American Association for Cancer Research (AACR), 52 American Cancer Society (ACS), 53 American Institute for Cancer Research (AICR), 54 Dana-Farber Cancer Institute, 354 Fox Chase Cancer Center, 487 Fred Hutchinson Cancer Research Center, 488 Jonsson Comprehensive Cancer Center (JCCC), 664 M. D. Anderson Cancer Center, 748 Mayo Clinic Cancer Center, 765 Memorial Sloan-Kettering Cancer Center, 780 National Cancer Institute (NCI), 829 National Science Foundation (NSF), 830 Prevent Cancer Foundation, 997 Robert H. Lurie Cancer Center, 1054 Procedures ABCD, 1 Abdominoperineal resection (APR), 1 Accelerated partial breast irradiation (APBI), 3 Acupuncture and acupressure for cancer patients, 8 Adjuvant therapy, 20 Afterloading radiation therapy, 32 Alkaline phosphatase test (ALP), 44 Alpha-fetoprotein (AFP) levels, 48 Amputation, 56 Angiography, 68 Anoscopy, 70 APC gene testing, 94 Arterial embolization, 101 Autologous blood transfusion, 115 Axillary dissection, 116 Barium enema, 120 Barium swallow, 121 Bethesda criteria, 135 Bilobectomy, 138 Biopsy, 142 Bone marrow aspiration and biopsy, 161 Bone marrow transplantation (BMT), 163 Bone scan, 166 1415
Salem Health: Cancer Endoscopic retrograde cholangiopancreatography (ECRP), 417 Endoscopy, 417 Enterostomal therapy, 422 Esophagectomy, 438 Exenteration, 450 External beam radiation therapy (EBRT), 454 Fecal occult blood test (FOBT), 467 Flow cytometry, 484 Gallium scan, 495 Gamma Knife, 497 Gene therapy, 512 Genetic testing, 517 Gerson therapy, 527 Gleason grading system, 532 Glossectomy, 535 Gonioscopy, 536 Grading of tumors, 537 Hepatic arterial infusion (HAI), 568 Hormone receptor tests, 601 HRAS gene testing, 609 5-Hydroxyindoleacetic acid (5HIAA) test, 613 Hyperthermia therapy, 617 Hyperthermic perfusion, 618 Hysterectomy, 620 Hysterography, 621 Hystero-oophorectomy, 622 Hysteroscopy, 623 Ileostomy, 625 Imaging tests, 626 Immunochemical fecal occult blood test (iFOBT), 632 Immunocytochemistry and immunohistochemistry, 633 Immunoelectrophoresis (IEP), 634 Infusion therapies, 647 Intensity-modulated radiation therapy (IMRT), 652 Iridium seeds, 658 Ki67 test, 670 Lactate dehydrogenase (LDH) test, 678 Laparoscopy and laparoscopic surgery, 681 Laryngectomy, 686 Laryngoscopy, 687 Laser therapies, 688 Leukapharesis, 698 Limb salvage, 708 Linear accelerator, 709 Liver biopsy, 714 Lobectomy, 723 Loop electrosurgical excisional procedure (LEEP), 727 Lumbar puncture, 728 Lumpectomy, 730 Lymphadenectomy, 738
Lymphangiography, 740 Magnetic resonance imaging (MRI), 750 Mammography, 754 Mastectomy, 761 Mediastinoscopy, 768 Microwave hyperthermia therapy, 791 Mohs surgery, 796 Needle biopsies, 836 Needle localization, 838 Nephrostomy, 839 Nuclear medicine scan, 859 Ommaya reservoir, 878 Oophorectomy, 888 Oral and maxillofacial surgery, 893 Orchiectomy, 898 Palpation, 920 Pancreatectomy, 921 Pap test, 928 Paracentesis, 929 Pelvic examination, 940 Percutaneous transhepatic cholangiography (PTHC), 943 Pericardiocentesis, 946 Peritoneovenous shunts, 946 Pheresis, 958 Pleural biopsy, 972 Pleurodesis, 975 Pneumonectomy, 977 Polypectomy, 982 Positron emission tomography (PET), 984 Progesterone receptor assay, 1003 Prostate-specific antigen (PSA) test, 1006 Prostatectomy, 1008 Protein electrophoresis, 1010 Proton beam therapy, 1014 Radiation therapies, 1023 Radical neck dissection, 1027 Radiofrequency ablation, 1027 Radionuclide scan, 1030 Receptor analysis, 1033 Reconstructive surgery, 1034 Rehabilitation, 1038 Salpingectomy and salpingo-oophorectomy, 1060 Screening for cancer, 1067 Sentinel lymph node (SLN) biopsy and mapping, 1073 Sigmoidoscopy, 1082 Splenectomy, 1103 Sputum cytology, 1105 Staging of cancer, 1108 Stem cell transplantation, 1114 Stent therapy, 1116 1416
Category List Stereotactic needle biopsy, 1118 Stereotactic radiosurgery (SRS), 1119 Surgical biopsies, 1135 Testicular self-examination (TSE), 1156 Thermal imaging, 1157 Thoracentesis, 1158 Thoracoscopy, 1160 Thoracotomy, 1161 Thyroid nuclear medicine scan, 1172 TNM staging, 1173 Tracheostomy, 1179 Transfusion therapy, 1180 Transrectal ultrasound, 1185 Transvaginal ultrasound, 1186 Tumor markers, 1191 Ultrasound tests, 1199 Umbilical cord blood transplantation, 1201 Upper gastrointestinal (GI) endoscopy, 1202 Upper gastrointestinal (GI) series, 1203 Urinalysis, 1207 Urography, 1213 Urostomy, 1216 Vascular access tubes, 1225 Vasectomy and cancer, 1226 Wire localization, 1250 X-ray tests, 1252
End-of-life care, 404 Esophageal speech, 436 Ethnicity and cancer, 444 Family history and risk assessment, 461 Fertility issues, 471 Financial issues, 481 Genetic counseling, 515 Genetic testing, 517 Geography and cancer, 522 Grief and bereavement, 541 Health maintenance organizations (HMOs), 557 Hereditary cancer syndromes, 574 Home health services, 597 Hospice care, 606 Informed consent, 646 Insurance, 648 Journaling, 665 Karnofsky performance status (KPS), 669 Latinos/Hispanics and cancer, 690 Living will, 719 Living with cancer, 720 Long-distance caregiving, 726 Managed care, 757 Medical marijuana, 768 Medicare and cancer, 772 Native North Americans and cancer, 832 Occupational exposures and cancer, 871 Overtreatment, 911 Personality and cancer, 947 Poverty and cancer, 987 Prayer and cancer support, 989 Preferred provider organizations (PPOs), 990 Pregnancy and cancer, 992 Psychosocial aspects of cancer, 1018 Relationships, 1041 Second opinions, 1070 Self-image and body image, 1071 Sexuality and cancer, 1074 Singlehood and cancer, 1084 Social Security Disability Insurance (SSDI), 1096 Statistics of cancer, 1111 Stress management, 1125 Support groups, 1132 Survival rates, 1140 Survivorship issues, 1143 Transitional care, 1182 Watchful waiting, 1242
Social and personal issues Advance directives, 24 African Americans and cancer, 28 Africans and cancer, 31 Aging and cancer, 34 Aids and devices for cancer patients, 38 Antiperspirants and breast cancer, 88 Anxiety, 93 Ashkenazi Jews and cancer, 107 Asian Americans and cancer, 109 Cancer clusters, 218 Caregivers and caregiving, 242 Case management, 247 Childbirth and cancer, 263 Cognitive effects of cancer and chemotherapy, 290 Counseling for cancer patients and survivors, 324 Depression, 357 Developing nations and cancer, 366 Do-not-resuscitate (DNR) order, 380 Elderly and cancer, 396 Electrolarynx, 399
1417
u
Index
A page number or range in boldface type indicates that an entire entry devoted to that topic appears in the set. Compounds are listed under their main root (hence, 4-Aminobiphenyl appears under “A”). AACR. See American Association for Cancer Research ABCD, 1, 996, 1383 Abdominal dropsy. See Ascites Abdominal tap. See Paracentesis Abdominoperineal resection (APR), 1-2 Ablation, 336, 617, 1027, 1383. See also Cryoablation; radiofrequency ablation Abscess, 1383 ACC. See Adenoid cystic carcinoma Accelerated partial breast irradiation (APBI), 3-4 Acetamides. See Pesticides Acetophenetidin. See Phenacetin Achlorhydria, 4 Acoustic neuromas, 4-6 Acquired immunodeficiency syndrome (AIDS), 1383 Acquired immunodeficiency syndromerelated cancers. See AIDS-related cancers Acromegaly, 1383 Acrylamides, 6-8 ACS. See American Cancer Society Actinic keratosis, 1383 Actinolite. See Asbestos Actinon. See Radon Active surveillance. See Watchful waiting Acupressure, 8-10 Acupuncture, 8-10 Acute, 1383 Acute lymphocytic leukemia (ALL), 11-13 Acute myelocytic leukemia (AML), 13-16 Acute normovolemic hemodilution. See Autologous blood transfusion Adamantinomas. See Craniopharyngiomas Adeno-, 1383 Adenocarcinomas, 16-17, 554 Adenoid cystic carcinoma (ACC), 17 Adenomas, 1383 Adenomas, bronchial, 197 Adenomatoid tumors, 18 Adenomatosis polyposis coli gene testing. See APC gene testing Adenomatous polyps, 18-19, 95 Adenopathy, 1383
Adenosine triphosphate (ATP), 1383 Adenosquamous carcinoma, 1383 Adenoviruses, 19-20 Adjunct therapy, 1383 Adjuvant therapy, 20-21 Adnexal mass, 1383 Adolescent cancer. See Young adult cancers Adrenal gland cancers, 21-23 Adrenal glands, 1383 Adrenalectomy, 1383 Adrenocortical, 1383 Adrenocortical cancer, 23-24 Adult T-cell leukemia/lymphoma (ATLL), 1383 Adult T-cell lymphoma virus. See Human T-cell leukemia virus Advance directives, 24-26 Advanced Breast Biopsy Instrument (ABBI) biopsy. See Core needle biopsy Adverse drug reactions. See Side effects Aflatoxins, 26-28, 715 AFP. See Alpha-fetoprotein levels African Americans and cancer, 28-31, 444 Africans and cancer, 31-32 Afterloading radiation therapy, 32-34 Agent Orange, 34 Ageusia. See Taste alteration Aggravating factor, 1383 Aggressive, 1383 Aging, 34-38, 396. See also Elderly and cancer Agnogenic myeloid metaplasia (AMM), 1383. See also Myelofibrosis Agranulocytosis. See Neutropenia AICR. See American Institute for Cancer Research AIDS-associated Kaposi sarcoma. See Kaposi sarcoma Aids for cancer patients, 38-39 AIDS-related cancers, 590-593 Air pollution, 39-42 AJCC staging system, 1383 Alanine aminopeptidase (AAP), 1383 Alanine transferase, 1383 Alcohol and alcoholism, 42-43, 1000; risk, 1054
1419
Aleukemia, 43-44 Aleukemic megakaryocytic myelosis. See Myelofibrosis Alkaline phosphatase test (ALP), 44-45 Alkaloids, 968-971 Alkeran. See Melphalan ALKP. See Alkaline phosphatase test Alkylating agents in chemotherapy, 45-47, 83, 269 ALL. See Acute lymphocytic leukemia All heal. See Mistletoe Allicin, 499-500 Allium sativum. See Garlic Allogeneic bone marrow transplantation, 1383 Allogeneic stem cell transplantation, 1383 Allow natural death. See Do-notresuscitate (DNR) order Alopecia, 47-48 ALP. See Alkaline phosphatase test Alpha-fetoprotein (AFP) levels, 48-49 Alprazolam. See Benzodiazepines Alveolar rhabdomyosarcomas. See Rhabdomyosarcomas Alveolar soft-part sarcomas, 49-50 Ambochlorin. See Chlorambucil Amelanotic melanoma, 1383 Amenorrhea, 50-51 American Association for Cancer Research (AACR), 52-53 American Cancer Society (ACS), 53-54 American Indians. See Native North Americans and cancer American Institute for Cancer Research (AICR), 54-56 American Society for the Control of Cancer. See American Cancer Society Amigdalina B-17. See Laetrile 4-Aminobiphenyl, 56 AML. See Acute myelocytic leukemia Amosite. See Asbestos Ampullary cancer, 1384 Amputation, 56-58 Amygdalin. See Laetrile Amyloidosis, 58-59 Anal cancer, 1, 59-61 Analgesic, 1384 Anaphylactic shock, 1384
Salem Health: Cancer Anaplastic, 1384 Anaplastic large cell lymphoma (ALCL), 1384. See also Cutaneous T-cell lymphoma Anaplastic thyroid cancer, 1384 Anastomosis, 1384 Androblastoma, 1384. See also Sertoli cell tumors Androgens, 61, 72 Anemia, 62-63; aplastic, 95-97; Fanconi, 464-466; hemolytic, 566 Anesthetic, 1384 Aneurysmal bone cysts. See Spinal axis tumors Angiofollicular lymph node hyperplasia. See Castleman disease Angiogenesis, 64-66; inhibitors, 66-68, 141 Angiography, 68-69 Angioimmunoblastic T-cell lymphoma, 1384 Angioleiomyomas. See Leiomyomas Angiomatosis retinae. See Von HippelLindau (VHL) disease Angiomatous lymphoid. See Castleman disease Angiomyolipoma, 1384 Angiosarcomas, 69-70 Animal cancer management. See Veterinary oncology Anorectal excision. See Abdominoperineal resection Anorexia, 98, 1243, 1384. See also Appetite loss; Cachexia; Weight loss Anoscopy, 70-71 Anterior mediastinotomy, 1384 Anterior pelvic exenteration, 1384 Anterior urethral cancer, 1384 Anthracene. See Coal tars and coal tar pitches Anthraquinones, 71 Anthrax, 71-72 Antiandrogens, 72-73 Antiangiogenic, 1384 Antibiotics, cytotoxic, 85 Antibody, 1384 Antibody therapy, 1384 Anticoagulant, 1384 Antidiarrheal agents, 73-75 Antiemetics, 81, 1384 Antiestrogens, 75-76, 441 Antifungal therapies, 76-78 Antigen NY-CO-13. See TP53 protein Antigens, 205-206, 223, 629, 633, 1006, 1384
Antiglobulin test, 1384 Antimetabolites in chemotherapy, 78-81, 83 Antimitotic agent, 1384 Antimitotics, 84 Antinausea medications, 81-83 Antineoplastics in chemotherapy, 45, 83-86 Antioxidants, 86-88; herbs as, 573-574 Antiperspirants and breast cancer, 88-90 Antiviral therapies, 90-93 Anus, 70; cancer, 1, 59; removal, 1 Anxiety, 93-94, 1125; medications, 132 APC gene testing, 94-95 Apheresis, 1384. See also Pheresis Aplastic anemia, 95-97 Appendix cancer, 97-98 Appetite loss, 98-100. See also Anorexia; Cachexia; Weight loss APR. See Abdominoperineal resection Aptyalism. See Dry mouth Aromatase inhibitor, 1384 Aromatherapy, 310 Arsenic compounds, 100-101 Arterial access device, 1384 Arterial embolization, 101-102 Arteriogram, 1384 Arteriography, 68 Artificial larynx. See Electrolarynx Artificial sweeteners, 102-103 Asbestos, 41, 103-105, 786 Ascites, 105-107 Ashkenazi Jews and cancer, 107-109, 444 Asialia. See Dry mouth Asian Americans and cancer, 109-112, 444 Asian ginseng. See Ginseng, panax Aspartame. See Artificial sweeteners Aspiration, 1384 ASPS. See Alveolar soft-part sarcomas Assay, 1384 Asthenia. See Fatigue Astrocytomas, 112-114, 173 Ataxia, 1385 Ataxia telangiectasia (AT), 114-115 Ataxia telangiectasia variant V1. See Nijmegen breakage syndrome Ativan. See Benzodiazepines Atrial myxoma. See Carney complex Atypical mole syndrome. See Dysplastic nevus syndrome Atypical teratoid/rhabdoid tumor, 1385 Autoimmune hemolytic anemia, 1385 Autologous blood transfusion, 115-116
1420
Autologous bone marrow transplantation, 1385 Autologous stem cell transplantation, 1385 Autonomic nervous system (ANS), 1385 Avobenzone. See Sunscreens Axillary dissection, 116-117 Azasan. See Azathioprine Azathioprine, 117 Azoospermia. See Sterility B cell, 1385 B-cell acute lymphocytic leukemia, 1385 B-cell lymphoma, 1385 Baccaredda-Sézary syndrome. See Sézary syndrome Bacillus Calmette Guérin (BCG), 118 Bacteria, 71, 118-120, 558, 641; risk, 1054. See also Helicobacter pylori; Salmonella typhi Baldness, 47 Barbiturate, 1385 Barium enema, 120-121 Barium swallow, 121-123 Barrett esophagus, 123-124, 438, 995 Basal cell carcinomas, 124-126, 1088 BCC. See Basal cell carcinomas BCG. See Bacillus Calmette Guérin BCME. See Bis(chloromethyl) ether Beckwith-Wiedemann syndrome (BWS), 126-128 Bednar tumor. See Dermatofibrosarcoma protuberans Bellini duct carcinoma (BDC), 1385 Bench Jones protein, 1385 Benign, 1385 Benign prostatic hyperplasia (BPH), 128 Benign tumors, 18, 128-130 Benzene, 130-131 Benzidine, 131-132 Benzodiazepines, 132-133 Benzopyrene. See Coal tars and coal tar pitches Bereavement, 541-543 Berlin breakage syndrome. See Nijmegen breakage syndrome Beryllium and beryllium compounds, 133-134 Beta-carotene, 135 Beta-naphthylamine. See 2-Naphthylamine Bethesda criteria, 135-136 BHDS. See Birt-Hogg-Dubé syndrome Biafine cream, 1385 Bilateral cancer, 1385
Index Bile duct cancer, 136-138 Biliary, 1385 Bilobectomy, 138 BioBands. See Motion sickness devices Bioflavonoids, 138-139 Biological response modifier (BRM) therapy, 1385 Biological therapy, 139-142, 635. See also Immunotherapy Biology, cancer, 213-216 Biomarkers. See Tumor markers Biopsy, 142-145, 1385; bone marrow, 161; computed tomography (CT)guided, 313; core needle, 321; liver, 714; needle, 836-838; pleural, 972; sentinel lymph node (SLN), 1073; stereotactic needle, 1118; surgical, 1135 Birt-Hogg-Dubé syndrome (BHDS), 145-146 Birth control pills, 146-148 Bis(chloromethyl) ether, 148-149 Bis(2-ethylhexyl) phthalate. See Di(2-ethylhexyl) phthalate Bis-2-hydroxyethylamine. See Diethanolamine Bisphenol A (BPA), 149-150 Bisphosphonates, 151 Bivinyl. See 1,3-Butadiene Black light. See Ultraviolet radiation Bladder cancer, 118, 151-154, 871, 1183 Bladder imaging, 347 Blastomas; hemangioblastomas, 559; medulloblastomas, 775; nephroblastomas, 839; neuroblastomas, 841; pineoblastomas, 963; pleuropulmonary, 975; retinoblastomas, 1046 Bleeding disorders. See Thrombocytopenia Blister gas. See Mustard gas Blood; clotting, 378, 615; urine containing, 564; vomiting of, 561 Blood-brain barrier (BBB), 1385 Blood-brain barrier disruption (BBBD), 1385 Blood cancers, 11, 13, 154-158, 276, 279, 424, 550, 562, 698, 744, 823; myeloma, 822. See also Acute lymphocytic leukemia; Acute myelocytic leukemia; Aleukemia; Burkitt lymphoma; Chronic lymphocytic leukemia; Chronic myeloid leukemia; Cutaneous T-cell lymphoma; Down syndrome and
leukemia; Eosinophilic leukemia; Hairy cell leukemia; Hodgkin disease; Leukemias; Lymphomas Blood transfusion, autologous, 115-116 Blood urea nitrogen (BUN), 1385 Blood vessels; blockage, 101, 402; cancer, 69; formation, 64, 66 Blue nevi (LAMB) syndrome. See Carney complex BMT. See Bone marrow transplantation BNCT. See Boron neutron capture therapy Boder-Sedgwick syndrome. See Ataxia telangiectasia Body image, 1071-1072 Bolus infusion, 1385 Bone; loss, 151; pain, 165-166; scan, 166-167 Bone cancers, 158-161, 271, 447, 530; Paget disease, 912 Bone marrow aspiration, 161-163 Bone marrow biopsy, 161-163 Bone-marrow suppression. See Myelosuppression Bone marrow transplantation (BMT), 163-165 Bone metastasis, 1385 Bone-seeking radioisotope, 1385 Bone tumor-epidermoid cyst-polyposis. See Gardner syndrome Boron neutron capture therapy (BNCT), 167-168 Botanicals. See Pesticides Botryoid rhabdomyosarcomas. See Rhabdomyosarcomas Bourneville disease. See Tuberous sclerosis Bowen disease, 168-170, 995 BPA. See Bisphenol A BPH. See Benign prostatic hyperplasia BPI. See Brief Pain Inventory Braces. See Aids for cancer patients Brachytherapy, 32, 170-172 BRAF gene, 172-173 Brain cancers, 112, 173-176, 425, 533, 559, 775. See also Acoustic neuromas; Astrocytomas; Carcinomatous meningitis; Gliomas; Leptomeningeal carcinomas; Meningeal carcinomatosis; Meningiomas; Neuroblastomas; Oligodendrogliomas; Primary central nervous system lymphomas; Spinal axis tumors Brain scan, 176-178 Brain stem gliomas, 1385
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Brain surgery. See Craniotomy Brain tumor-polyposis syndrome. See Turcot syndrome Brain tumors, 1195 Brassicaceae family. See Cruciferous vegetables BRCA1 gene, 108, 178-180 BRCA2 gene, 108, 178-180 Breakthrough pain, 180 Breast cancers, 61, 75, 116, 178, 185-188, 193, 283, 309, 387, 441, 573, 599, 601, 656, 725, 730, 754, 761, 790; antiperspirants and, 88-90; children and adolescents, 180-182; cutaneous, 341-342; estrogen-receptor-sensitive, 442; men, 182-184; pregnant women, 184-185, 992; radiation, 3; screening, 754 Breast-conserving surgery, 1385. See also Lumpectomy Breast duct endoscopy, 1386 Breast examination; clinical, 283; self, 193 Breast forms. See Aids for cancer patients Breast self-examination (BSE), 193-194 Breast X ray. See Mammography Breasts; calcifications, 211; cancer, 3, 61, 75, 88, 116, 178, 180, 182, 184-188, 193, 283, 309, 341, 387, 441-442, 573, 599, 601, 730, 754, 761, 992; fibrocystic changes, 475-478; imaging, 194, 389, 754; implants, 188-190; invasive ductal carcinoma, 656; lobular carcinoma in situ, 725; medullary carcinoma of the, 774; microcalcifications in, 790; nipple discharge, 854; reconstruction, 190-193; removal, 761; ultrasound, 194-195 Breslow’s staging, 195 Brief Pain Inventory (BPI), 196 Broad ligament tumor. See Fallopian tube cancer Brompton cocktail, 196-197 Bronchial adenomas, 197 Bronchoalveolar lung cancer, 197-199 Bronchogenic carcinoma, 1386 Bronchography, 199 Bronchopneumonia. See Pneumonia Bronchoscopy, 199-200, 1386 Broviac catheters. See Vascular access tubes BSE. See Breast self-examination Bulsulfan. See 1,4-Butanediol dimethanesulfonate
Salem Health: Cancer Burgdorf’s reaction. See Hand-foot syndrome Burkitt lymphoma, 200-202, 1386 1,3-Butadiene, 202-203 1,4-Butanediol dimethanesulfonate, 203-204 BWS. See Beckwith-Wiedemann syndrome C-H-RAS. See HRAS gene testing c-Myc. See MYC oncogene CA 15-3 test, 205 CA 19-9 test, 205-206 CA 27-29 test, 206 CA 125 test, 206-207 Cachexia, 207-208, 1243. See also Anorexia; Appetite loss; Weight loss Cadmium and cadmium compounds, 208-209 Caffeine, 209-211 Caisse, Rene, 71, 441 Calcifications of the breast, 211. See also Microcalcifications Calcium, 212; abnormal levels, 614 CAM. See Complementary and alternative therapies Camellia sinesis. See Green tea Campylobacter pylori. See Helicobacter pylori Cancell, 212-213 Cancer, 1386 Cancer biology, 213-216 Cancer care team, 216-218 Cancer clusters, 218-220 Cancer detection. See Screening Cancer education, 220-221 Cancer markers. See Tumor markers Cancer medicine. See Oncology Cancer nurse specialist. See Oncology clinical nurse specialist Cancer of the adrenal cortex, 1386 Cancer of unknown primary origin (CUP), 1386 Cancer Research and Prevention Foundation. See Prevent Cancer Foundation Cancer Research Foundation of America. See Prevent Cancer Foundation Cancer social worker. See Oncology social worker Cancerous tumors. See Malignant tumors Canctron. See Cancell Candidiasis, 221-223 Canes. See Aids for cancer patients Capillary hemangiomas. See Orbit tumors
Capsebon. See Cadmium and cadmium compounds Carbamates. See Pesticides Carbogen, 1386 Carbohydrate antigen 15-3. See CA 15-3 test Carbohydrate antigen 19-9. See CA 19-9 test Carbohydrate antigen 27-29. See CA 27-29 test Carbon black. See Soots Carcinoembryonic antigen antibody (CEA) test, 223-224 Carcinogen, 1386 Carcinogenesis, 1386 Carcinogens, 34; known, 26, 40, 56, 100, 103, 117, 130-131, 133, 148, 202-203, 208, 224-227, 268-269, 274, 288, 292, 345-346, 373, 376, 399, 433, 447, 569570, 603, 657, 779, 792, 812, 826, 851, 1032, 1083, 1097, 1127, 1200, 1251; reasonably anticipated, 6, 40, 227-230, 368, 399, 486, 550, 851, 949, 955, 981, 1200; suspected, 42, 88, 118, 146, 149, 249, 368, 373, 490, 881, 901, 971, 1084 Carcinoid syndrome, 230-232 Carcinoid tumors, 230-232 Carcinoma of unknown primary origin (CUP), 232-233 Carcinomas, 233-235, 1386; adenocarcinomas, 16, 554; adenoid cystic carcinoma (ACC), 17; basal cell, 124-126, 1088; cholangiocarcinomas, 136; choriocarcinomas, 272; comedo, 309; ductal carcinoma in situ (DCIS), 185, 387; duodenal, 393; hereditary nonVHL clear cell renal cell, 580; hereditary papillary renal cell, 581; invasive ductal, 656; invasive lobular, 657; leptomeningeal, 696; lobular carcinoma in situ (LCIS), 185, 725; medullary carcinoma of the breast, 774; Merkel cell carcinomas (MCC), 783; mucinous, 803; squamous cell, 554, 1088, 1106; teratocarcinomas, 1152; transitional cell, 1183; trichilemmal, 1187; tubular, 1188; unknown primary origin, 232; yolk sac, 1256 Carcinomatosis, 235-236 Carcinomatous meningitis, 237-238, 781 Carcinosarcomas, 238, 1386 Cardiac sarcoma, 1386
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Cardiomyopathy, 239-240 Cardiopulmonary resuscitation (CPR), 240-242 Care team, cancer, 216-218 Caregiving, 242-245; long-distance, 726 Carney complex, 245 Carotene. See Beta-carotene Carotenoids, 135, 245-246 Carson, Rachel, 950 Cartilage supplements, 246-247 Case management, 247-248 Castleman disease, 248-249 Catheter, 1386 Cauterize, 1386 Cavernous hemangiomas. See Orbit tumors CBC. See Complete blood count CBE. See Clinical breast exam CDKN2A. See Cyclin-dependent kinase inhibitor-2A CEA test. See Carcinoembryonic antigen antibody test Cell phones, 249-250 CELLO. See Barrett esophagus Cellular adoptive immunotherapy, 1386 Cellular tumor antigen p53. See TP53 protein Central nervous system cancers, 173-176, 425, 533, 559; lymphomas, 1003 Central nervous system primitive neuroectodermal tumor, 1386 Central nervous system prophylaxis, 1386 Cerebellar hemangioblastoma, 1386 Certified social worker in health care. See Oncology social worker Cervical cancer, 251-253, 317, 543, 611; pregnancy, 992 Cervical intraepithelial neoplasia (CIN), 1386 Cesamet. See Delta-9tetrahydrocannabinol Chemoembolization, 253-254 Chemoimmunotherapy, 1386 Chemokines. See Cytokines Chemoprevention, 254-257, 1000 Chemoprotective agent, 1386 Chemoradiation, 1386 Chemotherapy, 257-261, 1386; adjuvant, 20; alkylating agents, 45, 83; androgen drugs, 61; angiogenesis inhibitors, 66, 141; antiandrogens, 72; antiestrogens, 75; antimetabolites, 78, 83; antineoplastics, 83; cyclooxygenase 2 (COX-2) inhibitors, 344; cytokines, 141, 350, 635; interferon, 141, 653;
Index interleukins, 141, 637, 654; matrix metalloproteinase inhibitors, 764; monoclonal antibodies, 141, 800; plant alkaloids and terpenoids, 968; proteasome inhibitors, 1010; side effects, 1079; topoisomerase inhibitors, 84, 1175; tyrosine kinase inhibitors, 1196 Chemotherapy-induced acral erythema. See Hand-foot syndrome Chewing tobacco, 261-262 Childbirth and cancer, 263-264 Childhood autonomic nervous system tumors. See Neuroblastomas Childhood cancers, 264-268, 775, 841, 1046, 1248 Chinese ginseng. See Ginseng, panax Chinese medicine. See Traditional Chinese medicine Chlorambucil, 268 Chlorinated aromatics. See Pesticides Chloro(chloromethoxy) methane dichloromethyl ether. See Bis(chloromethyl) ether 1-(2-Chloroethyl)-3-(4methylcyclohexyl)-1-nitrosourea (MeCCNU), 269 Chloroethylene. See Vinyl chloride Chloromethyl methyl ether, technicalgrade, 148-149 Cholangiocarcinoma, 136, 1386 Cholangiosarcoma, 1386 Cholecystectomy, 269-271 Chondrosarcoma, 1386 Chordomas, 271-272 Chorioadenoma destruens, 1386. See also Gestational trophoblastic tumors Choriocarcinomas, 272-274 Choroid plexus tumor, 1386 CHPP. See Continuous hyperthermic peritoneal perfusion Chromaffin cell tumors. See Pheochromocytomas Chromium hexavalent compounds, 274 Chromosome analysis. See Cytogenetics Chromosomes, 348; cancer and, 274-276, 853 Chronic, 1386 Chronic granulocytic leukemia. See Chronic myeloid leukemia Chronic lymphocytic leukemia (CLL), 276-279 Chronic myeloid leukemia (CML), 279-281 Chrysene. See Coke oven emissions
Chrysotile. See Asbestos Cicloral. See Cyclosporin A Cigarettes and cigars, 281-283 Clark’s nevus. See Dysplastic nevus syndrome Clear cell adenocarcinoma, 1386 Clinical breast exam (CBE), 283-285 Clinical resistance, 1386 Clinical trials, 285-288, 646 CLL. See Chronic lymphocytic leukemia Clusters, cancer, 218-220 CML. See Chronic myeloid leukemia CMME. See Bis(chloromethyl) ether Co Q 10. See Coenzyme Q10 Coal tars and coal tar pitches, 288 Cobalt 60 radiation, 289 Coenzyme Q10, 289-290 Cognitive effects of cancer and chemotherapy, 290-291 Coke oven emissions, 292 Cold nodule, 292-293 Colectomy, 293-294 Colloid carcinomas. See Mucinous carcinomas Coloanal anastomosis, 294-296 Colon; cancer, 135, 293-294, 300, 304, 374, 467, 625, 632, 645; imaging, 297, 1082; polyps, 95, 296-297, 498, 579, 582; removal, 1, 293 Colon cancer nonpolyposis type 2. See MLH1 gene Colonoscopy, 297-299 Colony-stimulating factors (CSFs), 141, 299-300 Colorectal, 1386 Colorectal cancer, 97, 293-294, 300-304, 374, 467, 625, 632, 645, 1036; hereditary nonpolyposis, 135; screening, 297, 304-306, 1082. See also Anal cancer; Colon; Colostomy; Colposcopy; Crohn disease; Gastrointestinal cancers; Hereditary mixed polyposis syndrome; Hereditary polyposis syndromes; Inflammatory bowel disease; Juvenile polyposis syndrome; Rectal cancer Coloring agent. See Hair dye Colostomy, 306-308 Colposcopy, 308-309 Comedo carcinomas, 309 Complementary and alternative therapies, 71, 86, 212, 245-246, 289, 309-312, 339, 355, 370, 400, 441, 531, 540, 573, 651, 679, 793, 937, 955, 1065, 1128. See also Anthraquinones;
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Antioxidants; Cancell; Carotenoids; Cartilage supplements; Coenzyme Q10; Curcumin; Delta-9tetrahydrocannabinol; Dietary supplements; Electroporation therapy; Essiac; Garlic; Ginseng, panax; Green tea; Herbs; Integrative oncology; Laetrile; Macrobiotic diet; Mistletoe; PC-SPES; Phenolics; Saw palmetto; Sun’s soup Complete blood count (CBC), 312-313, 1387 Complete hysterectomy, 1387 Complete metastasectomy, 1387 Complete remission, 1387 Complications. See Side effects Computed tomography (CT)-guided biopsy, 313-315 Computed tomography (CT) scan, 176, 315-317, 626, 1387 Concurrent therapy, 1387 Cone biopsy, 317 Congenital mesoblastic nephroma, 1387 Congenital myasthenia gravis. See Myasthenia gravis Conization, 317-318 Consolidation therapy, 1387 Consumptive coagulopathy. See Disseminated intravascular coagulation Continuous hyperthermic peritoneal perfusion (CHPP), 318 Contraindication, 1387 Contrast material, 1387 Conventional medicine, 1387 Cord blood transplantation. See Umbilical cord blood transplantation Cordectomy, 318-319 Cordotomy, 319-321 Core needle biopsy, 321 Corticosteroids, 321-322 Cosmetic surgery. See Reconstructive surgery Cotton mouth. See Dry mouth Coughing, 322-323; blood, 566 Coumestans. See Phytoestrogens Coumestrol. See Phytoestrogens Counseling, 324-326 Cowden syndrome, 326-327 COX-2 inhibitors. See Cyclooxygenase 2 inhibitors CPR. See Cardiopulmonary resuscitation Craniopharyngiomas, 327-329 Craniosynostosis, 329-331 Craniotomy, 331-332
Salem Health: Cancer Cribriform carcinoma. See Adenoid cystic carcinoma Cristobalite. See Silica, crystalline Crocidolite. See Asbestos Crohn disease, 332-335 Cruciferous vegetables, 335-336 Cryoablation, 336-338 Cryoprecipitate transfusion. See Transfusion therapy Cryptorchidism, 338-339 CsA. See Cyclosporin A CSFs. See Colony-stimulating factors CT scan. See Computed tomography scan CTCL. See Cutaneous T-cell lymphoma Culdoscopy, 339 CUP. See Carcinoma of unknown primary origin Curcumin, 339-340 Cushing syndrome, 340-341, 966 Cutaneous anaplastic large-cell lymphoma. See Cutaneous T-cell lymphoma Cutaneous breast cancer, 341-342 Cutaneous T-cell lymphoma (CTCL), 342-344, 817 CYA. See Cyclosporin A Cyclin-dependent kinase inhibitor-2A (CDKN2A), 344 Cyclooxygenase 2 (COX-2) inhibitors, 344-345 Cyclophosphamide, 345-346 Cyclosporin A, 346 Cystic duct cholangiography. See Percutaneous transhepatic cholangiography Cystography, 347 Cystoprostatectomy, 1387 Cystosarcoma phyllodes (CSP), 1387. See also Phyllodes tumors Cystoscopy, 347-348 Cystourethrectomy, 1387 Cytogenetics, 348-349 Cytokines, 141, 350, 635 Cytology, 350-353; sputum, 1105 Cytometry, flow, 484-486 Cytopenia, 1387 Cytotoxic antibiotics, 85 Cytoxan. See Cyclophosphamide Daidzein. See Phytoestrogens Dana-Farber Cancer Institute, 354-355 D&C. See Dilation and curettage DCIS. See Ductal carcinoma in situ DDS. See Denys-Drash syndrome DEA. See Diethanolamine
Death and dying, 404, 541, 606, 918 Debulking, 1387 DEHP. See Di(2-ethylhexyl) phthalate Delta-9-tetrahydrocannabinol, 355-356. See also Medical marijuana Denys-Drash syndrome, 357 Deoxyribonucleic acid (DNA), 78, 274; damage to, 86, 491 Deoxyribonucleic acid (DNA) testing. See Genetic testing Depression, 357-360 Dermatofibrosarcoma protuberans (DFSP), 360-362 Dermatology oncology, 362-365 Dermoid cysts. See Orbit tumors DES. See Diethylstilbestrol Desmoid tumors, 365 Desmoplastic melanoma, 1387 Desmoplastic small round cell tumor (DSRCT), 365-366 Developing nations and cancer, 366-368 Devices for cancer patients, 38-39 DFSP. See Dermatofibrosarcoma protuberans Di(2-ethylhexyl) phthalate (DEHP), 368 Diarrhea, 73, 369-370, 506 Diazepam. See Benzodiazepines DIC. See Disseminated intravascular coagulation Dichlorodiphenyltrichloroethane (DDT), 949 Dietary supplements, 311, 370-373 Diethanolamine (DEA), 373 Diethylstilbestrol (DES), 373-374 Diferuloylmethane. See Curcumin Diffuse hyperplastic perilobar nephroblastomatosis (DHPLN), 1387 Diffuse large B-cell lymphoma, 1387. See Richter syndrome Digital infrared thermal imaging. See Thermal imaging Digital rectal exam (DRE), 374-375 Dilation and curettage (D&C), 375-376 Dimethylchloroether. See Bis(chloromethyl) ether Dimethylene oxide. See Ethylene oxide Dinitroanilines. See Pesticides Dinitrophenols. See Pesticides Diolamine. See Diethanolamine Dioxins, 376-377 Dip. See Chewing tobacco Direct Black 38. See Benzidine Direct Blue 6. See Benzidine Direct Brown 95. See Benzidine
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Disseminated intravascular coagulation (DIC), 378 Distant metastasis, 1387 Dithiocarbamates. See Pesticides Diverticulitis, 378-380 Diverticulosis, 378-380 DNA. See Deoxyribonucleic acid Do-not-resuscitate (DNR) order, 25, 380-381 Donor lymphocyte infusion, 1387 Down syndrome and leukemia, 381-382 Doxorubicin-induced cardiomyopathy. See Cardiomyopathy DPC4 gene testing, 382-383 DRE. See Digital rectal exam Dronabinol. See Delta-9tetrahydrocannabinol Dropsy of pericardium. See Pericardial effusion Drug resistance, 383-385 Dry heaves. See Nausea Dry mouth, 385-386 DSRCT. See Desmoplastic small round cell tumor Duct ectasia, 386-387 Ductal carcinoma, 1387 Ductal carcinoma in situ (DCIS), 185, 309, 387-388 Ductal lavage, 389 Ductogram, 389-390 Duke Comprehensive Cancer Center, 390-392 Dukes’ classification, 392 Duodenal carcinomas, 393 Durable power of attorney, 25, 1387 Dyes, 131; hair, 550 Dysgeusia. See Taste alteration Dysplasia. See Premalignancies Dysplastic nevus syndrome, 394 Early-stage cancer, 1387 Eaton-Lambert syndrome. See LambertEaton myasthenic syndrome EBRT. See External beam radiation therapy EBV. See Epstein-Barr virus Echogram. See Ultrasound Ecloril. See Chlorambucil Ectomesenchymoma, 1387 -ectomy, 1387 Edema, 395-396 Education, cancer, 220-221, 720 Elderly and cancer, 34, 396-398; Medicare, 772; side effects, 1081. See also Aging
Index Electrolarynx, 399 Electromagnetic radiation, 399-400 Electroporation therapy, 400-401 Electrosurgery, 401-402 EM radiation. See Electromagnetic radiation Embolization, 402-403; arterial embolization, 101; chemoembolization, 253 Embryonal cell cancer, 403-404, 525 Emesis. See Nausea EMG syndrome. See BeckwithWiedemann syndrome EMR. See Electromagnetic radiation End-of-life care, 404-406, 606, 719, 917. See also Advance directives; Cardiopulmonary resuscitation; Death and dying; Do-not-resuscitate order; Living will; Palliative treatment; Transitional care Endocrine, 1387 Endocrine cancers, 406-409. See also Adrenal gland cancers; Adrenocortical cancer; Multiple endocrine neoplasia type 1 (MEN 1); Multiple endocrine neoplasia type 2 (MEN 2); Neuroendocrine tumors; Pancreatic cancers; Parathyroid cancer; Pituitary tumors; Thyroid cancer Endocrinology oncology, 409-412 Endolymphatic stromal myosis. See Uterine cancer Endometrial cancer, 412-414 Endometrial carcinoma. See Uterine cancer Endometrial hyperplasia, 414-416 Endometrial stromal sarcoma. See Uterine cancer Endorectal ultrasound, 416-417 Endoscopic retrograde cholangiopancreatography (ERCP), 417 Endoscopic ultrasound (EUS), 1387 Endoscopy, 143, 417-419; anoscopy, 70; bronchoscopy, 199; colonoscopy, 297; colposcopy, 308; culdoscopy, 339; cystoscopy, 347; hysteroscopy, 623; laparoscopy, 681; laryngoscopy, 687; mediastinoscopy, 768; sigmoidoscopy, 1082; thoracoscopy, 1160; upper gastrointestinal (GI), 1202 Endotheliomas, 420-421 Enema, barium, 120-121 Enlarged liver. See Hepatomegaly Entelev, 212
Enteritis, 421-422 Enterostomal therapy, 422-424 Eosinophilic granulomatosis. See Histiocytosis X Eosinophilic leukemia, 424 Ependymomas, 425-426 Epidemiology, 426-429 Epidermoid cancers of mucous membranes, 429-431 Epiloia. See Tuberous sclerosis Epithelial carcinoma, 1388 Epithelial ovarian cancer, 1388 Epithelial tumors of the thymus. See Thymomas Epstein-Barr virus, 431-433 EPT. See Electroporation therapy ERBB2. See HER2/neu protein ERCP. See Endoscopic retrograde cholangiopancreatography ERD. See Estrogen receptor downregulator Erionite, 433 Erythrocyte sedimentation rate (ESR), 1388 Erythroleukemia, 1388 Erythroleukoplakia, 1388 Erythropenia. See Anemia Erythroplakia, 433-434 Erythroplasia of Queyrat. See Penile cancer Esophageal cancer, 434-436 Esophageal speech, 436-438 Esophageal stent, 1388 Esophagectomy, 438-439 Esophagitis, 439-441 Esophagogastroduodenoscopy. See Endoscopy Esophagram, 1388 Esophagraphy. See Barium swallow Esophagus, 123, 436; cancer, 434, 438; inflammation, 439; removal, 438 Essiac, 71, 441 Estrogen, 75, 146, 441-442 Estrogen receptor downregulator (ERD), 441-442 Estrogen-receptor-sensitive breast cancer, 75, 442-444 Ethnicity and cancer, 28, 107, 109, 444447, 690, 832, 1122. See also African Americans and cancer; Africans and cancer; Ashkenazi Jews and cancer; Asian Americans and cancer; Latinos and cancer; Native North Americans and cancer Ethylene carboxamide. See Acrylamides
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Ethylene monochloride. See Vinyl chloride Ethylene oxide, 447 Ewing family of tumors (EFTs), 1388 Ewing sarcoma, 447-450 Examinations; breast self-examination (BSE), 193; clinical breast exam (CBE), 283; digital rectal exam (DRE), 374; gonioscopy, 536; palpation, 920; pelvic, 940; testicular self-examination (TSE), 1156 Excision, 1388 Excisional biopsy, 1388 Excisional skin surgery, 1388 Exenteration, 450-451 Exercise, 451-454, 1000, 1053 Exhaustion. See Fatigue Exomphalos-macroglossia-gigantism syndrome. See Beckwith-Wiedemann syndrome Expectant management. See Watchful waiting Expectorating. See Coughing External beam radiation therapy (EBRT), 454 Extracranial germ-cell tumor, 1388 Extrahepatic bile duct cancer, 1388 Extrahepatic cholangiocarcinoma. See Bile duct cancer Extrapleural pneumonectomy, 1388 Eye cancers, 455-458, 897, 1046 Eye socket tumors. See Orbit tumors Eyelid cancer, 458-459 Eyes; cancer, 455, 536, 897, 1046; examinations, 536 Eysenck Personality Questionnaire, 947 FA. See Fanconi anemia Fallopian tube cancer, 460-461, 544 Familial adenomatous polyposis (FAP), 18, 95, 365, 498, 582, 1388 Familial cancer syndromes. See Hereditary cancer syndromes Familial dysplastic nevi, 1388 Familial isolated hyperparathyroidism (FIHP), 1388 Familial medullary thyroid cancer, 1388 Familial medullary thyroid carcinoma. See Multiple endocrine neoplasia type 2 Familial polyposis coli. See Gardner syndrome Family history and risk assessment, 461-464
Salem Health: Cancer Family practice specialist. See Primary care physician Fanconi anemia, 464-466 FAP. See Familial adenomatous polyposis Fast neutron beam radiation, 1388 Fatigue, 466-467 Fatty liver. See Hepatomegaly Fecal occult blood test (FOBT), 467-469; immunochemical, 632 Female gynecologic examination. See Pelvic examination Fertility drugs and cancer, 469-470 Fertility issues, 471-472, 643, 1120 Fever, 472-474 Fiber, 474-475 Fibroadenomas, 475-476 Fibrocystic breast changes, 475, 476478 Fibroids, 1388 Fibromatosis, 1388 Fibrosarcomas; soft-tissue, 478-481 Financial issues, 481-483, 648 Fine needle aspiration (FNA) biopsy, 1388 First Nations. See Native North Americans and cancer 5HIAA test. See 5-Hydroxyindoleacetic acid test 5Q minus syndrome, 484 Flor-Essence, 71 Flow cytometry, 484-486 Fluid around the heart. See Pericardial effusion Fluorides. See Pesticides Fluoroscopy, 1388 FOBT. See Fecal occult blood test FOLFOX, 1388 Folic acid, 486 Follicular large-cell lymphoma, 1388 Follicular lymphoma, 1388 Follicular mixed-cell lymphoma, 1388 Follicular thyroid cancer, 1389 Formaldehyde, 486-487 Formononetin. See Phytoestrogens Fox Chase Cancer Center, 487-488 Fred Hutchinson Cancer Research Center, 488-490 Free radicals, 86, 490-491 Fruits, 135, 245, 491-492 Functional magnetic resonance imaging (fMRI), 1389 Fungal infection. See Candidiasis Fungating lesion, 1389 Fungi, 76
Galactogram. See Ductogram Gallbladder; cancer, 118, 493-495; removal, 269 Gallium scan, 495-497 Gamma globulin electrophoresis. See Immunoelectrophoresis Gamma irradiation, 1389 Gamma Knife, 497-498 Gangliocytomas. See Pituitary tumors Gardner syndrome, 498-499, 582 Garlic, 499-500 Gastrectomy, 1389 Gastric cancer, 118, 558, 1121; hereditary diffuse, 576-577 Gastric polyps, 500-501 Gastrinomas, 501-502 Gastrointestinal cancers, 59, 97, 136, 300, 304, 434, 493, 502-506, 508, 511, 715, 923, 1036, 1091, 1121. See also Anal cancer; Appendix cancer; Barrett esophagus; Bile duct cancer; Colorectal cancer; Duodenal carcinomas; Esophageal cancer; Gallbladder cancer; Gastrinomas; Gastrointestinal stromal tumors (GISTs); Hereditary diffuse gastric cancer; Leiomyosarcomas; Leptomeningeal carcinomas; Liver cancers; Pancreatic cancers; Rectal cancer; Small intestine cancer; Stomach cancers Gastrointestinal complications of cancer treatment, 506-508 Gastrointestinal oncology, 508-511 Gastrointestinal stromal tumors (GISTs), 511-512 Gastroscopy, 1389 GCTs. See Giant cell tumors Gelatinous carcinomas. See Mucinous carcinomas Gene therapy, 19, 512-515 General practitioner. See Primary care physician Genes; APC gene, 94; BRAF gene, 172; BRCA1 and BRCA2 genes, 178; cyclin-dependent kinase inhibitor-2A (CDKN2A), 344; DPC4 gene, 382; HRAS gene, 609; MLH1 gene, 795; MSH gene, 803; mutations, 813; PMS gene, 976; RB1 gene, 880, 1032; RhoGD12 gene, 1050; SCLC1 gene, 1067; tumor-suppressor, 94, 344, 1194 Genetic counseling, 515-516 Genetic testing, 517-519
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Genetics, 512, 515, 517, 519-522; risk and, 1053 Gengraf. See Cyclosporin A Geography and cancer, 522-525 Germ-cell tumors, 272, 525-527, 1099, 1153-1154 German or Eastern European Jews. See Ashkenazi Jews and cancer Germinoma, 1389. See also Pituitary tumors Gerson therapy, 527 Gestational trophoblastic tumors (GTTs), 527-530 Giant cell tumors (GCTs), 530-531 Ginseng, panax, 531-532 GISTs. See Gastrointestinal stromal tumors Gleason grading system, 532 Glial brain tumors. See Oligodendrogliomas Glial tumor, 1389 Glioblastomas. See Brain cancers Glioma-polyposis syndrome. See Turcot syndrome Gliomas, 425, 533-534; astrocytomas, 112; oligodendrogliomas, 875 Glomangiomas, 534 Glomus tumors, 534-535 Glossectomy, 535-536 Glucagonoma, 1389 Glutamine, 536 Glycitein. See Phytoestrogens Gonioscopy, 536-537 Grading of tumors, 532, 537-538 Graft-versus-host disease (GVHD), 538-539, 1389 Granulocyte colony-stimulating factor. See Cytokines Granulocytic leukemia. See Acute myelocytic leukemia Granulocytic sarcoma, 1389 Granulosa cell tumors, 540 Green tea, 540-541 Greenockite. See Cadmium and cadmium compounds Grief, 541-543; stages of, 542 Groshong catheters. See Vascular access tubes Growth factor receptors, 879 GTTs. See Gestational trophoblastic tumors Guaiac smear test. See Fecal occult blood test Guanine nucleotide binding protein. See RhoGD12 gene
Index Gum cancer. See Oral cancers Gurnistical tumors. See Renal pelvis tumors GVHD. See Graft-versus-host disease Gynecologic cancers, 251, 412, 460, 543-547, 905, 1217, 1223, 1237. See also Cervical cancer; Endometrial cancer; Fallopian tube cancer; Ovarian cancers; Uterine cancer; Vaginal cancer; Vulvar cancer Gynecologic oncology, 547-549 H. pylori. See Helicobacter pylori Hacking. See Coughing HAI. See Hepatic arterial infusion Hair dye, 550 Hair loss. See Alopecia Hairy cell leukemia, 550-552 Hand-foot syndrome (HFS), 552-554 Hartmatomas. See Hereditary polyposis syndromes Harvey murine sarcoma virus oncogene. See HRAS gene testing HBV. See Hepatitis B virus HCG. See Human chorionic gonadotropin HCV. See Hepatitis C virus HD. See Hodgkin disease HDGC syndrome. See Hereditary diffuse gastric cancer HDR. See High dose rate remote afterloading Head cancers, 554-556 Health care proxy (HCP), 1389 Health maintenance organizations (HMOs), 557-558, 758 Heat therapy. See Microwave hyperthermia therapy Helicobacter pylori, 4, 118, 558-559 Hemangioblastomas, 559 Hemangiopericytomas, 559-560 Hemangiosarcomas, 560-561 Hematemesis, 561-562 Hematologic oncology, 562-564 Hematology, pediatric, 938-940 Hematoma, 1389 Hematopoiesis, 1389 Hematopoietic growth factors, 299 Hematopoietic neoplasms. See Blood cancers Hematuria, 564-565 Hemilaryngectomy, 1389 Hemochromatosis, 565 Hemolytic anemia, 566 Hemoptysis, 566-567 Hemorrhage, 1389
Hemorrhoids, 567-568 Hepatectomy, 1389 Hepatic, 1389 Hepatic arterial infusion (HAI), 568-569 Hepatic arterial occlusion, 1389 Hepatic veno-occlusive disease, 1389 Hepatitis B virus (HBV), 110, 569-570 Hepatitis C virus (HCV), 570-571 Hepatobiliary, 1389 Hepatoblastoma, 1389 Hepatocellular carcinoma (HCC), 1389. See also Liver cancers Hepatoma, 1389 Hepatomegaly, 571-573 HER2/neu protein, 573, 879 Herbal Essence. See Essiac Herbicides, 34 Herbs, 310, 371; antioxidants, 573-574 Hereditary cancer syndromes, 574-576 Hereditary diffuse gastric cancer, 576-577 Hereditary leiomyomatosis and renal cell cancer (HLRCC), 577-579 Hereditary mixed polyposis syndrome, 579, 582 Hereditary nonpolyposis colon cancer (HNPCC), 1389 Hereditary nonpolyposis colorectal cancer (HNPCC), 135 Hereditary non-VHL clear cell renal cell carcinomas, 580 Hereditary pancreatitis, 580-581 Hereditary papillary renal cell carcinomas, 581-582 Hereditary polyposis syndromes, 582-584 Herpes simplex virus, 584-585 Herpes zoster virus, 586-587 Hexavalent chromium. See Chromium hexavalent compounds HFS. See Hand-foot syndrome Hickman catheters. See Vascular access tubes High-dose chemotherapy, 1389 High-dose radiation (HDR), 1389 High dose rate brachytherapy. See Iridium seeds High dose rate remote afterloading (HDR), 32 High dose rate remote radiation therapy, 1389 High-energy photon therapy, 1389 High-grade lymphoma, 1389 High-grade squamous intraepithelial lesion (HSIL), 1390 High-risk cancer, 1390
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Hispanics and cancer, 444, 690-692 Histamine 2 antagonists, 587-588 Histiocytoma, malignant fibrous, 752 Histiocytosis X, 588-590 HIV-related cancers, 90, 590-593 HLRCC. See Hereditary leiomyomatosis and renal cell cancer HMOs. See Health maintenance organizations HMPS. See Hereditary mixed polyposis syndrome HNPCC. See Hereditary nonpolyposis colorectal cancer Hodgkin disease, 593-596, 744 Home health services, 597-599 Homeopathic medicine, 1390 Homeopathy, 310 Homologous uterine sarcoma. See Uterine cancer Hormonal therapies, 61, 75, 599-601; adjuvant, 20 Hormone receptor tests, 601-602 Hormone replacement therapy (HRT), 603-605 Hormone-response assay. See Progesterone receptor assay Horner syndrome, 605-606 Hospice care, 404, 606-608, 919 Hot flashes, 608-609 HP. See Hereditary pancreatitis HPRCC. See Hereditary papillary renal cell carcinomas HPV. See Human papillomavirus HRAS gene testing, 609 HRT. See Hormone replacement therapy HSV. See Herpes simplex virus HTLV. See Human T-cell leukemia virus Human chorionic gonadotropin (HCG), 609-610 Human epidermal growth factor receptor 2. See HER2/neu protein Human growth factors and tumor growth, 610-611 Human herpesvirus 4. See Epstein-Barr virus Human papillomavirus (HPV), 611-612, 894 Human T-cell leukemia virus (HTLV), 612 Hurthle cell neoplasm, 1390 Hydatidiform mole, 527, 612-613 Hydroperitoneum. See Ascites 5-Hydroxyindoleacetic acid (5HIAA) test, 613-614 Hyper-, 1390
Salem Health: Cancer Hyperadrenocorticism. See Cushing syndrome Hyperalimentation, 1390 Hypercalcemia, 614-615 Hypercoagulation disorders, 615-617 Hypercortisolism. See Cushing syndrome Hypereosinophilic syndrome. See Eosinophilic leukemia Hyperfractionation, 1390 Hypernephroma, 1390 Hyperpyrexia. See Fever Hypersensitivity, 1390 Hyperthermia therapy, 617-618; microwave, 791 Hyperthermic perfusion, 618-619 Hyperuricemia, 1390 Hypo-, 1390 Hypofractionation, 1390 Hypofunctioning thyroid nodule. See Cold nodule Hypogeusia. See Taste alteration Hypopharyngeal cancer, 619, 1390 Hysterectomy, 608, 620-621 Hysterography, 621-622 Hystero-oophorectomy, 622-623 Hysteroscopy, 623-624 IBD. See Inflammatory bowel disease ICC. See Immunocytochemistry Idiopathic pneumonia syndrome, 1390 IEP. See Immunoelectrophoresis iFOBT. See Immunochemical fecal occult blood test IHC. See Immunocytochemistry Ileocolitis. See Crohn disease Ileostomy, 625-626 Imaging tests, 68, 120-121, 194, 199, 297, 315, 347, 389, 416-417, 495, 621, 626-629, 740, 750, 754, 943, 984, 1082, 1157, 1185-1186, 1199, 1203, 1213, 1252 Iminodiethanol. See Diethanolamine Immature teratoma, 1390 Immune response to cancer, 629-632 Immune system, 139 Immunochemical fecal occult blood test (iFOBT), 632-633 Immunocytochemistry, 633-634 Immunoelectrophoresis (IEP), 634-635 Immunoglobulin light-chain amyloidosis. See Amyloidosis Immunohistochemistry, 633-634 Immunotherapy, 85, 139, 635-638. See also Biological therapy Implantable pump, 1390
Implanted intrathecal device. See Ommaya reservoir Implants, breast, 188-190 IMRT. See Intensity-modulated radiation therapy Imuran. See Azathioprine Incidence, 1390 Incision, 1390 Incisional biopsy, 1390 Incontinence, 1390 Indolent, 1390 Indoles, 638 Induction therapy, 1390 Infection, 638-641 Infectious cancers, 641-643. See also Bacteria; Oncogenic viruses; Viruses Infertility, 471, 643-645 Infiltrating breast cancer. See Medullary carcinoma of the breast Infiltrating cancer, 1390 Infiltrating ductal carcinomas. See Invasive ductal carcinomas Infiltrating lobular carcinomas. See Invasive lobular carcinomas Inflammation of the pancreas. See Pancreatitis Inflammatory bowel disease, 645 Informed consent, 646-647 Infusion therapies, 647-648 Inguinal orchiectomy. See Orchiectomy Insurance, 648-651; managed care, 757; Medicare, 772; Native North Americans, 833; preferred provider organizations (PPOs), 990. See also Health maintenance organizations; Managed care; Medicare; Preferred provider organizations Integrative oncology, 651-652 Intensity-modulated radiation therapy (IMRT), 652-653 Inter-, 1390 Interferon, 141, 653-654 Interleukins, 141, 637, 654-655 Interstitial cell tumors. See Leydig cell tumors Interstitial radiation therapy, 1390 Intestinal polyps. See Polyps Intra-, 1390 Intra-arterial chemotherapy. See Hepatic arterial infusion Intracranial tumor, 1390 Intrahepatic cholangiocarcinoma. See Bile duct cancer Intrahepatic infusion, 1390
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Intraluminal intubation and dilation, 1390 Intramuscular (IM), 1390 Intraocular cancers. See Eye cancers Intraoperative radiation therapy (IORT), 1390 Intraperitoneal (IP), 1390 Intraperitoneal chemotherapy, 1390 Intraperitoneal infusion, 1390 Intraperitoneal radiation therapy, 1390 Intrathecal chemotherapy, 1390 Intravenous pyelogram (IVP), 1390 Intravenous pyelography. See Urography Intraventricular infusion, 1390 Invasive cancer, 655-656 Invasive ductal carcinomas, 656 Invasive lobular carcinomas, 657 Inverted papilloma, 1391 Ionizing radiation, 657-658 Iridium seeds, 658-659 Iron-poor blood. See Anemia Irradiation, 1391 Islet cell tumors, 659-661 Isoflavones, 661 Isolated hepatic perfusion, 1391 Isolated limb perfusion, 1391. See also Hyperthermic perfusion Isolated lung perfusion, 1391 Itching, 661-663 -itis, 1391 Jaundice, 1391 JCCC. See Jonsson Comprehensive Cancer Center Jewett staging system. See ABCD Jews, Ashkenazi, 107-109, 444 Jim’s Juice. See Cancell Jonsson Comprehensive Cancer Center (JCCC), 664-665 Journaling, 665 J-pouch coloanal anastomosis, 1391 JPS. See Juvenile polyposis syndrome JS-101. See Cancell JS-114. See Cancell Juvenile fibroadenomas. See Fibroadenomas Juvenile myasthenia gravis. See Myasthenia gravis Juvenile myelomonocytic leukemia (JMML), 1391 Juvenile polyposis syndrome, 582, 665666 Kahler disease, 1391 Kampfstoff LOST. See Mustard gas Kaposi sarcoma, 590, 667-669
Index Karnofsky performance status (KPS), 669-670 Keratoacanthoma, 1391 Keratosis, 670 Keyhole surgery. See Laparoscopy Ki67 test, 670-671 Kidney cancer, 577, 580-581, 671-674, 1043; malignant rhabdoid tumor, 753 Klatskin tumor, 1391. See also Bile duct cancer Klinefelter syndrome, 674-675 Korean ginseng. See Ginseng, panax KPS. See Karnofsky performance status Krukenberg tumors, 675-676 KS. See Kaposi sarcoma Kübler-Ross model, 542 Lacrimal gland tumors, 677-678 Lactate dehydrogenase (LDH) test, 678 Laetrile, 310, 679 Lambert-Eaton myasthenic syndrome (LEMS), 679-681 Langerhans cell histiocytosis, 588 Laparoscopic surgery, 681-682 Laparoscopy, 681-682 Large-cell carcinoma, 1391 Lariciresinol. See Phytoestrogens Laryngeal cancer, 318, 399, 682-685 Laryngeal nerve palsy, 685-686 Laryngectomy, 686-687 Laryngoscopy, 687-688 Laser therapies, 688-690 Late-stage cancer, 1391 Latinos and cancer, 444, 690-692 Laxatives, 692 LC. See Leptomeningeal carcinomas LCIS. See Lobular carcinoma in situ LDH test. See Lactate dehydrogenase test LEEP. See Loop electrosurgical excisional procedure Leiomyomas, 693-694 Leiomyomatosis, 577 Leiomyosarcomas, 694-696 LEMS. See Lambert-Eaton myasthenic syndrome Leptomeningeal carcinomas, 696-697 Leukapharesis, 698 Leukemias, 43, 154, 698-702, 1391; acute lymphocytic leukemia (ALL), 11; acute myelocytic leukemia (AML), 13; chronic lymphocytic leukemia (CLL), 276; chronic myeloid leukemia (CML), 279; Down syndrome and, 381; eosinophilic, 424; hairy cell, 550;
human T-cell leukemia virus (HTLV), 612 Leukemic reticuloendothelosis. See Hairy cell leukemia Leukeran. See Chlorambucil Leukoencephalopathy, 702-704 Leukopenia, 704 Leukoplakia, 704-706 Leydig cell tumors, 706 Li-Fraumeni syndrome (LFS), 706-708 Ligation, 1391 Light-emitting diode (LED) therapy, 1391 Limb removal, 56, 708 Limb salvage, 708-709 Limited-stage small cell lung cancer, 1391 Lindau tumors. See Hemangioblastomas Linear accelerator, 709-710 Linfolysin. See Chlorambucil Lip cancers, 710-712 Lipoma, 1391 Liposarcomas, 712-713 Liver biopsy, 714-715 Liver cancers, 101, 136, 568, 715-718; hepatitis and, 569 Liver enlargement, 571 Living will, 25, 719-720 Living with cancer, 720-723 Lobectomy, 723-724 Lobular carcinoma in situ (LCIS), 185, 725-726 Localized cancer, 1391 Locally advanced cancer, 1391 Long-distance caregiving, 726-727 Loop electrosurgical excisional procedure (LEEP), 317, 727-728 Lorazepam. See Benzodiazepines Lost. See Mustard gas Louis-Bar syndrome. See Ataxia telangiectasia Low-grade lymphoma, 1391 Low-grade squamous intraepithelial lesion (LSIL), 1391 Lower gastrointestinal (GI) series, 1391 Lumbar puncture, 728-730 Lumpectomy, 730-732, 761 Lumps, 732-733; removal, 730 Lung cancers, 16, 40, 133, 138, 148, 433, 733-736, 871; bronchoalveolar, 197. See also Adenocarcinomas; Bronchoalveolar lung cancer; Mesothelioma Lung removal; bilobectomy, 138; lobectomy, 723; pneumonectomy, 977
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Lutein, 737 Lycopene, 737-738 Lymph nodes, 116, 1391 Lymphadenectomy, 738-740 Lymphangiography, 740-741 Lymphangiosarcomas, 741-742 Lymphedema, 742-743 Lymphocytes, 139 Lymphocytosis, 743-744 Lymphoepithelioma, 1391 Lymphography, 1391 Lymphoid tumors. See Orbit tumors Lymphokines. See Cytokines Lymphomas, 154, 677, 744-747, 1391; Burkitt, 200; cutaneous T-cell lymphoma (CTCL), 342; Hodgkin disease, 593; mantle cell lymphoma (MCL), 759; mucosa-associated lymphoid tissue (MALT), 804; nonHodgkin, 855; pesticides, 949; primary central nervous system, 1003; Waldenström macroglobulinemia (WM), 1240 Lymphomatoid papulosis. See Cutaneous T-cell lymphoma Lymphoplasmacytic lymphoma. See Waldenström macroglobulinemia Lymphoscintigraphy, 1391 Lytic lesion, 1392 M. D. Anderson Cancer Center, 748750 Macrobiotic diet, 750 Magnetic resonance imaging (MRI), 176, 750-752, 1392 Magnetic resonance perfusion imaging, 1392 Magnetic resonance spectroscopic imaging (MRSI), 1392 Magnetic-targeted carrier, 1392 Maintenance therapy, 1392 Malignant, 1392 Malignant ascites, 1392 Malignant fibrous histiocytoma (MFH), 752-753 Malignant meningioma, 1392 Malignant mesothelioma, 1392 Malignant mixed Müllerian tumor (MMMT), 1392 Malignant peripheral nerve sheath tumor (MPNST), 1392 Malignant pleural effusion, 1392 Malignant rhabdoid tumor of the kidney, 753-754 Malignant tumors, 754
Salem Health: Cancer MALT lymphomas. See Mucosaassociated lymphoid tissue lymphomas Mammography, 754-757 Mammosite. See Radiation therapies Mammotome, 1392 Managed care, 557, 757-759 Mandelonitrile-beta-glucuronide. See Laetrile Mantle cell lymphoma (MCL), 759-761 Margin, 1392 Marginal zone lymphoma (MZL), 1392 Marijuana, medical, 355, 768 Marinol. See Delta-9tetrahydrocannabinol Mast cell tumors, 763 Mastectomy, 761-763 Mastitis, 386 Mastocytomas, 763-764 Matairesinol. See Phytoestrogens Mateine. See Caffeine Matrix metalloproteinase inhibitors, 764-765 Mature and immature teratomas. See Germ-cell tumors Mature T-cell lymphoma, 1392 Mature teratoma, 1392 Maxillectomy. See Oral surgery Maxillofacial surgery, 893-894 Maximum inspiratory pressure test (MIP test), 1392 Maximum tolerated dose, 1392 Mayo Clinic Cancer Center, 765-766 MCC. See Merkel cell carcinomas MCL. See Mantle cell lymphoma MDR. See Drug resistance and multidrug resistance Mean survival time, 1392 MeCCNU. See 1-(2-Chloroethyl)-3(4-methylcyclohexyl)-1-nitrosourea Median survival time, 1392 Mediastinal tumors, 766-768 Mediastinoscopy, 768 Medical marijuana, 768-770. See also Delta-9-tetrahydrocannabinol Medical nutrition therapy, 1392 Medical oncology, 770-772 Medicare, 772-774 Medullary carcinoma of the breast, 774-775 Medullary thyroid cancer, 1392 Medulloblastomas, 775-776 Melanomas, 116, 776-779, 1088, 1392; staging, 1, 195 Melphalan, 779
Memorial Sloan-Kettering Cancer Center, 780-781 MEN 1. See Multiple endocrine neoplasia type 1 MEN 2. See Multiple endocrine neoplasia type 2 Meningeal carcinomatosis, 781-782 Meningiomas, 173, 782-783 Meningitis; carcinomatous, 237-238 Menstruation, absent, 50 Mercurials. See Pesticides Merkel cell carcinomas (MCC), 783-785 Mesenchymal cystic hamartomas. See Pleuropulmonary blastomas Mesenchymomas, 785-786 Mesothelioma, 103, 433, 786-788 Metaplastic carcinoma, 1392 Metastasectomy, 1392 Metastasis, 788-790 Metastasize, 1392 Metastatic squamous neck cancer with occult primary, 790 Metronomic therapy, 1392 MF. See Mycosis fungoides MFH. See Malignant fibrous histiocytoma Microcalcifications, 790-791 Microwave hyperthermia therapy, 791-792 Mineral oils, 792 Mistletoe, 793 Mitochondrial DNA mutations, 794-795 Mitotic inhibitors, 84 Mixed glioma, 1393 MLH1 gene, 795-796 MM. See Multiple myeloma Modified radical mastectomy, 1393 Mohs surgery, 796 Molar pregnancy, 527, 612, 1393 Molecular marker, 1393 Molecular oncology, 796-798 Moles, 394, 798-800 Monoclonal antibodies, 141, 637, 800-802 Mortality rates, 1140 Motion sickness devices, 802 Mouth cancer. See Oral cancers Mouth surgery. See Oral surgery MRI. See Magnetic resonance imaging MRT. See Malignant rhabdoid tumor of the kidney MSH genes, 803 Mucinous carcinomas, 803-804 Mucinous cyst adenocarcinoma. See Appendix cancer
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Mucocutaneous myxoma. See Carney complex Mucosa-associated lymphoid tissue (MALT) lymphomas, 804-806, 1393 Mucositis, 806-807, 1124 Mucous membranes, epidermoid cancers of, 429-431 Müllerian tumor, 1393 Multidisciplinary, 1393 Multidrug resistance (MDR), 383-385 Multifocal demyelinating disease. See Leukoencephalopathy Multiple endocrine neoplasia type 1 (MEN 1), 807-808, 844 Multiple endocrine neoplasia type 2 (MEN 2), 808-809, 956 Multiple hamartoma syndrome. See Cowden syndrome Multiple myeloma, 58, 809-812 Music therapy products. See Aids for cancer patients Mustard gas, 812-813 Mutagenesis, 813-815 Myasthenia gravis, 815-817 MYC oncogene, 817 Mycosis fungoides, 817-819 Myelodysplastic syndromes, 819-820 Myelofibrosis, 820-822 Myeloma, 154, 822-823; multiple, 58, 809 Myeloproliferative disorders, 823-825 Myelosuppression, 825 Myleran. See 1,4-Butanediol dimethanesulfonate Myopericytoma. See Hemangiopericytomas Myxoid neurofibroma. See Carney complex Nabilone. See Delta-9tetrahydrocannabinol NAP Herbal Tea. See Essiac 2-Naphthylamine, 826 Narcotics. See Opioids Nasal cavity cancers, 826-829 Nasopharyngeal cancer. See Throat cancer National Cancer Institute (NCI), 829-830 National Science Foundation (NSF), 830-831 Native North Americans and cancer, 832-833 Naturopathy, 310 Nausea, 81, 506, 834-836. See also Antinausea medications
Index NCI. See National Cancer Institute Neck cancers, 554-556; metastatic squamous with occult primary, 790 Neck dissection, 1393; radical, 1027 Necrosis, 1393 Needle biopsies, 142, 836-838 Needle localization, 838. See also Wire localization Negative axillary lymph node, 1393 Neoadjuvant therapy, 1393 Neonatal myasthenia gravis. See Myasthenia gravis Neoplastic syndromes. See Premalignancies Neoral. See Cyclosporin A Neosar. See Cyclophosphamide Nephrectomy, 1393 Nephroblastomas, 839 Nephrostomy, 839-840 Nephrotomogram, 1393 Nephrotoxic, 1393 Nephroureterectomy, 1393 Nerve block, 1393 Nerve-sparing radical prostatectomy, 1393 NET. See Neuroendocrine tumors Neuroblastomas, 841-842 Neuroectodermal tumors, 842-844 Neuroendocrine tumors, 844-845 Neurofibromatosis type 1 (NF1), 845-847 Neurofibromatosis type 2 (NF2), 4 Neurologic oncology, 847-849 Neuromas, 1393; acoustic, 4-6 Neuropathy, 1393 Neurotoxicity, 1393 Neutropenia, 849-850 Nevi. See Moles New York Cancer Hospital. See Memorial Sloan-Kettering Cancer Center NF1. See Neurofibromatosis type 1 NF2. See Neurofibromatosis type 2 NHL. See Non-Hodgkin lymphoma Nickel compounds and metallic nickel, 851 Night sweats, 852-853 Nijmegen breakage syndrome, 853 Nipple discharge, 854 Nitrogen mustards, 45, 268 Nitrosoureas, 45, 269 No code. See Do-not-resuscitate (DNR) order Nodule, cold, 292-293 Nonfunctioning tumor, 1393 Non-Hodgkin lymphoma, 744, 855-858
Nonseminoma, 1393. See also Germ-cell tumors Non-small-cell lung cancer, 1393 Nonsteroidal anti-inflammatory drugs (NSAIDs), 858-859, 915 NSC-3088. See Chlorambucil NSF. See National Science Foundation Nuclear medicine scan, 495, 859-861; thyroid, 1172 Nurses; oncology clinical, 885 Nutrition, 38, 1243; cancer prevention and, 86, 135, 138, 212, 245, 335, 370, 474, 486, 491, 573, 638, 661, 737-738, 750, 861-864, 877, 937, 962, 999, 1250; cancer treatment and, 527, 864867, 1080, 1128. See also Antioxidants; Beta-carotene; Bioflavonoids; Calcium; Carotenoids; Coenzyme Q10; Cruciferous vegetables; Dietary supplements; Fiber; Folic acid; Fruits; Garlic and allicin; Ginseng, panax; Green tea; Herbs as antioxidants; Isoflavones; Lutein; Lycopene; Macrobiotic diet; Omega-3 fatty acids; Phytoestrogens; Resveratrol; Soy foods; Sun’s soup; Wine Oat cell carcinoma. See Lung cancers Obesity-associated cancers, 30, 868-870, 1052 Occult primary tumor, 1393 Occupational exposures, 871-873. See also Asbestos; Carcinogens, known; Carcinogens, reasonably anticipated; Coke oven emissions; Pesticides; Silica, crystalline; Wood dust Occupational therapy, 873-875 OCs. See Organochlorines Ocular melanoma, 1393 OD. See Oligodendrogliomas Oligoastrocytoma, 1393 Oligodendrogliomas, 173, 875-877 Omega-3 fatty acids, 877-878 Omentectomy, 1393 Ommaya reservoir, 878 Oncogenes, 878-881, 1050; MYC oncogene, 817; proto-oncogenes, 1015 Oncogenic viruses, 881-882 Oncology, 882-885; dermatology, 362; endocrinology, 409; gastrointestinal, 508; gynecologic, 547; hematologic, 562; integrative, 651; medical, 770; molecular, 796; neurologic, 847; ophthalmic, 889; pediatric, 938-940;
1431
pharmacy, 952; radiation, 1021; surgical, 1138; urologic, 1214; veterinary, 1226; viral, 1230 Oncology clinical nurse specialist, 885887 Oncology social worker, 887-888 Oophorectomy, 608, 888-889 Open biopsy, 1393 Open colectomy, 1393 Operable, 1393 Ophthalmic oncology, 889-891 Opioids, 892, 915 Opportunistic infection, 1393 Oral, 1393 Oral cancers, 433, 894-897 Oral contraceptives. See Birth control pills Oral surgery, 893-894 Orbit tumors, 897-898 Orchiectomy, 898-899 Organ transplantation, 899-901 Organochlorines (OCs), 901-902 Organophosphates. See Pesticides Oriental ginseng. See Ginseng, panax Oriental medicine. See Traditional Chinese medicine Oropharyngeal cancers, 894-897 Orthopedic surgery, 902-903 Osteitis deformans. See Paget disease of bone Osteosarcoma, 1393. See also Bone cancers Ostomy, 1393 Otolaryngology, 903-905 Ovarian ablation, 1393 Ovarian cancers, 106, 540, 544, 888, 905-908; epithelial, 909 Ovarian cysts, 908-909 Ovarian epithelial cancer, 909-911 Ovary removal, 888, 1060 Overtreatment, 911 Oxygen therapy, 1393 P14ARF. See Cyclin-dependent kinase inhibitor-2A P16INK4a. See Cyclin-dependent kinase inhibitor-2A P53. See TP53 protein Paget disease of bone, 912-914 Paget disease of the nipple. See Breast cancers PAHs. See Polycyclic aromatic hydrocarbons Pain, 196; bone, 165; breakthrough, 180. See also Acupuncture;
Salem Health: Cancer Cyclooxygenase 2 (COX-2) inhibitors; Medical marijuana; Nonsteroidal antiinflammatory drugs (NSAIDs); Opioids Pain management medications, 892, 914-917 Palliative treatment, 196, 404, 606, 917-919 Palmar-plantar erythrodysesthesia. See Hand-foot syndrome PALP. See Placental alkaline phosphatase Palpation, 920 Panax ginseng, 531-532 Pancoast tumor, 1394 Pancolitis, 920-921 Pancreatectomy, 921-923 Pancreatic cancers, 659, 923-927 Pancreatitis, 927-928; hereditary, 580581 Pap test, 928-929 Papillary renal cell carcinomas, hereditary, 581 Papillary serous carcinoma, 1394 Papillary thyroid cancer, 1394 Papillary tumor, 1394 Papilledema, 1394 Para-aminobiphenyl. See 4-Aminobiphenyl Paracentesis, 929-930 Paraganglioma, 1394 Paralysis of the larnyx. See Laryngeal nerve palsy Paranasal sinus cancers, 826-829 Paraneoplastic syndromes, 931-932 Parasitic cancer. See Infectious cancers Parathyroid cancer, 932-934 Parathyroidectomy, 1394 Parotidectomy, 1394 Partial cystectomy, 1394 Partial hysterectomy, 1394 Partial laryngectomy, 1394 Partial mastectomy, 1394 Partial nephrectomy, 1394 Partial oophorectomy, 1394 Partial remission, 1394 Partial vulvectomy, 1394 Pathologic fracture, 1394 Pathology, 934-937 Pathology report, 1394 Patient advocate, 1394 Patient-controlled analgesia (PCA), 1394 PBSCT. See Peripheral blood stem cell transplantation PC-CARE. See PC-SPES
PC-SPES, 937-938 PCC. See Pheochromocytomas PCP. See Primary care physician P-(di-2-chlorethyl)-aminophenylbutryric acid. See Chlorambucil PDT. See Photodynamic therapy Pediatric hematology, 938-940 Pediatric oncology, 938-940 Pelvic examination, 940-941 Pelvic exenteration, 1394 Pelvic lymphadenectomy, 1394 Penectomy, 942, 1394 Penile cancer, 941-943 Penis; cancer, 941; removal, 942 Percutaneous ethanol injection, 1394 Percutaneous transhepatic cholangiodrainage (PTCD), 1394 Percutaneous transhepatic cholangiography (PTHC), 943-944 Perfusion; continuous hyperthermic peritoneal, 318; hyperthermic, 618 Periampullary cancer, 1394 Pericardial effusion, 944-946 Pericardiocentesis, 946 Perihilar cancer. See Bile duct cancer Perineal colostomy, 1394 Perineal prostatectomy, 1394 Peripheral blood lymphocyte therapy, 1394 Peripheral blood stem cell transplantation (PBSCT), 163 Peripheral venous catheter, 1394 Peritoneal cancer, 1395 Peritoneal fluid, 105 Peritoneovenous shunts, 946-947 Peritonitis, 1395 Permixon. See Saw palmetto Personality and cancer, 947-948 Pesticides, 948-951 PET. See Positron emission tomography Peutz-Jeghers syndrome (PJS), 582, 951-952 PgR assay. See Progesterone receptor assay Pharmacy oncology, 952-955 Pharyngeal cancer, 619 Phenacetin, 955 Phenolics, 138, 955-956 Phenoxy compounds. See Pesticides Phenylbutyric acid nitrogen mustard. See Chlorambucil Pheochromocytomas, 956-958 Pheresis, 958-959 Photo-beam radiation, 1395 Photocoagulation, 1395
1432
Photodynamic therapy (PDT), 959-960 Photopheresis, 1395 Phyllodes tumors, 960-961 Phytochemicals, 492 Phytoestrogens, 962-963 Piles. See Hemorrhoids Pineoblastomas, 963-965 Pineocytoma, 1395 Pinhole surgery. See Laparoscopy Pituitary tumors, 965-967 PJS. See Peutz-Jeghers syndrome Placental alkaline phosphatase (PALP), 968 Plant alkaloids and terpenoids in chemotherapy, 968-971 Plaque radiotherapy, 1395 Plasma cell myeloma, 1395 Plasma cell tumor, 1395 Plasmacytoma, 1395 Plasticizers, 971-972 Plastics, 149 Pleural biopsy, 972-973 Pleural effusion, 973-975 Pleural tap. See Thoracentesis Pleurectomy, 1395 Pleurodesis, 975 Pleuropulmonary blastomas, 975-976 PMS genes, 976-977 Pneumatic larynx, 1395 Pneumonectomy, 977-978 Pneumonia, 979-980 Poikiloderma congenitale. See RothmundThomson syndrome Pollution, air, 39-42 Polycyclic aromatic hydrocarbons, 981 Polycythemia vera, 981-982 Polypectomy, 982-983 Polyphenolic phytoalexin. See Resveratrol Polyposis syndromes; hereditary, 582584; hereditary mixed, 579, 951; juvenile, 665-666 Polyps, 983-984; adenomatous, 18-19, 95; colon, 18, 95, 296, 498, 579, 582, 665; gastric, 500; removal, 982 Polyps and spots syndrome. See PeutzJeghers syndrome (PJS) Ponicidin. See PC-SPES Port, 1395 Positive axillary lymph node, 1395 Positron emission tomography (PET), 984-987 Posterior pelvic exenteration, 1395 Posterior urethral cancer, 1395 Postremission therapy, 1395
Index Post-transplant lymphoproliferative disorder (PTLD), 1395 Poverty, 987-989; Native North Americans, 833 Power of attorney, 1395 PPOs. See Preferred provider organizations Prayer, 989-990 Precancerous, 1395 Precancerous dermatitis, 1395 Preferred provider organizations (PPOs), 758, 990-991 Pregnancy, 184, 992-994; molar, 527, 612 Premalignancies, 994-997 Prevent Cancer Foundation, 997-999 Prevention, 999-1001; chemoprevention, 254; exercise, 451 Preventive mastectomy, 1395 Primary care physician, 1001-1003 Primary central nervous system lymphomas, 1003 Primary tumor, 1395 Primitive neuroectodermal tumor (PNET), 1395 Proctoscopy, 1395 Proctosigmoidoscopy, 1395 Profound hypochlorhydria. See Achlorhydria Progesterone, 146 Progesterone receptor assay, 10031004 Prognosis, 1395 Progression-free survival, 1395 Propenamide. See Acrylamides Prophylactic cranial irradiation, 1395 Prophylactic surgery, 1395 Prostate cancer, 72, 374, 532, 1004-1006, 1008; imaging, 1185; staging, 1. See also Benign prostatic hyperplasia (BPH); Digital rectal exam (DRE); Endorectal ultrasound; Gleason grading system; Prostate-specific antigen (PSA) test; Prostatectomy; Prostatitis; Transrectal ultrasound; Watchful waiting Prostate disorders, 128, 1004, 1009 Prostate-specific antigen (PSA) bounce, 1395 Prostate-specific antigen (PSA) failure, 1396 Prostate-specific antigen (PSA) test, 1006-1008 Prostatectomy, 1008-1009 Prostatitis, 1009-1010
Prostheses, 39, 58, 1396 Protease inhibitors, 90 Proteasome inhibitors, 1010 Protein electrophoresis, 1010-1011 Proteins, 610; alpha fetoprotein, 48; HER2/neu, 573; TP53, 1177 Proteomics, 1012-1013 Proton beam therapy, 1014-1015 Proto-oncogenes, 1015-1016 Pruritus, 1396. See Itching PSA test. See Prostate-specific antigen test Psoralen and ultraviolet A therapy (PUVA therapy), 1396 Psycho-oncology, 1016-1018 Psychosocial aspects of cancer, 919, 1018-1020. See also Anxiety; Caregiving; Depression; Grief; Relationships; Self-image; Stress management; Support Groups; Survivorship issues PTHC. See Percutaneous transhepatic cholangiography Punch biopsy, 1396 PV. See Polycythemia vera Quadrantectomy, 1396 Quality of life, 1396 Quartz. See Silica, crystalline Radiation; cell phones, 249; cobalt 60, 289; electromagnetic, 399; ionizing, 657; ultraviolet, 1200 Radiation dermatitis, 1396 Radiation enteritis, 1396 Radiation fibrosis, 1396 Radiation necrosis, 1396 Radiation oncology, 1021-1023 Radiation surgery, 1396 Radiation therapies, 3, 167, 170, 289, 658, 1014, 1023-1026; afterloading, 32; external beam, 454, 1024; intensity-modulated, 652; intraoperative, 1025; systemic, 1025 Radical cystectomy, 1396 Radical hysterectomy, 1396 Radical local excision, 1396 Radical lymph node dissection, 1396 Radical neck dissection, 1027 Radical nephrectomy, 1396 Radical perineal prostatectomy, 1396 Radical retropubic prostatectomy, 1396 Radical vulvectomy, 1396 Radiofrequency ablation, 1027-1030 Radioimmunoguided surgery, 1396
1433
Radiologic exam, 1396 Radiology, 1396 Radionuclide scan, 495, 626, 1030 Radiopharmaceuticals, 1030-1032 Radiosurgery. See Gamma Knife Radon, 1032 Rathke cleft cysts. See Pituitary tumors Rathke pouch tumors. See Craniopharyngiomas RB1 gene, 880, 1032-1033 Receptor analysis, 1033-1034 Recklinghausen’s tumors. See Adenomatoid tumors Reconstruction, breast, 190-193 Reconstructive surgery, 1034-1036 Rectal cancer, 1, 135, 294, 300, 304, 374, 467, 1036-1038 Rectal reconstruction, 1396 Rectum, 70; cancer, 1, 135, 294, 300, 304, 374, 467, 1036; imaging, 416; removal, 1, 294 Recurrence, 1038 Refractory cancer, 1396 Regional lymph node dissection, 1396 Regression, 1396 Rehabilitation, 1038-1041 Relationships, 1041-1043 Remission, 1396 Remission induction therapy, 1396 Renal cell cancer, 577 Renal cell carcinomas, hereditary papillary, 581-582 Renal pelvis tumors, 1043-1044 Report on Carcinogens (RoC), 10441045 Resection, 1396 Restasis. See Cyclosporin A Resveratrol, 1045-1046 Retinoblastomas, 1046-1047 Retinol. See Beta-carotene Retropubic prostatectomy, 1396 Return of cancer. See Recurrence Rhabdoid tumor, 1397 Rhabdomyosarcomas, 1048-1050 RhoGD12 gene, 1050 Richter syndrome, 1050-1051 Risk factor, 1397 Risks, 1052-1054; assessment and family history, 461-464 Robert H. Lurie Cancer Center, 10541056 RoC. See Report on Carcinogens Rothmund-Thomson syndrome, 10561057 Rous sarcoma virus (RSV), 880
Salem Health: Cancer Saccharin. See Artificial sweeteners Salivary gland cancer, 17, 1058-1060 Salmonella typhi, 118 Salpingectomy, 1060-1062 Salpingo-oophorectomy, 1060-1062 Sandimmune. See Cyclosporin A Sarcoma botyroides. See Vaginal cancer Sarcomas, 1397; alveolar soft-part, 49-50; angiosarcomas, 69; carcinosarcomas, 238; dermatofibrosarcoma protuberans (DFSP), 360; Ewing, 447; fibrosarcomas, 478; hemangiopericytomas, 559; hemangiosarcomas, 560; Kaposi, 590, 667; leiomyosarcomas, 694; liposarcomas, 712; lymphangiosarcomas, 741; rhabdomyosarcomas, 1048; soft-tissue, 712, 1062-1065; synovial, 1149 Sarcomatoid carcinoma, 1397 Saridon. See Phenacetin Saw palmetto, 1065-1066 Scans; bone, 166; brain, 176; computed tomography (CT), 315, 626; gallium, 495; nuclear medicine, 859; radionuclide, 626, 1030; thyroid nuclear medicine, 1172 SCC. See Squamous cell carcinomas Schwannoma tumors, 173, 1066; vestibular, 4 Scintimammography, 1397 SCLC1 gene, 1067 Screening, 1000, 1054, 1067-1070; breast cancer, 193, 283, 754; breast selfexamination (BSE), 193; clinical breast exam (CBE), 283; colorectal cancer, 297, 304, 374, 467, 1082; digital rectal exam (DRE), 374; fecal occult blood test (FOBT), 467; immunochemical fecal occult blood test (iFOBT), 632; mammography, 754; prostate cancer, 374; prostatespecific antigen (PSA) test, 1006 Seborrheic keratosis. See Keratosis Second opinions, 1070-1071 Segmental resection, 1397 Selective estrogen receptor modulators (SERMs), 76, 441 Self-image, 1071-1072 Seminal vesicle biopsy, 1397 Seminoma, 1397. See Germ-cell tumors Semustine. See 1-(2-Chloroethyl)-3(4-methylcyclohexyl)-1-nitrosourea Senfgas. See Mustard gas
Sentinel lymph node (SLN) biopsy and mapping, 1073 Sepsis, 638-641 Serenoa repens. See Saw palmetto SERMs. See Selective estrogen receptor modulators Serotonin, 613 Serous endometrial carcinoma. See Uterine cancer Sertoli cell tumors, 1073-1074 Sestamibi scan, 1397 Sexuality and cancer, 722, 1074-1076 Sézary syndrome, 1076-1078 Shark cartilage. See Cartilage supplements Shave biopsy, 1397 Sheridan’s Formula. See Cancell Shunts, 1397 Shunts, peritoneovenous, 946 SIADH. See Syndrome of inappropriate antidiuretic hormone production Sicca syndrome. See Sjögren syndrome Side effects, 98, 834, 1078-1082; taste alteration, 1151 Side-to-end coloanal anastomosis, 1397 Sigmoidoscopy, 1082-1083 Signet ring cell carcinoma, 1397 Silent Spring (Carson), 950 Silica, crystalline, 103, 1083-1084 Simian virus 40, 1084 Singlehood, 1084-1086 Sipple syndrome. See Multiple endocrine neoplasia type 2 Sjögren syndrome, 1086-1087 Skin cancers, 124, 168, 195, 341, 360, 362, 399, 458, 776, 783, 1088-1091, 1106, 1127, 1129; staging, 1. See also Basal cell carcinomas; melanomas; squamous cell carcinomas Skinning vulvectomy, 1397 Sleep hyperhydrosis. See Night sweats Sleeve lobectomy, 1397 SLN biopsy and mapping. See Sentinel lymph node biopsy and mapping Small-cell lung cancer, 1397 Small intestine cancer, 393, 1091-1093 Smokeless tobacco. See Chewing tobacco Smoker’s keratosis. See Leukoplakia Smoking cessation, 1000, 1093-1095 Smoldering myeloma, 1397 Social Security Disability Insurance (SSDI), 1096-1097 Social worker, oncology, 887 Soft-tissue sarcomas, 1397 Solid tumor, 1397
1434
Somatostatin receptor scintigraphy (SRS), 1397 Soots, 1097 Soy foods, 1098-1099 Spermatocytomas, 1099-1100 Spinal axis tumors, 1100-1102 Spinal cord compression, 1102-1103 Spiral computed tomography (CT) scan, 1397 Splenectomy, 1103-1105 Sputum; blood in, 566; cytology, 11051106 Squamous cell carcinomas, 554, 1088, 1106-1108 SRS. See Stereotactic radiosurgery SS. See Sjögren syndrome SSDI. See Social Security Disability Insurance Staging, 1108-1111; ABCD, 1; Breslow’s staging, 195; colorectal cancer, 392; Dukes’ classification, 392; Gleason grading system, 532; melanomas, 1, 195; prostate cancer, 1; TNM staging, 1173 Statistics, 1111-1114, 1140 Stem cell transplantation, 163, 1114-1116 Stent therapy, 1116-1118 Stereotactic needle biopsy, 1118 Stereotactic radiosurgery (SRS), 497, 1025, 1119-1120 Sterility, 471, 643, 1120-1121 Steroids, 61, 321 Stewart-Treve syndrome. See Lymphangiosarcomas Stomach cancers, 119, 558, 576, 675, 1121-1124; polyps, 500 Stomas, 306, 422, 625, 839, 1216 Stomatitis, 1124-1125 Stomatitis sicca. See Dry mouth Stress management, 1125-1127 Stromal tumor, 1397 Subcutaneous port, 1397 Sunlamps, 1127-1128 Sun’s soup, 1128-1129 Sunscreens, 1129-1130 Superior vena cava syndrome, 1130-1131 Supplements; antioxidants, 86; betacarotene, 135; calcium, 212; cartilage, 246; dietary, 311, 370 Support groups, 1132-1135 Supraglottic laryngectomy, 1397 Surgical biopsies, 1135-1138 Surgical oncology, 1138-1140 Survival rates, 1140-1143 Survivorship issues, 1143-1144
Index Sweeteners, artificial, 102-103 Symptoms, 852, 1144-1147 Syndrome of inappropriate antidiuretic hormone production (SIADH), 1147-1149 Syngeneic, 1397 Synovial sarcomas, 1149-1150 Systemic therapy, 1397 T-cell depletion, 1397 T-cell lymphoma, 1397; cutaneous, 342-343, 344 Tamoxifen, 75 Taste alteration, 1151-1152 TCM. See Traditional Chinese medicine Tea of Life. See Essiac Teas, 71, 540 Teen cancer. See Young adult cancers Telangiectasias, 114 Teratocarcinomas, 1152-1153 Teratomas, 1153-1154 Terminal disease, 1398 Terminally ill, 404, 606 Terpenoids, 968-971 Testicle removal, 898 Testicles, undescended. See Cryptorchidism Testicular cancer, 338, 1154-1156 Testicular self-examination (TSE), 1156-1157 Testosterone, 61 THC. See Delta-9-tetrahydrocannabinol Thermal ablation, 1398 Thermal imaging, 1157-1158 Thermotherapy, 1398 Thiocarbamates. See Pesticides Thiocyanates. See Pesticides Thiotepa, 1158 Thioureas. See Pesticides Third-line therapy, 1398 Third World nations and cancer. See Developing nations and cancer Thomson’s disorder. See RothmundThomson syndrome Thoracentesis, 1158-1160 Thoracoscopy, 1160-1161 Thoracotomy, 1161-1162 Three-dimensional conformal radiation therapy, 1398 Throat cancer, 619, 682, 894, 1058, 1162-1164. See also Head and neck cancers; Hypopharyngeal cancer; Laryngeal cancer; Oral and oropharyngeal cancers; Tobaccorelated cancers
Thrombectomy, 1398 Thrombocytopenia, 1164-1166 Thrombolysis, 1398 Thrush. See Candidiasis Thymomas, 1166 Thymus cancer, 1167-1169 Thyroid cancer, 1169-1171 Thyroid nuclear medicine scan, 1172-1173 Thyroidectomy, 1398 Time to progression, 1398 Tissue flap reconstruction, 1398 TNF. See Tumor necrosis factor TNM staging, 1173-1174 Tobacco, chewing, 261-262 Tobacco-related cancers, 30, 56, 110, 261, 281, 710, 733, 827, 894, 923, 1052, 1174-1175. See also Chewing tobacco; Cigarettes and cigars; Head and neck cancers; Lung cancer; Smoking cessation Tomography, 1398 Tongue cancer, 1398 Tongue removal, 535 Topical, 1398 Topical chemotherapy, 1398 Topoisomerase inhibitors, 84, 11751177 Total-body irradiation, 1398 Total mastectomy, 1398 Total nodal irradiation, 1398 Total pancreatectomy, 1398 Total parenteral nutrition (TPN), 1398 Total skin electron beam radiation therapy (TSEB radiation therapy), 1398 TP53 protein, 1177-1179 Trabecular cancer, 1398 Tracheostomy, 1179-1180 Traditional Chinese medicine, 8, 310. See also Acupuncture; Ginseng, panax Trans-3,4′,5-trihydroxystilbene. See Resveratrol Transfusion therapy, 1180-1182 Transitional care, 1182-1183 Transitional cell carcinomas, 1183-1185 Transperineal biopsy, 1398 Transplantation, 538; bone marrow, 163; organ, 899; stem cell, 163, 1114; umbilical cord blood, 1201 Transrectal biopsy, 1398 Transrectal ultrasound, 1185-1186 Transsphenoidal surgery, 1398 Transurethral biopsy, 1398
1435
Transurethral resection of the prostate (TURP), 1398 Transvaginal ultrasound, 1186-1187 Treatment field, 1398 Tremolite. See Asbestos Trichilemmal carcinomas, 1187 Tridymite. See Silica, crystalline Trimethylxanthine. See Caffeine TSE. See Testicular self-examination Tuberous sclerosis, 1187-1188 Tubular carcinomas, 1188-1189 Tubulovillous adenoma, 1398 Tumor flare, 1189 Tumor load, 1398 Tumor lysis syndrome, 1189-1191 Tumor markers, 48, 205-206, 223, 1191-1193 Tumor necrosis factor (TNF), 1193 Tumor protein 53. See TP53 protein Tumor-suppressor genes, 94, 344, 880, 1194-1195 Tumor volume, 1398 Tumors, 1398; benign, 18, 128-130; malignant, 754 Turcot syndrome, 1195-1196 Turmeric, 339 Tyrosine kinase inhibitors, 1196-1198 Ulcerative colitis. See Inflammatory bowel disease Ultrasound, 626, 1199-1200; breast, 194; endorectal, 416; transrectal, 1185; transvaginal, 1186 Ultrasound-guided biopsy, 1398 Ultraviolet radiation, 1129, 1200-1201 Umbilical cord blood transplantation, 1201-1202 Unilateral, 1398 Unilateral salpingo-oophorectomy, 1398 Universal colitis. See Pancolitis Unresectable gallbladder cancer, 1398 Unsealed internal radiation therapy, 1398 Upper gastrointestinal (GI) endoscopy, 1202-1203 Upper gastrointestinal (GI) series, 12031205 Urethral cancer, 1205-1206 Urinalysis, 1207-1209 Urinary diversion, 1399 Urinary system cancers, 151, 577, 580581, 671, 753, 1043, 1209-1212 Urine; blood in, 564; testing of, 1207 Urography, 1213-1214 Urologic oncology, 1214-1216 Urostomy, 1216-1217
Salem Health: Cancer Uterine cancer, 272, 543, 1217-1219. See also Endometrial cancer; Fertility drugs and cancer; Gynecologic cancers Uterus; cancer, 272, 543, 1217; imaging, 621, 623, 1186 UV. See Ultraviolet radiation V-Ha-ras Harvey rat sarcoma viral oncogene homolog. See HRAS gene testing V-raf murine sarcoma viral oncogene homolog B1. See BRAF gene Vaccines; preventive, 141, 1220-1221; therapeutic, 141, 1221-1223 Vaginal cancer, 544, 1223-1225 Vaginectomy, 1399 Valium. See Benzodiazepines Vascular access tubes, 1225-1226 Vasectomy, 1226 Vegetables, 135, 245; cruciferous, 335-336 Ventilator, 1399 Vestibular schwannomas. See Acoustic neuromas Veterinary oncology, 1226-1230 VHL disease. See Von Hippel-Lindau disease Video-assisted resection, 1399 Villous adenoma, 1399 Vinca alkaloids, 84 Vinyl amide. See Acrylamides Vinyl chloride, 1230 Vinylethylene. See 1,3-Butadiene Viral oncology, 1230-1232 Virtual colonoscopy, 297-299 Viruses, 90, 641; adenoviruses, 19; Epstein-Barr virus, 431; hepatitis B
virus (HBV), 569; hepatitis C virus (HCV), 570; herpes simplex virus, 584; herpes zoster virus, 586; HIV and AIDS, 590; human papillomavirus (HPV), 611; human T-cell leukemia virus (HTLV), 612; oncogenic, 881; related cancers, 1232-1235; risk, 1054; simian virus 40, 1084; Rous sarcoma virus, 880 Viscum album Lorantaceae. See Mistletoe Visual pathway gliomas, 1399 Vitalitea. See Essiac Vitamins, 289, 370, 486 Voice box cancer. See Laryngeal cancer Vomiting, 81, 506, 834-836; blood, 561 Von Hippel-Lindau (VHL) disease, 956, 1235-1237 Von Recklinghausen disease. See Neurofibromatosis type 1 Vulvar cancer, 544, 1237-1239 WAGR syndrome. See Wilms’ tumor aniridia-genitorurinary anomaliesmental retardation syndrome Waldenström macroglobulinemia (WM), 1240-1242 Wasting syndrome, 207 Watchful waiting, 1242-1243 Wedge resection, 1399 Weight loss, 1243-1245. See also Anorexia; Appetite loss; Cachexia Wermer syndrome. See Multiple endocrine neoplasia type 1 Whipple procedure, 1399. See also Pancreatectomy Whitmore-Jewett staging system. See ABCD
1436
Whole genome association study (WGA study), 1399 Wide local excision, 1399 Wiedemann-Beckwith syndrome. See Beckwith-Wiedemann syndrome Wilms’ tumor, 357, 839, 1245-1248 Wilms’ tumor aniridia-genitourinary anomalies-mental retardation (WAGR) syndrome, 1248-1249 Wine, 1250 Wire localization, 838, 1250-1251 WM. See Waldenström macroglobulinemia Wood dust, 1251 Woringer-Kolopp disease. See Cutaneous T-cell lymphoma X-ray tests, 68, 120-121, 417, 621, 626, 754, 943, 1203, 1252-1254 X-ray therapy, 1399 Xanthophyll. See Lutein Xeroderma pigmentosa, 1254-1255 Xerostomia. See Dry mouth XXY syndrome. See Klinefelter syndrome Yeast infection. See Candidiasis Yellow cross liquid. See Mustard gas Yolk sac carcinomas, 1256 Young adult cancers, 1256-1259 Yperite. See Mustard gas Zagari disease. See Dry mouth Zollinger-Ellison syndrome, 501, 1260-1261
